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Halitim, P., A. Tissot, L. Boussamet, A. Garcia, C. Fourgeux, P. Lacoste, B. Marie, J. Poschmann, S. Brouard, and L. Berthelot. "Étude de la physiopathologie de la dysfonction chronique du greffon pulmonaire par analyse transcriptomique sur cellule unique d’explants pulmonaires." Revue des Maladies Respiratoires 41, no. 3 (March 2024): 202–3. http://dx.doi.org/10.1016/j.rmr.2024.01.044.
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Melzi, Silvia, Guillaume Marcy, Cyril Degletagne, and Christelle Peyron. "Analyses transcriptomiques à cellule unique et à noyau unique de l’hypothalamus dans un état neuro-inflammatoire induit par le LPS." Médecine du Sommeil 20, no. 1 (March 2023): 5–6. http://dx.doi.org/10.1016/j.msom.2023.01.155.
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Galatanu, Olga. "Analyse du discours." Diversité 140, no. 1 (2005): 55–62. http://dx.doi.org/10.3406/diver.2005.2370.
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«Cellule d’innovation», «pôle académique de l’innovation», «recherche et innovation en Pays de la Loire», «action et/ ou structure innovante», «projet de loi d’orientation de la recherche et de l’innovation», «Pourquoi innover ? Un discours sur quelles pratiques ?»… La construction discursive du concept d’innovation par une linguiste.
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Granier, Sébastien. "Compter les protéines d’une cellule unique." médecine/sciences 23, no. 5 (May 2007): 478–79. http://dx.doi.org/10.1051/medsci/2007235478.
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Hellbacher, E., V. Van Hoef, A. Johansson, A. Knight, I. Gunnarsson, A. Bruchfeld, P. Eriksson, et al. "POS1438 ANALYSIS OF THE PLASMA PROTEOME PROVIDES MECHANISTIC INSIGHTS INTO THE PATHOPHYSIOLOGY OF ANCA-ASSOCIATED VASCULITIS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1073.2–1073. http://dx.doi.org/10.1136/annrheumdis-2023-eular.5500.
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BackgroundThe pathogenesis of ANCA-associated vasculitis (AAV) remains largely unknown. Proteinase 3 (PR3)- and myeloperoxidase (MPO)-AAV are two cateogories of AAV with distinct genetic background, but mechanistic differences between the two are poorly characterized. We hypothesized that in-depth studies of the plasma proteome in patients with active AAV would provide clues to the molecular and cellular mechanisms behind these disorders.ObjectivesTo improve our understanding of the disease mechanisms behind AAV and pathophysiological differences between PR3- and MPO-AAV.MethodsPlasma samples were collected at six Swedish rheumatological and/or nephrological centers from 42 PR3-AAV- and 25 MPO-AAV patients with active disease prior to commencement of therapy and from 138 healthy matched controls. All patients were classified into granulomatosis with polyangiitis or microscopic polyangiitis according to the European Medicines Agency algorithm. Samples were analysed for the relative levels of 181 proteins associated with inflammation or cardiovascular disease, using proximity extension assay (OLINK Proteomics). Differentially expressed proteins (DEPs) between groups were analyzed using ANOVA, where proteins with a fold change ≥ 1.5 and adjusted P value < 0.05 were considered as significant DEPs. Partial least square discriminant analysis (PLS-DA) was used to identify proteins contributing most to PR3-AAV/MPO-AAV separation from healthy controls. The STRING database was used to analyse protein–protein interaction networks. Gene ontology, KEGG and Reactome databases were used for pathway enrichment analyses using ClueGO.ResultsIn comparison with healthy controls, 63 DEPs were identified for PR3-AAV and 62 for MPO-AAV; of these, 49 DEPs were common to both AAV groups. Pathway enrichment analysis of the 49 common DEPs identified IL-17-, IL-10-, TNF-α- and NF-kappa B signaling and neutrophil chemotaxis among the significantly enriched processes. The 14 DEPs unique for PR3-AAV formed a functional and physical protein-protein interaction network in STRING analysis, with significant enrichment for regulation of B cell proliferation, activation of matrix metalloproteinases, collagen degradation and IL-17- and TNF-α signaling pathways. The 13 DEPs unique for MPO-AAV did not show any significant functional enrichment. Of the top 15 proteins contributing most to group separation in the PLS-DA analysis, 11 proteins where common to both PR3- and MPO-AAV and 4 proteins were unique for PR3-AAV and MPO-AAV, respectively (Table 1).ConclusionCombining quantitative proteomics and bioinformatics