Articles de revues sur le sujet « Geraldine R »

Ensayo analítico que nuclea el debate en torno al libro de Ricardo Salvatore (2018) Paisanos itinerantes. Orden estatal y experiencia subalterna en Buenos Aires durante la era de Rosas. Buenos Aires: Prometeo. Se ofrecen algunas reflexiones en torno a la obra y notas críticas sobre los comentarios de Geraldine Davies Lenoble, Judith Farberman y Roy Hora.

Reviewers for the Journal of the Botanical Research Institute of Texas, Volume 17: Abbott, J. Richard—Ackerfield, Jennifer—Allen, Geraldine—Almeida, Odair José Garcia de—Barrett, Russell—Bennett, Bradley C.—Briggler, Malissa—Brokaw, Joshua M.—Carter, Richard—Cohen, James—Costea, Mihai—Cripps, Cathy—Dillon, Michael O.—Franck, Alan R.—Fuentes, Sara—Gandhi, Kanchi—Goldenberg, Renato—Gostel, Morgan—Graham, Shirley A.—Gustafson, Mark P.—Hansen, Bruce F.—Harrower, Emma—Hellenthal, Barbara J.—Hernández, Alexis López—Higinio Sandoval-Ortega, Manuel—Holmgren, Pat—Howard, Rebecca—Keeley, Sterling—Keith, Eric—Lance, Ron—Lavin, Matt—Lemke, David E.—Loeuille, Benoit—McPherson, Gordon—Moore, Gerry—O’Kane, Steven—Pandey, Arun—Peterson, Paul—Pfingsten, Ian—Philley, Kevin—Rosen, David—Serviss, Brett—Singhurst, Jason—Sinn, Brandon T.—Soreng, Robert—Soteropoulos, Diana L.—Sperry, Ben—Stapf, María S. de —Staples, George—Stuessy, Tod—Sullivan, Heather—Sundell, Eric—Ulloa, Carmen—Van Kley, James E.—Versiane, Ana Flávia Alves—Walsh, Neville.

THE PERSONALITY OE IRELAND. HABITAT. HERITAGE AND HISTORY by E. Estyn Evans. Cambridge: University Press. 1973. 123 pp. £2.70. Reviewed by: T. J. HughesHISTORY IN THE ORDNANCE MAP: AN INTRODUCTION FOR IRISH READERS, by John H. Andrews. Dublin : the Ordnance Survey, l974. 63 pp. £1.00. Reviewed by: Gordon L. DaviesINISHKILLANE — CHANGE AND DECLINE IN THE WEST OF IRELAND. by Hugh Brody. London: Allen Lane, the Penguin Press, 1973. 286 pp. £2.95. Reviewed by: William J. SmythNORTHERN IRELAND. by M.A. Busteed (PROBLEM REGIONS OF EUROPE. edited by D. I. Srargill). London: Oxford University Press, 1974. 48 pp. £1.00. Reviewed by: N. C. MitchclHAS IRELAND A POPULATION PROBLEM ? by R. E. Blackith. P. Dowding and F. J. Purcell. Dublin: the Irish Conservation Society, 1973. 57 pp. £0.50. Reviewed by: A. J. ParkerTHE DOWNSHIRE ESTATES IN IRELAND, 1801–1845, by W. A. Maguire. Oxford: the Clarendon Press, 1972. 284 pp. £0.00. Reviewed by: R. H. BuchananOFFICE LOCATION IN IRELAND: THE ROLE OF CENTRAL DUBLIN, by Michael J. Bannou. Dublin: An Foras Forbartha, 1973. 144 pp. £1.75. Reviewed by: A. J. ParkerIRISH RAILWAYS SINCE 1916. by Michael H. C. Baker. London: Ian Allan. 1972. 224 pp. £3.16. Reviewed by: James E. KillenA RAILWAY ATLAS OF IRELAND, by S. Maxwell Hajducki. Newton Abbot: David and Charles. 1074. 70 pp. £4.25. Reviewed by: James E, KillenACHILL. by Kenneth McNally. Newton Abbot : David and Charles. 1973. 239 pp. £3.50.; THE ARAN ISLANDS, by Daphne Pochin Mould. Newton Abbot: David and Charles. 1072. 171 pp. £2.75. Reviewed by: J. P. HaughtonTHE LIBERTIES OF DUBLIN, edited by Elgy Gillespie. Dublin : E. and T. O'Brien Ltd.. 11 Clare Street. 1973. 1211 pp. £1.65. Reviewed by: J. A. K. GrahameAN ATLAS OF IRISH HISTORY, by Ruth Dudley Edwards. London: Methuen 1973. 261 pp. £2.70 (hardback), £1.50 (paperback). Reviewed by: A. A. HornerTHE HERITAGE OF HOLY CROSS, by Geraldine Carville. Belfast : Blackstaff Press, 1973. 175 pp. £5 (hardback), £1.75 (paperback). Reviewed by:STUDIES OF FIELD SYSTEMS IN THE BRITISH ISLES,edited by A. R. H. Baker and R. A. Butlill. Cambridge: the University Press, 1973. 702 pp. £11.00. Reviewed by: J. H. AndrewsMAN MADE THE LAND: ESSAYS IN ENGLISH HISTORICAL GEOGRAPHY, edited by Man R. H. Baker and J. B. Harley. Newton Abbot : David & Charles, 1973. 208 pp. with 263 illustrations. £6.25.; ENGLISH LANDSCAPES, by W. G. Hoskins. London: British Broadcasting Corporation. 1973. 120 pp. with 84 illustrations. £0.75. Reviewed by: Kobin K. GlasscockTHE GLYNNS: Journal of the Glens of Antrim Historical Society, Vol. 1. 1973. 45 pp. £0.50. Reviewed by: J. A. K. Grahame

BackgroundA physician global assessment (DOCGL) distinguishes active from control treatments in rheumatoid arthritis (RA) effectively in clinical trials. However, RA trials select for patients who have high inflammatory activity, generally only 5-30% of all RA patients. In routine care, DOCGL, and all clinical RA measures and indices, may be elevated not only by inflammatory activity but also by joint damage and/or patient distress, complicating interpretation of RA indices and clinical decisions. A RheuMetric checklist provides feasible physician 0-10 subscale estimates of inflammation (DOCINF), damage (DOCDAM), and distress (DOCSTR), in addition to DOCGL.ObjectivesTo analyze criterion validity and specificity of 0-10 RheuMetric physician estimates for inflammation, damage, and distress, by comparing these estimates to reference RA core data set measures, as well as joint deformity/limited motion (DJC), radiographic scores and indices for FM and DEP.MethodsA cross-sectional assessment was performed at one routine care visit in Liverpool, Australia. Rheumatologists recorded RheuMetric, with 4 0-10 scales for DOCGL, DOCINF, DOCDAM, DOCSTR, and 28 joint counts for swelling (SJC), tenderness (TJC), and limited motion/deformity (DJC), laboratory tests, and radiographic scores. Patients completed a multi-dimensional health assessment questionnaire (MDHAQ), which includes RAPID3 (routine assessment of patient index data), FAST4 (fibromyalgia assessment screening tool) and MDS2 (MDHAQ depression screen). RheuMetric estimates of inflammation, damage and distress were compared to reference and other measures using correlations and linear regressions.ResultsIn 173 RA patients, variation in RheuMetric DOCINF was explained significantly by SJC and inversely by disease duration, DOCDAM by DJC, radiographic scores, and physical function, and DOCSTR by fibromyalgia and depression.ConclusionRheuMetric DOCINF, DOCDAM, and DOCSTR estimates were correlated significantly and specifically with reference measures of inflammation, damage, and distress, documenting criterion validity.Table 1.Significant VariablesMultivariable analysesDOCINF r square=0.56B (95% CI)StandardisedBP-valueSwollen joint count (SJC)0.428 (0.342; 0.515)0.641<0.001Disease duration-0.030 (-0.054; -0.005)-0.1370.018DOCDAM r square=0.51B (95% CI)StandardisedBP-valueDeformity/limited motion joint count (DJC)0.153 (0.087; 0.220)0.4000.000Radiographic Sharp van der Heijde score0.023 (0.007; 0.039)0.2480.006MDHAQ Physical function (FN)0.265 (0.039; 0.492)0.2290.022DOCSTRDOCSTR rsquare=0.42B (95% CI)StandardisedBP-valueMDHAQ FAST4 fibromyalgia assessment screening tool1.858 (0.530; 3.187)0.3020.006MDHAQ MDS2 (MDHAQ depression screen)1.164 (0.228; 2.103)0.2040.015REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNicholas Rodwell: None declared, Geraldine Hassett: None declared, Paul Bird Consultant of: Dr Bird consults for multiple companies, Theodore Pincus: None declared, Joseph Descallar: None declared.

This is the third volume in the series publishing the cleaning and excavation of the site of Vronda in the Kavousi area. The first volume, Kavousi IIA, was devoted to the excavation, stratigraphy, and architecture of the houses and their finds on the summit of the Vronda ridge (Buildings A-B, C-D, J-K, and Q), along with earlier (Building P) and later (Building R) structures around them. The second volume, Kavousi IIB , focuses on the buildings on the slopes of the Vronda ridge (Building Complexes E, I-O-N, and L-M, Building F, the pottery kiln, as well as other areas excavated on the periphery). The present volume brings the evidence from all houses together and provides a reconstruction of life and society at Vronda in the LM IIIC period.

Abstract Introduction: Patients with stage III colon cancer are routinely treated with resection followed by adjuvant chemotherapy (ACT) with a fluoropyrimidine and oxaliplatin. This one-size-fits-all approach does not account for heterogeneity in tumor biology and fails to cure ~30% of patients, highlighting the urgency for biomarkers to better understand and predict resistance to ACT or to offer alternative targeted treatment. Aim: To identify molecular characteristics predictive of resistance to standard ACT in stage III colon cancer. Methods: Patients with resected stage III colon cancer who received ACT (93% CAPOX, 7% CAP) were selected from the Prospective Dutch Colorectal Cancer cohort (PLCRC). RNA exome capture sequencing was performed on resected FFPE tumor tissue to compare differential gene expression, hallmark pathway enrichment, immune cell deconvolution and consensus molecular subtypes (CMS) between patients with versus without recurrence after surgery and ACT. Postsurgery circulating tumor DNA (ctDNA) detected in PLCRC-PROVENC3 (separate abstract) was used to select a subgroup with minimal residual disease (MRD) postsurgery, as sensitivity analysis of patients with recurrence despite ACT (chemoresistant) versus curation by ACT (chemosensitive). Results: For 264 out of 278 patients (95%), tumor-derived RNA sequencing libraries were of sufficient quality. 67 patients (25%) with recurrence (median after 13 months [IQR 7-23]) were compared to 178 patients with at least 2 year recurrence-free follow-up (median 42 months [IQR 30-53]). A total of 320 genes were differentially expressed between patients with versus without recurrence. Genesets defining epithelial-mesenchymal transition (p = 0.002) and angiogenesis (p &lt; 0.001) were enriched in the primary tumor of patients with recurrence, in part explained by the estimated larger fraction of stroma (Wilcoxon effect size r 0.18, p &lt; 0.001) and cancer-associated fibroblasts (CAFs) (r 0.19, p = 0.003). In contrast, the fraction of CD4+ T cells was lower (r 0.14, p = 0.001). Consistently, CMS4 was found more frequently in tumors from patients with versus without recurrence (57% versus 34%, p &lt; 0.001). Of the subgroup with ctDNA-based MRD postsurgery (26 out of 171 assessed patients), 19 patients (73%) with recurrence (median after 12 months [IQR 7-17]) were compared to 7 patients without recurrence (minimum follow-up 32 months). This sensitivity analysis showed similar trends in pathways, immune cells and CMS as the main analysis, with a more pronounced effect size for CAFs (r 0.27). Conclusion: Stage III colon tumors of patients who experience recurrence after resection and ACT are enriched for stroma and CAFs, while displaying less CD4+ T cells. The observed trends are sustained in the patients with MRD postsurgery. These findings may help to better predict resistance to standard ACT and elucidate targets for alternative personalized treatment. Citation Format: Ingrid Franken, Steven Ketelaars, Carmen Rubio-Alarcón, Sietske van Nassau, Suzanna Schraa, Gerrit Meijer, Mark Sausen, Miriam Koopman, Geraldine Vink, Sanne Abeln, Remond Fijneman, Jeanine Roodhart, on behalf of the PLCRC-MEDOCC group. Molecular characterization of stage III colon cancer patients with recurrence after adjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2496.

RESUMENMiguel Archer forma parte del enorme contingente de exiliados que dejaron Irlanda durante el siglo xviii y se establecieron a comienzos de la centuria en la villa de Bilbao. Junto a su mujer, María Geraldino –también irlandesa–, crio una próspera y exitosa familia, al tiempo que se posicionaba sólidamente en el comercio y la sociedad bilbaína. Archer trabajó en múltiples ámbitos para el Consulado de Bilbao, vínculo que su hijo Miguel hizo perdurar y engrandecer durante años. El padre ejerció durante más de 30 años como arqueador y corredor de navíos en el puerto bilbaíno, cargo que fue legándose sucesivamente a través de varios miembros de la familia. El hijo fue designado maestro de la recién creada y pionera Escuela de Náutica de Bilbao –que años después le propiciaría el nombramiento como capitán de fragata–, así como toda una suerte de comisiones relacionadas con la ingeniería civil –en muchos casos de gran relevancia– que las instituciones vizcaínas precisaban. Sin embargo, en lo más alto de los logros que la familia había alcanzado, en 1752 las calamidades comenzaron a recaer sobre los Archer-Geraldino en una sucesión de tragedias que acabarían con la casi totalidad de la familia en unos pocos años. Palabras clave: Archer, Geraldino, Consulado de Bilbao, corredor de navíosTopónimos: Bilbao, IrlandaPeríodo: siglo xviii ABSTRACTMiguel Archer is part of the huge number of exiled Catholics that were forced to leave Ireland during the early modern period. He settled in Bilbao in the early 18th century, where he married Maria Geraldino, also an Irishwoman, and both raised a prosperous and successful family whereas Archer took hold in the trade and society of Bilbao. He worked for the Consulate of Bilbao in different ways; and likewise the link was preserved and enlarged by his son Miguel. The father acted as a ship tonnage surveyor and sworn translator –successively bequeathed to other relatives– in the port of Bilbao for more than thirty years. The son was nominated lecturer of the newly created and pioneer Navigation School of Bilbao –lately enabling his appointment as navy commander in Spanish Armada– as well as many commissions related to civil engineering issues very relevant for the Biscayan public bodies. Nevertheless, in the summit of the family achievements, in 1752 a series of misfortunes arose to the Archer-Geraldinos and they were nearly extinguished as a result of a succession of tragedies in very few years. Keywords: Archer, FitzGerald/Geraldine, Consulate of Bilbao, sworn translatorPlace name: Bilbao, IrelandPeriod: 18th century REFERENCIASBilbao Acedos, A. (1999): “Los Irlandeses y el sector del curtido en Bizkaia en el siglo xviii”, Bidebarrieta, 4, pp. 295-309.— (2004): Los irlandeses de Bizkaia “Los chiguiris”. Siglo xviii, Bilbao, Fundación BBK.Binasco, M. (2018): Rome and Irish Catholicism in the Atlantic World, 1622-1908, London, Palgrave Macmillan.Cagigal Montalbán, E. 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Lyons (eds.), Irish communities in early modern Europe, Dublin, Four Court Press, pp. 267-293.—(2009): Ireland and Spain in the Reign of Philip II, Dublin, Four Court Press.García Hernán, E. y Pérez Tostado, I. (eds.) (2010): Irlanda y el Atlántico Ibérico. Movilidad, participación e intercambio cultural, Valencia, Albatros Ediciones.García Hernán, E. y Lario de Oñate, M. C. (eds.) (2013): La presencia irlandesa durante las Cortes de Cádiz en España y América, 1812, Valencia, Albatros Ediciones.Guiard Larrauri, T. (1972): Historia del Consulado y Casa de Contratación de la villa de Bilbao, Bilbao, La Gran Enciclopedia Vasca, vols. 1 y 2.Larrea Sagarmínaga, M. Á. y Labayru y Goicoechea, E. J. (1974): Historia general del señorío de Bizcaya: Caminos de Vizcaya en la segunda mitad del siglo xviii, Bilbao, La Gran Enciclopedia Vasca.Llombart, J. y Hormigón, M. (1990): “Un libro de texto de la Escuela de Náutica de Bilbao en el siglo xviii”, en R. Codina y R. M. 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(1986): “The Irish on the Continent, 1691-1800”, en T. W. Moody y W. E. Vaughan (eds.), A New History of Ireland, IV: Eighteenth Century Ireland, 1691-1800, Oxford, Oxford University Press, pp. 629-656.Téllez Alarcia, D. (2012): El ministerio Wall: la “España discreta” del “ministro olvidado”, Madrid, Marcial Pons Historia.Villar García, M. B. (coord.) (2000): La emigración irlandesa en el siglo xviii, Málaga, Universidad de Málaga.Worthington, D. (2010): British and Irish Emigrants and Exiles in Europe: 1603-1688, Leiden-Boston, Brill.

Abstract Purpose: Long non-coding RNAs (lncRNAs) regulate several biochemical pathways and contribute to the pathophysiology of cancer. In previous analyses, we identified 27 lncRNAs whose expression respond to hormone therapy in prostate cancer patients. Furthermore, in castration-resistant prostate cancer (CRPC), their levels were restored to those observed in therapy-naïve primary tumors. Nevertheless, lncRNAs contribution in tumorigenesis is still not understood. Since one mechanism of action of lncRNAs is acting as sponges of miRNAs, our main goal was to identify lncRNA-miRNA-mRNA networks altered during prostate cancer progression. Methods: We performed a bioinformatics-based analysis using public datasets comprising 40 primary prostate tumors (11 paired pre- and post-androgen deprivation therapy (ADT) and 29 pre-ADT) and 8 CRPC. We used miRNet (a miRNA-centric network visual analytics platform) to seek miRNAs that target both lncRNAs and mRNAs, and constructed ceRNA networks. Results: We identified 105 mRNAs differentially expressed in both post- vs pre-ADT primary tumors and CRPC vs post-ADT. We found that PCGEM1 (lncRNA) expression correlates with ASPM (mRNA) expression (r=0.51, p=8.2E-13), and these two RNAs have target sequences for the binding of hsa-miR-506-3p and hsa-miR-124-3p. These results identified a possible PCGEM1-hsa-miR-506-3p/hsa-miR-124-3p-ASPM ceRNA involved in prostate cancer progression to castration resistance. Other ceRNAs identified included RAB3B mRNA (RAS oncogene family) and are: PCGEM1-hsa-miR-124-3p-RAB3B, LINC01087-hsa-miR-130a-3p-RAB3B, and LINC01671-hsa-miR-145-5p-RAB3B. Conclusion: These results give new insights in ceRNA dysregulation in prostate cancer; and ultimately, they might help to identify new prognostic biomarkers for prostate cancer and new druggable targets for avoiding/delaying progression to CRPC. Citation Format: Sabrina Ledesma-Bazan, Florencia Cascardo, Juan Bizzotto, María Sol Ruiz, Elba Vazquez, Geraldine Gueron, Javier Cotignola. Competing Endogenous RNA (ceRNA) Networks Implicated in Prostate Cancer Progression to Castration Resistance Identified Through Bioinformatics Analyses [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 25.

