Journal articles: 'CIB2'

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Huang, Hao, Joel N. Bogstie, and Hans J. Vogel. "Biophysical and structural studies of the human calcium- and integrin-binding protein family: understanding their functional similarities and differences." Biochemistry and Cell Biology 90, no. 5 (October 2012): 646–56. http://dx.doi.org/10.1139/o2012-021.

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The human calcium- and integrin-binding protein 1 (CIB1) plays important roles in various cellular functions. In this study, three other members of this protein family (CIB2–4: CIB2, CIB3, and CIB4) were purified and subsequently characterized using biophysical and structural approaches. As expected from sequence alignments, CIB2–4 were shown to bind calcium (Ca2+) and magnesium (Mg2+) ions. Binding of Ca2+ or Mg2+ ions changes the secondary structure of CIB2–4 and the exposure of hydrophobic surface area. Ca2+ and Mg2+ ions also stabilize the tertiary structures for CIB2 and CIB3. Through in vitro binding experiments, we show that CIB2 can interact with the integrin αIIb cytoplasmic domain and the integrin α7b membrane-proximal fragment. Fluorescence experiments using a 7-azatryptophan labeled peptide demonstrate that CIB2, CIB3, and CIB4 are binding partners for the integrin αIIb subunit, which suggests that they are potentially involved in regulating integrin αIIb subunit activation. The distinct responses of αIIb to the different CIB3 and CIB4 metal (Ca2+ and Mg2+) binding states imply a potential connection between the calcium and integrin signaling pathways.

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Xu, Zoulan, Haruhiko Miyata, Yuki Kaneda, Julio M. Castaneda, Yonggang Lu, Akane Morohoshi, Zhifeng Yu, Martin M. Matzuk, and Masahito Ikawa. "CIB4 is essential for the haploid phase of spermatogenesis in mice†." Biology of Reproduction 103, no. 2 (April 25, 2020): 235–43. http://dx.doi.org/10.1093/biolre/ioaa059.

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Abstract Spermatogenesis is a complex developmental process that involves the proliferation of diploid cells, meiotic division, and haploid differentiation. Many genes are shown to be essential for male fertility using knockout (KO) mice; however, there still remain genes to be analyzed to elucidate their molecular mechanism and their roles in spermatogenesis. Calcium- and integrin-binding protein 1 (CIB1) is a ubiquitously expressed protein that possesses three paralogs: CIB2, CIB3, and CIB4. It is reported that Cib1 KO male mice are sterile due to impaired haploid differentiation. In this study, we discovered that Cib4 is expressed strongly in mouse and human testis and begins expression during the haploid phase of spermatogenesis in mice. To analyze the function of CIB4 in vivo, we generated Cib4 KO mice using the CRISPR/Cas9 system. Cib4 KO male mice are sterile due to impaired haploid differentiation, phenocopying Cib1 KO male mice. Spermatogenic cells isolated from seminiferous tubules demonstrate an essential function of CIB4 in the formation of the apical region of the sperm head. Further analysis of CIB4 function may shed light on the etiology of male infertility caused by spermatogenesis defects, and CIB4 could be a target for male contraceptives because of its dominant expression in the testis.

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Dal Cortivo, Giuditta, and Daniele Dell’Orco. "Calcium- and Integrin-Binding Protein 2 (CIB2) in Physiology and Disease: Bright and Dark Sides." International Journal of Molecular Sciences 23, no. 7 (March 24, 2022): 3552. http://dx.doi.org/10.3390/ijms23073552.

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Calcium- and integrin-binding protein 2 (CIB2) is a small EF-hand protein capable of binding Mg2+ and Ca2+ ions. While its biological function remains largely unclear, an increasing number of studies have shown that CIB2 is an essential component of the mechano-transduction machinery that operates in cochlear hair cells. Mutations in the gene encoding CIB2 have been associated with non-syndromic deafness. In addition to playing an important role in the physiology of hearing, CIB2 has been implicated in a multitude of very different processes, ranging from integrin signaling in platelets and skeletal muscle to autophagy, suggesting extensive functional plasticity. In this review, we summarize the current understanding of biochemical and biophysical properties of CIB2 and the biological roles that have been proposed for the protein in a variety of processes. We also highlight the many molecular aspects that remain unclarified and deserve further investigation.

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Liang, Xiaoping, Xufeng Qiu, Gilman Dionne, Christopher L. Cunningham, Michele L. Pucak, Guihong Peng, Ye-Hyun Kim, Amanda Lauer, Lawrence Shapiro, and Ulrich Müller. "CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of hair cells." Neuron 109, no. 13 (July 2021): 2131–49. http://dx.doi.org/10.1016/j.neuron.2021.05.007.

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Häger, M., Å. Mikael, V. Allamand, and M. Dubeej-Hjalt. "C.P.2.15 Cib2 in muscular dystrophy." Neuromuscular Disorders 17, no. 9-10 (October 2007): 848. http://dx.doi.org/10.1016/j.nmd.2007.06.291.

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Jacoszek, Agnieszka, Agnieszka Pollak, Rafał Płoski, and Monika Ołdak. "Advances in genetic hearing loss: CIB2 gene." European Archives of Oto-Rhino-Laryngology 274, no. 4 (October 22, 2016): 1791–95. http://dx.doi.org/10.1007/s00405-016-4330-9.

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Booth, K. T., K. Kahrizi, M. Babanejad, H. Daghagh, G. Bademci, S. Arzhangi, D. Zareabdollahi, et al. "Variants in CIB2 cause DFNB48 and not USH1J." Clinical Genetics 93, no. 4 (February 12, 2018): 812–21. http://dx.doi.org/10.1111/cge.13170.

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Temple, Brenda R., Holly R. Gentry, Jan C. DeNofrio, Weiping Yuan, and Leslie V. Parise. "Characterization of calcium- and integrin-binding protein 1 (CIB1) knockout platelets: Potential compensation by CIB family members." Thrombosis and Haemostasis 100, no. 05 (2008): 847–56. http://dx.doi.org/10.1160/th08-06-0351.

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SummaryPlatelet aggregation requires activation of the αIIbβ3 integrin,an event regulated by the integrin cytoplasmic tails. CIB1 binds to the cytoplasmic tail of the integrin αIIb subunit. Previous overexpression and knockdown studies in murine megakaryocytes demonstrated that CIB1 inhibits integrin αIIbβ3 activation.Here we analyzed Cib1-/- mice to determine the function of CIB1 in platelets in vitro and in vivo. We found that although these mice had no overt platelet phenotype, mRNA level of CIB1 homolog CIB3 was increased in Cib1-/- megakaryocytes. In vitro binding experiments showed that recombinant CIB1, -2 and -3 bound specifically to an αIIb cytoplasmic tail peptide. Subsequent protein modeling experiments indicated that CIBs 1–3 each have a highly conserved hydrophobic binding pocket. Therefore, the potential exists for compensation for the loss of CIB1 by these CIB family members, thereby preventing pathologic thrombus formation in Cib1-/- mice.

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Abeshi, Andi, Alice Bruson, Tommaso Beccari, Munis Dundar, Leonardo Colombo, and Matteo Bertelli. "Genetic testing for Usher syndrome." EuroBiotech Journal 1, s1 (October 27, 2017): 108–10. http://dx.doi.org/10.24190/issn2564-615x/2017/s1.34.

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Abstract We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for Usher syndrome (USH). USH is mostly transmitted in an autosomal recessive manner and is caused by variations in the ADGRV1, CDH23, CIB2, CLRN1, HARS, MYO7A, PCDH15, PDZD7, USH1C, USH1G, USH2A, WHRN genes. Prevalence is estimated to be 1:30,000. Clinical diagnosis is based on audiogram, vestibular tests, visual acuity test, fundus examination, color test, optical coherence tomography and electroretinography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

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Zhu, Wenying, Kate E. Jarman, Noor A. Lokman, Heidi A. Neubauer, Lorena T. Davies, Briony L. Gliddon, Houng Taing, et al. "CIB2 Negatively Regulates Oncogenic Signaling in Ovarian Cancer via Sphingosine Kinase 1." Cancer Research 77, no. 18 (July 20, 2017): 4823–34. http://dx.doi.org/10.1158/0008-5472.can-17-0025.

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Michel, Vincent, Kevin T. Booth, Pranav Patni, Matteo Cortese, Hela Azaiez, Amel Bahloul, Kimia Kahrizi, et al. "CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival." EMBO Molecular Medicine 9, no. 12 (December 2017): 1711–31. http://dx.doi.org/10.15252/emmm.201708087.

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Häger, Mattias, Maria Giulia Bigotti, Renata Meszaros, Virginie Carmignac, Johan Holmberg, Valérie Allamand, Mikael Åkerlund, et al. "Cib2 Binds Integrin α7Bβ1D and Is Reduced in Laminin α2 Chain-deficient Muscular Dystrophy." Journal of Biological Chemistry 283, no. 36 (July 7, 2008): 24760–69. http://dx.doi.org/10.1074/jbc.m801166200.