analyses, we have identified a large group of DEPs characterizing both active PR3- and MPO-AAV and have determined their associated biological mechanisms. DEPs unique for PR3-AAV formed an interconnected protein network associated with biological processes of high relevance for AAV-pathogenesis. In conclusion, these findings may provide new insights into similarities and differences in the pathogenesis of MPO- and PR3-AAV.Table 1.PLS-DA results showing the top 15 proteins contributing most to separation of PR3-AAV and MPO-AAV patients, respectively, from healthy controls.Common for MPO-AAV and PR3-AAV vs healthy controlsUnique for MPO-AAV vs healthy controlsUnique for PR3-AAV vs healthy controlsCCL23EPHB4EN-RAGECD40LTBRMCP-3IL2-RAPLCPRTN3OPNRETNST2TGF-alphaTIMP-1TNF-R1TNF-R2TNFRSF14U-PARVEGFAREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Tyml, Tomáš, Shailesh V. Date, and Tanja Woyke. "A single-cell genome perspective on studying intracellular associations in unicellular eukaryotes." Philosophical Transactions of the Royal Society B: Biological Sciences 374, no. 1786 (October 7, 2019): 20190082. http://dx.doi.org/10.1098/rstb.2019.0082.
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Single-cell genomics (SCG) methods provide a unique opportunity to analyse whole genome information at the resolution of an individual cell. While SCG has been extensively used to investigate bacterial and archaeal genomes, the technique has been rarely used to access the genetic makeup of uncultivated microbial eukaryotes. In this regard, the use of SCG can provide a wealth of information; not only do the methods allow exploration of the genome, they can also help elucidate the relationship between the cell and intracellular entities extant in nearly all eukaryotes. SCG enables the study of total eukaryotic cellular DNA, which in turn allows us to better understand the evolutionary history and diversity of life, and the physiological interactions that define complex organisms. This article is part of a discussion meeting issue ‘Single cell ecology’.
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Chin, Venessa T., James Conway, Adnan Nagrial, Lorraine A. Chantrill, Angela Chou, Angela Steinmann, Anthony Gill, et al. "Targeting the Rho-ROCK pathway to treat pancreatic cancer: The use of unique preclinical models to ascertain the effects on cancer growth and metastasis." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 312. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.312.
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312 Background: Pancreatic cancer (PC) is a highly lethal and genetically heterogenous disease. Genomic sequence data from the Australian Pancreatic Cancer Genome Initiative (APGI) has identified a subset of patients with ROCK-1 amplification. ROCK-1 is a downstream target of Rho, a small GTPase that plays an important role in regulating proliferation, invasion and metastasis of cancer cells. Our aim was to analyse the effects of inhibiting ROCK-1 using specific small molecule inhibitors (Fasudil and Y-27632) in well annotated and robust pre-clinical model systems generated as part of our APGI efforts. Methods: Patient derived cell lines (PDCL) and xenografts (PDX) were used to test the effectiveness of ROCK-1 inhibitors (RI). Colony formation and 3-D organotypic assays tested cellular proliferation and invasion. In vivo, pre-clinical trials assessed the effect gemcitabine (G) +/- RI on a range of PDXs with varying tumour ROCK expression, including one G resistant model. A PDCL shown to form metastases when injected orthotopically into mice has been labeled with firefly luciferase. The effect of RI on metastasis formation will be assessed in vivo using real time imaging. Results: ROCK inhibition has a differential effect on colony formation on PDCLs in vitro, and inhibits cellular invasion. A statistically significant increase in median survival in the G + RI group compared with G alone, was seen in 3 PDXs, including the G resistant tumour. 1 PDX showed a decrease in tumour size at 200 days in the G + RI group. Conclusions: ROCK inhibition has a differential effect in vitro, but an anti-tumour effect in vivo, including overcoming resistance to G. This suggests that effects on the tumour micro-environment are an important mechanism of action. RI have the potential to be an effective therapy in PC.
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Bajaj, Anubha. "The Flowing Cellule-Medullary Thyroid Carcinoma." Journal of Clinical and Biomedical Investigation 1, no. 1 (February 22, 2021): 1–4. http://dx.doi.org/10.52916/jcbi21404.