Background:Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the axial skeleton comprising two subtypes within the same spectrum: radiographic (r-axSpA) and non-radiographic (nr-axSpA). Previous studies have shown that clinical presentation and treatment response of males and females may differ1 despite similar disease burden.2 Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, has demonstrated superior efficacy to placebo in the treatment of patients with r-axSpA (COAST-V/W [bDMARD- naïve/TNFi-experienced]) and nr-axSpA (COAST-X [bDMARD-naïve]).3Objectives:Assess baseline characteristics and treatment response to IXE categorised by sex in patients with r-axSpA and nr-axSpA for up to 52 weeks.Methods:Patients fulfilled the ASAS classification criteria for r-axSpA or nr-axSpA. Patients were randomized to receive 80 mg subcutaneous IXE every 2 weeks (Q2W) or 4 weeks (Q4W), or to placebo (PBO) [16 weeks COAST-V/W; 52 weeks COAST-X]. Baseline characteristics and treatment outcomes were assessed. Patients were categorised by sex, missing data was controlled for using non-responder imputation (NRI) and modified baseline observation carried forward (mBOCF) analysis was conducted on continuous efficacy variables.Results:At baseline, females were older, with significantly higher pain and fatigue scores and peripheral joint symptoms (table 1). ASAS40 response rate with IXEQ4W was achieved in 39% of males with r-axSpA by week 16, and 44% by week 52. Females achieved 16.7% at week 16, and 33.3% at week 52. In nr-axSpA, 46% of IXEQ4W males achieved ASAS40 at week 16 and 30% at week 52. 23.9% of females achieved ASAS40 at week 16, increasing to 30.4% at week 52.Table 1.Baseline Characteristics of Patients Categorised by SexPatients with r-axSpA(COAST-V/W)(n=376)Patients with nr-axSpA(COAST-X)(n=198)CharacteristicMale (n=298)Female (n=78)p valueMale (n=99)Female (n=99)p valueAge at onset (yrs), mean (SD)26.5 (8.7)30.1 (10.1)0.002*27.9 (7.7)32.0 (10.7)0.002*Symptom duration (yrs), mean (SD)16.7 (10.5)17.8 (12.2)0.4209.5 (9.2)12.3 (11.3)0.057ASDAS, mean (SD)4.0 (0.8)3.9 (0.7)0.3043.7 (0.8)3.9 (0.8)0.143BASDAI, mean (SD)7.10 (1.4)7.4 (1.5)0.1796.9 (1.4)7.4 1.4)0.013*Fatigue/tiredness (BASDAI Q1), mean (SD)7.4 (1.6)7.8 (1.5)0.036*7.0 (1.6)7.9 (1.5)<0.001*Spinal pain (BASDAI Q2), mean (SD)7.9 (1.5)8.0 (1.5)0.6827.5 (1.4)7.9 (1.5)0.029*Pain/swelling in other joints (BASDAI Q3), mean (SD)6.5 (2.1)6.9 (2.2)0.1296.6 (2.3)7.2 (1.9)0.039*Tenderness to touch/pressure (BASDAI Q4), mean (SD)6.8 (1.8)7.0 (1.9)0.3396.6 (1.9)6.8 (1.8)0.404Morning stiffness (BASDAI Q5), mean (SD)7.5 (1.6)7.7 (1.8)0.5047.3 (1.7)7.7 (1.9)0.137Morning stiffness duration (BASDAI Q6), mean (SD)6.5 (2.3)6.5 (2.8)0.9446.3 (2.3)6.6 (2.5)0.392Spinal pain at night NRS, mean (SD)7.4 (1.5)7.8 (1.7)0.033*7.0 (1.8)7.6 (1.8)0.027*BASFI, mean (SD)6.8 (1.8)7.0 (2.0)0.4666.2 (1.8)6.7 (2.1)0.108SF-36 PCS, mean (SD)30.9 (8.3)28.9 (8.2)0.07533.1 (7.7)32.1 (7.2)0.348p-value from Fisher’s exact test analysis of variance (ANOVA) with sex as a factor for continuous data. Data includes pooled IXEQ2W and IXEQ4W.Conclusion:This analysis demonstrates that for the axSpA disease spectrum, females present with higher disease burden as reflected by higher scores in fatigue/tiredness, and spinal pain at night. Our findings indicate that males and females respond to IXE; however, females experience this benefit later in their treatment course, with a more prolonged attainment of peak response.References:[1]van der Horst-Bruinsma IE, et al. Ann Rheum Dis. 2019;78:1550-1558.[2]Zhao SS, et al. Rheumatology. 2019;58:2025-2030.[3]Deodhar A, et al. Lancet. 2020;395:53-64.Figure 1.COAST-V/W ASAS40 (ITT, NRI) Patients initially randomized to PBO in COAST-V/W switched to IXEQ2W or Q4W at week 16 by study design; PBO data are summarised up to week 16.Acknowledgements:Writing support was provided by Dr Geraldine Fahy, an employee of Eli Lilly and CompanyDisclosure of Interests:Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer, UCB, MSD, Consultant of: Abbvie, UCB, MSD, Lilly, Novartis, Grant/research support from: MSD, Pfizer, AbbVie, Rebecca Bolce Shareholder of: Eli Lilly, Employee of: Eli Lilly, Theresa Hunter Shareholder of: Eli Lilly, Employee of: Eli Lilly, David Sandoval Shareholder of: Eli Lilly, Employee of: Eli Lilly, Danting Zhu Employee of: Eli Lilly, Vladimir J. Geneus Employee of: Eli Lilly, Jeffrey Lisse Shareholder of: Eli Lilly, Employee of: Eli Lilly, Soyi Liu Leage Shareholder of: Eli Lilly, Employee of: Eli Lilly, Marina Magrey Consultant of: Novartis, Eli Lilly, Pfizer, Abbvie, UCB and Jansen, Grant/research support from: Amgen, AbbVie, and UCB Pharma

Mac Giolla Phádraig Clerics 1394-1534 AD is a three-part series, which provides an account of all known individual Mac Giolla Phádraig clerics in the late medieval era and details their temporalities, occupations, familial associations, and broader networks. The ultimate goal of the series is the full contextualisation of all available historical records relating to Mac Giolla Phádraig clerics alongside the genealogical record that can be extracted by twenty-first century science – that being the science of Y-DNA. The Papal Registers, in particular, record numerous occurrences of Mac Giolla Phádraig clerics, predominantly in the dioceses of Cill Dalua (Killaloe) and Osraí (Ossory), from the late fourteenth to the early sixteenth century. Yet, no small intrigue surrounds their emergence. Part I of Mac Giolla Phádraig Clerics 1394-1534 AD examines the context surrounding the earliest appointments of Mac Giolla Phádraig clerics, which is in neither Cill Dalua nor Osraí but the diocese of Luimneach (Limerick). Once that context is understood, a pattern of associations emerges. A ‘coincidental’ twenty-first century surname match from the Fitzpatrick Y-DNA project leads to a review of the relationship between the FitzMaurice of Ciarraí (Kerry) clerics and Jordan Purcell, Bishop of Cork and Cloyne (1429-1472). The ‘coincidence’ then leads to an examination of a close Y-DNA match between men of the surnames Purcell and Hennessey. That match, coupled with the understanding that Nicholas Ó hAonghusa (O’Hennessey), elected Bishop of Lismore and Waterford (1480-1483) but with opposition, is considered a member of Purcell’s household, transforms the ‘coincidence’ into a curiosity. Part I morphs into a conversation, likely uncomfortable for some, relating to clerical concubinage, illegitimacy, and the ‘lubricity’ of the prioress and her nuns at the Augustinian nunnery of St Catherine's O’Conyll. The nunnery was located at Mainistir na gCailleach Dubh (Monasternagalliaghduff), which lay just a stone’s throw from where Bishop Jordan Purcell and Matthew Mac Giolla Phádraig, the first Mac Giolla Phádraig cleric recorded in the Papal Registers, emerged. Part I makes no judgments and draws no firm conclusions but prepares the reader for Part II by ending with some questions. Do the Mac Giolla Phádraig clerics of Osraí, who rose to prominence in the late-fifteenth century, have their origins in Deasmhumhain (Desmond)? Could the paternal lineages of Mac Giolla Phádraig clerics be, at least from the mid-fourteenth century, with the house of the Geraldine FitzMaurice clerics of Ciarraí? And, could some of the modern-day descendants of the Mac Giolla Phádraig clerics be those Costigans, FitzGeralds, and Fitzpatricks who are found under haplotype R-A1488?

Higher Education Studies wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated. Higher Education Studies is recruiting reviewers for the journal. If you are interested in becoming a reviewer, we welcome you to join us. Please find the application form and details at http://recruitment.ccsenet.org and e-mail the completed application form to hes@ccsenet.org. Reviewers for Volume 9, Number 4 Abdelaziz Mohammed, Albaha University, Saudi Arabia Alina Mag, University Lucian Blaga of Sibiu, Romania Ana Maria Carneiro, University of Campinas, Brazil Anna Liduma, University of Latvia, Latvia Antonina Lukenchuk, National Louis University, USA Arwa Aleryani, Saba University, Yemen Aynur Y&uuml;rekli, İzmir University of Economics, Turkey Bahar G&uuml;n, İzmir University of Economics, Turkey Bo Chang, Ball State University, USA Deniz Ayse Yazicioglu, Istanbul Technical University, Turkey Dibakar Sarangi, Teacher Education and State Council for Educational research and Training, India Donna.Smith, The Open University, UK Geraldine N. Hill, Elizabeth City State University, USA H&uuml;seyin Ser&ccedil;e, Sel&ccedil;uk University, Turkey Jisun Jung, University of Hong Kong, Hong Kong Kartheek R. Balapala, University Tunku Abdul Rahman, Malaysia Laith Ahmed Najam, Mosul University, Iraq Lung-Tan Lu, Fo Guang University, Taiwan Mei Jiun Wu, University of Macau, China Meric Ozgeldi, Mersin University, Turkey Najia Sabir, Indiana University Bloomington, USA Okedeyi Sakiru Abiodun, Adeniran Ogunsanya College of Education, Nigeria Prashneel Ravisan Goundar, Fiji National University, Fiji Qing Xie, Jiangnan University, China Rafizah Mohd Rawian, Universiti Utara Malaysia, Malaysia Ranjit Kaur Gurdial Singh, The Kilmore International School, Australia Sadeeqa Sadeeqa, Lahore College For Women University Lahore, Pakistan Samuel Byndom, Parkland College, USA Semiyu Adejare Aderibigbe, American University in the Emirates, UAE Suat Capuk, Adiyaman University, Faculty of Education, Turkey Teguh Budiharso, Center of Language and Culture Studies, Indonesia Tuija A. Turunen, University of Lapland, Finland Xiaojiong Ding, Shanghai Normal University, China Zahra Shahsavar, Shiraz University of Medical Sciences, Iran

Abstract Introduction: Surgery followed by adjuvant chemotherapy (ACT) is standard of care in stage III colon cancer. However, 50% of the patients would be cured by surgery alone and are being overtreated, while 30-35% will experience a recurrence despite adjuvant treatment, resulting in only 15-20% of the patients benefitting from ACT. Therefore, there is a need for prognostic biomarkers to better stratify this group of patients for ACT decisions. Recent observational and interventional studies in non-metastatic colon cancer have shown that detection of cell-free circulating tumor DNA (ctDNA) in blood after surgery is highly prognostic for development of recurrence. Hence, ctDNA analysis is a promising approach to guide treatment decisions in stage III colon cancer, but studies with large well-defined patient cohorts are needed to prove clinical utility. Aim: Determine the prognostic value of ctDNA in stage III colon cancer patients treated with ACT to reduce futile treatment. Methods: 241 stage III colon cancer patients treated with ACT were included in the prospective observational study “PROVENC3” (PROgnostic Value of Early Notification by Ctdna in Colon Cancer stage 3), a substudy of the Prospective Dutch Colorectal Cancer cohort (PLCRC). The PLCRC infrastructure accrued patients with colorectal cancer in 23 participating hospitals in the Netherlands. After informed consent, blood was collected pre-surgery, post-surgery, post-ACT and every six months up to 3 years. Tumor-informed detection of ctDNA was performed through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), germline DNA (40x), and plasma cell-free DNA (30x). Results: Patient accrual was completed in 2021, with a median follow-up of 35.6 months. In total, 1090 blood samples have been collected to date. Analytical studies demonstrated a limit of detection of the test of 0.005% ctDNA utilizing contrived reference models derived from six independent cell lines, with a specificity of 99.6% across 119 noncancerous donor plasma specimens. From the PROVENC3 study, ctDNA analyses are ongoing for pre-surgery (n=68) and post-surgery (n=241 patients) blood samples. Preliminary results demonstrated a ctDNA detection rate of 93.4% pre-surgery and 17.1% post-surgery, which was associated with disease recurrence. Final analysis will enable determination of: 1) the proportion of ctDNA-positive/negative patients after surgery and the corresponding recurrence rates; 2) the prognostic value of post-surgery ctDNA; and 3) the lead time between post-surgery ctDNA detection and recurrence. Future Perspective: Ultimately, the results of this study will be used to model and design a ctDNA-guided interventional trial in stage III colon cancer patients, to reduce futile ACT and its associated side-effects. Citation Format: Carmen Rubio-Alarcon, Steven L. Ketelaars, Ingrid A. Franken, Sietske C. van Nassau, Dave E. van der Kruijssen, Suzanna J. Schraa, Theodora C. Linders, Pien Delis-van Diemen, Maartje Alkemade, Anne Bolijn, Marianne Tijssen, Margriet Lemmens, Miranda van Dongen, Mirthe Lanfermeijer, Annegien Broeks, Lana Meiqari, Linda J. Bosch, Victor E. Velculescu, Amy Greer, Samuel V. Angiuoli, Andrew Georgiadis, David Riley, James R. White, Christopher Greco, Liam Cox, Daan van den Broek, Cornelis J. Punt, Veerle M. Coupé, Miriam Koopman, Jeanine Roodhart, Gerrit A. Meijer, Mark Sausen, Geraldine R. Vink, Remond J. Fijneman. PLCRC-PROVENC3: assessing the prognostic value of post-surgery liquid biopsy cell-free circulating tumor DNA in stage III colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3358.

Abstract The androgen receptor (AR) serves as a pivotal transcription factor in prostate cancer (PCa) development. Its transcriptional activity is linked to the number of glutamines in the N-terminal domain. While current screening for PCa and prognostic biomarkers include serum prostate-specific antigen (PSA) levels and histopathological characteristics (specifically, ISUP grade and margin involvement), the heterogeneity of these tumors underscores the need for additional markers to enhance clinical management. Thus, this study aimed at characterizing an Argentinian PCa patient cohort based on the CAG polymorphism (CAG)n in AR and establish associations between genotypes and clinical-pathological characteristics to refine disease prognosis. We designed a hospital-based case-case study for PCa patients to determine the association between AR polymorphisms and PCa biochemical relapse after radical prostatectomy (RP). We retrospectively recruited 112 patients histologically diagnosed with PCa at the Hospital de Clínicas José de San Martín, Buenos Aires, Argentina. All patients underwent RP as their primary therapeutic strategy. All patients were, by definition, Hispanics, predominantly of Caucasian ancestry and, at a lesser extent, Amerindian or African. Written informed consent and institutional review board approval were acquired. Blood samples were collected post-RP for genomic DNA extraction using the CTAB method. (CAG)n in AR was genotyped by fluorescent PCR followed by capillary electrophoresis, and correlations between genotypes and clinical-pathological variables were analyzed using R. Results categorized patients into three subgroups based on the length of the CAG tandem repeat in AR: long (&gt;23 repeats, n=29), medium (20-23 repeats, n=44), and short (&lt;20 repeats, n=38). No associations were found between the length of the polymorphism and age of diagnosis, pre-RP PSA serum values, ISUP grade, and margin involvement. However, patients with family cancer history had a higher frequency of the intermediate-length allele (p=0.02). Moreover, among patients with pre-RP PSA &lt;10 ng/ml and intermediate-length allele had 2.72-fold risk of biochemical recurrence (BCR) (HR=2.72, 95%CI=1.05-7.03, p=0.039). Furthermore, multivariable BCR analysis including the ISUP grade and margin involvement as co-variates showed that the (CAG)n in AR was independent of these histopathological parameters (HRadj=3.37, 95%IC=1.24-9.10, padj=0.017). Altogether, the AR polymorphism is associated with family history of cancer. Consequently, determining the number of CAG repetitions in AR through a blood sample could serve as an independent prognostic marker in patients with PSA &lt;10 ng/ml prior to PR, independent of the histopathological features. Citation Format: Gastón Mario Pascual, Agustina Sabater, Juan Bizzotto, Rocio Seniuk, Pablo Sanchis, Carlos M. Roggero, Carlos Scorticati, Osvaldo Mazza, Elba Vazquez, Ayelen Toro, Geraldine Gueron, Javier Cotignola. Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3420.

Abstract Introduction: Surgery followed by adjuvant chemotherapy (ACT) is standard of care in stage III colon cancer. However, only 15-20% of patients benefit from ACT, as half of patients are cured by surgery, and 25-30% still experience a recurrence. Detection of circulating tumor DNA (ctDNA) after resection of the primary tumor is a strong prognostic biomarker in non-metastatic colon cancer and offers a promising approach to better stratify stage III colon cancer patients for ACT treatment decisions. Aim: The PROVENC3 study aims to determine the clinical validity of post-surgery ctDNA detection in patients with stage III colon cancer treated with ACT. Methods: Blood was collected pre-surgery, post-surgery and post-ACT for stage III colon cancer patients treated with ACT. Tumor-informed detection of ctDNA was performed through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), germline DNA (40x), and plasma cell-free DNA (30x). The primary outcome was time to recurrence (TTR). Results: Results from 209 patients (median follow up: 40 months) show that ctDNA-positive patients post-surgery (n=28) had a higher risk of developing a recurrence than ctDNA-negative patients (HR: 6.3, [95%CI: 3.5-11.3], P&lt;10−8). 38% of patients with a recurrence within 3 years were ctDNA-positive post-surgery. Combination of post-surgery ctDNA status with established clinicopathological risk classification of low-risk (T1-3 and N1) and high-risk (T4 and/or N2) resulted in a 3-year cumulative recurrence risk of 82% for clinical high-risk ctDNA-positive patients compared to 7% for clinical low-risk ctDNA-negative patients (HR 28.9 [95%CI: 10.6-78.2]; P&lt;10−10). Results from 170 patients with post-ACT blood available showed that post-ACT ctDNA-positive patients (n=24) were at a higher risk of developing a recurrence (HR 7.9 [95%CI: 3.5-15.9]; P&lt;10−8) than ctDNA-negative patients. The patients experiencing a recurrence had higher aggregate ctDNA variant allele frequencies than patients not experiencing a recurrence post-surgery or post-ACT (P&lt;0.001 and P&lt;0.001, respectively). Conclusion: Post-surgery ctDNA detection by tumor-informed WGS is a strong prognostic biomarker in stage III colon cancer patients, and improves the current risk stratification. Importantly, the post-surgery ctDNA-positive patients who did not experience a recurrence were likely cured by ACT. These data enable the design of clinical practice-changing ctDNA-guided interventional trials in stage III colon cancer to personalize adjuvant treatment decisions. Citation Format: Carmen Rubio Alarcon, Andrew Georgiadis, Ingrid A. Franken, Haoyue Wang, Sietske C. van Nassau, Suzanna J. Schraa, Dave E. van der Kruijssen, Karlijn van Rooijen, Theodora C. Linders, Pien Delis-van Diemen, Maartje Alkemade, Anne Bolijn, Marianne Tijssen, Margriet Lemmens, Lana Meiqari, Steven L. Ketelaars, Adria Closa Mosquera, Miranda M. van Dongen, Mirthe Lanfermeijer, Birgit I. Lissenberg-Witte, Linda J. Bosch, Teunise Bisschop-Snetselaar, Bregje Adriaans, Amy Greer, David Riley, James R. White, Christopher Greco, Liam Cox, Jesse Fox, Kaitlin Victor, Catherine Leech, Samuel V. Angiuoli, Niels F. Kok, Cornelis J. Punt, Daan van den Broek, Miriam Koopman, Gerrit A. Meijer, Victor E. Velculescu, Jeanine M. Roodhart, Veerle M. Coupé, Mark Sausen, Geraldine R. Vink, Remond J. Fijneman. Clinical validity of post-surgery circulating tumor DNA testing in stage III colon cancer patients treated with adjuvant chemotherapy: The PROVENC3 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6559.