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Shaikh, Hina, Ali M. Waryah, Ashok K. Narsani, Muhammad Iqbal, Mohsin Shahzad, Yar M. Waryah, Naila Shaikh, and Amber Mahmood. "Genetic Testing of Non-familial Deaf Patients for CIB2 and GJB2 Mutations: Phenotype and Genetic Counselling." Biochemical Genetics 55, no. 5-6 (October 31, 2017): 410–20. http://dx.doi.org/10.1007/s10528-017-9828-3.

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Riazuddin, Saima, Inna A. Belyantseva, Arnaud P. J. Giese, Kwanghyuk Lee, Artur A. Indzhykulian, Sri Pratima Nandamuri, Rizwan Yousaf, et al. "Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48." Nature Genetics 44, no. 11 (September 30, 2012): 1265–71. http://dx.doi.org/10.1038/ng.2426.

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Seco, Celia Zazo, Arnaud P. Giese, Sobia Shafique, Margit Schraders, Anne M. M. Oonk, Mike Grossheim, Jaap Oostrik, et al. "Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells." European Journal of Human Genetics 24, no. 4 (July 15, 2015): 542–49. http://dx.doi.org/10.1038/ejhg.2015.157.

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Colucci, Federica, Patrizia Menegoni, Mariella Nocenzi, and Ombretta Presenti. "L'evoluzione dei modelli di consumo e degli stili alimentari tra sostenibilitŕ e benessere." RIVISTA DI STUDI SULLA SOSTENIBILITA', no. 2 (January 2013): 47–67. http://dx.doi.org/10.3280/riss2012-002004.

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I consumi agro-alimentari, dal dopoguerra ad oggi, sono stati caratterizzati da successive trasformazioni che č possibile leggere attraverso l'evoluzione di quegli stessi fattori - da quello economico, a quello politico e tecnologico, fra gli altri - che hanno determinato l'attuale identitŕ culturale degli italiani. Ne emerge un profilo consumistico degli italiani legato al cibo che č analizzato in questo lavoro alla luce dei valori culturali dominanti. Un'introduzione sociologica sul significato del nesso fra etica e alimentazione nella contemporanea societŕ della ricerca della safety/ security e della sostenibilitŕ condurrŕ all'osservazione di nuove tipologie di consumo e di cibo, con particolare riguardo alle potenzialitŕ di mercato dei cibi funzionali.

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Patel, Kunjan, Arnaud P. Giese, J. M. Grossheim, Rashima S. Hegde, Maria Delio, Joy Samanich, Saima Riazuddin, et al. "A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family." PLOS ONE 10, no. 10 (October 1, 2015): e0133082. http://dx.doi.org/10.1371/journal.pone.0133082.

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Jan, A. "Mutations in CIB2 calcium and integrin-binding protein disrupt auditory hair cell calcium homeostasis in Usher syndrome type 1J and non-syndromic deafnessDFNB48." Clinical Genetics 83, no. 4 (April 2013): 317–18. http://dx.doi.org/10.1111/cge.12100.

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Patel, Kunjan, Arnaud P. Giese, J. M. Grossheim, Rashmi S. Hegde, Maria Delio, Joy Samanich, Saima Riazuddin, et al. "Correction: A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family." PLOS ONE 10, no. 10 (October 16, 2015): e0141259. http://dx.doi.org/10.1371/journal.pone.0141259.

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Adeyemo, Adebolajo, Rabia Faridi, Parna Chattaraj, Rizwan Yousaf, Risa Tona, Samuel Okorie, Thashi Bharadwaj, et al. "Genomic analysis of childhood hearing loss in the Yoruba population of Nigeria." European Journal of Human Genetics 30, no. 1 (November 26, 2021): 42–52. http://dx.doi.org/10.1038/s41431-021-00984-w.

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AbstractAlthough variant alleles of hundreds of genes are associated with sensorineural deafness in children, the genes and alleles involved remain largely unknown in the Sub-Saharan regions of Africa. We ascertained 56 small families mainly of Yoruba ethno-lingual ancestry in or near Ibadan, Nigeria, that had at least one individual with nonsyndromic, severe-to-profound, prelingual-onset, bilateral hearing loss not attributed to nongenetic factors. We performed a combination of exome and Sanger sequencing analyses to evaluate both nuclear and mitochondrial genomes. No biallelic pathogenic variants were identified in GJB2, a common cause of deafness in many populations. Potential causative variants were identified in genes associated with nonsyndromic hearing loss (CIB2, COL11A1, ILDR1, MYO15A, TMPRSS3, and WFS1), nonsyndromic hearing loss or Usher syndrome (CDH23, MYO7A, PCDH15, and USH2A), and other syndromic forms of hearing loss (CHD7, OPA1, and SPTLC1). Several rare mitochondrial variants, including m.1555A>G, were detected in the gene MT-RNR1 but not in control Yoruba samples. Overall, 20 (33%) of 60 independent cases of hearing loss in this cohort of families were associated with likely causal variants in genes reported to underlie deafness in other populations. None of these likely causal variants were present in more than one family, most were detected as compound heterozygotes, and 77% had not been previously associated with hearing loss. These results indicate an unusually high level of genetic heterogeneity of hearing loss in Ibadan, Nigeria and point to challenges for molecular genetic screening, counseling, and early intervention in this population.

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Blazejczyk, Magdalena, Adam Sobczak, Katarzyna Debowska, Marta B. Wisniewska, Aneta Kirilenko, Slawomir Pikula, Jacek Jaworski, Jacek Kuznicki, and Urszula Wojda. "Biochemical characterization and expression analysis of a novel EF-hand Ca2+ binding protein calmyrin2 (Cib2) in brain indicates its function in NMDA receptor mediated Ca2+ signaling." Archives of Biochemistry and Biophysics 487, no. 1 (July 2009): 66–78. http://dx.doi.org/10.1016/j.abb.2009.05.002.

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Horn, Vera. "Assaporare la Tradizione: Cibo, Identità e Senso di Appartenenza nella Letteratura Migrante." Revista de Italianística, no. 19-20 (December 30, 2010): 155. http://dx.doi.org/10.11606/issn.2238-8281.v0i19-20p155-175.

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Come sostiene Vito Teti, il cibo per l’immigrato è una formadi difesa di un’identità culturale e riflette il bisogno di riconoscersi e diaggregarsi. Il bisogno di trovare senso e posto in un nuovo luogo vengonosegnati da un attaccamento ai cibi perduti, con un senso di sacralità che accompagnail pasto. A partire dalla premessa di Teti, verranno presi in considerazionei romanzi Volevo diventare bianca di Nassera Chohra (1993)e Scontro di civiltà per un ascensore a Piazza Vittorio di Amara Lakhous(2006) e i racconti Curry di pollo di Laila Wadia; Salsicce di Igiaba Scego e Il cuoco di Arbëria di Carmine Abate. Tali testi impongono uno sguardo determinante sul cibo come un indice culturale che può rappresentare ocostruire l’identità o determinare l’appartenenza ad una certa comunità, così come rifiutare decisamente qualsiasi contaminazione con la cultura della società ospitante o tentativo di assimilazione o, diversamente, offrire un punto di vista fondato sull’ibridismo; inoltre può favorire la formazione di stereotipi. In questo modo vengono definite prospettive diverse di costruzione dell’identità, sintetizzate da Stuart Hall nel binomio traduzione/tradizione.

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Huang, Shiyuan, Chunhua Xiang, and Yi Song. "Identification of the shared gene signatures and pathways between sarcopenia and type 2 diabetes mellitus." PLOS ONE 17, no. 3 (March 10, 2022): e0265221. http://dx.doi.org/10.1371/journal.pone.0265221.

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Background Sarcopenia is characterized by the age-associated loss of skeletal muscle mass and strength that develops progressively and plays an important role in the disability of the elderly. It has received growing attention over the last decade and has been implicated as both a cause and consequence of type 2 diabetes mellitus (T2DM). The existence of T2DM could increase the risk of developing sarcopenia through multiple mechanisms including advanced glycation end-product accumulation. Meanwhile, sarcopenia would alter glucose disposal and may contribute to the development and progression of T2DM due to reduced muscle mass. Methods We implemented transcriptomic analysis of skeletal muscle biopsy specimens in sarcopenia patients and proliferating myoblasts or differentiated myotubes from individuals with T2DM. Related microarray data were selected from Gene Expression Omnibus (GEO) to screen the genes, which were differentially expressed for sarcopenia and T2DM. Multiple combinatorial statistical methods and bioinformatics tools were used to analyze the common DEGs. Meanwhile, functional enrichment analysis was also carried out. Furthermore, we constructed the protein-protein interaction (PPI), as well as transcription factor (TF)-gene interactions network and TF-miRNA coregulatory network. Finally, based on the common DEGs, drug compounds were speculated using the Drug Signatures database (DSigDB). Results A total of 1765 and 2155 DEGs of sarcopenia and T2DM were screened, respectively. 15 common genes (LXN, CIB2, PEA15, KANK2, FGD1, NMRK1, PLCB1, SEMA4G, ADARB1, UPF3A, CSTB, COL3A1, CD99, ETV3, FJX1) correlated with sarcopenia and T2DM simultaneously were then identified, and 3 genes (UPF3A, CSTB and PEA15) of them were regarded as hub genes. Functional enrichment analysis revealed several shared pathways between two diseases. In addition, according to the TF-gene interactions network and TF-miRNA coregulatory network, part of TF and miRNA may be identified as key regulator in sarcopenia and T2DM at the same time (e.g., CREM and miR-155). Notably, drug compounds for T2DM and sarcopenia were also suggested, such as coenzyme Q10. Conclusion This study revealed that sarcopenia and T2DM may share similar pathogenesis and provided new biological targets and ideas for early diagnosis and effective treatment of sarcopenia and T2DM.