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Astroblastoma is an uncommon, controversial neoplasm of the Central Nervous System (CNS) emerging from the glia. “Astroblastoma” as a terminology was initially coined in 1924 for a tumefaction characteristically emerging as a unique astrocytic glioma comprised of tumour cells configuring perivascular pseudo-rosettes and appearing immune reactive to Glial Fibrillary Acidic Protein (GFAP). Bucy and Bailey in 1930 delineated diverse macroscopic and microscopic features of the neoplasm with description of individual astroblasts as unipolar cells with broad “feet” amalgamating adjacent to vascular articulations. Subsequently in 1933, Cox categorized astroblastoma as a neoplasm transitioning between astrocytoma and glioblastoma multiforme.
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Delahaye-Duriez, Andrée, Brigitte Benzacken, Michael Johnson, and Enrico Petretto. "Intégration des données de RNAseq sur cellule unique du cerveau." Morphologie 101, no. 335 (December 2017): 240–41. http://dx.doi.org/10.1016/j.morpho.2017.07.006.
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Senadeera, Wijitha, Jasmine Banks, Giuseppina Adiletta, and Kate Brewer. "Microstructural Approach Application for Morphological Change Determinations of Grapes during Drying." Processes 12, no. 4 (April 2, 2024): 720. http://dx.doi.org/10.3390/pr12040720.
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Grape dehydration is practiced widely in the food industry with large yields of sultanas produced globally. This paper proposes an investigation into the microstructure changes of grapes as they are dried by imaging specimens at intervals during dehydration at two temperatures using scanning electron microscopy. Two main methods were developed to obtain the complex boundaries of cells present in grape tissue in over 36 SEM images. Segmentation of the binary image using an adapted watershed function obtained the most consistent and accurate morphological shape. This was compared to a secondary method which used Canny’s edge detection function, morphological closing and skeletonizing to outline the cellular microstructure. MATLAB was utilised to convert these boundaries into measurable areas so that quantitative data on average cell area, perimeter and cell axis lengths were acquired. It was found that over the drying time, the cell area and perimeter were reduced as expected. Some variability in the data was clear due to only single samples being analysed for each temperature and time combination. Trends in cell perimeter, diameter and shape will be used to demonstrate relationships between morphological structure, drying temperature, and duration. Detailed images of the microstructure were obtained, and a unique image processing algorithm was developed to quantitatively analyse the properties of this microstructure. The development of automatic image processing techniques and algorithms will enable quantitative data to be extracted from any image and extend to any plant/food material.
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Ronzitti, Emiliano, Dimitrii Tanese, Alexis Picot, Benoît C. Forget, Valentina Emiliani, and Eirini Papagiakoumou. "Holographie numérique pour la photostimulation de circuits neuronaux." Photoniques, no. 92 (July 2018): 34–37. http://dx.doi.org/10.1051/photon/20189234.
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Le développement de techniques originales de manipulation de la lumière ont permis de grandes avancées dans le domaine de l’optogénétique. Elles permettent d’étudier et de stimuler la communication au sein des circuits neuronaux et du cerveau avec une précision spatiale et temporelle correspondant à l’activation d’une cellule unique au sein d’un circuit.
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PACH, JÁNOS, and GÁBOR TARDOS. "Conflict-Free Colourings of Graphs and Hypergraphs." Combinatorics, Probability and Computing 18, no. 5 (September 2009): 819–34. http://dx.doi.org/10.1017/s0963548309990290.
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A colouring of the vertices of a hypergraphHis calledconflict-freeif each hyperedgeEofHcontains a vertex of ‘unique’ colour that does not get repeated inE. The smallest number of colours required for such a colouring is called theconflict-free chromatic numberofH, and is denoted by χCF(H). This parameter was first introduced by Even, Lotker, Ron and Smorodinsky (FOCS2002) in ageometricsetting, in connection with frequency assignment problems for cellular networks. Here we analyse this notion for general hypergraphs. It is shown that$\chi_{\rm CF}(H)\leq 1/2+\sqrt{2m+1/4}$, for every hypergraph withmedges, and that this bound is tight. Better bounds of the order ofm1/tlogmare proved under the assumption that the size of every edge ofHis at least 2t− 1, for somet≥ 3. Using Lovász's Local Lemma, the same result holds for hypergraphs in which the size of every edge is at least 2t− 1 and every edge intersects at mostmothers. We give efficient polynomial-time algorithms to obtain such colourings.Our machinery can also be applied to the hypergraphs induced by the neighbourhoods of the vertices of a graph. It turns out that in this case we need far fewer colours. For example, it is shown that the vertices of any graphGwith maximum degree Δ can be coloured with log2+εΔ colours, so that the neighbourhood of every vertex contains a point of ‘unique’ colour. We give an efficient deterministic algorithm to find such a colouring, based on a randomized algorithmic version of the Lovász Local Lemma, suggested by Beck, Molloy and Reed. To achieve this, we need to (1) correct a small error in the Molloy–Reed approach, (2) restate and re-prove their result in adeterministicform.