Abstract Introduction: Stage III colon cancer patients are offered surgery followed by adjuvant chemotherapy (ACT) according to Dutch clinical guidelines. However, only 15-20% of the patients benefit from ACT: 50% would be cured by surgery alone and are thus being overtreated, while 30-35% will experience a recurrence despite adjuvant treatment. Therefore, there is a need for prognostic biomarkers to better stratify this group of patients for ACT. Recent studies in non metastatic colorectal cancer have shown that detection of cell-free circulating tumor DNA (ctDNA) in blood after surgery indicates presence of minimal residual disease, and is highly prognostic for relapse. Hence, ctDNA based liquid biopsies could be a promising approach to guide post-surgery treatment decisions in stage III colon cancer. Aim: Determine the prognostic value of post-surgery ctDNA in stage III colon cancer patients treated with ACT in order to reduce futile treatment. Study design and Methods: The Prospective Dutch Colorectal Cancer Cohort study PLCRC (www.PLCRC.nl) offers a nationwide infrastructure to accrue colorectal cancer patients in nearly all (&gt;60) hospitals in the Netherlands. Patients give informed consent for collection of clinical data, tissue and blood samples. “PROVENC3” (PROgnostic Value of Early Notification by Ctdna in Colon Cancer stage 3) is a prospective observational subcohort of PLCRC consisting of 267 stage III colon cancer patients treated with ACT,open for patient accrual in 25 hospitals. Blood samples are collected pre-surgery, post-surgery, post-ACT and longitudinally every six months up to 3 years. We will apply tumor-informed detection of ctDNA mutations by integrated analysis of targeted sequencing of a panel of 30 genes in cfDNA (PGDx elio plasma resolveassay) with a panel of 500 genes in DNA from formalin-fixed paraffin-embedded tumor tissue (PGDx elio tissue complete assay). The clinical, pathological, and molecular data will be integrated in cBioPortal. Results and future directions: 267 patients have been included. Approximately 950 blood samples have been collected to date. Once sequencing data is obtained, multivariate Cox regression analysis will be used to assess the association between post-surgery ctDNA detection and progression-free and overall survival. Ultimately, the results of this study will be used to design an ethically acceptable and cost-effective ctDNA-guided interventional trial in stage III colon cancer patients, in order to improve the risk stratification and reduce futile ACT and its associated side-effects. Citation Format: Carmen Rubio Alarcon, Dave E. van der Kruijssen, Suzanna J. Schraa, Sietske C. Nassau, Leticia G. León, Lana Meiqari, Linda J. Bosch, John K. Simmons, Mark Sausen, Amy Greer, Samuel V. Angiuoli, Jeanine M. Roodhart, Victor E. Velculescu, Daan van den Broek, Cornelis J. Punt, Veerle M. Coupé, Miriam Koopman, Gerrit A. Meijer, Geraldine R. Vink, Remond J. Fijneman. Prognostic value of post-surgery liquid biopsy cell-free circulating tumor DNA in stage III colon cancer patients - PLCRC-PROVENC3 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 536.

Abstract Eighty percent of prostate cancers (PCa) metastasize to bone, showing a significant source of patient morbidity. PCa stem-like cells (PCSCs) are capable to quiescently outlast retaining the ability to proliferate and regenerate, consequently remaining able to develop therapy-resistant tumors and metastatic lesions. We have previously reported that the overexpression of heme oxygenase 1 (HO-1), the rate limiting enzyme in heme degradation, leads to a less aggressive PCa phenotype. However, its effect on metastasis-stemness (MS) remains unknown. In this work, we address the biological significance of HO-1 in association with relevant MS genes for PCa progression. Clonogenic assays performed in PCa cells (PC3 and C4-2B) to assess colony formation, evidenced a reduction on the stem-like properties of tumor cells treated with hemin (FDA approved drug and specific HO-1 inducer). RNA-seq analysis to identify MS genes that could be modulated by HO-1 induction, revealed 32 MS-genes that were modulated in PC3-hemin vs. PC3-control cells. We then mined the Oncomine database (n = 1,128) and found that 15/32 HO-1-modulated MS genes were significantly dysregulated in PCa compared with normal gland. To extend our findings, further computational analyses were conducted, and a custom-made bioinformatics tool (Gene Hunter) was created to analyze gene expression and clinicopathological profiles across multiple publicly available PCa datasets with normal, adjacent, tumoral and metastatic samples (n = 1,629). We found that ADAM15, BCL2L1, LTBR, MBNL2 and SPINT1 are consistently dysregulated across different comparisons, with expression profiles in tumors that could be reverted by hemin treatment, according to our RNA-seq results. We constructed a risk score that efficiently stratified patients in high, intermediate and low-risk of biochemical-relapse groups (p&lt;0.01). We also performed multiple survival analyses including, overall, progression-free, relapse-free and metastasis-free survival data. We found that high MBNL2, a gene previously reported to be related to embryonic stem cell differentiation and to antimetastatic effects in other tumors, was associated with lower risk of relapse, progression and metastasis (p&lt;0.05). Of note, the expression of MBNL2 was downregulated in PCa samples compared with normal gland or normal adjacent tissue. Interestingly MBNL2 expression can be reverted by HO-1 induction in PCa cells, as validated by RT-qPCR. Accordingly, those patients with high expression of MBNL2 showed a decreased risk of biochemical-relapse when they presented high HMOX1 levels (HR = 0.4615, p = 0.0186). Altogether, we highlight the relevance of HO-1 in modulating MS-associated genes in PCa and point out to MBNL2 as a potential druggable target for disease intervention. Citation Format: Agustina A. Sabater, Ayelen R. Toro, Pablo A. Sanchis, Gaston M. Pascual, Rocio A. Seniuk, Elba S. Vazquez, Javier Cotignola, Juan A. Bizzotto, Sofia Lage-Vickers, Geraldine Gueron. HMOX1 modulates tumor stemness and metastatic properties in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2437.

Abstract Background: Accurate monitoring of treatment response in patients with metastatic colorectal cancer (mCRC) is important to decide when to adjust treatment regimen or to proceed to local therapy of metastases. At present, clinical response is determined by computed tomography (CT) imaging-based assessment of changes in tumor size. However, this monitoring approach is constrained by limited sensitivity in detecting lymph node and peritoneal metastases, as well as inter-reader variability. Detection of circulating tumor DNA (ctDNA) is indicative of the amount of neoplastic cells and may have added clinical value to CT imaging for assessment of treatment response and guidance in treatment decision making in mCRC patients. We recently developed a tumor mutation-independent ctDNA test that utilizes low-coverage whole genome sequencing to analyze the plasma cell-free DNA (cfDNA) fragmentome to measure the ctDNA tumor fraction: the DELFI-tumor fraction (DELFI-TF) score. Aim: The DOLPHIN study aims to investigate whether the DELFI-TF ctDNA assay can provide a sensitive, affordable and broadly applicable ctDNA test to monitor treatment response of mCRC patients. Methods: The prospective, observational, multi-center DOLPHIN study is a substudy of the Prospective Dutch ColoRectal Cancer cohort (PLCRC). Clinical data, images and blood samples from 400 patients receiving systemic therapy in 8-10 Dutch hospitals will be collected. Blood samples will be drawn longitudinally in conjunction with regularly scheduled CT imaging. Plasma cfDNA will be analyzed for tumor-specific fragmentation patterns using the DELFI-TF score. Droplet digital PCR ctDNA-testing of RAS/RAF hotspot mutations will be performed as reference, when feasible. Primary endpoint is the association between ctDNA changes and clinical response. Secondary endpoints are the association between ctDNA changes and radiological response according to RECIST and to serum carcinoembryonic antigen (CEA) at various time points during systemic treatment, lead time of ctDNA-testing compared to CT imaging to detect progressive disease, and the prognostic value of longitudinal ctDNA-testing. Results: Since the inclusion of the first patient in March 2023, 117 patients have been included in the DOLPHIN study (November 2023). Seven hospitals throughout the Netherlands are currently open for patient inclusion and more sites have been approached to participate. Discussion: The DOLPHIN study will assess the added clinical value of longitudinal ctDNA-testing in treatment response monitoring of mCRC patients and whether imaging can be complemented and/or partly replaced by ctDNA-testing. The results of this study may lead to novel strategies for monitoring treatment response and to ctDNA-guided treatment decision making in mCRC patients. Citation Format: Denise E. van Steijn, Remond J. Fijneman, Geraldine R. Vink, Jeanine M. Roodhart, Miriam Koopman, Max J. Lahaye, Manon N.G. Braat, Veerle M. Coupé, Daan A. van den Broek, Gerrit A. Meijer, Haoyue Wang, Marjolein J. Greuter, Birgit I. Lissenberg-Witte, Lorenzo Rinaldi, E Peters, Alissa Konicki, Nicholas C. Dracopoli, Niels F. Kok, Victor E. Velculescu. Monitoring treatment response in patients with metastatic colorectal cancer using cfDNA fragmentomics testing: The DOLPHIN trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3673.

Abstract Background: It is hypothesized that chemotherapy alters the tumor microenvironment (TME) by increasing T cell infiltration and enhancing antigen presentation to T cells, and thereby may enhance immune-mediated cytotoxicity and tumor response to immunotherapy. The goal of this trial (DURVA+) is to evaluate and compare the immune-modulating effects of six different chemotherapy agents with Durvalumab (D), a PD-L1 checkpoint inhibitor. We report here the first analysis of one of the arms of DURVA+: D plus capecitabine (C). Methods: This is a non-randomized phase 2 trial for adult patients (pts) with refractory advanced solid tumors. Pts received C at a dose of 1250 mg/m2 bid on days 1-14 of 21-day cycle. For the first 3 cycles, D is administered every 2 weeks at a dose of 750 mg IV starting on C1D8. From cycle 4 onwards, D was given at a dose of 1125 mg IV every 3 week (day 1 of each 21-day cycle). Tumor biopsies were required at baseline, C1D8 (prior to durvalumab), C3D8, and optional at progression. Radiologic tumor assessment occurs every 4 cycles by RECIST. iRECIST is assessed as a secondary endpoint. Baseline and at least one on-treatment biopsy were obtained for 11 patients, at least 8 of which are evaluable for pharmacodynamic (PD) response (treatment-induced changes in immune cell tumor content and function). Results: As of Nov 10, 2021, 14 pts were enrolled to this arm. Median age 57 (range 31-73 years), 7 males and 7 females, 4 black, 8 white, 2 unknown race. Majority of pts had colorectal carcinoma (ca) (n=8), other include (n=1 each): appendiceal, anal squamous cell ca, leiomyosarcoma, pancreatic ca, breast ca, and nasopharyngeal squamous cell ca. Median lines of prior treatment was 3.5 (1-13), 4 pts previously received ICI. Median number of days on study treatment were 83 days. One pt experience partial response (breast) and five pts experienced SD (3 colon, 1 pancreatic, 1 non-uterine leiomyosarcoma) for a median duration of 136 days as of Jan 3, 2022 (data cutoff); one pt with pancreatic ca experienced a 27% reduction in sum of target lesions. Treatment related adverse events (TrAE) of all grades occurred in 13 pts, serious TrAEs (more than grade 2) occurred in 8 pts and included anemia, pulmonary embolism, hyperbilirubinemia, palmar plantar syndrome, neutropenia, lymphopenia and diarrhea. Immune-mediated AEs included transaminitis/hepatitis (n=4, all grade 1/2), hypothyroidism (n=2, grade 1/2), rash (n=1, grade 1) and colitis (grade 3). PD studies are still ongoing. Conclusion: The combination of durvalumab with capecitabine is feasible with no unexpected adverse events. PD assessment is ongoing to examine the hypothesis that chemotherapy alters tumor micronenvironment (TME) and T cell activation. The study was sponsored by NCI, and was funded in part by NCI Contract HHSN261200800001E. DURVA+ is registered with ClinicalTrials.gov, NCT03907475. Citation Format: Mohamad Adham Salkeni, Geraldine O’Sullivan Coyne, Naoko Takebe, Elad Sharon, Howard Streicher, Jessica Mukherjee, Ashley Bruns, Arjun Mitra, Abdul R. Naqash, Larry Rubinstein, Kristin K. Fino, King L. Fung, Katherine Ferry-Galow, Ralph Parchment, Helen Chen, James Doroshow, Alice Chen. Safety and efficacy of Anti-PD-L1 antibody MEDI4736 (durvalumab) in combination with capecitabine in patients with advanced solid tumors (DURVA+) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT115.

Abstract Introduction: Targeted next-generation sequencing (NGS) of cell-free DNA in plasma, referred to as liquid biopsy, has become a valuable diagnostic tool in clinical oncology. However, detection of variants related to clonal hematopoiesis (CH) is a major confounder that significantly impairs the clinical utility of liquid biopsies. Here we developed a machine-learning model to determine tumor versus CH origin of variants identified in plasma-only NGS. Methods: We assembled a training cohort of 352 variants identified by targeted deep plasma sequencing from 199 patients with stage I-IV breast, colorectal, esophageal, lung, and ovarian cancer, coupled with matched white blood cell (WBC) and tumor tissue NGS to allow determination of the reference origin for each plasma variant. We employed Extreme Gradient Boosting (XGBoost) to integrate fragment, variant, gene, and patient level features to predict tumor versus CH plasma variant origin, evaluating the performance of this approach within the training cohort using 10-fold cross-validation. We applied the fixed model to two independent validation cohorts: a small cell lung cancer (SCLC) cohort comprising of 74 variants from targeted plasma NGS from 26 patients and a multi-cancer cohort of 409 variants detected using the MSK-Impact panel from 74 patients with breast, colorectal, and prostate cancer. Results: Variant allele frequencies (VAF) did not differentiate tumor from CH variants, as the VAFs between tumor (median VAF 0.53%) and CH (median VAF 0.409%) variants in the training cohort were largely overlapping (area under the ROC curve-AUC 0.54, 95% confidence interval-CI 0.48-0.61). Similarly, individual fragmentomic features (mutant fragment length, cut points, and endpoint motifs) had limited ability to distinguish tumor from CH variants (AUC range 0.51-0.76). Using serial plasma samples, we identified stable statistical measures of differences in fragment feature distributions between mutant and wild type fragments; these were subsequently incorporated into an XGBoost machine-learning model along with variant, gene and patient features to predict tumor versus CH variant origin. Our model predicted variant origin with an AUC of 0.95 (95% CI 0.87-1) from 10-fold cross validation in the training cohort. The performance of the model was tested in independent SCLC and multi-cancer validation cohorts; the fixed model predicted plasma variant origin with an AUC of 0.87 (95% CI 0.73-1) and 0.89 (95% CI 0.86-0.92) respectively. Conclusion: We developed a machine-learning model that integrates patient, gene, variant and fragment features to predict tumor versus CH origin of plasma variants across solid tumors and NGS sequencing platforms. The ability to identify bona fide tumor variants in plasma-only sequencing fills a critical need in the clinical implementation of liquid biopsy-guided cancer therapy by reducing misinterpretation due to CH contamination. Citation Format: Jenna V. Canzoniero, Archana Balan, Jillian Phallen, Blair V. Landon, Lavanya Sivapalan, Benjamin Green, Zineb Belcaid, Susan C. Scott, Gavin Pereira, Vincent K. Lam, Ali H. Zaidi, Ronan J. Kelly, Christine L. Hann, Wade T. Iams, Christine M. Lovly, Patrick M. Forde, Gerrit A. Meijer, Geraldine R. Vink, Remond J. Fijneman, The MEDOCC Group, Victor E. Velculescu, Robert B. Scharpf, Valsamo Anagnostou. A machine learning approach to determine the cellular origin of variants in liquid biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3366.

Abstract Introduction: Clear cell sarcoma (CCS) constitutes &lt;1% of sarcomas and frequently presents in adolescents and young adults. Chondrosarcoma is one of the most common bone malignancies in adults, occurring as conventional chondrosarcoma (CS) or the more-aggressive dedifferentiated chondrosarcoma (dCS). There is no standard of care therapy approved for these malignancies. The activity of immune checkpoint inhibition (ICI) in alveolar soft part sarcoma, together with case reports of ICI activity in these other sarcoma subtypes, prompted us to conduct a phase 2 clinical trial of atezolizumab (atezo), in patients (pts) with advanced CCS, CS, or dCS (NCT04458922). Methods: We evaluated the effect of targeting PD-L1 with atezo upon the growth and immune landscape of CCS, CS, and dCS. Pts received intravenous atezo 1200 mg/m2 once every 21 days. Prior ICI therapy was not allowed. Tumor biopsy pairs for immuno-pharmacodynamic (IO-PD) studies were collected at baseline and on Cycle 3 Day 1(C3D1); paraffin sections were analyzed using immunofluorescence (IF) microscopy after staining with two multiplexed antibody panels (CD4/FOXP3 and PD-L1/CD8/CD3ζ pY142). Biomarker-positive cells within the tumor area and margins were quantified using image analysis algorithms. Activated cytotoxic T lymphocytes (CTLs) were defined as CD8+ CD3ζ pY142+ and reported as the percentage of the total CD8+ cell density. Results: Nine pts were enrolled per disease cohort. No RECIST objective responses were observed; accrual was closed due to futility. Median progression-free survival (PFS) was 2.66 months (range: 1.3 to 11.7) in CCS, 3.22 (range: 1.4 to 8.9) in CS, and 2.04 (range: 0.4 to 11.7) in dCS. IF microscopy of biopsy pairs from five CCS pts revealed varied immune landscapes: 4/5 C3D1 biopsies contained PD-L1+ cells, 4/5 contained CD8+ cells, and 3/5 contained activated CTLs. Immune phenotype did not generally correlate with response; however, the highest percentage of activated CTLs occurred in the CCS pt with the longest PFS and this pt showed an increase in PD-L1+ cells on treatment—consistent with target engagement of the PD-L1/PD-1 immune checkpoint. dCS biopsy pairs (N=3) also contained a range of biomarker densities that did not correlated with PFS. In dCS and CCS, on-treatment increases in the percentage of activated CTLs were accompanied by increased Treg cell density in some pts. In contrast, CS biopsies (N=5) were uniformly devoid of infiltrating immune cells. Conclusion: The tumor microenvironment of CS is an immune desert, while dCS and CCS tumors contain a range of immune cell compositions. Atezo treatment increased the percentage of activated CTLs and density of PD-L1+ cells in some tumors, but an increase in Treg cells may explain why that pharmacodynamic evidence of ICI activity (the increase in activated CTLs) was not associated with clinical response. Funded NCI Contract No. HHSN261201500003I. Citation Format: Katherine V. Ferry-Galow, Kristin K. Fino, Geraldine O'Sullivan Coyne, Nancy Moore, Elad Sharon, Melissa Burgess, James Chen, Anthony P. Conley, Elizabeth J. Davis, Priscilla Merriam, Albiruni R. Abdul Razak, Brian Van Tine, Jared C. Foster, Naoko Takebe, Christina L. Rosenberger, James H. Doroshow, Alice P. Chen, Ralph E. Parchment. Atezolizumab clinical trial biopsies reveal varied immune landscapes in clear cell sarcoma and chondrosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT263.