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Haga, Sanae, Takeaki Ozawa, Naoki Morita, Mami Asano, Shigeki Jin, Yimin, and Michitaka Ozaki. "Photo-Activatable Akt Probe: A New Tool to Study the Akt-Dependent Physiopathology of Cancer Cells." Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 26, no. 3 (April 10, 2018): 467–72. http://dx.doi.org/10.3727/096504017x15040166233313.

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Akt is commonly overexpressed and activated in cancer cells and plays a pivotal role in cell survival, protection, and chemoresistance. Therefore, Akt is one of the target molecules in understanding characters of cancer cells and developing anticancer drugs. Here we examined whether a newly developed photo-activatable Akt (PA-Akt) probe, based on a light-inducible protein interaction module of plant cryptochrome2 (CRY2) and cryptochrome-interacting basic helix‐loop‐helix (CIB1), can regulate Akt-associated cell functions. By illuminating blue light to the cells stably transfected with PA-Akt probe, CRY2-Akt (a fusion protein of CRY2 and Akt) underwent a structural change and interacted with Myr-CIBN (myristoylated N-terminal portion of CIB1), anchoring it at the cell membrane. Western blot analysis revealed that S473 and T308 of the Akt of probe-Akt were sequentially phosphorylated by intermittent and continuous light illumination. Endogenous Akt and GSK-3β, one of the main downstream signals of Akt, were also phosphorylated, depending on light intensity. These facts indicate that photo-activation of probe-Akt can activate endogenous Akt and its downstream signals. The photo-activated Akt conferred protection against nutritional deprivation and H2O2 stresses to the cells significantly. Using the newly developed PA-Akt probe, endogenous Akt was activated easily, transiently, and repeatedly. This probe will be a unique tool in studying Akt-associated specific cellular functions in cancer cells and developing anticancer drugs.

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Maridueña-Zavala, Maria Gabriela, Adela Quevedo, Karla Aguaguiña, Lissette Serrano, and Daynet Sosa del Castillo. "Colección de cultivos microbianos CIBE (CCM-CIBE): Una colección para la investigación." Bionatura 6, no. 1 (February 15, 2021): 1664–68. http://dx.doi.org/10.21931/rb/2021.06.01.32.

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Los microorganismos han sido fuente de importantes innovaciones industriales y su preservación ha contribuido al desarrollo de investigaciones. Sin embargo, en el Ecuador son pocas las iniciativas que buscan conservar microorganismos con potencial biotecnológico. La Colección de cultivos microbianos CCM-CIBE busca proteger la microbiodiversidad del Ecuador y contribuir a su estudio a través de la identificación, la conservación y la distribución de microorganismos. En nuestra colección empleamos métodos de conservación a largo plazo como conservación en agua, conservación en aceite mineral, crioconservación y liofilización. Así mismo, la CCM-CIBE cuenta con capacidades para brindar servicios de tenencia de microorganismos y recibir depósitos públicos o privados, garantizados a través de controles de viabilidad y seguridad de las cepas, así como de la información relacionada con cada microorganismo. Actualmente la colección cuenta con hongos, levaduras y bacterias patógenos de cultivos agrícolas, controladores biológicos, microorganismos presentes en procesos de fermentación que buscan fomentar el estudio de nuestra microbiodiversidad y contribuir a la mejora de procesos del sector agrícola, industria farmacéutica y de alimentos.

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Del Vecchio, Annalice. "Mangiare e parlare: il cibo come simbolo in Conversazione in Sicilia." Revista Italiano UERJ 12, no. 2 (July 13, 2022): 11. http://dx.doi.org/10.12957/italianouerj.2021.67528.

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ABSTRACT: Questo articolo analizza il cibo come parte dei simboli e delle immagini presenti nel romanzo Conversazione in Sicilia, di Elio Vittorini. L’autore italiano utilizza il parlare di cibo, così come fa con altri temi del libro, per “dire senza dichiarare”, allorquando, metaforicamente, trasforma l’atto di mangiare, o di non poter mangiare, in critica sociale e politica, in un momento storico particolare per l’Italia, allora governata dal regime fascista. Il cibo, simbolo di abbondanza, quando non c’è diventa ancora più presente nel pensiero degli italiani poveri, come una smania, un’ossessione. Il cibo rappresenta anche un viaggio verso un tempo perduto, il tempo mitico dell’infanzia, quando i sapori, la consistenza e l’odore dei cibi fanno sì che il personaggio recuperi la memoria del passato e riacquisti in questo modo la capacità di sentire ciò che aveva perso durante un periodo di profonda apatia. Queste simbologie, da un lato politiche e sociali, dall’altro più psicologiche e soggettive, “si sovrappongono e si ripetono acquistando nuove sfumature”, come scrive Samy Ramez nell’articolo Simbolo e immagine in Conversazione in Sicilia di Elio Vittorini.Parole chiave: Letteratura italiana. Neorealismo italiano. Elio Vittorini. Alimentazione. Cibo nella letteratura. RESUMO: Este artigo analisa a comida como parte dos símbolos e imagens que estruturam o romance Conversazione in Sicilia, de Elio Vittorini. Ao falar sobre comida, entre outros temas presentes no livro, o autor pode “dizer sem declarar”, criando metáforas que transformam o ato de comer (ou de não poder comer) em crítica social e política ao momento histórico que se vivia na Itália governada pelo regime fascista. O alimento, símbolo de abundância, quando ausente, torna-se ainda mais presente no pensamento dos italianos pobres, quase como uma obsessão. A comida também oferece uma viagem a um tempo perdido, o tempo mítico da infância, quando os sabores, a textura e os cheiros dos alimentos fazem o personagem recuperar a memória do passado e, assim, reconquistar a capacidade de sentir que havia perdido durante um período de profunda apatia. Essas simbologias, por um lado, políticas e sociais e, por outro, psicológicas e mais subjetivas, o tempo todo superpõem-se e se repetem “adquirindo novas nuances”, como escreve Samy Ramez no artigo Simbolo e immagine in Conversazione in Sicilia di Elio Vittorini.Palavras-chave: Literatura italiana. Neorrealismo italiano. Elio Vittorini. Alimentazione. Cibo nella letteratura. ABSTRACT: This work analyses the presence of food among the symbols and images of Elio Vittorini’s novel Conversazione in Sicilia. The Italian author uses the act of talking about food, as he does with other subjects in the book, to “say without asserting”. He metaphorically transforms the act of eating (or not being able to eat) in a political and social critic to that historical moment in Italy when the country was governed by the fascists. When it lacks, food becomes even more alive in the mind of Italian poor people, like an obsession. Food also offers a trip to a lost time, the mythical time of childhood, as the flavors, the textures and the smell of food allow the character to recover the memory of his past and, doing so, regain the ability to feel. These symbols, on the one hand political and social, and on the other psychological and subjective, “overlap and repeat [throughout the book] gaining new nuances”, as writes Samy Ramez in the article Simbolo e immagine in Conversazione in Sicilia di Elio Vittorini.Keywords: Italian literature. Italian Neorealism. Elio Vittorini. Food. Food in literature.

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Michel, Katherine, Christine Colie, Robert D. Burk, L. Stewart Massad, Cuiwei Wang, Michaeline Hebron, Charbel Moussa, et al. "60941 Vaginal pH predicts cervical intraepithelial neoplasia-2 regression in women living with human immunodeficiency virus." Journal of Clinical and Translational Science 5, s1 (March 2021): 23–24. http://dx.doi.org/10.1017/cts.2021.465.

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ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.

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Yuan, Weiping, Tina M. Leisner, Andrew W. McFadden, Shantres Clark, Sylvia Hiller, Nobuyo Maeda, Deborah A. O'Brien, and Leslie V. Parise. "CIB1 Is Essential for Mouse Spermatogenesis." Molecular and Cellular Biology 26, no. 22 (November 15, 2006): 8507–14. http://dx.doi.org/10.1128/mcb.01488-06.