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Quesada, Stanislas, and Philippe Jay. "De nouveaux types cellulaires identifiés par séquençage haut débit sur cellule unique." médecine/sciences 32, no. 5 (May 2016): 447–49. http://dx.doi.org/10.1051/medsci/20163205007.
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Katz-Jaffe, Mandy G., Donald W. Linck, William B. Schoolcraft, and David K. Gardner. "A proteomic analysis of mammalian preimplantation embryonic development." Reproduction 130, no. 6 (December 2005): 899–905. http://dx.doi.org/10.1530/rep.1.00854.
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Genetic studies on the mammalian preimplantation embryo are providing a wealth of information regarding gene expression. However, changes in the transcriptome do not always reflect cellular function or the complexity and diversity of the mammalian proteome with post-translational modifications or protein–protein interactions. To elucidate embryonic cellular function, a detailed understanding at the protein level is necessary. The aim of this study was to generate protein profiles of mammalian embryos throughout development, and to investigate the effects of oxygen concentration on the embryonic proteome. A protocol was developed to analyse small groups of embryos (n = 5) by time-of-flight mass spectrometry. F1 mice zygotes were cultured in G1/G2 sequential media with recombinant albumin (2.5 mg/ml) in 6% CO2 and O2 concentrations of either 5% or 20%. In vivo-developed embryos were flushed from the reproductive tract (day 4). Protein profiles were generated for all embryonic samples and statistical analysis revealed 32 potential proteins/biomarkers with significant changes (P < 0.05). Embryos generated under 5% O2 more closely resembled in vivo-developed embryos. Under 20% O2 conditions, embryos showed down-regulation of 10 proteins/biomarkers (masses between 4 to 20 kDa) (P < 0.05) confirming the pathological effects of oxygen during embryonic development. These data demonstrate for the first time the complexity of the mammalian preimplantation proteome. The unique protein profiles of in vivo-developed embryos and a panel of selected biomarkers represent optimal cellular function, against which comparisons can be made to facilitate improvements in mammalian assisted reproduction techniques procedures.
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FAVERDIN, P., and M. PICARD. "Dossier : Préhensibilité des aliments par les herbivores et les volailles - Avant-propos." INRAE Productions Animales 10, no. 5 (December 9, 1997): 375. http://dx.doi.org/10.20870/productions-animales.1997.10.5.4013.
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Le groupe "Ingestion" du Département Elevage et Nutrition des Animaux contribue, par des échanges interdisciplinaires, à une meilleure compréhension des facteurs de variation de la consommation alimentaire et à favoriser le développement de nouvelles méthodes de mesures qui puissent être appliquées à différents types d’élevages.
La palatabilité d’un aliment, analysée dans le dossier précédent (INRA Prod. Anim., 9, 337-366) dépend pour une large mesure de l’expérience alimentaire d’un animal. La mesure de la palatabilité pendant des tests de courte durée ne permet donc que difficilement de caractériser l’ingestibilité d’un aliment chez les animaux mono ou polygastriques.
Une prévision intégrée de la consommation peut être obtenue grâce à un modèle global comme celui proposé par Sauvant et al (réunion du groupe ingestion du 9-10-95). Au coeur de ce modèle, la bouchée (ou la becquée) représente l’acte élémentaire conduisant à l’ingestion. De durée comparable chez l’herbivore ruminant et chez le poulet granivore, il est le premier contact physique entre l’animal et l’aliment. A ce titre, il est apparu important au groupe "Ingestion" de dresser un état des connaissances sur cet acte central de la prise alimentaire.