Abstract Background The fecal immunochemical test (FIT) is widely used in population based colorectal cancer (CRC) screening programs. Recently, circulating cell-free DNA (cfDNA) analyses have emerged as a new avenue for early cancer detection. The performance of cfDNA methods in comparison with FIT is currently unknown. The present study compared pre-operative cfDNA analyses to FIT for detection of patients with CRC who participated in a population-based screening program. Methods In the Dutch national CRC screening program, individuals aged 55-75 years are biennially invited to perform a single FIT. The database of the Dutch CRC screening program was queried to identify individuals with FIT data who also participated in two cfDNA studies, PLCRC-MEDOCC and PLCRC-PROVENC3 (AACR abstract C. Rubio Alarcón). Sensitivities with 95% confidence intervals (CI) for detecting individuals with CRC were determined for FIT, tumor-informed cfDNA analyses, as well as both tests combined. For FIT, sensitivities were determined at 20 µg and 47 µg hemoglobin (Hb)/g feces positivity cut-offs as these represent the most commonly used international and Dutch cut-offs, respectively. Liquid biopsy analyses were performed using next generation sequencing of cfDNA. Tumor-specific alterations were identified through parallel next generation sequence analysis of resected tumor tissues. Results The query identified 120 individuals with stage I (n=3, 2.5%), stage II (n= 57, 47.5%) and stage III (n=60, 50.0%) CRC who had participated in the Dutch CRC screening program and either PLCRC-MEDOCC or PLCRC-PROVENC3. All FIT samples were collected at a median time of 38 days before diagnosis (IQR 27-112 days). FIT sensitivity for detection of individuals with CRC was 83.3% (100/120 CRCs, 95% CI 75.4-89.5%) at a 20 µg Hb/g feces cut-off and 80.0% (96/120, 95% CI 71.7-86.7%) at a 47 µg Hb/g feces cut-off. Tumor-informed cfDNA analyses detected 75.8% (91/120, 95% CI 67.2-83.2%) of individuals with CRC in this population. The combination of cfDNA analyses and and FIT (20 µg Hb/g feces cut-off) identified almost all individuals with CRCs (119/120, sensitivity 99.2%, 95% CI 97.0-100%). The individual who was missed had a cancer that was a T3N0 microsatellite stable moderately differentiated adenocarcinoma in the ascending colon. Discussion While both FIT and cfDNA analyses identified most CRC cases (75-83%) in this series, both tests also demonstrated a substantial level of complementarity, indicating that in principle combining FIT with cell-free DNA testing would allow to increase sensitivity of CRC screening. Since the cell-free DNA tests used here are tumor-informed, which in real life screening practice is not feasible, it remains to be determined to what extent this result can be reached using non-tumor-informed approaches. Citation Format: Pieter Henk Abraham Wisse, Carmen Rubio-Alarcon, Suzanna J. Schraa, Adria C. Mosquera, Mark Sausen, Remond J. Fijneman, Geraldine R. Vink, Meike de Wit, Jillian Phallen, Victor E. Velculescu, Beatriz Carvalho, Gerrit A. Meijer. Comparison of FIT and cell-free DNA analyses for detection of individuals with colorectal cancer in population based screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6079.

Abstract Background: Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor with few effective treatment options. Cediranib (C) and sunitinib (S) are potent oral inhibitors of all 3 VEGF receptors. Cediranib showed substantial single-agent activity (objective response rate [ORR] = 35%) in our previous trial in patients (pts) with metastatic ASPS (NCT00942877). Here we report a phase 2 randomized multicenter trial of single agent C or S in pts with ASPS (NCT01391962). Methods: We conducted a multicenter phase 2 trial with an optimal 2-stage design targeting an ORR of 40%. Enrolled pts were &gt;16 years with metastatic ASPS, previously not treated (N) and unresectable, or previously treated (T), who have progressed per RECIST 1 within the 6-month period preceding enrollment. Pts were randomized to receive C (30 mg) or S (37.5 mg) orally, once a day, in 28-day cycles and could crossover to the other treatment arm at disease progression. ORR (primary endpoint), median progression-free survival (mPFS), and PFS rate at 24 weeks for the 2 arms (C and S) were evaluated; T and N cohorts were assessed separately in each arm. Arm accrual closed if ≤ 1 of the first 10 enrolled pts responded to the first treatment. Results: Thirty-four pts (47% white, 29.4% black, 17.6% Asian, 5.8% Pacific Islander) were enrolled; 29 pts were evaluable for response. One pt on each of the initial treatment arms had a confirmed partial response (PR), rates of 6.7% (1/154) and 7.1% (1/14) for C and S tx or tx-naive, respectively. Among pts who crossed over, there was 1 PR in a pt receiving C after initially responding (PR) on S (1/9; ORR 11.1%). Twenty-four pts had a best response of stable disease (86.7% and 78.6%) for C and S, respectively. The mPFS was 7.6 months (mo) (95% CI: 3.7-9.9 mo) and 5.5 mo (95% CI: 1.8-14.5 mo) for C and S, respectively administered as first therapy (p=0.92). PFS rate at 24 weeks was 62.5% (95% CI: 29.5-76.2%) and 50% (95% CI: 25.9-70.1%) for pts receiving C and S respectively, as initial therapy. There was no difference in mPFS between T or N pts in the C (6.7 mo [95% CI: 1.4-9.9 mo] vs 8.3 mo [95% CI: 2.7 - 16.6 mo]; P=0.35) arm, but some evidence of a potential difference in the S (4.8 mo [95% CI: 0.9-7.9 mo] vs 14.7 mo 95% CI: 1.8 - 21.6 mo]; P=0.058) arm. Overall, 43.7% (C) and 77.8% (S) of pts experienced grade ≥3 adverse events (AEs) at least possibly related to the study drug. Common grade ≥3 AEs included: diarrhea (C), neutropenia (S), hypertension (C and S). AEs were in line with the known safety profiles of each agent. As of August 2021, 1 pt (unevaluable for ORR) remains on study. Conclusions: The study did not meet its endpoints for ORR. There were no differences in mPFS for the 2 treatment arms. The selection of pts with more aggressive disease, who had progressed in the 6 months prior to enrollment, may account for the low patient response rates compared to our previous study of cediranib in ASPS. Funded by NCI Contract No. HHSN261200800001E. The study was a collaboration between NCI and Pfizer. Citation Format: Naoko Takebe, James Nguyen, Shivaani Kummar, Albiruni Abdul Razak, Sant P. Chawla, Suzanne George, Shreyaskumar R. Patel, Mary Louise Keohan, Sujana Movva, Geraldine O’Sullivan, Khanh Do, Larry Anderson, Lamin Juwara, Brooke Augustine, Seth Steinberg, Laura Kuhlmann, S. Percy Ivy, James H. Doroshow, Alice P. Chen. Randomized phase 2 trial of sunitinib or cediranib in alveolar soft part sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT168.

Abstract Background: Talazoparib is a poly (ADP-ribose) polymerase inhibitor (PARPi) with increased trapping of PARP-DNA complexes compared to other PARPi in clinical development. Talazoparib has single-agent synthetic lethality in BRCA1/2- and PTEN-deficient cell lines, has potent antitumor activity in animal models of tumors harboring mutations in DNA repair pathways, and has FDA-approved indications in advanced BRCA-mutated and HER2-negative breast cancer and in homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer in combination with enzalutamide. This pilot study evaluated the pharmacodynamic (PD) effects of talazoparib on DNA damage response (DDR) markers in tumor biopsy tissue in both patients (pts) who are PARPi-naïve and pts who have received prior PARPi other than talazoparib to investigate for potential differential PARPi PD responses in DNA replication stress. Methods: We are conducting a multicenter phase 2 trial in adult pts with eligible deleterious germline or somatic mutations in BRCA1/2 or genes involved in DDR including ATM, ARID1A, IDH1, BAP1, ATR, CHK2, and PALB2. Pts were enrolled and assessed in two cohorts: 1) pts who were PARPi-naïve, and 2) pts who were treated with and had documented progression on a PARPi other than talazoparib. Talazoparib is administered orally at a dose of 1000 µg/day (D) in 28 D cycles (C). The primary objective is determining the replication stress PD effect of talazoparib as evaluated by activation of Rad51 combined with a lack of γH2AX activation. Paired tumor biopsies (baseline and C2D1) will be analyzed for DDR markers (γH2AX, pNBS1, and Rad51) by IFA. Responses and adverse events (AEs) are defined by RECIST 1.1 and CTCAE v5.0, respectively. Results: The PARPi-naïve cohort had 15 pts enrolled with a median age of 58 years (range 38-76) and median prior lines of systemic therapy of 2 (range 1-5). The PARPi-treated cohort had 8 pts enrolled with a median age of 72 years (range 35-85) and median prior lines of systemic treatment of 5.5 (range 1-10). A total of 11 sets of pre-treatment and post-treatment tumor biopsies have been received to date and analyses of DDR markers are ongoing. Of 11 pts in the PARPi-naïve cohort evaluable for response, 6 pts had stable disease (SD) as best response with 2 pts (nasal cavity cancer with ARID1A alteration, bile duct cancer with IDH1 alteration) who received talazoparib for ≥ 6 C. Of 7 pts in the PARPi-treated cohort evaluable for response, 4 pts had SD as best response. Treatment-related AEs of ≥ grade 2 with ≥ 5% incidence included anemia (n=10, 43.5%), leukopenia (n=7, 30.4%), lymphopenia (n=6, 26.1%), thrombocytopenia (n=6, 26.1%), and neutropenia (n=4, 17.4%). Conclusions: Study enrollment and analyses of PD DDR markers in paired tumor biopsies are both ongoing with data to be presented at the conference. No responses have been observed to date, which may be due to prior therapies, tumor histologies, mutational selection or dose delivered with further characterization anticipated via PD DDR marker data. Citation Format: Brian Ko, Geraldine H O'Sullivan Coyne, Abdul Rafeh Naqash, Thomas J George, David DeRemer, Larry Rubinstein, Jennifer Zlott, Deborah Wilsker, Donna Ketchum, Stephanie Runkle, Katherine V Ferry-Galow, Ralph E Parchment, Naoko Takebe, Sarah Shin, Andrea R Voth, Jiuping Ji, S. Percy Ivy, James H Doroshow, Alice P Chen. Pharmacodynamics-driven phase 2 trial of talazoparib in patients with advanced solid tumors and aberrations in genes involved in DNA damage response [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B138.

Neste estudo pretendemos analisar o modo como alunos da licenciatura em Letras-Português da Universidade Federal de Pernambuco, durante o estágio curricular, atuam para ensinar seus alunos a refletir sobre a língua, concretizando um dos eixos de ensino desse componente curricular que é a análise linguística. A pesquisa, do tipo qualitativo-descritiva, teve como corpus projetos e relatórios de estágio, além de depoimentos dos estagiários, captados no seminário de encerramento das atividades de regência de turma do ensino fundamental. Para montar o referencial teórico, buscamos autores que tratam da formação docente, do estágio e do ensino de análise linguística. Os resultados mostraram que os futuros professores trabalham numa perspectiva sociointeracionista e exploram uma diversidade de gêneros textuais, como indicado nas orientações mais recentes para o ensino de língua portuguesa. No entanto, a maioria deles explicita pouco os procedimentos didáticos realizados, não indica as dificuldades dos alunos quando da avaliação da aprendizagem e aborda determinados conhecimentos linguísticos de forma expositiva e dedutiva.Referências:ALMEIDA FILHO, J. C. Crise, transições e mudança no currículo de formação de professores de línguas. In: FORTKAMP, M. B. M.; TOMITCH, L. M.B. (org.). Aspectos da linguística aplicada: estudos em homenagem ao professor Hilário Inácio Bohn. Florianópolis: Insular, 2000. p. 33-47.AZEVEDO, T. M. Ensinar gêneros? Desenredo, Passo Fundo, RS, v. 10, n. 1, p. 92-103 - jan./jun. 2014.AZEVEDO, T. M. Transposição didática de gêneros discursivos: algumas reflexões. Desenredo. Passo Fundo, RS, v. 6, n. 2, p. 198-214 - jul./dez. 2010.BARBOSA, J. Análise e reflexão sobre a língua e as linguagens: ferramentas para os letramentos. In: RANGEL, E. O.; ROJO, R. H. R. (org.) Língua Portuguesa no Ensino Fundamental. Coleção Explorando o Ensino. vol. 19. Brasília: MEC/SEB, 2010, p. 155-182.CALLIAN, G. R.; BOTELHO, L. S. A análise linguística e o ensino de língua portuguesa: em busca do desenvolvimento da competência discursiva. Educação em Destaque. Juiz de Fora, MG, v. 5, n. 1, p. 1-21, 2014.DICKEL, A. Ensino de gramática: das polêmicas às proposições. In: SEMINÁRIO NACIONAL SOBRE LINGUAGENS E ENSINO, 7, 2012, Pelotas. Anais... Pelotas: UCPel, 2012.DUTRA. C. M. D.; LOULA, L. D. Incompreensão e desalinhamento teórico-metodológico como possíveis entraves à prática de análise linguística em sala de aula. Domínios de Lingu@gem, Uberlândia, MG, vol. 11, n. 3, p. 526-547, jul./set. 2017.EMILIO, A. Gramática, deve-se ou não se deve ensinar? Línguas Letras. Cascavel, PR, v. 9. n. 16, p. 27-35. 2007.GERALDI, J. W. Concepções de linguagem e ensino de português. In: GERALDI, J. W. (org.). O texto na sala de aula. São Paulo: Ática, 1997[1984], p. 39-46.GERALDI, J. W. Unidades básicas do ensino de português. In: GERALDI, J. W. (org.). O texto na sala de aula: leitura e produção. Cascavel: Assoeste, 1984, p. 49-69.LARROSA, Jorge. Algunas notas sobre la experiencia y sus lenguajes. In: BARBOSA, R. L. L. (org.). Trajetórias e perspectivas da formação de educadores. São Paulo: Ed. Unesp, 2004. p.19-34.LOMBARDI, R. F. e ARBOLEA, T. A. Formando professores pesquisadores do ensino de língua materna. In: CONGRESSO LATINO-AMERICANO SOBRE FORMAÇÃO DE PROFESSORES DE LÍNGUA. 1, Florianópolis, Anais... 2006, p. 614-619.MENDONÇA, M. Análise linguística: por que e como avaliar. In: Marcuschi, B. SUASSUNA, L. (org.). Avaliação em língua portuguesa: contribuições para a prática pedagógica. Belo Horizonte: Autêntica, 2007, p. 95-110.NÓBREGA, J. J.; SUASSUNA, L. Aula de gramática ou de análise linguística? Investigando objetos de estudo e objetivos norteadores. Linguagens, Educação e Sociedade. Teresina, PI, n. 31, p. 246-269, jul. 2014.OLIVEIRA, M. B. F. Revisitando a formação de professores de língua materna: teoria, prática e construção de identidades. Linguagem em (Dis)curso. Tubarão, SC, v. 6, n. 1, p. 101-117, jan./abr. 2006.PETRONI, M. R.; JUSTINO, A. R.; MELO, E. S. O. Ainda sobre a formação do professor de língua portuguesa no Brasil. Interacções, Santarém, PT, n. 19, p. 28-37, 2011.PIMENTA, S. G.; LIMA, M. S. L. Estágio e docência: diferentes concepções. Poiésis. Tubarão, SC, vol. 3, números 3 e 4, p. 5-24, 2006.RAUBER, A. L. A formação do professor de Língua Portuguesa: o diálogo entre teoria e prática. In: MAGALHÃES, J. S.; TRAVAGLIA, L. C. (org.). Múltiplas perspectivas em linguística. Uberlândia/MG: EDUFU, 2008, v. 01, p. 346-356.REINALDO, M. A. G. M. O conceito de análise linguística como eixo de ensino de língua portuguesa no Brasil. Estudos Linguísticos, n. 8. Edições Colibri/CLUNL, Lisboa, p. 229-241, 2012.REMENCHE, M. L. R.; ROHLING, N. Análise linguística e formação de professores: um discurso sobre a dicotomia teoria e prática. In: SIMPÓSIO MUNDIAL DE ESTUDOS DE LÍNGUA PORTUGUESA. SIMELP. 5, 2017. Salento. Atas... Salento: Università del Salento, 2017.SILVA, N. I. Ensino tradicional de gramática ou prática de análise linguística: uma questão de (con)tradição nas aulas de português. Revista Brasileira de Linguística Aplicada. Belo Horizonte, MG, v. 10, n. 4, p. 949-973, 2010.SILVA, W. R.; FAJARDO-TURBIN, A. E. F. Relatório de estágio supervisionado como registro da reflexão pela escrita na profissionalização do professor. Polifonia, Cuiabá, MT, v. 18, n. 23, p. 103-128, jan./jun., 2011.SIQUEIRA, R. A. R.; MESSIAS, R. A. L. Reflexão e ações na formação e atuação do professor de língua portuguesa: o diálogo como condição de autoria na prática educativa. In: Linguagem Ensino, Pelotas, RS, v.11, n.2, p.377-392, jul./dez. 2008.SUASSUNA, L. Ensino de análise linguística: situando a discussão. In: SILVA, A.; PESSOA, A. C.; LIMA, A. (org.). Ensino de gramática: reflexões sobre a língua portuguesa na escola. Belo Horizonte, MG: Autêntica Editora, 2012, p. 11-28.TARDIF, M.; LESSARD, C.; LAHAYE, L. Os professores face ao saber: esboço de uma problemática do saber docente. Teoria e Educação, Porto Alegre, RS, v. 04, p. 215-233, 1991.VIEIRA, S. R. Prática de análise linguística sem ensino de gramática? Reflexões e propostas. In: ATAÍDE, C. et al. (org.). GELNE 40 anos. Experiências teóricas e práticas nas pesquisas em Linguística e Literatura. Paulo: Blucher, 2017, p. 299-318. Recebido em 05-01-2021Revisões requeridas em 28-04-2021Aceito em 12-05-2021