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ABSTRACT CIB1 is a 22-kDa calcium binding, regulatory protein with ∼50% homology to calmodulin and calcineurin B. CIB1 is widely expressed and binds to a number of effectors, such as integrin αIIb, PAK1, and polo-like kinases, in different tissues. However, the in vivo functions of CIB1 are not well understood. To elucidate the function of CIB1 in whole animals, we used homologous recombination in embryonic stem cells to generate Cib1 −/− mice. Although Cib1 −/− mice grow normally, the males are sterile due to disruption of the haploid phase of spermatogenesis. This is associated with reduced testis size and numbers of germ cells in seminiferous tubules, increased germ cell apoptosis, and the loss of elongated spermatids and sperm. Cib1 −/− testes also show increased mRNA and protein expression of the cell cycle regulator Cdc2/Cdk1. In addition, mouse embryonic fibroblasts (MEFs) derived from Cib1 −/− mice exhibit a much slower growth rate compared to Cib1 +/+ MEFs, suggesting that CIB1 regulates the cell cycle, differentiation of spermatogenic germ cells, and/or differentiation of supporting Sertoli cells.

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Naik, Meghna U., and Ulhas P. Naik. "CIB1 Positively Regulates Outside-In Signaling through αIIbβ3 by Enhancing FAK and Src Activity." Blood 108, no. 11 (November 16, 2006): 3917. http://dx.doi.org/10.1182/blood.v108.11.3917.3917.

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Abstract Integrin αIIbβ3, the platelet fibrinogen receptor, mediates outside-in signaling upon fibrinogen binding. Calcium- and integrin-binding protein 1 (CIB1) specifically interacts with the cytoplasmic domain of αIIb and is involved in platelet spreading. Here we show that CIB1 binding to αIIb is an essential step in the propagation of outside-in signaling through integrin αIIbβ3. Incorporation of BAPTA-AM completely blocked outside-in signaling and CIB-1 binding to aIIb, suggesting that an intracellular Ca2+ rise induced by fibrinogen binding is required for CIB1 interaction with αIIb. When CIB1-binding to αIIb was inhibited by introduction of a function blocking antibody or a synthetic peptide corresponding to αIIb tail, CIB1 localization at the tip of the filopodia, but filopodia formation was not blocked. This result suggests that interaction of CIB1 with αIIb is not required for filopodia formation, but is needed for CIB1 accumulation at the filopodia, as well as platelet spreading. Immunoprecipitation experiments showed that during outside-in signaling, CIB1 associates with FAK. Although association of FAK and CIB1 does not require dynamic rearrangement of the cytoskeleton, their accumulation at the filopodia and the activation of FAK is dependent on cytoskeletal rearrangement, as treatment with cytochalasin D after the platelets form filopodia affects CIB1 localization. Interestingly, the interaction of CIB1 with αIIb upon fibrinogen binding is also necessary for FAK and Src activation. However, Src activity is not required for CIB1 accumulation at the filopodia since this accumulation was not stopped by the Src inhibitor PP2, despite blocking platelet spreading. Our results suggest that during outside-in signaling an intracellular Ca2+ rise occurs that facilitates CIB1 interaction with αIIb. CIB1 recruits FAK to this complex and is localized to the filopodia dependent upon dynamic cytoskeletal rearrangement. Furthermore, activation of Src and FAK requires interaction of CIB1 with αIIb. Although Src activity is not required for the accumulation of CIB1 at the filopodia, it is required for platelet spreading on immobilized fibrinogen. Thus we provide evidence for initial sequence of outside-in signaling in platelets.

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Kostyak, John C., Meghna U. Naik, and Ulhas P. Naik. "Calcium- and integrin-binding protein 1 regulates megakaryocyte ploidy, adhesion, and migration." Blood 119, no. 3 (January 19, 2012): 838–46. http://dx.doi.org/10.1182/blood-2011-04-346098.

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Abstract Megakaryocytes are large, polyploid cells that produce platelets. We have previously reported that calcium- and integrin-binding protein 1 (CIB1) regulates endomitosis in Dami cells. To further characterize the role of CIB1 in megakaryopoiesis, we used a Cib1−/− mouse model. Cib1−/− mice have more platelets and BM megakaryocytes than wild-type (WT) controls (P < .05). Furthermore, subsequent analysis of megakaryocyte-CFU production revealed an increase with Cib1 deletion compared with WT (P < .05). In addition, BM from Cib1−/− mice, cultured with thrombopoietin (TPO) for 24 hours, produced more highly polyploid megakaryocytes than WT BM (P < .05). Subsequent analysis of TPO signaling revealed enhanced Akt and ERK1/2 phosphorylation, whereas FAKY925 phosphorylation was reduced in Cib1−/− megakaryocytes treated with TPO. Conversely, platelet recovery in Cib1−/− mice after platelet depletion was attenuated compared with WT (P < .05). This could be the result of impaired adhesion and migration, as adhesion to fibrinogen and fibronectin and migration toward an SDF-1α gradient were reduced in Cib1−/− megakaryocytes compared with WT (P < .05). In addition, Cib1−/− megakaryocytes formed fewer proplatelets compared with WT (P < .05), when plated on fibrinogen. These data suggest that CIB1 plays a dual role in megakaryopoiesis, initially by negatively regulating TPO signaling and later by augmenting proplatelet production.

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Zayed, Mohamed A., Andrew McFadden, Weiping Yuan, Mary E. Hartnett, Dan Chalothorn, James Faber, and Leslie V. Parise. "Critical Role of CIB1 in Endothelial Cell Function and In Vivo Ischemia-Induced Angiogenesis." Blood 108, no. 11 (November 16, 2006): 1800. http://dx.doi.org/10.1182/blood.v108.11.1800.1800.

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Abstract CIB1, a 22kDa EF-hand containing calcium binding protein, was originally identified in a yeast two-hybrid screen as a binding partner for the cytoplasmic tail of the platelet integrin αIIb. CIB1 also associates with a number of kinases and modulates their activity, suggesting that CIB1 is an important regulatory molecule. Recently, we found that CIB1 is expressed in multiple endothelial cell (EC) types. We therefore tested the role of CIB1 in EC function in vitro, and in angiogenesis both ex vivo and in vivo. To test the role of CIB1 in EC function in vitro, we reduced endogenous CIB1 levels in ECs by RNA interference with an shRNA-delivered by lentivirus. CIB1 depletion significantly decreased EC haptotaxis on fibronectin and EC vascular tube formation on growth factor-reduced Matrigel. Treatment with FGF-2, an angiogenic factor, did not counter the observed inhibition of haptotaxis and tube formation by shRNA against CIB1. However, CIB1 overexpression enhanced FGF-2-induced EC haptotaxis relative to control cells. Similarly, ECs derived from CIB1 null mice exhibited a significant decrease in haptotaxis, tube formation, and proliferation compared to ECs isolated from wild-type littermate controls. In ex vivo aortic ring and tibialis anterior muscle culture assays, CIB1 null cultures supplemented with serum or FGF-2 demonstrated reduced blood vessel sprouting compared to wild-type littermate control cultures. Finally, in vivo assays for hyperoxic retinal angiogenesis and hind-limb induced-ischemia revealed a decrease in post-ischemia retinal neovascularization and Doppler hind-limb blood perfusion recovery, although developmental retinal angiogenesis in CIB1 null mice appeared normal. In conclusion, these findings support a critical role for CIB1 in EC function that appears to be important for ischemia-induced angiogenesis.

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de Jong, Sarah Jill, Amandine Créquer, Irina Matos, David Hum, Vignesh Gunasekharan, Lazaro Lorenzo, Fabienne Jabot-Hanin, et al. "The human CIB1–EVER1–EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses." Journal of Experimental Medicine 215, no. 9 (August 1, 2018): 2289–310. http://dx.doi.org/10.1084/jem.20170308.

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Patients with epidermodysplasia verruciformis (EV) and biallelic null mutations of TMC6 (encoding EVER1) or TMC8 (EVER2) are selectively prone to disseminated skin lesions due to keratinocyte-tropic human β-papillomaviruses (β-HPVs), which lack E5 and E8. We describe EV patients homozygous for null mutations of the CIB1 gene encoding calcium- and integrin-binding protein-1 (CIB1). CIB1 is strongly expressed in the skin and cultured keratinocytes of controls but not in those of patients. CIB1 forms a complex with EVER1 and EVER2, and CIB1 proteins are not expressed in EVER1- or EVER2-deficient cells. The known functions of EVER1 and EVER2 in human keratinocytes are not dependent on CIB1, and CIB1 deficiency does not impair keratinocyte adhesion or migration. In keratinocytes, the CIB1 protein interacts with the HPV E5 and E8 proteins encoded by α-HPV16 and γ-HPV4, respectively, suggesting that this protein acts as a restriction factor against HPVs. Collectively, these findings suggest that the disruption of CIB1–EVER1–EVER2-dependent keratinocyte-intrinsic immunity underlies the selective susceptibility to β-HPVs of EV patients.