Les organes qui permettent aux animaux de reconnaître et saisir de la nourriture sont adaptés depuis des millions d’années à des conditions environnementales complexes. "La connaissance de la nutrition peut masquer le fait que les animaux sont des nutritionnistes depuis que la première cellule assimila des nutriments et se reproduisit à la fin du précambrien, il y a quelques milliards d’années et que les herbivores paissent efficacement depuis 65 millions d’années sans l’assistance des hommes." (Provenza 1995 in: Ruminant Physiology, F. Enke Verlag (ed), Stuttgart (Deu), 233-247).
Les conditions d’élevage placent aujourd’hui l’animal dans des situations différentes selon le type de production. Dans ce dossier deux situations opposées sont décrites. Les conditions hétérogènes du parcours étudiées par Michel Meuret imposent une gestion spatio-temporelle optimale des ressources disponibles. A l’autre extrême les volailles reçoivent un aliment unique dans un environnement simplifié analysé par Michel Picard et al. Entre ces deux situations il existe une communauté d’approche méthodologique que Sophie Prache et Jean-Louis Peyraud illustrent en analysant d’abord la préhension de l’herbe par les ruminants. Au-delà des mécanismes physiologiques de régulation et malgré les particularités de chacune des espèces animales, ces articles montrent qu’il est important de ne pas négliger les aspects de structure et de spatialisation des aliments dans le déterminisme de la prise alimentaire.
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Schwarzwaelder, Kerstin, Manfred Schmidt, Annette Deichmann, Steven J. Howe, Marion G. Ott, Stefan Stein, Ulrich Siler, et al. "The Clonal Inventory of Gene Corrected Hematopoiesis in Three Successful Clinical Gene Therapy Trials." Blood 110, no. 11 (November 16, 2007): 3733. http://dx.doi.org/10.1182/blood.v110.11.3733.3733.
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Abstract To enhance the safety and efficacy of future gene therapy trials using integrating vector systems it is necessary to analyse the clonality of the genetically modified cell pool. The comparative analyses of integration site distribution and cellular gene expression will further reveal causal mechanisms of in vivo clone selection. We followed the repopulation clonality of 21 patients which participated in 3 successful clinical gene therapy trials via linear amplification mediated PCR (LAM PCR). We identified the integration sites (IS) of pre and post transplantation samples by Sanger sequencing and accomplished RNA analyses. The comparative results from all trials showed that vector integration is favoured in gene coding regions, in particular transcriptional start sites. In both X-SCID trials significantly more post transplantation IS were located in or in the vicinity of genes encoding proteins with kinase or transferase activity. In pre transplantation samples no uniform gene class was overrepresented. In both trials we detected common insertion sites mainly post transplantation and the effect was more pronounced in the trial where 4 patients developed vector induced leukemia. Notably, we detected no significant differences regarding the IS distribution in leukemic versus non leukemic patients. The gene corrected repopulation of patient 1 and 2 of the X-CGD trial was polyclonal until 542 and 777 days after transplantation, respectively. 5 months after therapy dominant clones appeared. In patient 1, between 616 and 820 days post transplantation (post mortem time point) the number of participating clones and the contribution of a dominant clone decreased while the contribution of another dominant clone increased. In both patients the integrated vector induced the upregulation of the genes MDS1/EVI1, PRDM16 or SETBP1 and thus led to the in vivo expansion of affected cell clones. From these trials we sequenced >2000 unique IS by Sanger sequencing and several thousand via pyrosequencing (datamining is ongoing). Our data show that the integration site distribution was non random, that the integrated vector influenced the cellular gene expression which caused subtle to massive changes in the repopulation clonality and that it will soon be possible to define the clonal inventory of patients using next generation sequencing technologies.
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Monneau, Yoan R., Lingjie Luo, Nehru Viji Sankaranarayanan, Balaji Nagarajan, Romain R. Vivès, Françoise Baleux, Umesh R. Desai, Fernando Arenzana-Seidedos, and Hugues Lortat-Jacob. "Solution structure of CXCL13 and heparan sulfate binding show that GAG binding site and cellular signalling rely on distinct domains." Open Biology 7, no. 10 (October 2017): 170133. http://dx.doi.org/10.1098/rsob.170133.