Sob o viés metodológico da etnossociologia clínica (ANDRADE, 2019), este artigo analisa narrativas de vida coletadas em uma disciplina de estágio de observação do curso de Letras: Língua Portuguesa da Universidade Federal do Ceará. Em vista da impossibilidade das aulas presenciais, por conta da pandemia de Covid-19, as práticas de formação docente tiveram que ser repensadas. Nesse contexto, as narrativas de vida surgem como catalisadoras de experiências, permitindo ao professor em formação reconfigurar saberes e conhecimentos adquiridos em seu itinerário, (res)significando concepções de linguagem. Assim, as narrativas de vida podem se tornar um produtivo meio de prática (auto)(trans)formativa. O estudo se abaliza nos postulados teóricos de Koch (2013), Geraldi (2011) e Volóchinov (2018) sobre concepções de linguagem, e em Andrade, Lima e Serra (2020a, 2020b), Kleiman (2008), Josso (2004), Ribeiro (2008), Signorini (2006) e Delory-Momberger (2008) sobre a possibilidade (auto)(trans)formativa das narrativas de vida. Os resultados apontam que os professores em formação afirmam ter experienciado o ensino de língua sob o prisma da linguagem como expressão do pensamento e/ou instrumento de comunicação, desejando, por isso, quando em exercício de sua docência, efetivarem práticas mais afeitas à perspectiva sociointeracional, utilizando o potencial reflexivo dos planos de aula, amparados na metodologia sequência didática.Referências:ANDRADE, F. R. da S. Autoconceitos de leitura erigidos a partir de narrativas de vida de professores alfabetizadores. 2019. 192 f. – Dissertação (Mestrado) – Universidade Federal do Ceará, Departamento de Letras Vernáculas, Programa de Pós-graduação em Linguística, Fortaleza, 2019.ANDRADE, F. R. da S.; LIMA, P. S. R. de; SERRA, D. G. A ressignificação do ensino de leitura propiciada pela formação docente: um estudo de caso a partir de narrativas de vida. Fólio - Revista de Letras, v. 12, n. 1, p. 441-463, jan./jul. 2020.ANDRADE, F. R. da S.; LIMA, P. S. R. de; SERRA, D. G. A narrativa de vida como construtora das concepções docentes de leitura: um estudo de casa. Letra Magna, v. 16, n. 25, p. 1-21, jan./jun. 2020.BRASIL. Ministério da Educação. Parâmetros Curriculares Nacionais: 3º e 4º ciclos do Ensino Fundamental: Língua Portuguesa. Brasília/DF: MEC/SEF, 1998.BRASIL. Ministério da Educação. Base nacional comum curricular. Brasília/DF: MEC/SEF, 2018.CAVALCANTE, M. C. B.; MELO, C. T. V. Gêneros orais na escola. In: SANTOS, C.F.; MENDONÇA, M.; CAVALCANTE, M. C. B. Diversidade Textual: os gêneros na sala de aula. Belo Horizonte: Au­têntica; 2007. p. 89-102.DELORY-MOMBERGER, C. Biografia e educação: figuras do indivíduo-projeto. Tradução: M. da Conceição Passeggi, J. G. da Silva Neto e Luís Passeggi. Natal: EDUFRN; São Paulo: Paulus, 2008.FREITAS, L. P. de; LUNA, T. S. e. Concepções de texto e escrita nas propostas de produção textual do novo Enem. In: MARCUSCHI, B.; SIMÕES, T. (Org.) Avaliação de Língua Portuguesa no Novo Enem. São Paulo: UniAnchieta, 2017, p. 243-280.GERALDI, J. W. Concepções de linguagem e ensino de português. In: GERALDI, J. W. (org.) O texto na sala de aula. São Paulo: Ática, 2011, p. 33-38.JOSSO, M. C. Experiências de vida e formação. Tradução: José Cláudio e Júlia Ferreira. São Paulo: Cortez, 2004.KLEIMAN, Â. (Org.). A formação do professor: perspectivas da lingüística aplicada. Campinas, SP: Mercado de Letras, 2008.KOCH, I. V. A inter-ação pela linguagem. 11. ed. São Paulo: Contexto, 2013.RIBEIRO, P. B. O discurso docente (re)velado no gênero memorial. 2008. 293 f. Tese (Doutorado em Letras) – Programa de Pós-Graduação em Letras, Pontifícia Universidade Católica de Minas Gerais, Belo Horizonte, 2008.SCHNEUWLY, B; DOLZ, J. Gêneros orais e escritos na escola. Tradução e organização de Roxane Rojo e Glaís Cordeiro. Campinas: Mercado de Letras, 2004.SIGNORINI, I. Prefácio. In: SIGNORINI, I. (org.) Gêneros catalisadores, letramento e formação do professor. São Paulo: Parábola, 2006, p. 7-16.SILVA, E. T. Concepções de leitura e suas consequências no ensino. Perspectiva, Florianópolis, v. 17, n. 31, p. 11-19, jan./jun. 1999.STREET, B. V. Letramentos sociais: abordagens críticas do letramento no desenvolvimento, na etnografia e na educação. Tradução de Marcos Bagno. São Paulo: Parábola Editorial, 2014.VASCONCELOS, S. M. F. Clínica do Discurso: a arte da escuta. Fortaleza: Premius, 2005.VASCONCELOS, S. M. F. Professor: que história é essa? Revista Educação em Questão, Natal, v. 25, n. 11, p. 62-79, jan./abr. 2006.VOLÓCHINOV, V. Marxismo e filosofia da linguagem. Tradução, notas e glossário de Sheila Grillo e Ekaterina Vólkova Américo. 2. ed. São Paulo: Editora 34, 2018.Recebido em 04-02-2021Revisões requeridas em 07-04-2021Aceito em 10-05-2021

Levando em conta a acepção de que as identidades e os modos de existirsão socialmente produzidos a partir de diferentes práticas discursivas, forjandoprocessos de diferenciação dos sujeitos e legitimando o pertencimento a determinados grupos, o presente artigo analisa os discursos sobre o ser-mulher trans* no videodocumentário Laerte-se, considerando as múltiplas vozes que ecoam nessa narrativa multissemiótica. Para tanto, a análise tomou como base os estudos sobre gênero, sexualidade e identidade tais como: Beauvoir (1980), Butler (2001), De Lauretis (1994), Geraldi (2010), Moita Lopes (2013). O gênero documentário é um objeto diverso, tanto em sua roteirizarão – vozes da protagonista, do produtor, do diretor –, quanto em sua composição – imagens, músicas, enunciados, depoimentos, encenações –, fazendo ecoar e entrelaçar diferentes discursos sobre a identidade trans* para um mesmo produto midiático. Os resultados apontam para quatro eixos de centralização: o íntimo, o privado, o profissional e o ficcional – explicitando a construção identitária do ser-mulher trans do sujeito Laerte que transita entre a dualidade masculina-feminina, instaurada e reforçada socialmente, e a manifestação política do (r)existir como trans*.

O objetivo deste artigo é analisar, a partir de enunciados de alunos, situações de produção em práticas de escrita, de aulas de Língua Portuguesa (LP) do Ensino Fundamental de uma escola municipal do Alto Vale do Itajaí, SC. Os enunciados integram uma pesquisa de cunho qualitativo, sob a perspectiva dialógica da linguagem. Os dados advêm de entrevista coletiva semiestruturada realizada com alunos de um 6º e um 9º ano em 2014. Os resultados indicam que, para esses alunos, as produções de escrita são comumente respostas a uma prática social escolarizada. Por outro lado, tais propostas de escrita passam a ser mais significativas quando construídas em momentos de interação em sala de aula, ao se inserirem no cotidiano desses alunos e ao serem desenvolvidas para além de atividades com fins de atribuição de nota.REFERÊNCIASANTUNES, I. Aula de Português: encontro e interação. São Paulo: Parábola Editorial, 2003. BAKHTIN, M. Estética da criação verbal. 4. ed. São Paulo: Martins Fontes, 2003.BAKHTIN, M. Problemas da Poética de Dostoiévski. 2. ed. Rio de Janeiro: Forense Universitária, 1997.BAKHTIN, M.; VOLOCHINOV, V. N. Marxismo e filosofia da linguagem. 11. ed. São Paulo: Hucitec, 2004. BOGDAN, R.; BIKLEN, S. Investigação qualitativa em educação: uma introdução à teoria e aos métodos. Portugal: Porto, 1994.BRASIL. Secretaria de Educação Fundamental. Parâmetros curriculares nacionais: terceiro e quarto ciclos do ensino fundamental: Língua Portuguesa. Brasília: MEC/SEF, 1998.BUNZEN, C. Da era da composição à era dos gêneros: o ensino de produção de texto no ensino médio. In: BUNZEN, C.; MENDONÇA, M. (Orgs.). Português no ensino médio e formação do professor. São Paulo: Parábola Editorial, 2006. p. 139-161AUTOR 1; A., xxxxx Rev. Bakhtiniana, 2013.GERALDI, J. W. Portos de passagem. 4. ed. São Paulo: Martins Fontes, 1991.GERALDI, J. W. O texto na sala de aula. 3. ed. São Paulo: Ática, 2001.KLEIMAN, B. A. Letramentos e suas implicações para o professor de língua materna. Revista Siano. Santa Cruz do Sul. v. 32, n. 53, p. 1-25, dez. 2007. KRAMER, S. Entrevistas coletivas: uma alternativa para lidar com diversidade, hierarquia e poder na pesquisa em ciências humanas. In: FREITAS, M. T; SOUZA, S. J.; KRAMER, S. Ciências humanas e pesquisa. Porto Alegre: Artmed, 2007. p.57-71.PRETI D. (org) O discurso oral culto 2.ed. São Paulo: Humanitas Publicações – FFLCH USP, 1999 – (Projetos Paralelos. v.2)Recebido em 21-12-2017 e aceito em 06-08-2018.

Abstract Bacheler, N. M., Schobernd, Z. H., Berrane, D. J., Schobernd, C. M., Mitchell, W. A., and Geraldi, N. R. 2013. When a trap is not a trap: converging entry and exit rates and their effect on trap saturation of black sea bass (Centropristis striata) – ICES Journal of Marine Science, 70: 873–882. Catch rates are often used to index the abundance of marine organisms, but catch saturation (i.e. declining catch rate as fishing time increases) can decouple catch and abundance. Researchers have struggled to account for saturation when using trap catch to infer population dynamics. We used the underwater video to document entries and exits of black sea bass (Centropristis striata) from chevron traps (n = 26) to quantify catch saturation. Black sea bass catch varied between 3 and 188 individuals for soak times of ∼90 min. Overall, 3564 black sea bass entered the traps and 1826 exited; therefore, over half (51%) of black sea bass entering traps exited before traps were retrieved. Black sea bass catch rates were non-linear and asymptotic for most (81%) trap samples, despite short soak times. Moreover, catch saturation occurred at 50 min, when the entry rate declined and the exit rate increased to a point where their confidence intervals overlapped. Several lines of evidence suggest that the level of black sea bass catch once saturation occurred may be positively related to true abundance, but additional research is needed to more fully test this hypothesis.