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Naik, Meghna Ulhas, and Ulhas P. Naik. "Integrin αIIb cytoplasmic Tail Is Essential for Integrin Outside-in Signaling and Regulation of in Vivo Thrombosis." Blood 124, no. 21 (December 6, 2014): 4160. http://dx.doi.org/10.1182/blood.v124.21.4160.4160.

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Abstract Platelet aggregation plays an important role in physiological hemostasis and pathological thrombosis. Platelet agonists induce a series of events called inside-out signaling that lead to the activation of integrin αIIbβ3. Fibrinogen binding to the activated integrin relay signals termed as outside-in signaling that regulate thrombus growth and stability. Talin and kindlin bind to the integrin β3 cytoplasmic tail to induce inside-out signaling. Although, integrin αIIb cytoplasmic domain also bind to a number of proteins, its importance in hemostasis or thrombosis is not well understood. Previously, we have identified a calcium- and integrin-binding protein (CIB1) that specifically interacts with the integrin αIIb cytoplasmic tail. Using a novel technique to inhibit interaction of CIB1 with integrin αIIb in intact human platelets, we have shown that CIB1 regulates outside-in signaling through integrin αIIbβ3. Recently, using Cib1-/- mice, we showed that CIB1 is a key regulator of thrombosis in vivo. Interestingly, agonist-induced platelet aggregation and secretion was normal in Cib1-/- platelets. Furthermore, expression or activation of integrin αIIbβ3 was also not affected by Cib1 deficiency, suggesting that integrin inside-out signaling is not affected in Cib1-/- platelets. However, adhesion and spreading on immobilized fibrinogen (Fg) was severely affected in Cib1-/- platelets. When we analyzed the rate of clot retraction, we found that significantly (P<0.001) delayed clot retraction was observed in Cib1-/- platelets compared to WT littermates, suggesting that integrin outside-in signaling is impaired in the absence of Cib1. To delineate the molecular mechanism regulated by CIB1 during platelet spreading and clot retraction, we analyzed the known signaling events activated during outside-in signaling. We found that Fg-dependent activation of ERK1 and p38 MAP kinase was significantly reduced in Cib1-/- null platelets. Furthermore, phosphorylation of the myosin light chain was also blocked in Cib1-/- platelets adhered to immobilized Fg. Furthermore, outside-in signaling-dependent tyrosine phosphorylation of β3 was greatly reduced in Cib1-/- platelets. When analyzed for the candidate tyrosine kinase responsible for reduced β3 phosphorylation, both Src and FAK activation was significantly reduced in Cib1-/- platelets. Furthermore, downstream signaling events such as activation of PAK1, PI3K, PDK1, as well as Akt were significantly affected in Cib1-/- platelets adhered to immobilized Fg. To test if impaired inhibition of GSK3-β is the cause of defective outside in signaling in Cib1-/- platelets we treated Cib1-/- platelets with SB216763, a specific GSK3-β inhibitor. We found that inhibition of GSK3-β rescued defective platelet adhesion and clot retraction observed in Cib1-/- platelets. It also rescued activation of p38 and Erk2 activation as well as MLC phosphorylation. However, activation of FAK, Src, PAK1, PI3K, PDK1, and Akt was not rescued, suggesting that these are upstream of GSK3-β. Furthermore, we found that outside-in dependent recruitment of FAK to the integrin-c-Src complex is greatly reduced in the absence of Cib1 suggesting that integrin αIIb cytoplasmic domain serves as a docking site for CIB1 so that it can recruit FAK to the integrin-c-Src complex and propagate outside-in signaling leading to GSK3-β inhibition, which is crucial for thrombus growth and stability. These in vivo and in vitro results clearly show that CIB1 regulates thrombosis by regulating outside-in signaling without affecting inside-out signaling through integrin αIIbβ3. Our results highlight an essential function to integrin αIIb cytoplasmic tail in regulating integrin outside-in signaling and thus thrombus growth and stability. Disclosures No relevant conflicts of interest to declare.

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Naik, Meghna Ulhas, and Ulhas Naik. "CIB1 Regulates Thrombosis through Integrin αaIIbβ3 Outside-in Signaling, but Not Inside-out Signaling." Blood 114, no. 22 (November 20, 2009): 2992. http://dx.doi.org/10.1182/blood.v114.22.2992.2992.

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Abstract Abstract 2992 Poster Board II-969 Platelet aggregation plays an important role in physiological hemostasis and pathological thrombosis. Platelet agonists induce a series of signaling events called inside-out that leads to the activation of integrin αaIIbβ3. Upon ligand binding to integrin αaIIbβ3, a cascade of signaling known as outside-in signaling is induced through the integrin that regulates platelet aggregation and clot retraction. The regulation of these signaling events is not well understood. Previously, we had identified a calcium- and integrin-binding protein (CIB1) that specifically interacts with integrin αaIIbβ3. Using a novel technique to inhibit interaction of CIB1 with integrin αaIIbβ3 in intact platelets, we have shown that CIB1 regulates outside-in signaling through integrin αaIIbβ3. Recently, using Cib1-/- mice, we confirmed that CIB1 is a key regulator of hemostasis. FeCl3-induced carotid artery thrombosis, a well recognized in vivo model of thrombosis showed a significantly extended time of occlusion in Cib1-/- mice compared to wild type (WT) mice. Since CIB1 is expressed both in the endothelium and in platelets, the observed defect could arise from the lack of CIB1 in either cell types. To identify the specific involvement of platelets, we performed a collagen-epinephrine-induced pulmonary thromboembolism assay. In this assay, pulmonary vessel occlusion occurs due to platelet thrombus formation without injury to the endothelium. We found no difference in the number of Cib1-/- mice and WT mice that died within two minutes (n=20). When analyzed for the extent of pulmonary vascular occlusion by Evans blue exclusion as well as histochemical analysis, no difference between Cib1-/- and WT mice was observed. Consistent with this finding, agonist-induced platelet aggregation and secretion was normal in Cib1-/- platelets. Furthermore, expression or activation of integrin αaIIbβ3 was also not affected by Cib1 deficiency. When we analyzed the rate of clot retraction, we found that incomplete and significantly (P<0.001) delayed clot retraction was observed in Cib1-/- platelets compared to WT littermates. To delineate the molecular mechanism regulated by CIB1, we analyzed the known signaling cascade involved in clot retraction. We found that outside-in signaling-induced activation of ERK1 and p38 MAP kinase was significantly reduced in Cib1-/- null platelets. Furthermore, phosphorylation of the myosin light chain during outside-in signaling was blocked in Cib1-/- platelets. Interestingly, agonist-induced tyrosine phosphorylation of integrin β3 chain was unaffected in Cib1-/- platelets, but Mn2+-induced outside-in signaling-dependent tyrosine phosphorylation of β3 was greatly reduced. When analyzed for the candidate tyrosine kinase responsible for β3 phosphorylation, both Src and FAK activation was significantly reduced in Cib1-/- platelets. These in vivo and in vitro results clearly show that CIB1 regulates thrombosis by regulating outside-in signaling without affecting inside-out signaling through integrin αaIIbβ3. Disclosures: No relevant conflicts of interest to declare.

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Wang, Xianwang, Xiaochun Peng, Xueqing Zhang, Hanyi Xu, Chengbiao Lu, Lian Liu, Jiaxing Song, and Yingjie Zhang. "The Emerging Roles of CIB1 in Cancer." Cellular Physiology and Biochemistry 43, no. 4 (2017): 1413–24. http://dx.doi.org/10.1159/000481873.

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Calcium and integrin-binding protein 1 (CIB1) is an EF-hand calcium binding protein, which is involved in many cellular processes, including calcium signaling, cell survival and proliferation, cell migration, cell adhesion and apoptosis. A number of studies have found that CIB1 is ubiquitously expressed and is related to various human diseases, such as cancer, Alzheimer’s disease (AD), cardiac hypertrophy and male infertility. The mechanism of CIB1 in human diseases is still not clear, although multiple functions of CIB1 are modulated by interacting with numerous interacting partners. As a calcium binding protein, the roles of CIB1 in calcium signaling by binding calcium or modulating some key modulators, such as calcineurin, integrin, inositol 1,4,5-trisphosphate receptor (IP3R) and taste 1 receptor member 2 (TAS1R2). The tumor promoting mechanisms of CIB1 have been described in different aspects, including promoting tumor cell cycle and proliferation, inhibiting tumor cell apoptosis, and mediating tumor cell migration and angiogenesis. In addition, multiple functions of CIB1, such as neural development, taste or gustation functions, and virus infection are also elucidated. These recent advances have significantly expanded our understanding of the knowledge of CIB1 and highlighted the potential mechanisms of CIB1 in tumor progression.