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Chemokines promote directional cell migration through binding to G-protein-coupled receptors, and as such are involved in a large array of developmental, homeostatic and pathological processes. They also interact with heparan sulfate (HS), the functional consequences of which depend on the respective location of the receptor- and the HS-binding sites, a detail that remains elusive for most chemokines. Here, to set up a biochemical framework to investigate how HS can regulate CXCL13 activity, we solved the solution structure of CXCL13. We showed that it comprises an unusually long and disordered C-terminal domain, appended to a classical chemokine-like structure. Using three independent experimental approaches, we found that it displays a unique association mode to HS, involving two clusters located in the α-helix and the C-terminal domain. Computational approaches were used to analyse the HS sequences preferentially recognized by the protein and gain atomic-level understanding of the CXCL13 dimerization induced upon HS binding. Starting with four sets of 254 HS tetrasaccharides, we identified 25 sequences that bind to CXCL13 monomer, among which a single one bound to CXCL13 dimer with high consistency. Importantly, we found that CXCL13 can be functionally presented to its receptor in a HS-bound form, suggesting that it can promote adhesion-dependent cell migration. Consistently, we designed CXCL13 mutations that preclude interaction with HS without affecting CXCR5-dependent cell signalling, opening the possibility to unambiguously demonstrate the role of HS in the biological function of this chemokine.
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Mikaelsson, Eva, Mahmood Jeddi-Tehrani, Anders ÖSterborg, Fazel Shokri, Hodjattallah Rabbani, and Håkan Mellstedt. "Small Leucine Rich Proteoglycans as Novel Tumor Markers In Chronic Lymphocytic Leukemia." Blood 116, no. 21 (November 19, 2010): 694. http://dx.doi.org/10.1182/blood.v116.21.694.694.
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Abstract Abstract 694 Background: Small leucine rich proteoglycans (SLRPs) are a family of glycosylated proteins normally expressed in the extracelluar matrix (ECM) of collagen rich tissues. The biological role of the SLRPs is multifactoral, but mostly these proteins are secreted and bind to membrane receptors or ECM proteins affecting cell proliferation and cell migration. Some SLRPs (eg. Decorin, Lumican) have been reported to be expressed in cancer, but the expression as well as the glycosylation pattern differ. Microarray studies have revealed that the SLRP family member fibromodulin (FMOD) gene is overexpressed in chronic lymphocytic leukemia (CLL). We later reported the specific expression of FMOD in CLL and mantle cell lymphoma (MCL). FMOD is located on chromosome 1q32 adjacent to two other members of the SLRP family, proline/arginine-rich end leucine-rich repeat protein (PRELP) and opticin (OPTC). Aims: To analyse 1) the expression of PRELP and OPTC in CLL and other hematological malignancies. 2) the glycosylation pattern of PRELP and OPTC, and cellular localization of OPTC in CLL cells. Methods: PRELP: Gene expression was tested by RT-PCR and realtime-PCR. Protein expression was tested by western blot. Chemical deglycosylation was performed to characterize the glycosylation pattern of the PRELP protein. OPTC: Cell fractionation was performed using four different methods. Protein expression (molecular weight and cellular location) was tested by western blot. Chemical deglycosylation was performed to characterize the glycosylation pattern of the OPTC protein. Results: PRELP was expressed at the gene level (RT-PCR) in all CLL patients tested (n=30) and in 3/5 patients with mantle cell lymphoma, but not in normal leukocytes (n=10) or in other hematological malignancies (7 different types, n=35). The PRELP protein was detected in all CLL samples tested but not in leukocytes of healthy donors (western blot). Molecular analysis of the CLL PRELP protein revealed a unique unglycosylated 38 kDa core protein, with an intact signal peptide. This protein was not detected in serum that, in combination with the uncleaved signal peptide, suggests cellular retention. A “normal” OPTC protein (50 kDa) was detected in cell lysates of both CLL tumor cells (n=30) and normal leukocytes (n=10). However, the CLL cells also expressed a 37 kDa OPTC that was not detected in healthy controls. This 37 kDa OPTC was detected in all CLL samples and molecular analysis revealed a unique unglycosylated core protein that was located in the cell nucleus and endoplasmatic reticulum of the CLL cells. Conclusion: The unique expression of the SLRPs PRELP and OPTC in CLL (in addition to the previously reported FMOD) is unexpected and merits further studies since the specific expression of three closely related SLRP genes may indicate a role in the pathobiology of the disease. Disclosures: No relevant conflicts of interest to declare.