Este artigo tem como objetivo analisar o trabalho com gênero do discurso em plano de aula de língua portuguesa do Portal do Professor. O foco recai sobre o exame dos aspectos temáticos, estilísticos e composicionais do gênero do discurso notícia explorado em um plano recortado como corpus do estudo. Interessa responder a seguinte questão: propõe-se efetivamente um trabalho com gênero do discurso e que considere suas especificidades? Como ancoragem teórica, o trabalho assume, principalmente, estudos do denominado Círculo de Bakhtin (BAKHTIN; 2016; MEDVIÉDEV, 2016; VOLÓCHINOV, 2017) sobre a abordagem dialógica e ideológica da linguagem, com ênfase nas discussões sobre gêneros do discurso, e trabalhos de estudiosos que discutem questões ligadas ao ensino de língua materna, dentre os quais Barbosa (2000), Rodrigues (2001), Maieski (2005) e Acosta (2008. As análises realizadas apontam que não há, no plano de aula analisado, uma adequada exploração do conteúdo temático, do estilo e da estrutura composicional enquanto partes constituintes do gênero explorado, uma vez que a proposta de abordagem desses aspectos tanto fica restrita a uma exploração superficial e de maneira genérica do enunciado, quanto se dá a partir de partes fragmentadas deste, desconsiderando, portanto, a concretude do enunciado notícia e suas especificidades.REFERÊNCIASACOSTA, P, R. O gênero jornalístico notícia: dialogismo e valoração. Dissertação (Mestrado em Linguística). Programa de Pós-graduação em Linguística. Florianópolis: UFSC, 2008. ALVES, W. M.; BESSA, J. C. R. Orientações para escrita da redação do Enem em vídeos do Youtube. Hipertextus Revista Digital, v. 19, p. 1-23, 2018.AZZARI, E. F. EFL collaborative writing: text production and online resources. Diálogo das Letras, Pau dos Ferros, v. 8, n. 1, p. 52-65, jan./abr. 2019.BAKHTIN, M. Os gêneros do discurso. Organização, tradução, posfácio e notas de Paulo Bezerra. São Paulo: Editora 34, 2016.BARBOSA. J. P. Do professor suposto pelos PCNs ao professor real de língua portuguesa: são os PCNs praticáveis? In: ROJO. R. (Org). A prática de linguagem em sala de aula: praticando os PCNs. São Paulo: Mercado de Letras, 2000, p. 149-175.BARBOSA. M. S; NUNES. R. H. Os PCNs: uma experiência de formação de professores do Ensino Fundamental. In: ROJO. R. (Org). A prática de linguagem em sala de aula: praticando os PCNs. São Paulo: Mercado das Letras, 2000, p. 93-126.BELEN, B. de C. O blog como ferramenta pedagógica no ensino de produção escrita em língua inglesa no PARFOR. Diálogo das Letras, Pau dos Ferros, v. 03, n. 01, p. 87-106, jan./jun. 2014.BEZERRA, B. G. Gêneros no contexto brasileiro: questões [meta] teóricas e conceituais. São Paulo: Parábola Editorial, 2017.BENASSI, M. V. B. O gênero notícia: uma proposta de análise e intervenção. In: CELLI – COLÓQUIO DE ESTUDOS LINGUÍSTICOS E LITERÁRIOS. 3, 2007, Maringá. Anais... Maringá, 2009, p. 1791-1799. Disponível em:ple.uem.br/3celli_anais/trabalhos/estudos_linguísticos/069.pdf. Acesso em: 06 jun. 2018.BESSA, J. C. R.; BERNARDINO, R. A. S. Equívocos em torno da escrita: o caso das dicas de produção de textos em vídeos do YouTube. Domínios de Lingu@Gem, v. 11, p. 174, 2016.BRASIL. SEF. Parâmetros curriculares nacionais: terceiro e quarto ciclos do ensino fundamental: língua portuguesa. Brasília: MEC/SEF, 1998.CASSETTARI, M. I. Tipo, gênero textual e gênero do discurso: em busca de uma definição para o ensino. Diálogo das Letras, Pau dos Ferros, v. 01, n. 02, p. 132 – 151, jul./dez. 2012.DEMO, P. O educador e a prática da pesquisa. Ribeirão Preto: Editora Alphabeto, 2009.DEMO, P. Aprender como autor. São Paulo: Atlas, 2015.DOLZ, J.; SCHNEUWLY, B. Gêneros e progressão em expressão oral e escrita: elementos para reflexões sobre uma experiência suíça (francófona). Tradução de Roxane Rojo. Enjeux, p. 31 -49, 1996. ENGEL, T. G; SILVEIRA, D.T. Métodos de pesquisa. Porto Alegre: Editora da UFRGS, 2009.FARACO, C. A. Linguagem diálogo: as ideias Linguísticas do círculo de Bakhtin. Curitiba: Parábola Editorial, 2009.GERALDI, J. W. Dialogia: do discurso à estrutura sintática. In: RODRIGUES. R. H.; ACOSTA. R. P. (Org). Estudos dialógicos da linguagem e pesquisa em linguística aplicada. São Carlos: Pedro João Editores, 2016, p. 179-189.KERSCH, D. F.; MARQUES, R. G. Redes sociais digitais na escola: possibilidades de conexão, produção de sentido e aprendizagem. Diálogo das Letras, Pau dos Ferros, v. 06, n. 02, p. 343-362, jul./dez. 2017.LAVILLE, C.; DIONNE, J. A construção do saber: manual de metodologia da pesquisa em ciências humanas. Tradução de Heloisa Monteiro e Francisco Settineri. Portalegre: Artes Médicas, Sul Ltda,; Belo Horizonte: Editora UFMG, 1999.MAIESKI, M. N. O gênero do discurso artigo como objeto de ensino-aprendizagem: uma proposta de integração da prática de produção textual à leitura e à análise linguística. 2005. 209f. Dissertação (Mestrado em Linguística) – Programa de Pós-Graduação em Linguística, Universidade de Santa Catarina, 2005.MEDVIÉDEV. P. N. O método formal nos estudos literários: introdução crítica a uma poética sociológica. Tradição de Ekaterina Vólkova Américo e Sheila Camargo Grillo. São Paulo: contexto, 2016.MENDONÇA, M. C. A produção textual na esfera escolar: considerações sobre a “escrita como trabalho”. Diálogo das Letras, Pau dos Ferros, v. 8, n. 1, p. 3-15, jan./abr. 2019.MORAN, J. M. Como utilizar a internet na Educação. Ciência da Informação, BRASÍLIA, v. 26, n. 2, p. 146-153, 1997.RIBEIRO, A. E. Tecnologia digital e ensino: breve histórico e seis elementos para a ação. Linguagem Ensino, Pelotas, v.19, n.2, p. 91-111, jul./dez. 2016.RODRIGUES, R. H. A constituição e funcionamento do gênero jornalístico artigo: cronotopo e Dialogismo. 2001. 347f. Tese (Doutorado em Linguística Aplicada e Estudos da Linguagem). Pontifícia Universidade Católica de São Paulo, São Paulo, 2001.ROJO, R. Gêneros do discurso e gêneros textuais: questões teóricas e aplicadas. In: MEURER, J. L.; BONINI, A.; MOTTA-ROTH, D. (Org.). Gêneros: teorias, métodos, debates. São Paulo: Parábola, 2005, p.184-207.SILVA, S. L. Algumas considerações sobre memorial de leitura e a constituição do ethos discursivo na formação inicial do professor de língua portuguesa. Diálogo das Letras, Pau dos Ferros, v. 03, n. 02, p. 05–22, jul./dez. 2014.SARMENTO, C. A. O tratamento dado aos gêneros discursivos em análise linguística: um estudo de planos de aula do Portal do Professor. 2018. 121 f. Dissertação (Mestrado em Ensino) – Programa de Pós-Graduação em Ensino. Universidade do Estado do Rio Grande do Norte, Pau dos Ferros, 2018.SOBRAL, A. 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The present article is a research clipping whose general objective was to understand how the organizational structure of a public school made possible the work with students with disabilities for the realization of the truly inclusive education proposal. In this work we discuss the collaboration/partnership in a perspective that articulates the different segments of professionals of the school in the interlocution with the family, perspective that seeks to potentiate the learning of a student’s with disabilities. We present an experience developed with a student of Early Childhood education, in the context of a municipal school in the interior of the state of São Paulo, where the vice-director/researcher presents collaborative processes developed between teacher regent, a teacher of Specialized Educational Assistance (AEE) and an educational agent, subjects who were responsible for preparing and developing projects, activities and teaching materials for the referred student. The data produced for this work are: Teacher's Diary, student’s Individual Development Plan (PDI), evaluation record of the student’s mother, daily register of the vice-director and the reflective register of the teachers and educational agent about their experiences with the student with disabilities. The production of the data was analyzed from the indexing paradigm. Collaboration/partnership was made possible through the constitution of a group of individuals who support each other, experienced joint actions and had feelings of productive belonging, around the common goal of guaranteeing student’s learning. The participation of the family was paramount to the achievement of the objectives proposed with the student with disabilities.ResumoO presente artigo é um recorte de pesquisa que teve como objetivo geral compreender de que forma a estrutura organizativa de uma escola pública possibilitou o trabalho com os alunos público-alvo da educação especial (PAEE) para a efetivação da proposta de educação verdadeiramente inclusiva. Neste trabalho discutimos a colaboração/parceria numa perspectiva que articula os diferentes segmentos de profissionais da escola na interlocução com a família, perspectiva que almeja potencializar a aprendizagem do aluno PAEE. Apresentamos experiência desenvolvida com aluno da Educação Infantil, no contexto de uma escola municipal do interior do estado de São Paulo, em que a vice-diretora/pesquisadora apresenta processos colaborativos desenvolvidos entre professora regente, professora do Atendimento Educacional Especializado (AEE) e agente educacional, sujeitos que se responsabilizaram por elaborar e desenvolver projetos, atividades e materiais pedagógicos para o referido aluno. Os dados produzidos para este trabalho contemplam: Diário de Bordo das professoras, Plano de Desenvolvimento Individual (PDI) do aluno, registro avaliativo da mãe do aluno, caderno de registro cotidiano da vice-diretora e registro reflexivo das professoras e agente educacional sobre suas experiências junto ao aluno PAEE. A produção dos dados foi analisada a partir do paradigma indiciário. A colaboração/parceria foi possibilitada através da constituição de um grupo onde os sujeitos se apoiaram mutuamente, experimentaram ações conjuntas e tinham sentimentos de pertença produtiva, em torno do objetivo comum de garantir a aprendizagem do aluno PAEE. A participação da família foi primordial para o alcance dos objetivos propostos com o aluno PAEE.ResumenEl presente artículo es un recorte de una investigación que tuvo como objetivo general comprender de qué forma la estructura organizativa de una escuela pública posibilitó el trabajo con los alumnos con discapacidad para la realización de la propuesta educativa verdaderamente inclusiva. En este trabajo discutimos la colaboración/asociación en una perspectiva que articula los diferentes segmentos de profesionales de la escuela en la interlocución con la familia, perspectiva que pretende potencializar el aprendizaje del aluno con discapacidad. Presentamos la experiencia desarrollada con un alumno de la Educación Infantil, en el contexto de una escuela municipal del interior del estado de São Paulo, donde la vice-directora/investigadora presenta los procesos colaborativos desarrollados entre la profesora de la sala, la profesora del Atendimiento Educacional Especializados (AEE) e la agente educacional, sujetos que se responsabilizaron por elaborar y desarrollar proyectos, actividades e materiales pedagógicos para el alumno referido. Los datos producidos para este trabajo contemplan: Diario de Bordo de las profesoras, Plano de Desenvolvimiento Individual (PDI) del alumno, registro evaluativo de la madre del alumno, cuaderno de registro cotidiano de la vice-directora e registro reflexivo de las profesoras e agente educacional sobre sus experiencias con el alumno con discapacidad. La producción de los datos fue analizada a partir del paradigma indiciario. La colaboración/asociación fue posible a través de la constitución de un grupo en el cual los sujetos se apoyan mutuamente, experimentan acciones conjuntas y tuvieron sentimientos de pertenencia productiva, en torno al objetivo común de garantizar el aprendizaje del alumno con discapacidad. La participación de la familia fundamental para el logro de los objetivos propuestos con el alumno con discapacidad.Palavras-chave: Educação inclusiva, Aluno PAEE, Práticas colaborativas.Keywords: Inclusive education, Student with disabilities, Collaborative practices.Palavras clave: Educación inclusiva, Alumno com discapacidade, Prácticas inclusivas.ReferencesBETEGHELLI, Tagiane Giorgetti dos Santos. A professora coordenadora na educação infantil: na composição da organização do trabalho pedagógico e da formação dos educadores. 2018, 203p. Dissertação (Mestrado em Educação). Universidade Estadual Paulista. Instituto de Biociências. Rio Claro/SP: Unesp, 2018.BRASIL. Marcos Políticos-Legais da Educação Especial na Perspectiva da Educação Inclusiva. Ministério da Educação. Secretaria de Educação Especial. Brasília: Secretaria de Educação Especial, 2010.CAPELLINI, Vera Lúcia Messias Fialho (org.); ZANATA, Eliana Marques; PEREIRA, Verônica Aparecida. Práticas educativas: ensino colaborativo. Práticas em Educação Especial e Inclusiva na área da deficiência mental. Bauru/SP: MEC/FC/SEE, 2008.CAPELLINI, Vera Lúcia Messias Fialho. Formação Continuada por meio da Consultoria Colaborativa: compromisso com o ensino-aprendizagem de todos os alunos. In: MENDES, Enicéia Gonçalves; ALMEIDA, Maria Amélia (orgs.). A Pesquisa sobre inclusão escolar em suas múltiplas dimensões: teoria, política e formação. Marília: ABPEE, 2012.CHALUH, Laura Noemi. Do trabalho coletivo na escola: encontros na diferença. Pro-Posições. Campinas, vol. 21, nº 2 (62), maio/ago., 2010, pp. 207-223.FERNANDES, Carla Helena. Relatório Final de Estágio Pós-Doutoral. 2017, 300p. Universidade Estadual Paulista “Júlio de Mesquita Filho”. Rio Claro/SP: Unesp, 2017.GINZBURG, Carlo. Mitos, emblemas, sinais: morfologia e história. São Paulo: Companhia das Letras, 1989.JESUS, Denise Meirelles de; GONÇALVES, Agda Felipe Silva; VIEIRA, Alexandro Braga; EFFGEN, Ariadna Pereira Siqueira. As políticas públicas em ação no estado do Espírito Santo: o que dizem as superintendências e as secretarias municipais de educação. In: MENDES, Enicéia Gonçalves; ALMEIDA, Maria Amélia (orgs.). A pesquisa sobre inclusão escolar em suas múltiplas dimensões: teoria, política e formação. Marília: ABPEE, 2012.LIMA, M. E. C. C.; GERALDI, C. M. G.; GERALDI, J.W. O trabalho com narrativas na investigação em educação. Educação em Revista. Belo Horizonte, vol.31, nº.01, jan-mar., 2015, pp. 17-44.MAZZOTTA, Marcos José da Silveira. Educação Especial no Brasil: História e Políticas Públicas. 3ª ed. São Paulo: Cortez, 2001.MENDES, Enicéia Gonçalves; VILARONGA, Carla Ariela Rios; ZERBATO, Ana Paula. Ensino colaborativo como apoio à inclusão escolar: unindo esforços entre educação comum e especial. São Carlos: EdUFSCar, 2014.ORSATI, Fernanda T. Acomodações, modificações e práticas efetivas para a sala de aula inclusiva. Temas sobre Desenvolvimento, 19 (107). São Paulo: pp. 213-222, 2013.PRIMO, Dorian Regina B. S.; MOTTA JÚNIOR, Ademar Simões da. A influência da ludicidade na aquisição da aprendizagem de crianças com necessidades educativas especiais nas séries iniciais. In: CARVALHO, Edemir de; CARVALHO, Carmem Silvia B. F. (orgs.). Práticas Pedagógicas: entre as teorias e metodologias, as necessidades educativas especiais. Marília: Oficina Universitária. São Paulo: Cultura Acadêmica, 2012.RIO CLARO. Projeto Político Pedagógico da Escola Municipal Professor Victorino Machado. Rio Claro: Secretaria Municipal da Educação, 2015.RIO CLARO. Reorientação Curricular da Rede Municipal de Educação de RioClaro. Rio Claro, SP: Secretaria Municipal da Educação, 2008.RIZZI, E.; GONZALEZ, M.; XIMENES, S. Direito humano à educação. Coleção Manual de Direitos Humanos. 2ª ed. Organização: Plataforma Dhesca Brasil e Ação Educativa. Brasília: vol. 7, novembro de 2011.ROSALEN, Patrícia C. Práticas colaborativas no trabalho com alunos Público-alvo da Educação Especial (PAEE): o cotidiano de uma escola polo. 2019, 242p. Dissertação (Mestrado em Educação). Universidade Estadual Paulista. Instituto de Biociências. Rio Claro/SP: Unesp, 2019.SÁNCHEZ, Pilar Arnaiz. A educação inclusiva na Espanha. In: FÁVERO, Osmar; FERREIRA, Windys; IRELAND, Timothy; BARREIROS, Débora (orgs.). Tornar a educação inclusiva. Brasília: UNESCO, 2009.SASSAKI, Romeu Kasumi. Inclusão: o paradigma do século 21. Inclusão – Revista da Educação Especial. Brasília, vol. 1, nº 1, out. 2005, pp. 19-23.SIGOLO, Sílvia Regina R. L. Envolvimento Familiar e Educação Inclusiva: uma mútua contribuição. In: MENDES, Enicéia Gonçalves; ALMEIDA, Maria Amélia (orgs.). A pesquisa sobre inclusão escolar em suas múltiplas dimensões: teoria, política e formação. Marília: ABPEE, 2012.VELTRONE, Aline Aparecida; MENDES, Enicéia Gonçalves. Percepções dos alunos com deficiência intelectual sobre sua matrícula na classe especial e classe comum. Revista Eletrônica de Educação, vol. 5, nº. 2. São Carlos/SP: UFSCar, Programa de Pós-Graduação em Educação, novembro de 2011, pp. 59-81.ZERBATO, Ana Paula; MENDES, Enicéia Gonçalves. Desenho universal para a aprendizagem como estratégia de inclusão escolar. Educação Unisinos, vol. 22, nº 2, abril-junho 2018, pp.147-155.e3579065

This present work has as a goal presenting an experience that begins from a writing practice, called to report, and lived through the subject entitled Professional Education: Contemporary Challenges from the Post-Graduation Program Science Education – Federal University of Rio Grande – FURG (Brazil). It is argued about the composition of a researcher in an environment full of dialogue, reading and critical analysis of texts, articulated with many writings and group discussions. In order to comprehend this experience, it is used theoretical contributions; their ideas go towards the importance of the writing when it comes to the constitution of the ongoing formation of the person. The subject proposal was based on the writing of three individual texts from the critical analysis of the three articles, on a group text related to an article about professional education, as well as the reading and a critical analysis from at least one text from a colleague, according to criteria related to form and content, totaling five writings. From this experience, it can be said that being a researcher is searching for information due to a problem, a topic, a concern, besides the necessity of expressing through writing and reflecting critically about the discussed topics. It was a group practice that required constantly dialogues established with the authors, the colleagues and the teacher, adding the learning about how to analyze an article meticulously, from the investigation about who is the author, his/her formation, to structural aspects of the text. The activities were considered as something very pleasurable, beyond evaluations or obligations, used as inspiration for the reflections, other readings and writings.ResumoO artigo tem como objetivo relatar uma experiência a partir de uma prática de escrita, denominada de relatoria, vivenciada na disciplina Educação Profissional: Desafios Contemporâneos do Programa de Pós-Graduação em Educação em Ciências da Universidade Federal do Rio Grande – FURG, Brasil. Argumenta-se sobre a constituição da pesquisadora em formação num ambiente de muito diálogo, de leitura e análise crítica de textos, articulado com diversas produções escritas e discussões coletivas. Para compreender essa experiência narrada, utilizam-se teóricos que apontam a importância da escrita na constituição do sujeito em formação. A proposta da disciplina envolveu a escrita de três textos individuais a partir da análise crítica de três artigos, um texto coletivo relacionado a um artigo sobre Educação Profissional, bem como a leitura e análise crítica coletiva de pelo menos um texto de um colega, seguindo critérios quanto à forma e ao conteúdo, totalizando em cinco produções realizadas. Decorre desta experiência, a constatação de que ser pesquisador é estar em busca de informações acerca de um problema, um assunto, uma inquietação, além da necessidade de se posicionar por escrito e refletir criticamente sobre os temas abordados. Foi uma prática coletiva que demandou constantes diálogos estabelecidos com autores, com colegas e com a professora, incluindo o aprendizado de como analisar um artigo minuciosamente, desde a investigação sobre quem é o autor, sua formação, até aspectos estruturais do texto. As atividades foram assumidas como algo prazeroso, muito além de avaliações ou obrigações, servindo de inspiração para reflexões, outras leituras e produções textuais.Keywords: Researcher, Writing, Formation.Palavras-chave: Pesquisador, Escrita, Formação.ReferencesBENJAMIN, W. Magia e técnica, arte e política: ensaios sobre literatura e história da cultura. São Paulo: Brasiliense, 1994.BRUNER, J. The narrative construction of reality. Critical Inquiry, Chicago, v. 18, n.1, p. 1-21, 1991.CLANDININ, J.; CONNELLY, M. Narrative inquiry: experience and story in qualitative research. São Francisco: Jossey-Bass, 2000.CUNHA, M. I. Conta-me agora! As narrativas como alternativas pedagógicas na pesquisa e no ensino. Revista da Faculdade de Educação, vol. 23, n. 1-2. São Paulo, jan. de 1997. Disponível em <http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-25551997000100010>. Acesso em: 22 jul. 2017.DEMO, P. Pesquisa: princípio científico e educativo. São Paulo: Cortez Editora, 2001.FREIRE, P. Pedagogia da autonomia. Saberes necessários à prática educativa. São Paulo: Paz e Terra, 1996.HOUAISS, Instituto Antônio. Minidicionário Houaiss da língua portuguesa. 2. ed. Rio de Janeiro: Objetiva, 2004.LARROSA, J. Sobre a lição. In: LARROSA, J. Pedagogia profana: danças, piruetas e mascaradas. Tradução de Alfredo Veiga-Neto. Belo Horizonte: Editora Autêntica, p. 139-146, 2001.LARROSA, J. A arte da conversa. In: SKLIAR, C. Pedagogia (improvável) da diferença. E se o outro não estivesse aí? Tradução de Giane Lessa. Rio de Janeiro: DP&A, p. 211-216, 2003.LARROSA, J. Tremores: escritos sobre experiência. Tradução de Cristina Antunes e João Wanderley Geraldi. Belo Horizonte: Autêntica Editora, 2015.MARQUES, M. O. Escrever é preciso: o princípio da pesquisa. 2ª ed. Ijuí: Unijuí, 2011.NACARATO, A. M.; LOPES, C. E. Indagações, reflexões e práticas em leituras e escritas na educação matemática. Campinas: Mercado das Letras, 2013.PERISSÉ, G. Ler, pensar e escrever. São Paulo: Saraiva, 2011.PRADO, G.V.T.; SOLIGO, R. Porque escrever é fazer história: revelações, subversões, superações. Campinas: Alínea, 2007.SANTOS, S. A narrativa como estratégia de formação e de reflexão sobre a prática docente. Revista Teoria e Prática da Educação, v. 11, n. 2, p. 207 – 217, maio/ago. 2008. Disponível em <http://www.dtp.uem.br/rtpe/volumes/v11n2/010-artigo-sydione-207-217.pdf. > Acesso em: 03 dez. 2016.