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Zhao, Jun, Xian Ming Lang, and Lei Chao. "The Pilot-Scale Study of Constructed Intensified Biological Bed on the Purification of Northern Transboundary Polluted River Water." Advanced Materials Research 347-353 (October 2011): 2727–34. http://dx.doi.org/10.4028/www.scientific.net/amr.347-353.2727.

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Constructed Intensified Biological Bed (CIBB) is a new sewage disposal technology based on subsurface flow constructed wetland and biological aerated filter. The CIBB was applied for serious polluted transboundary river water. The removal rates of pilot scale CIBB on simulated Tiaozi River system CODcr、NH3-N and TN were over 70%, 90%, 60% respectively. The hydraulic loading of CIBB reached 4.8m•d-1, and CODcr organic loading was 185g•(m3d) -1 and the ammonium loading was 19 g•(m3d) -1. If the CIBB is used on the Tiaozi River, CODcr and ammonium in outflow of CIBB system will reach class V standards of Environmental quality standard for surface water (GB3838-2002).

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Zhao, Qiao-Ling, Xing-Jia Shen, Liang-Jun Zhu, Yong-Zhu Yi, Shun-Ming Tang, Guo-Zheng Zhang, and Xi-Jie Guo. "Characterization of CIb1 Gene Promoter from Silkworm, Bombyx mori." Zeitschrift für Naturforschung C 62, no. 11-12 (December 1, 2007): 875–80. http://dx.doi.org/10.1515/znc-2007-11-1216.

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The hemolymph chymotrypsin inhibitor b1 (CIb1) of silkworm, Bombyx mori, plays an important role in innate immunity. In order to study its encoding gene CIb1, five heterogeneous promoter fragments of 844 bp, 682 bp, 516 bp, 312 bp and 82 bp in length were cloned from genomic DNA of the p50 silkworm strain. Characterization of the CIb1 promoter was performed in vitro using the firefly luciferase gene as reporter. The results showed that CIb1 promoter fragments have transcription activities in the B. mori ovary-derived BmN cell line. The 82 bp fragment (-72 to +10 nt) containing the eukaryotic core promoter elements revealed a basic transcription activity. The Bm1 element, upstream the transcription initiation site, showed a positive regulation function to the CIb1 promoter. CIb1 promoter-like fragments from the genomic DNA of the tetra hybrid silkworm Suju\Minghu provided a natural deletion model for the study of the CIb1 promoter. In vitro analysis indicated that the 132 bp fragment from -517 nt to -386 nt upstream of the transcription initiation site strongly suppressed the transcription activity of the CIb1 promoter, suggesting that the 132 bp fragment harbours strong negative cis-acting elements. Infection of Bombyx mori nucleopolyhedrovirus (BmNPV) increased the activity of the CIb1 promoter, having provided another evidence to the function of CIb1 in the innate immunity of silkworm.

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Kostyak, John C., and Ulhas P. Naik. "Dual Role for CIB1 in Thrombopoiesis: CIB1 Suppresses Megakaryocyte Quantities but Supports Adhesion, Migration, and Proplatelet Formation." Blood 118, no. 21 (November 18, 2011): 2384. http://dx.doi.org/10.1182/blood.v118.21.2384.2384.

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Abstract Abstract 2384 Megakaryocytes (MKs) are large polyploid cells that produce platelets through a process known as thrombopoiesis. Thrombopoietin (Tpo) is the major cytokine that regulates a variety of steps in this process, including hematopoietic stem cell (HSC) differentiation to MKs, proplatelet formation, and platelet release into the circulation. However, the molecular mechanism of thrombopoiesis is poorly understood. We have previously reported that calcium- and integrin-binding protein 1 (CIB1) regulates endomitosis in Dami cells. To further characterize the role of CIB1 in thrombopoiesis, we utilized a Cib1−/− mouse model. We observed that Cib1−/− mice have a slightly elevated number of platelets and bone marrow (BM)-derived MKs than wild-type (WT) controls (p<0.05). Rate of platelet clearance was comparable in Cib1−/− and WT mice, suggesting that the defective clearance is not the cause of the observed elevated platelet number. In order to determine if the HSC differentiation is dysregulated by the ablation of Cib1, we analyzed MK-colony forming unit production, which revealed an increase in the colony forming cells with Cib1 deletion compared to WT (p<0.05). Additionally, BM from Cib1−/− mice, cultured with Tpo for 24 hours, produced more highly polyploid MKs than WT BM (p<0.05). These results suggest that Cib1 may negatively regulate initial steps of megakaryopoiesis. Subsequent analysis of Tpo signaling revealed that activation of FAK, a known suppresser of Tpo signaling, is attenuated, as indicated by reduced FAKY925 phosphorylation in Cib1−/− BM-derived MKs treated with Tpo. Consequently, Akt and ERK1/2 activation downstream of Tpo was enhanced. These results suggested that Cib1 inhibits Tpo signaling by augmenting FAK activation. Interestingly, platelet recovery in Cib1−/− mice following platelet depletion by experimental immunothrombocytopenia was attenuated compared to WT (p<0.05). This could be due to impaired adhesion and migration of MKs on the extracellular matrix. Consistent with this notion, adhesion to fibrinogen and fibronectin and migration towards an SDF-1α gradient were significantly reduced in Cib1−/− MKs compared to WT (p<0.05). Additionally, Cib1−/− MKs formed fewer proplatelets compared to WT (p<0.05), when plated on fibrinogen. These data suggest that CIB1 plays a dual role in thrombopoiesis, initially by negatively regulating Tpo signaling, and later by supporting MK migration and proplatelet production. Disclosures: No relevant conflicts of interest to declare.

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Begaye, Brittany, Paolo Piaggi, Marie S. Thearle, Kaitlyn Haskie, Mary Walter, Mathias Schlögl, Susan Bonfiglio, Jonathan Krakoff, and Karyne L. Vinales. "Norepinephrine and T4 Are Predictors of Fat Mass Gain in Humans With Cold-Induced Brown Adipose Tissue Activation." Journal of Clinical Endocrinology & Metabolism 103, no. 7 (May 16, 2018): 2689–97. http://dx.doi.org/10.1210/jc.2018-00387.

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Abstract Context In healthy adults with detectable cold-induced brown adipose tissue activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined. Objective To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes. Design, Setting, Participants, and Interventions Twelve healthy volunteers (seven male and five female) with positive CIBA [>2 standardized uptake value (g/mL)] had 24-hour energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron emission tomography/computed tomography scans were performed after exposure to 16°C for 2 hours to quantify CIBA. Main Outcome Measures CIBA, 24hEE during EBL, and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 and free T4. Body composition at baseline and 6 months by dual-energy X-ray absorptiometry. Results Lower urinary norepinephrine and free T4 were associated with higher CIBA (r = −0.65, P = 0.03; and r = −0.75, P < 0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (P = 0.77). Lower CIBA (β = −3.5 kg/standardized uptake value; P < 0.01) predicted fat mass gain, whereas higher urinary norepinephrine and free T4 predicted future fat mass gain at 6 months (β = 3.0 kg per twofold difference in norepinephrine, P = 0.03; and β = 1.2 kg per 0.1-ng/dL difference in free T4, P = 0.03, respectively). Conclusion Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

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Tian, Rui, Zifeng Cui, Dan He, Xun Tian, Qinglei Gao, Xin Ma, Jian-rong Yang, et al. "Risk stratification of cervical lesions using capture sequencing and machine learning method based on HPV and human integrated genomic profiles." Carcinogenesis 40, no. 10 (May 17, 2019): 1220–28. http://dx.doi.org/10.1093/carcin/bgz094.

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Abstract From initial human papillomavirus (HPV) infection and precursor stages, the development of cervical cancer takes decades. High-sensitivity HPV DNA testing is currently recommended as primary screening method for cervical cancer, whereas better triage methodologies are encouraged to provide accurate risk management for HPV-positive women. Given that virus-driven genomic variation accumulates during cervical carcinogenesis, we designed a 39 Mb custom capture panel targeting 17 HPV types and 522 mutant genes related to cervical cancer. Using capture-based next-generation sequencing, HPV integration status, somatic mutation and copy number variation were analyzed on 34 paired samples, including 10 cases of HPV infection (HPV+), 10 cases of cervical intraepithelial neoplasia (CIN) grade and 14 cases of CIN2+ (CIN2: n = 1; CIN2-3: n = 3; CIN3: n = 9; squamous cell carcinoma: n = 1). Finally, the machine learning algorithm (Random Forest) was applied to build the risk stratification model for cervical precursor lesions based on CIN2+ enriched biomarkers. Generally, HPV integration events (11 in HPV+, 25 in CIN1 and 56 in CIN2+), non-synonymous mutations (2 in CIN1, 12 in CIN2+) and copy number variations (19.1 in HPV+, 29.4 in CIN1 and 127 in CIN2+) increased from HPV+ to CIN2+. Interestingly, ‘common’ deletion of mitochondrial chromosome was significantly observed in CIN2+ (P = 0.009). Together, CIN2+ enriched biomarkers, classified as HPV information, mutation, amplification, deletion and mitochondrial change, successfully predicted CIN2+ with average accuracy probability score of 0.814, and amplification and deletion ranked as the most important features. Our custom capture sequencing combined with machine learning method effectively stratified the risk of cervical lesions and provided valuable integrated triage strategies.

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Leisner, Tina M., Mingjuan Liu, Zahara M. Jaffer, Jonathan Chernoff, and Leslie V. Parise. "Essential role of CIB1 in regulating PAK1 activation and cell migration." Journal of Cell Biology 170, no. 3 (August 1, 2005): 465–76. http://dx.doi.org/10.1083/jcb.200502090.

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p21-activated kinases (PAKs) regulate many cellular processes, including cytoskeletal rearrangement and cell migration. In this study, we report a direct and specific interaction of PAK1 with a 22-kD Ca2+-binding protein, CIB1, which results in PAK1 activation both in vitro and in vivo. CIB1 binds to PAK1 within discrete regions surrounding the inhibitory switch domain in a calcium-dependent manner, providing a potential mechanism of CIB1-induced PAK1 activation. CIB1 overexpression significantly decreases cell migration on fibronectin as a result of a PAK1-and LIM kinase–dependent increase in cofilin phosphorylation. Conversely, the RNA interference–mediated depletion of CIB1 increases cell migration and reduces normal adhesion-induced PAK1 activation and cofilin phosphorylation. Together, these results demonstrate that endogenous CIB1 is required for regulated adhesion-induced PAK1 activation and preferentially induces a PAK1-dependent pathway that can negatively regulate cell migration. These results point to CIB1 as a key regulator of PAK1 activation and signaling.

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Nishii, Tomonori, Yu Oikawa, Yasumasa Ishida, Masashi Kawaichi, and Eishou Matsuda. "CtBP-interacting BTB Zinc Finger Protein (CIBZ) Promotes Proliferation and G1/S Transition in Embryonic Stem Cells via Nanog." Journal of Biological Chemistry 287, no. 15 (February 7, 2012): 12417–24. http://dx.doi.org/10.1074/jbc.m111.333856.

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Mouse embryonic stem cells (ESCs) require transcriptional regulation to ensure rapid proliferation that allows for self-renewal. However, the molecular mechanism by which transcriptional factors regulate this rapid proliferation remains largely unknown. Here we present data showing that CIBZ, a BTB domain zinc finger transcriptional factor, is a key transcriptional regulator for regulation of ESC proliferation. Here we show that deletion or siRNA knockdown of CIBZ inhibits ESC proliferation. Cell cycle analysis shows that loss of CIBZ delays the progression of ESCs through the G1 to S phase transition. Conversely, constitutive ectopic expression of exogenous CIBZ in ESCs promotes proliferation and accelerates G1/S transition. These findings suggest that regulation of the G1/S transition explains, in part, CIBZ-associated ESC proliferation. Our data suggest that CIBZ acts through the post-transcriptionally regulates the expression of Nanog, a positive regulator of ESC proliferation and G1/S transition, but does not affect Oct3/4 and Sox2 protein expression. Notably, constitutive overexpression of Nanog partially rescued the proliferation defect caused by CIBZ knockdown, indicating the role of CIBZ in ESC proliferation and G1/S transition at least in part depends on the Nanog protein level.

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Bulavenko, O. V., D. G. Konkov, N. V. Kuzminova, T. V. Lobastova, and I. V. Oleksienko. "Optimization of antenatal monitoring approaches of women with chronic inflammatory bowel diseases." Reproductive Endocrinology, no. 57 (March 31, 2021): 84–92. http://dx.doi.org/10.18370/2309-4117.2021.57.84-92.

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Chronic inflammatory bowel diseases (CIBD) affect patients at their peak of reproductive age. Clinical presentation of CIBD in pregnancy is associated with an increased risk of adverse effects in mother and fetus, including prematurity, low birth weight, increased indications for caesarean section. Thus optimizing of the CIBD diagnosis and treatment before and during pregnancy is essential to improve maternal and fetal outcomes.Research aim: to analyze the effectiveness of the CIBD clinical management at the stage of preconception and during pregnancy.Materials and methods. It was searched the Cochrane Library, WHO platform, clinical guidelines, and research reference database Medline. All potential studies have evaluated the clinical practice guidelines in women with CIBD for conception, pregnancy and breastfeeding. Recommendations related to the necessary laboratory and instrumental examination methods, therapeutic strategy, the safety of drugs for mother and fetus, the features of multidisciplinary antenatal observation, the timing and method of delivery of pregnant women with CIBD. Results. Treatment in the planning phase and pregnancy should be multidisciplinary, involving a gastroenterologist, obstetrician-gynecologist, primary care physician, pediatrician and a colorectal surgeon if necessary, as well as stakeholders from the association of patients with CIBD. Communication between these professionals is critical to avoid ambivalent or even conflicting counseling, which is an additional source of anxiety for patients, and also potentially dangerous for suboptimal prevention of clinical CIBD manifestation. Obtained results of the analysis will prevent laboratory and therapeutic polypharmacy and significantly improve the pregnancy outcome.Conclusions. Most women with CIBD had a physiological pregnancy and healthy children. However, some studies have linked CIBD to an increased risk of preterm birth and low birth weight infants. The development of national clinical guidelines will optimize and improve the quality of perinatal care to women with CIBD in the Ukraine, and will lead to a decrease in obstetric, fetal and neonatal complications.

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Naik, Ulhas Pandurang, and Meghna Ulhas Naik. "CIB1 Is Required for FAK Activation during Outside-in Signaling through Platelet Integrin αIIbβ3." Blood 112, no. 11 (November 16, 2008): 2873. http://dx.doi.org/10.1182/blood.v112.11.2873.2873.

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Abstract Platelets play an important role in the processes of hemostasis and thrombosis. Platelet integrin αIIbβ3 mediates bi-directional signaling during these processes. Agonist-dependent activation of integrin αIIbβ3 through inside-out signaling results in high-affinity binding of soluble ligands, such as fibrinogen. Fibrinogen binding induces a cascade of signaling through the integrin, termed outside-in signaling that results in platelet aggregation and clot retraction. Previously, we have characterized CIB1, a calcium- and integrin-binding protein that specifically interacts with the cytoplasmic domain of αIIb. Previous reports using in vitro and ex vivo studies implicated that CIB1 is involved in maintaining αIIbβ3 in its resting state, agonist-induced activation of the integrin, and outside-in signaling resulting in platelet spreading. Here, we show that platelet filopodia formation induced by fibrinogen binding to integrin αIIbβ3 needs Ca2+, but is independent of the Ca2+-dependent interaction of CIB1 with αIIb. Additionally, dynamic rearrangement of the cytoskeleton is required for the recruitment of FAK to the CIB1-αIIb complex at the filopodia and FAK activation. Moreover, disruption of the association of CIB1 and αIIb by incorporation of αIIb peptide or CIB1 antibody inhibited FAK activation. Furthermore, Cib1 null platelets acquired a spiky morphology and failed to fully spread on immobilized fibrinogen. Interestingly, FAK activation was significantly reduced in Cib1 null platelets exposed to immobilized fibrinogen. Our results suggest that during outside-in signaling, a rise in the intracellular Ca2+ level and filopodia formation occurs prior to the interaction of CIB1 with αIIb. Additionally, Ca2+ bound CIB1 recruits FAK to the αIIbβ3 complex at the filopodia, where FAK is activated, resulting in platelet spreading. Thus, our results have provided a mechanism through which CIB1 regulates outside-in signaling through integrin αIIbβ3.

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Mardiah, Tri, and Nurul Hidayati Rofiah. "IMPLEMENTASI PROGRAM CERDAS ISTIMEWA DAN BAKAT ISTIMEWA (CIBI) DALAM PENGEMBANGAN PRESTASI AKADEMIK DAN NON AKADEMIK DI SD MUHAMMADIYAH CONDONGCATUR." Jurnal Fundadikdas (Fundamental Pendidikan Dasar) 1, no. 3 (December 1, 2018): 161. http://dx.doi.org/10.12928/fundadikdas.v1i3.663.