Introdução: O número crescente de infecções causadas por fungos e o surgimento de microrganismos resistentes tem sinalizado a necessidade da busca por novos agentes antifúngicos, fomentando a pesquisa em moléculas promissoras, como os O-glicosídeos. Objetivo: Partindo dessa premissa, objetivamos a síntese e investigação da atividade antifúngica do benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo isolado e quando associado com a anfotericina B. Material e métodos: Inicialmente foi sintetizado o benzil 4,6-di-O-acetil-2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo a partir da reação entre o 3,4,6-tri-O-acetil-D-glucal e álcool benzílico via catálise ácida e irradiação ultrassônica seguida por sua hidrólise em meio básico para levar ao benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo. Este foi submetido à avaliação antifúngica por meio do método da microdiluição em caldo e estudo da associação com a anfotericina B pelo método de Checkerboard. Resultados: O benzil 4,6-di-O-acetil-2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo e o benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo foram obtidos em excelentes rendimentos 91 e 94 %, respectivamente. O benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo apresentou atividade antifúngica apenas contra as cepas de Candida albicans ATCC 76615, Candida albicans ATCC 76485 e Candida guilliermondiiLM 103, e sua associação com a anfotericina B foi classificada como indiferente. Conclusão: Estes resultados possibilitam futuros estudos envolvendo esta classe de moléculas, avaliação dos possíveis mecanismos de ação e avaliar outras atividades biológicas, uma vez que esta classe molecular sustenta a expectativa de baixa toxicidade, devido ao seu padrão de biocompatibilidade. Descritores: Síntese Química; Metabolismo dos Carboidratos; Fungos; Candida. Referências Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. FEMS Microbiol Rev. 2012;36:288-305. Vieira AJH, Santos JI. Mecanismos de resistência de Candida albicans aos antifúngicos anfotericina B, fluconazol e caspofungina. RBAC. 2017;49:235-9. De Rossi T, Lozovoy MAB, Silva RV, Fernandes EV, Geraldino TH, Costa IC, et al. Interações entre Candida albicans e Hospedeiro. Semina: Cienc Biol Saude. 2011;32:15-28. Ashong CN, Hunter AS, Mansouri MD, Cadle RM, Hamill RJ, Musher DM. Adherence to clinical practice guidelines for the treatment of candidemia at a Veterans Affairs Medical Center. Int J Health Sci. 2017;11:18-23. Kung HC, Huang PY, Chen WT, Ko BS, Chen YC, Chang SC, et al. 2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan. J microbiol Immunol infect. 2018;51:1-17. Patil S, Rao RS, Raj AT, Sanketh DS, Sarode S, Sarode G. 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e4480073The article addresses the categories Professional Choice and Professional Insertion relating the theoretical concepts to the experiences and professional trajectory of graduates of the Pedagogy course, of a Community University in Southern Brazil. The objective was to characterize the insertion process of the educators and to identify their professional trajectories with the conclusion of the course. Studies on the topic have increased in the literature in recent years due to the attractiveness of the profession, which would be linked to satisfaction of working with the learning of others. The methodology used the principles of qualitative research and the data collection was carried out through a semi structured interview with 14 (fourteen) graduates and 1 (one) graduating from the course and documentary analysis of the Pedagogy Course Report / Enade 2014, organized by National Institute of Educational Studies and Research Anísio Teixeira (Inep). The research was developed with the same group worked at different moments in the training process: as academic graduates of 2014, participants in Enade and as graduates of the Pedagogy course after five years of completing the course. The results showed that the choice and professional insertion are directly connected and related to the training spaces, the job market and social influences. The choice of the course is still motivated by the socioeconomic conditions of the young pedagogues and the professional insertion demonstrated as a time to establish themselves in the profession.ResumoO artigo aborda as categorias Escolha Profissional e Inserção Profissional relacionando os conceitos teóricos com as experiências e a trajetória profissional de egressas(os) do curso de Pedagogia, de uma Universidade Comunitária no Sul do Brasil. O objetivo foi de caracterizar o processo de inserção das(os) pedagogas(os) e identificar suas trajetórias profissionais com a conclusão do curso. Os estudos sobre o tema têm aumentado na literatura nos últimos anos em função da atratividade da profissão, que estaria ligada à satisfação de trabalhar com a aprendizagem do outro. A metodologia utilizou os princípios da pesquisa qualitativa e a coleta de dados realizada se deu por intermédio de entrevista semiestruturada com 14 (quatorze) egressas e 1 (um) egresso do curso e análise documental do Relatório do Curso de Pedagogia/Enade 2014, organizado pelo Instituto Nacional de Estudos e Pesquisas Educacionais Anísio Teixeira (Inep). A pesquisa foi desenvolvida com o mesmo grupo em momentos distintos do processo formativo: como acadêmicas(os) concluintes de 2014, participantes do Enade e como egressas(os) do curso de Pedagogia após cinco anos de conclusão do curso. Os resultados evidenciaram que a escolha e a inserção profissional estão diretamente conectadas e relacionadas com os espaços formativos, o mercado de trabalho e as influências sociais. A escolha do curso ainda é motivada pelas condições socioeconômicas das jovens pedagogas e a inserção profissional demonstrada como momento para se estabelecer na profissão.ResumenEl artículo aborda las categorías Elección profesional e Inserción profesional que relacionan los conceptos teóricos con las experiencias y la trayectoria profesional de los graduados del curso de Pedagogía, de una universidad comunitaria en el sur de Brasil. El objetivo era caracterizar el proceso de inserción de los educadores e identificar sus trayectorias profesionales con la conclusión del curso. Los estudios sobre el tema han aumentado en la literatura en los últimos años debido al atractivo de la profesión, que estaría vinculado con la satisfacción de trabajar con el aprendizaje de los demás. La metodología utilizó los principios de la investigación cualitativa y la recopilación de datos se realizó a través de una entrevista semiestructurada con 14 (catorce) graduados y 1 (uno) graduados del curso y análisis documental del Informe del Curso de Pedagogía / Enade 2014, organizado por Instituto Nacional de Estudios e Investigación Educativa Anísio Teixeira (Inep). La investigación fue desarrollada con el mismo grupo trabajó en diferentes momentos del proceso de capacitación: como graduados académicos de 2014, participantes en Enade y como graduados del curso de Pedagogía después de cinco años de completar el curso. Los resultados mostraron que la elección y la inserción profesional están directamente relacionadas y relacionadas con los espacios de capacitación, el mercado laboral y las influencias sociales. La elección del curso todavía está motivada por las condiciones socioeconómicas de los jóvenes pedagogos y la inserción profesional demostrada como un momento para establecerse en la profesión.Keywords: Professional choice, Professional insertion, Trainee of the graduate.Palavras-chave: Escolha profissional, Inserção profissional, Trajetória do egresso.Palabras clave: Elección profesional, Inserción profesional, Aprendiz del graduado.ReferencesALMEIDA, Maria Elisa Grijó Guahyba de; MAGALHAES, Andréa Seixas. Escolha profissional na contemporaneidade: projeto individual e projeto familiar. Revista Brasileira de Orientação Profissional, São Paulo, v. 12, n. 2, p. 205-214, dez. 2011. Disponível em http://pepsic.bvsalud.org/scielo.php?script=sci_arttextpid=S1679-33902011000200008lng=ptnrm=iso. Acesso em 19 ago. 2019.ALVES, Natália. Juventude e inserção profissional. Lisboa: Educa/UIDCE, 2008.BARDAGI, Marúcia Patta. LASSANCE, Maria Célia Pacheco; PARADISO, Angela Carina. Trajetória acadêmica e Satisfação com a Escolha Profissional de Universitários em Meio de Curso. Revista Brasileira de Orientação Profissional, São Paulo, v. 4, n.1/2, p. 153-166, 2003. Disponível em: http://pepsic.bvsalud.org/scielo.php?script=sci_arttextpid=S1679-33902003000100013. Acesso em 04 ago. 2018.BARDAGI, Marúcia Patta; LASSANCE, Maria Célia Pacheco; PARADISO, Ângela Carina and MENEZES, Ioneide Almeida de. Escolha profissional e inserção no mercado de trabalho: percepções de estudantes formandos. Psicol. Esc. Educ. vol.10, n.1, p. 69-82, 2006. Disponível em: http://www.scielo.br/scielo.php?pid=S1413-85572006000100007script=sci_arttext. Acesso em: 5 maio. 2018.BOCK, Silvio Duarte. Orientação profissional: avaliação de uma proposta de trabalho na abordagem sócio-histórica. 2001. 209p. Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação, Campinas, SP. Disponível em: http://www.repositorio.unicamp.br/handle/REPOSIP/253384. Acesso em: 27 jul. 2018.BRASIL. Constituição Federal do Brasil. Diário Oficial da União, Brasília, 5 de outubro de 1988. Disponível em: https://www.stf.jus.br/arquivo/cms/legislacaoConstituicao/anexo/CF.pdf. Acesso em: 22, jun. 2020.BRASIL. Diretrizes Curriculares Nacionais para o Curso de Graduação em Pedagogia, licenciatura. Resolução CNE/CP 1/2006. Diário Oficial da União, Brasília, 16 de maio de 2006. Disponível em: http://portal.mec.gov.br/cne/arquivos/pdf/rcp01_06.pdf. Acesso em: 2 jun. 2017.BRASIL. Lei de Diretrizes e Bases da Educação Nacional. Lei número 9394, 20 de dezembro de 1996. Brasília, DF. Disponível em: http://www.planalto.gov.br/ccivil_03/leis/l9394.htm. Acesso em 20 set. 2018.BRASIL. Lei n.13.005, de 25 de junho de 2014. Aprova o Plano Nacional de Educação – PNE e dá outras providências. Diário Oficial da União, Brasília, DF. 26 jun, 2014a. Disponível em: http://pne.mec.gov.br/18-planos-subnacionais-de-educacao/543-plano-nacional-de-educacao-lei-n-13-005-2014. Acesso em Acesso em 2 de junho de 2017.BRASIL. Ministério da Educação. Instituto Nacional de Estudos e Pesquisas Educacionais Anísio Teixeira. Exame Nacional de Desempenho dos Estudantes (Pedagogia) 2014. 2014b. Disponível em: http://enadeies.inep.gov.br/enadeIes/enadeResultado/. Acesso em: 12 dez. 2018.CHANLAT, Jean-François. Quais carreiras e para qual sociedade? Revista de Administração de Empresas, São Paulo, v.35, n.6, p. 67-75 nov./dez. 1995. Disponível em: http://www.scielo.br/pdf/rae/v35n6/a08v35n6.pdf. Acesso em 15 abr. 2017.DIAS, Maria Sara de Lima; SOARES, Dulce Helena Penna. A escolha profissional no direcionamento da carreira dos universitários. Psicologia: Ciência e Profissão, Brasília, v. 32, n. 2, p. 272-283, 2012. Disponível em: http://www.scielo.br/scielo.php?pid=S1414-98932012000200002script=sci_abstracttlng=pt. Acesso em: 27 jul. 2018.DUBAR, Claude. A socialização: construção das identidades sociais e profissionais. São Paulo: Martins Fontes, 2005.GATTI, Bernadete Angelina; BARRETTO, Elba Siqueira de Sá; ANDRÉ, Marli Eliza Dalmazo Afonso de; ALMEIDA, Patrícia Cristina Albieri de. Professores do Brasil: novos cenários de formação. Brasília: UNESCO, 2019. Disponível em: https://unesdoc.unesco.org/ark:/48223/pf0000367919. Acesso em 27 jul. 2018.GATTI, Bernadete Angelina et al. A Atratividade da Carreira Docente no Brasil. In: Estudos e Pesquisas Educacionais, n. 1, São Paulo, FVC/Fundação Victor Civita, 2010. Disponível em: https://abrilfundacaovictorcivita.files.wordpress.com/2018/04/estudos_e_pesquisas_educacionais_vol_1.pdf. Acesso em: 27 jul. 2018.JONHSON, Maria Cristina Folmer. C. Projeto de vida e trabalho: a orientação profissional na perspectiva de orientadores. Dissertação de Mestrado, Faculdade de Educação, Universidade Estadual de Campinas, São Paulo, 2000.MARCELO, Carlos; VAILLANT, Denise. Políticas y programas de inducción en la docencia en Latinoamérica. Cad. Pesqui. [on-line]. vol. 47, n. 166, p.1224-1249, 2017. Disponível em: http://www.scielo.br/scielo.php?script=sci_arttextpid=S0100-15742017000401224lng=ennrm=iso. Acesso em: 12 jul. 2018.NEIVA, Kathia Maria Costa. A Maturidade para a Escolha Profissional: Uma Comparação entre Alunos do Ensino Médio. Revista Brasileira de Orientação Profissional. v. 4 (1/2), p. 97-103, 2003. Disponível em: http://pepsic.bvsalud.org/scielo.php?script=sci_arttextpid=S1679-33902003000100009. Acesso em: 14 jun. 2016.NEPOMUCENO, Ricardo Ferreira; WITTER, Geraldina Porto.Influência da família na decisão profissional: opinião de adolescentes. Psicol. Esc. Educ. [online]. vol. 14, n. 1, p. 15-22, 2010. Disponível em: http://dx.doi.org/10.1590/S1413-85572010000100002. Acesso em: 14 de set. 2018.OSTROVSKI, Crizieli Silveira; RAITZ, Tânia Regina. Uma reflexão teórica sobre escolha e inserção profissional: transição da universidade ao mercado de trabalho. In: EDUCARE – XII Congresso Nacional de Educação. Curitiba: PUC, 2015.ROCHA-DE-OLIVEIRA, Sidinei. Inserção profissional: perspectivas teóricas e agenda de pesquisa. Revista Pensamento Contemporâneo em Administração, Rio de Janeiro, v. 6, n. 1, p. 124-135, jan./mar. 2012. Disponível em: http://www.spell.org.br/documentos/ver/30875/insercao-profissional--perspectivas-teoricas-e-agenda-de-pesquisa/i/pt-br. Acesso em: 14 jun. 2016.TARTUCE, Gisela Lobo B. P.; NUNES, Marina M. R.; ALMEIDA, Patrícia Cristina Albieri de. Alunos do ensino médio e atratividade da carreira docente no Brasil. Cadernos de Pesquisa, São Paulo, v. 40, n. 140, p. 445-477, maio/ago. 2010. Disponível em: http://dx.doi.org/10.1590/S0100-15742010000200008. Acesso em: 12 jul. 2018.VALLE, Ione Ribeiro. Carreira do magistério: uma escolha profissional deliberada. Revista Brasileira de Estudos Pedagógicos, Brasília, v. 87, n. 216, p. 178-187, maio/ago. 2006. Disponível em: http://www.rbep.inep.gov.br/index.php/RBEP/article/viewFile/32/34. Acesso em: 27 jul. 2018.METZNER, Cintia de Sousa. Os sentidos da formação e do trabalho: inserção profissional e a carreira docente em foco. Tese (Doutorado em Educação) Universidade do Vale do Itajaí. Itajaí/SC, p. 133. 2019. Disponível em: https://www.univali.br/Lists/TrabalhosDoutorado/Attachments/239/Cintia%20Metzner%20de%20Sousa.pdf. Acesso em Jun.2020.VANZUITA, Alexandre; RAITZ, Tânia Regina; GARANHANI, Marynelma Camargo. Escolha, formação e inserção profissional: a construção de identidade(s) profissional(is) de formandos em educação física. Espacios (CARACAS), vol. 38, n. 45, p. 17-31, 2017.VANZUITA, Alexandre; RAITZ, Tânia Regina; ZLUHAN, Mara Regina; FERREIRA, Danilo José; FERNANDES, Flávia de Souza. A construção de identidade(s) profissional(is) de formandos em educação física. Educação e Cultura Contemporânea, vol. 15, n. 40, p. 142-162, 2018.VANZUITA, Alexandre. A construção de identidade(s) profissional(is) de formandos em educação física da UFPR. 2018. 161f. 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Nitrogen is a paramount important essential element for all living organisms. It has been found to bea crucial structural component of proteins, nucleic acids, enzymes and other cellular constituents which are inevitable for all forms of life. In the atmosphere, the percentage of nitrogen is very high (N2, 78%) compared to other inorganic gases. However, most organisms have practically no direct access to this nitrogen. While plants can not directly uptake nitrogen from atmosphere, they are capable of assimilating other forms of nitrogen, for example ammonium (NH4+) and nitrate (NO3-). For agricultural crop production, artificial fixation of nitrogen is heavily utilized and it is an expensive process that requires high temperatures (at least 400 °C) and pressures (around 200 atm). It has been conspicuously demonstrated that indiscriminate use of fertilizer hampers soil physical, chemical and micro biological properties and also a potential risk to environment e.g. water quality. Besides, chemically manufactured fertilizers are depleted from soils in various ways, for instance; denitrifying bacteria, volatilization, and leaching. Consequently, it results relatively poor availability of nitrogen to get into plants. On the flipside, only 1-2% of the nitrogen fixation in the world occurs through the natural process of lightening. Notably, microbial fixation is well characterized in diazotrophs for example; Rhizobia and Frankia, and blue-green algae. Against the backdrop, we are accentuated on an environmentally friendlyand themost sustainable approach to increase productivity for legume and non-legume crops. Till today, the term biological nitrogen fixation (BNF) has received much attention as a sustainable alternative; this process facilitates atmospheric nitrogen to convert into ammonia by rhizobia in specialized plan organs termed “root nodules”. This review article seeks to better understand plant mechanisms involved in the development of root nodules in soybean. Soybean (Glycine max) is one of the most important oil crops and a source of animal feed protein in the world. It has a salient feature to fix atmospheric nitrogen through symbioses with compatible rhizobia that yields to determinate type nodule (Oldroyd, Murray et al. 2011). Biological nitrogen fixation in soybean nodules reduces the use of chemical nitrogen fertilizers resulting in cost-savings to producers and minimizes environmental damage due to nitrogen run-off. A better understanding of how nodules form and function is important for selection or generation of soybean genotypes with better nitrogen fixation capacity. Soybean nodules originate from root cortex via de novo cell differentiation (Oldroyd 2013). Consequently, two major nodule development zones are formed for instance; the nodule primordium (Npr) in the middle and it is encircled by nodule parenchyma (Npa). At later time point, the Npr gives rise to N-fixation zone and the Npa holds vascular bundles. It is not clear what early signaling pathways driving the conspicuous development of the nodule zones. My research is aimed at filling this knowledge gap by illustrating the molecular signatures that paves the way to cellular differentiation in root nodule development in soybean. Based on initial evidence obtained by the Subramanian lab, we hypothesize that microRNAs (miRNAs) play important regulatory roles in spatio-temporal expression of their target genes during nodule developmental in soybean. For instance, the regulation of auxin sensitivity by miR160 has been found to be crucial for formation of nodule primordia and vasculature in the parenchyma (Marie Turner 2013). Against this backdrop, this review article focused on nuclear and cytoplasmic transcriptome as well as miRNA profiles of parenchyma and primordial tissues and determine the relative abundance and differentially expressed mRNAs and regulatory role of miRNAs in cell differentiation and nodule development. Root nodule a sustainable alternative to fix atmospheric nitrogen Atmospheric nitrogen percentage is very high (N2, 78%) compared to other inorganic gases (Mary Elvira 1932). However, most of the organisms have practically no direct access to this nitrogen. Nevertheless, plants can not directly uptake nitrogen from atmosphere but they are capable of assimilating only very specific forms of nitrogen, for example ammonium (NH4+) and nitrate (NO3-) (Bytnerowicz and Fenn 1996, Peter M. Vitousek 1997) (Sponseller, Gundale et al. 2016). Virtually, nitrogen has been found to be a crucial structural component of proteins, nucleic acids, enzymes, and other cellular constituents which are inevitable for all forms of life (O'Brien, Vega et al. 2016). For agricultural crop production, artificial fixation of nitrogen is heavily utilized. It is an expensive process that requires high temperatures (approx. 400 °C) and pressures (approx. 200 atm) (Witschi 2000). It has been conspicuously demonstrated that indiscriminate use of N fertilizer hampers the diversity of the bacterial community and decreases soil C and N concentrations (Verzeaux, Alahmad et al. 2016). Notably, it has been demonstrated as a potential risk to environment e.g. water quality (Zhao, Sha et al. 2016) (Sponseller, Gundale et al. 2016). Besides, chemically manufactured fertilizers are depleted from soils in various ways, for instance; denitrifying bacteria, volatilization, and leaching (Johnson 1996, Peter M. Vitousek 1997). Consequently, it results relatively poor availability of nitrogen to get into plants. On the flipside, over 90 % of the nitrogen fixation in the world occurs through the natural process of lightening and microorganisms. Furthermore, microbial fixation is well characterized in diazotrophs for example; Rhizobia and Frankia, and blue-green algae (Cheng 2008). It has been demonstrated that Bradyrhizobium strains substantially escalated soybean grain yield, and protein content up to 57% and 26%, respectively (Zimmer, Messmer et al. 2016). Against the backdrop, we are accentuated on an environmentally friendly and a sustainable approach to increase the productivity for legume and non-legume crops. Literature mining depicted that biological nitrogen fixation in soybean nodules reduces the use of chemical nitrogen fertilizers resulting in cost-savings to producers and minimizes environmental damage due to nitrogen run-off. Rhizobia infection leads to the root nodule development In the natural environment, plants are continuously confronted with pathogenic and symbiotic microbes. Symbioses involves mutual exchange of diffusible signal molecules, first endophytic bacteria (rhizobia) are attracted by the plant root exudates flavonoids which are perceived and triggered the bacterial nodulation (nod) genes. Consequently, the bacteria synthesize specific lipochito-oligosaccharides, called nodulation (Nod) factors. This signal is perceived by the LysM receptor like kinase of host plant, it induces the root hair curling, and bacteria get access into the host epidermis through infection threads (ITs) and initiate cell division within the root cortex, leading to the progression of the root nodule meristem. In later stages of the interaction, bacteria are released from the infection threads into the plant cells, surrounded by membrane of plant origin. These bacteria multiply within the host cells and differentiate into the nitrogen fixing bacteroids (Udvardi and Day 1997) (Oldroyd 2013). Till now, integration of genetic and genomic approaches has revealed twenty-six genes to be involved in nodule development of Medicago truncatualaand Lotus japonicum (Kouchi, Imaizumi-Anraku et al. 2010). In addition, deep sequencing of the Medicago truncatularoot transcriptome has uncovered thousands of genes to be induced during Nod factor signaling and its resulting ethylene (ET) biosynthesis throughout the multiple development stages of indeterminate nodule (Larrainzar, Riely et al. 2015). Albeit the molecular mechanism of such regulation is not well understood. There has been a large-scale transcriptome analysis of B. japonicum-inoculated and mock-inoculated soybean root hairs. It has showed that a total of 1,973 soybean genes differentially expressed during root hair infection, particularly NFR5 and NIN genes (Libault, Farmer et al. 2010). Nevertheless, the signaling mechanisms directing the cellular differentiation of nodule are not known. Soybean root nodule organogenesis Soybean (Glycine max) has a genome size of 1.1 to1.5 Gb, it is partially diploidized tetraploid. It is one of the most important oil crops and a source of animal feed protein in the world (soybase.org/sb_about.php). It has a salient feature to fix atmospheric nitrogen through symbioses with compatible rhizobia that yields to determinate type nodule (Udvardi and Day 1997) (Oldroyd, Murray et al. 2011). Notwithstanding of the economic and environmental importance, there has been very few studies about quantitative trait loci (QTL) that controlling BNF traits, for instance nodule number, ration of nodule dry weight with nodule number, and shoot dry weight (SDW). It has been reported via composite interval mapping that approximately six QTLs bears very small effect on BNF traits (Santos, Geraldi et al. 2013). Besides, it has been demonstrated in earlier studies that nodules originate from root cortex via de novo cell differentiation into two different cell types, parenchymal and primordium (Celine Charon 1997) (Oldroyd&Downie 2008; Oldroyd 2013). In addition, early nodulin genes in legume for instance; Enod 40 gene reported to be expressed in root pericycle during the rhizobia infection and later it occupied in the dividing cortical cells (H. Kouchi and S. Hata 1993). Among the two major nodule development zones, the nodule primordium (Npr) in the middle which is encircled by nodule parenchyma (Npa). At later time point, the Npr gives rise to N-fixation zone and the Npa holds vascular bundles. Lately, a β- expansin gene, GmEXPB2 fused with GUS reporter gene which was observed to be preferentially expressed in nodule vascular trace and nodule vascular bundles. It indicated that GmEXPB2 might be crucial for nodule organogenesis. Over expression of GmEXPB2 contrast to suppressed GmEXPB2 transgenic lines found to be escalated nodule number, nodule mass and nitrogenase activity. It further suggested that GmEXPB2 might have influenced over root architecture, nodule formation and development, and profoundly yielding to biological N2 fixation (Li, Zhao et al. 2015). Even though, it is not clear what early signaling pathways driving the conspicuous development of the nodule zones. Against the back drop, to understand the regulation of auxin sensitivity by miR160 which is believed to be crucial for the formation of nodule primordia (Marie Turner 2013). Figure 1 a. Illustrating the progression of root nodule development through Rhizobial bacterial infection in the plant root leading to the determinate nodule (Oldroyd 2013). b. Nodule development zones A. Nodule primordial zone (Enod 40 gene) in the middle B. surrounding parenchyma (Enod 2 gene), differentiated from cortex (collected from Sen Subramanian lab). Regulatory small RNAs biogenesis and its molecular functions Regulatory small RNAs are ranged between 20 to 24 nucleotides which are ubiquitous elements of endogenous plant transcriptomics, a common response to exogenous viral infections and introduced double-stranded RNA (Axtell 2013). Three core enzymes families, for instance; RNAdependent RNA polymerase (RDR), Dicer like (DCL), and Argonaute (AGO) proteins paves the way of small RNA biogenesis and function in plants. Firstly, ribonuclease type III or DICERLIKE1 involves in the yield of a fold-back precursor RNA or primary miRNA (primiRNA) transcripts using an RNA templates in the nuclei. Later, the resulting miRNA-miRNA duplex which is originated in nucleus then translocated into cytoplasm. The guided miRNAmolecule is incorporated into ARGONAUTE (AGO) to form an active RISC complex to specific target RNAs that are complementary to the miRNA, and this process eventually follows up mRNA cleavage, represses the translation of the mRNAs or Chromatin modification. This phenomenon accentuated as an inhibition or silencing of the gene expression, which play a crucial role in the developmental process in plant and animal (Chapman and Carrington 2007) (Axtell 2013). Fig. 2 Regulation of gene expression events via RISC complex (modified from https://www.google.com/?gws_rd=ssl#q=mirna+picture+in+plants accessed on 7th February, 2016) Fig. 3 Gene expression events occurring in typical plant cell (modified https://www.google.com/search?q=transcription+and+translation accessed on 7th February, 2016) It has been found in several studies that most plant miRNAs are non-coding RNA, and small 21-24 nucleotide long (Cuperus, Fahlgren et al. 2011). It requires DCL1-clade DCL for their biogenesis and AGO1-clade AGO for their function (Wu, Zhou et al. 2010, Manavella, Koenig et al. 2012). In rice (Oryza sativa), DCL3 has been reported in the biogenesis of 24nt long miRNA that incorporated in AGO4 to regulate the target gene expression primarily through mRNA cleavage (Wu, Zhou et al. 2010). Argonaute proteins (AGO) form RNA inducing silencing complexes (RISC) with small RNAswhich is known as post-transcriptional gene silencing. It has typically four domains, for instance:N-terminal, PAZ, MID and PIWI domains. The MID-PIWI lobes are belongs to the C-terminus. It has been studied that MID-domains contains the specificity loop to recognize and bind to the 5’-phosphate of smRNAs. The PIWI domains contained the catalytic active site D-E-D-H/D. PAZ domain anchored the 2-nt overhang at the 3’ end of miRNAs. The N-terminal domain involved in the separation of miRNA-miRNA duplex and the slicer activity of the mRNA (Song, Smith et al.2004). There has been an expansion and duplications of AGO family members during plantevolution (Singh, Gase et al. 2015). The functional diversification of AGOs is indicating sRNAdirected regulatory pathways. The binding preference of AGO and sRNA is mainly assigned by the sequence of sRNA. In Arabidopsis, 10 AGO have been extensively studied (Liu et al. 2014). It has been demonstrated that AtAGO10 like AtAGO1, it recognized distinct structural features in miR165/miR166 duplex than involved by AtGO1. AtAGO10 found to regulate shoot apical meristem by decoying miR165/miR166 and subsequent repression of homeodomain-leucinezipper (HD-ZIP) gene expression (Zhu, Hu et al. 2011). Notably, 22 AGO proteins have been reported in Soybean (Glycine max). It has been found that genome duplication in Soybean resulted such a proliferation of AGOs. For example: its genome encodes two copies of AGO1, AGO2, AGO5, AGO4/9, AGO6 and AGO7 (Xiang Liu 2014). However, the molecular function of the plant AGO genes yet not very clear. There are several miRNA families that are conserved across the vast evolutionary distances from flowering plants to mosses (Cuperus, Fahlgren et al. 2011). It has been observed in another study that miRNA, and its target pairing found to be stable for a prolonged periods of plant evolution. On the flip side, another group demonstrated that conserved plant miRNAs and their targets are to somehow flexible. For instance; miR159 is a highly conserved miRNA that targets not only a subset of MYB mRNAs but also observed to target a non MYB mRNA, SGN-U567133 (Buxdorf, Hendelman et al. 2010). A mutant tomato transgenic line (miR159-resistant line) showed higher level of the SGN-U567133 transcript and exhibited defects in leaf and flower development. This result suggests that miR159 involves in a post-transcriptional regulation. Additionally, it is found to be crucial for the normal tomato development. Recently, the identification of miRNAs in the regulation of photoperiodic pathways in soybean have been reported through high throughput sequencing and qRT-PCR. Six libraries were constructed using Illumina Solexa, for instance; 0, 8, and 16 h under short day treatment, similar time points considered for the long the long day treatment. A total of 163 miRNAs families were reported which covered 318 plant miRNAs, and unclassified 81 novel predicted miRNAs. As expected, significant differences in abundance between short day and long day treatment was observed (Wenbin Li 2015). These findings provided evidence of miRNA in the regulation of flowering time that ultimately affects the seed yield and quality of soybean. The complex regulatory network of miRNA-mRNA interactions during viral infection has been revealed via small RNA seq (sRNA), degradome seq, and genome-wide transcriptome analysis. There has been a total of 253 soybean miRNAs found to be two-folds abundance compared with mock-inoculated control demonstrated through sRNA seq analysis. Among them 105 miRNAs were identified as potential targets of 125 transcripts that has been validated by degradome seq analyses. In addition, 2679 genes were detected via genome wide transcriptomic analysis. These genes have been differentially expressed during infection of soybean mosaic virus and among them 71 genes projected to induce in defense response (Hui Chen 2016). These findings suggested the regulatory role miRNA that governed the target gene expression during viral infection. Furthermore, the regulatory role of microRNAs (miRNAs) during Soybean- Bradyrhizobium japonicum mutualistic association was studied first by Subramanian et al. 2008. They sequenced approximately 350000 small RNAs of soybean root sample which were inoculated with B. japonicum. It helps to detect 20 conserved miRNAs loci based on the similarity to miRNAs in another plant species. In addition, 35 novel miRNAs were identified based on potential hairpin forming precursors in Soybean EST as well as shotgun genomic sequences (Subramanian, Fu et al. 2008). These findings advocated the potential role of miRNAs in the regulation of legumerhizobiumsymbiosis. In another study, 120 hairpin-forming precursor genes have been identified in soybean by Turner et al. In addition, they reported three novel miRNAs for instance; miR160, miR164 and miR393 found to be involved in auxin signaling (Turner, Yu et al. 2012). Moreover, the plant hormone auxin is thought to have a pivotal role in nodule organogenesis in determinate and indeterminate type of nodule. It indicates a redundancy and diversity of miRNAs family members that governs the formation of root nodule. It has been illustrated that auxin receptor gene family hushed by over expressed microRNA393. These plant roots found to be hypersensitive to auxin and yielded normal nodule. This observation advocated that only minimal/reduced auxin signaling is required for determinate nodule development. Likewise, overexpressed microRNA160 hushed a set of repressor auxin response transcription factor. These plant roots were hypersensitive to auxin and observed not to be reluctant in epidermal responses to rhizobia. Notably, it yielded to lower sized nodule primordium (Marie Turner 2013). This observation indicated that auxin hypersensitivity inhibits nodule organogenesis Organ specific expression of profile of miRNA and the potential targets were also studied. Two genes (Glyma10g10240 and Glyma17g05920) which were the target of miR169 but detected to be highly expressed in soybean nodule. Likewise, three potential targets of gma-new-miR13587 demonstrated to be highly expressed in the nodules than in the roots. As expected, gma-newmiR13587 found to be poorly expressed in the nodules than in the roots (Turner, Yu et al. 2012). There was an inverse expression pattern observed in between roots and nodules. Li et al., studied the transgene expression of three novel miRNAs namely, miR482, miR1512, and miR1515 in Soybean. They noticed a significant increase of nodule numbers while root length and later root density were normal in all tested miRNA lines. As expected, there were differential expression of these miRNAs in supernodulating and nonnodulating soybean mutants. They reported that 6 novel miRNAs decoyed 22 predicted target genes. And it was estimated via real time polymerase chain reaction and qRT-PCR (Li, Deng et al. 2010). It advocates that miRNAs have the signatory roles in soybean nodule development. Sequencing of small RNAs and Parallel analysis of RNA ends (PARE) libraries revealed to identify 284 nodule miRNAs, more than 500 target genes, and including 178 novel soybean miRNAs. It has been reported that ENOD93 only found to be expressed in nodule tissue not in other plant parts of Soybean. Ectopic expression of miR393j-3p and RNAi silencing approach to ENOD93 expression showed a significant reduction in nodule formation (Zhe Yan 2015). Therefore, this study showed a list of miRNAs and their potential target of nodulation genes. In the model legume (Medicago truncatula), 25 conserved miRNA families and 100 novel miRNA reads were detected by high-throughput sequencing. The expression of MtHAP2-1 (encodes a CCAAT binding transcription factor) to meristematic zones was restricted by miR169a which is found to be critical for the development of indeterminate type of nodule (Combier, Frugier et al. 2006). In another study, HDZIPIII transcripts were inhibited by overexpression of miR166, it dropped the number of symbiotic nodule and lateral root (Boualem, Laporte et al. 2008). To get insights into key genes of nodule zones, transcript profiles of specific cells/tissues were investigated at different time points from indeterminate nodules of M. truncatulausing laser capture micro dissection. It has been demonstrated from the comprehensive gene expression map that selected genes enriched in different cell/tissue types (Limpens, Moling et al. 2013). These findings indicated that organ specific gene expression could be controlled by the presence or absence of miRNAs. Recently, Agrobacterium rhizogenesmediated hairy root transformation has been applied as tool for exploring cell type specific gene expression in tomato. Cell type or tissue specific promoter introduced into INTACT and TRAP constructs via gateway cloning technology to develop binary vectors. INTACT method used to capture biotin tagged nuceli from specific cell types and TRAP method used for profiling of mRNAs or foot printing of individual ribosomes (Ron 2014). TRAP methodology is not required tissue fixation or single cell suspension. It has been successfully used to date in organisms ranging from D. melanogaster to mice and human cultured cells. Multiple ribosomes or Polyribosomes (polysomes) are engaged in translation on a single mRNA. To evaluate the translation state of an mRNA, ribosomal subunits, ribosomes, and polysomes can be isolated from detergent-treated cell extracts (Heiman, Kulicke et al. 2014). In this study, we would perform polysome isolation deploying gene cassettes ENOD40p:HF-GFP-RPL18 for primordial tissues, and ENOD2p:HF-GFP-RPL18 for parenchymal tissues in Glycine max root nodules that express an epitope tagged version of ribosomal protein L18. Over the last one decade, there has been several microarrays-based studies which characterized transcriptional variations deployed in nodule formation. It has been embedded with couple of shortcomings, for instance; relative late time points study, incomplete representation of plant genes,discrimination of close paralogs, and reduced sensitivity. Lately, next generation sequencingtechnology have widened the horizon of transcription analyses in different legume species to detectsymbiosis induced changes in late nodule developmental stages. Against this backdrop, we areaccentuated to reveal early transcriptional changes induced in determinate type of soybean noduleby Bradyrhizobium japonicum. In determinate type of nodule, two major nodule development zones are formed for instance, the nodule primordium (Npr) in the middle and it is encircled by nodule parenchyma (Npa). At later time point, the Npr converted to N-fixation zone and the Npa contained vascular bundles. Of these facts, it is not clear what early signaling pathways driving the conspicuous development of thenodule zones. In this context, mechanisms regulate the distinct gene expression profiles in Npr andNpa cell types has not understood clearly. The proposed research study is aimed at filling this knowledge gap byillustrating the molecular signatures that paves the way to cellular differentiation in root noduledevelopment in soybean considering four different time points (5 dai, 7 dai, 10 dai& 14 dai). The hypothesisis microRNAs(miRNAs) play important regulatory roles in spatio-temporal expression of their target genesduring nodule developmental in soybean. For example, a gradient of microRNA localizationbetween nodule primordium and parenchyma cells could result in distinct differentiation of thesecell types. To test this hypothesis, one has to obtain both cell type-specific miRNA andtranscriptome (miRNA target) profiles. Since, the majority of miRNA regulation occurs in thecytoplasm, we reasoned that comparison of nuclear and ribosomal transcriptome profiles wouldreveal genes whose expression is potentially regulated by post transcriptional mechanisms such asmiRNA cleavage. Combining this information with cell type-specific miRNA profiles, andto test the above hypothesis and identify key miRNA-target pairs important for nodule celldifferentiation. The use of translating ribosome affinity purification (TRAP) of nodule zonecells, namely from parenchyma and primordial tissues, to obtain cytoplasmic transcriptomes data. Techniques to determine cell type specific expression profiles: TRAP methods TRAP is termed translating ribosome affinity purification, combines cell-type-specific transgene expression with affinity purification of translating ribosomes. It supersedes the need for tissue fixation, and facilitates to study the cell type-specific mRNA profiles of any genetically defined cell type. It has been successfully used to date in organisms ranging from D. melanogaster to mice, and human cultured cells. Multiple ribosomes or Polyribosomes (polysomes) are engaged in translation on a single mRNA. To evaluate the translation state of an mRNA, ribosomal subunits, ribosomes, and polysomes can be isolated from detergent-treated cell extracts. In this study, the polysome isolation using gene cassettes ENOD40p:HF-GFP-RPL18 for primordial tissues, and ENOD2p:HF-GFP-RPL18 for parenchymal tissues in Glycine max root nodules that express an epitope tagged version of ribosomal protein L18 RPL18(Heiman, Kulicke et al. 2014, Ron 2014). Relative abundance and differentially expressed mRNAs profile in two different tissue specific zones would help to understand the effect of regulatory role of miRNAs in cell differentiation and nodule development. References: Axtell, M. J. (2013). "Classification and comparison of small RNAs from plants." Annu Rev PlantBiol 64: 137-159. 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Describes the 2000 Geraldine R. Dodge Poetry Festival, the largest poetry event in North America. Notes the festival was designed to create opportunities for personal communication between poets and teachers, who share so many similar concerns for the future of language arts education. Full text available in print version only.