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This study aims to answer: 1) the implementation of the CIBI program in developing academic and non-academic achievements at SD Muhammadiyah Condongcatur, 2) supporting and inhibiting factors for the implementation of the CIBI program in developing academic and non-academic achievements at SD Muhammadiyah Condongcatur.This type of research uses descriptive qualitative research. The subject of this study was a team of coordinators and students who participated in the CIBI program. Data collection techniques use triangulation techniques and sources. The data analysis technique uses interactive data models of Miles and Huberman.The results of the study are as follows: 1) Implementation of the CIBI program in developing academic and non-academic achievements at SD Muhammadiyah Condongcatur through 3 stages, namely the planning, implementation, and evaluation stages. Planning for the CIBI program includes determining objectives, stages of the program, preparation of teaching staff, student selection criteria, facilities and infrastructure, and program funding. The implementation of the CIBI program includes the learning process, time and schedule of implementation, teaching materials, learning materials, and learning methods. The evaluation of the CIBI program put forward the cognitive and psychomotor aspects of students, the preparation of instruments for the assessment of the CIBI program, and the follow-up of the CIBI program. 2) Supporting factors of the CIBI program in developing academic and non-academic student achievements include: there is a coordinating team that teaches in the CIBI program in accordance with their fields, the CIBI program facilities are very complete, and school funding supports. The inhibiting factor of the CI program in developing academic achievement is the lack of time and teaching staff, scheduling material distribution is very difficult to do, and the difficulty of how to give motivation is always stable. While the inhibiting factors of the BI program in developing non-academic achievements are weather conditions and students who take part in 2 activities outside of school.

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Connolly, T., and D. Beach. "Interaction between the Cig1 and Cig2 B-type cyclins in the fission yeast cell cycle." Molecular and Cellular Biology 14, no. 1 (January 1994): 768–76. http://dx.doi.org/10.1128/mcb.14.1.768-776.1994.

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In this report, we describe the cloning and characterization of a B-type cyclin, Cig2 from the fission yeast Schizosaccharomyces pombe. The cig2 gene encodes a 45-kDa protein that is most similar to a previously identified B-type cyclin in S. pombe, Cdc13. Deletion of cig2 had no observable effect on cell viability or progression through the cell cycle. Strains carrying the cig2 null allele do, however, exhibit an enhanced ability to undergo conjugation relative to a wild-type strain. The cig2 transcript was found to undergo periodic oscillation during the cell cycle, peaking at the G1/S-phase boundary. We have investigated the relationship between Cig2 and the other B-type cyclins, Cig1 and Cdc13, in the fission yeast. We found that cells carrying disruptions of both the cig1 and cig2 genes contain multiple nuclei with a 1C DNA content, suggesting that they are delayed in progression through the G1 phase of the cell cycle. The phenotype of this double mutant suggests that there is a delay in septum formation, possibly as a result of defective nuclear separation.

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Connolly, T., and D. Beach. "Interaction between the Cig1 and Cig2 B-type cyclins in the fission yeast cell cycle." Molecular and Cellular Biology 14, no. 1 (January 1994): 768–76. http://dx.doi.org/10.1128/mcb.14.1.768.

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In this report, we describe the cloning and characterization of a B-type cyclin, Cig2 from the fission yeast Schizosaccharomyces pombe. The cig2 gene encodes a 45-kDa protein that is most similar to a previously identified B-type cyclin in S. pombe, Cdc13. Deletion of cig2 had no observable effect on cell viability or progression through the cell cycle. Strains carrying the cig2 null allele do, however, exhibit an enhanced ability to undergo conjugation relative to a wild-type strain. The cig2 transcript was found to undergo periodic oscillation during the cell cycle, peaking at the G1/S-phase boundary. We have investigated the relationship between Cig2 and the other B-type cyclins, Cig1 and Cdc13, in the fission yeast. We found that cells carrying disruptions of both the cig1 and cig2 genes contain multiple nuclei with a 1C DNA content, suggesting that they are delayed in progression through the G1 phase of the cell cycle. The phenotype of this double mutant suggests that there is a delay in septum formation, possibly as a result of defective nuclear separation.

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Hu, Shan, Yu Chen, Zhi-Fu Wang, Qi-Liang Mao-Ying, Wen-Li Mi, Jian-Wei Jiang, Gen-Cheng Wu, and Yan-Qing Wang. "The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/973524.

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Cancer-induced bone pain (CIBP) is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE), isolated from the traditional Chinese herbal medicineScutellaria baicalensisGeorgi (or Huang Qin), has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could alleviate the mechanical allodynia in CIBP rats. Intrathecal 100 μg BE could inhibit the production of IL-6 and TNF-αin the spinal cord of CIBP rats. Moreover, intrathecal 100 μg BE could effectively inhibit the activation of p-p38 and p-JNK MAPK signals in CIBP rats. The analgesic effect of BE may be associated with the inhibition of the expression of the inflammatory cytokines IL-6 and TNF-αand through the activation of p-p38 and p-JNK MAPK signals in the spinal cord. These findings suggest that BE is a promising novel analgesic agent for CIBP.

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Singh, Charanjeet, J. Carlos Manivel, Alexander M. Truskinovsky, Kay Savik, Samy Amirouche, Jana Holler, Bharat Thyagarajan, H. Evin Gulbahce, and Stefan E. Pambuccian. "Variability of Pathologists' Utilization of p16 and Ki-67 Immunostaining in the Diagnosis of Cervical Biopsies in Routine Pathology Practice and Its Impact on the Frequencies of Cervical Intraepithelial Neoplasia Diagnoses and Cytohistologic Correlations." Archives of Pathology & Laboratory Medicine 138, no. 1 (January 1, 2014): 76–87. http://dx.doi.org/10.5858/arpa.2012-0472-oa.

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Context.—The use of p16 in cervical biopsies improves the accuracy of cervical intraepithelial neoplasia (CIN) diagnosis and grading and decreases its interpathologist variability. Objective.—To determine the impact of the frequency of use of p16 immunostains in cervical biopsies on pathologists' diagnoses of CIN grade 1 and grade 2 or above (CIN1 and CIN2+) and on cytohistologic correlations. Design.—We identified all cervical biopsy specimens with cytologic correlations subjected or not to p16 staining from January 1, 2005, to September 30, 2010; calculated each pathologist's percentage of p16 use; and correlated it with their major cytohistologic discrepancy rates, CIN2+ diagnoses, and CIN1/CIN2+ ratios. Results.—During the study period, each of the 23 pathologists interpreted 59 to 1811 (mean, 518) of 11 850 cervical biopsy specimens, used p16 for 0% to 21.31% (mean, 10.14%) of these, had CIN2+ detection rates of 9.5% to 24.1% (mean, 18.9%), and CIN1/CIN2+ ratios of 0.7 to 4.5 (mean, 1.5). Compared to the 12 “low users” of p16, who used p16 fewer times than the institution's mean for p16 use, the 11 “high users” of p16 diagnosed more biopsies (8391 versus 3459), had a lower rate of major cytohistologic discrepancies (12.62% versus 14.92%, P < .001), a higher rate of CIN2+ diagnoses (19.9% versus 16.4%, P < .001), a lower range of CIN2+ rates (15.0%–23.1% versus 9.5%–24.1%), and lower CIN1/CIN2+ ratios (1.2 versus 2.3). Conclusions.—We found a high intrainstitutional variability of p16 use in cervical biopsies, CIN2+ rates, and CIN1/CIN2+ ratios. Use of p16 for greater than 10% of cervical biopsies was associated with improved cytohistologic correlation rates and with lower variability in the frequencies of histologic diagnoses.

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Uleberg, Kai-Erik, Irene Tveiterås Øvestad, Ane Cecilie Munk, Cato Brede, Bianca van Diermen, Einar Gudlaugsson, Emiel A. M. Janssen, Anne Hjelle, and Jan P. A. Baak. "Prediction of Spontaneous Regression of Cervical Intraepithelial Neoplasia Lesions Grades 2 and 3 by Proteomic Analysis." International Journal of Proteomics 2014 (June 15, 2014): 1–14. http://dx.doi.org/10.1155/2014/129064.

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Regression of cervical intraepithelial neoplasia (CIN) 2-3 to CIN 1 or less is associated with immune response as demonstrated by immunohistochemistry in formaldehyde-fixed paraffin-embedded (FFPE) biopsies. Proteomic analysis of water-soluble proteins in supernatants of biopsy samples with LC-MS (LTQ-Orbitrap) was used to identify proteins predictive of CIN2-3 lesions regression. CIN2-3 in the biopsies and persistence (CIN2-3) or regression (≤CIN1) in follow-up cone biopsies was validated histologically by two experienced pathologists. In a learning set of 20 CIN2-3 (10 regressions and 10 persistence cases), supernatants were depleted of seven high abundance proteins prior to unidimensional LC-MS/MS protein analysis. Mean protein concentration was 0.81 mg/mL (range: 0.55–1.14). Multivariate statistical methods were used to identify proteins that were able to discriminate between regressive and persistent CIN2-3. The findings were validated in an independent test set of 20 CIN2-3 (10 regressions and 10 persistence cases). Multistep identification criteria identified 165 proteins. In the learning set, zinc finger protein 441 and phospholipase D6 independently discriminated between regressive and persistent CIN2-3 lesions and correctly classified all 20 patients. Nine regression and all persistence cases were correctly classified in the validation set. Zinc finger protein 441 and phospholipase D6 in supernatant samples detected by LTQ-Orbitrap can predict regression of CIN2-3.

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Journal articles on the topic 'CIB2'

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