The acknowledgements were ommitted from the article “Job Security for Occupational Health and Safety Professionals in the 21st Century: What You Need to Know About the Institute of Medicine (2000) Report” by Ann R. Cox, MN, RN, CAE, and Geraldine C. Williamson, MN, RN, CAE, on page 170 of the April issue of the AAOHN Journal (Vol. 49, No. 4). The acknowledgement should read: AAOHN acknowledges Nancy Menzel and Bonnie Rogers for their input in the development of Job Security for Occupational Health and Safety Professionals in the 21st Century: What You Need to Know About the Institute of Medicine (2000) Report.

John Randal Baker , who was born at Woodbridge in Suffolk on 23 October 1900, was well provided with genes and memes by both his parents and, as this account of his life unfolds, it will become clear that his interests and the qualities of his character were closely akin to those that had appeared in earlier generations of his family. John was the youngest of the five children, three girls and two boys, of Rear Admiral Julian Alleyne Baker, R. N., and of his wife Geraldine Eugénie, née Alison. On his mother’s side, his grandfather was General Sir Archibald Alison, G. C. B., who served in the Crimea, the Indian Mutiny and was second-in-command of the Ashanti expedition in West Africa in 1873. In 1882 it was his leadership of the Highland Brigade at the battle of Tel-el-Kebir that ended in the victory which proved to be the turning point of the Egyptian Campaign of that year. The General was a direct descendant of the Alisons whose family, together with that of the Gregorys, was discussed in Gabon’s Hereditary genius (1869) as an example of genius inherited over five generations.