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Torres, Adrian Gabriel. "Enjoy the Silence: Nearly Half of Human tRNA Genes Are Silent." Bioinformatics and Biology Insights 13 (January 2019): 117793221986845. http://dx.doi.org/10.1177/1177932219868454.
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Transfer RNAs (tRNAs) are key components of the translation machinery. They read codons on messenger RNAs (mRNAs) and deliver the appropriate amino acid to the ribosome for protein synthesis. The human genome encodes more than 500 tRNA genes but their individual contribution to the cellular tRNA pool is unclear. In recent years, novel methods were developed to improve the quantification of tRNA gene expression, most of which rely on next-generation sequencing such as small RNA-Seq applied to tRNAs (tRNA-Seq). In a previous study, we presented a bioinformatics strategy to analyse tRNA-Seq datasets that we named ‘isodecoder-specific tRNA gene contribution profiling’ (Iso-tRNA-CP). Using Iso-tRNA-CP, we showed that tRNA gene expression is cell type- and tissue-specific and that this process can regulate tRNA-derived fragments abundance. An additional observation that stems from that work is that approximately half of human tRNA genes appeared silent or poorly expressed. In this commentary, I discuss this finding in light of the current literature and speculate on potential functions that transcriptionally silent tRNA genes may play. Studying silent tRNA genes may offer a unique opportunity to unravel novel mechanisms of cell regulation associated to tRNA biology.
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Melekhova, Anna, Mirjam Leeder, Thanakorn Pungsrinont, Tim Schmäche, Julia Kallenbach, Marzieh Ehsani, Kimia Mirzakhani, Seyed Mohammad Mahdi Rasa, Francesco Neri, and Aria Baniahmad. "A Novel Splice Variant of the Inhibitor of Growth 3 Lacks the Plant Homeodomain and Regulates Epithelial–Mesenchymal Transition in Prostate Cancer Cells." Biomolecules 11, no. 8 (August 4, 2021): 1152. http://dx.doi.org/10.3390/biom11081152.
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Inhibitor of growth 3 (ING3) is one of five members of the ING tumour suppressor family, characterized by a highly conserved plant homeodomain (PHD) as a reader of the histone mark H3K4me3. ING3 was reported to act as a tumour suppressor in many different cancer types to regulate apoptosis. On the other hand, ING3 levels positively correlate with poor survival prognosis of prostate cancer (PCa) patients. In PCa cells, ING3 acts rather as an androgen receptor (AR) co-activator and harbours oncogenic properties in PCa. Here, we show the identification of a novel ING3 splice variant in both the human PCa cell line LNCaP and in human PCa patient specimen. The novel ING3 splice variant lacks exon 11, ING3∆ex11, which results in deletion of the PHD, providing a unique opportunity to analyse functionally the PHD of ING3 by a natural splice variant. Functionally, overexpression of ING3Δex11 induced morphological changes of LNCaP-derived 3D spheroids with generation of lumen and pore-like structures within spheroids. Since these structures are an indicator of epithelial–mesenchymal transition (EMT), key regulatory factors and markers for EMT were analysed. The data suggest that in contrast to ING3, ING3Δex11 specifically modulates the expression of key EMT-regulating upstream transcription factors and induces the expression of EMT markers, indicating that the PHD of ING3 inhibits EMT. In line with this, ING3 knockdown also induced the expression of EMT markers, confirming the impact of ING3 on EMT regulation. Further, ING3 knockdown induced cellular senescence via a pathway leading to cell cycle arrest, indicating an oncogenic role for ING3 in PCa. Thus, the data suggest that the ING3Δex11 splice variant lacking functional PHD exhibits oncogenic characteristics through triggering EMT in PCa cells.
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Privat-Maldonado, Angela, Charlotta Bengtson, Jamoliddin Razzokov, Evelien Smits, and Annemie Bogaerts. "Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments." Cancers 11, no. 12 (December 2, 2019): 1920. http://dx.doi.org/10.3390/cancers11121920.
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Tumours are complex systems formed by cellular (malignant, immune, and endothelial cells, fibroblasts) and acellular components (extracellular matrix (ECM) constituents and secreted factors). A close interplay between these factors, collectively called the tumour microenvironment, is required to respond appropriately to external cues and to determine the treatment outcome. Cold plasma (here referred as ‘plasma’) is an emerging anticancer technology that generates a unique cocktail of reactive oxygen and nitrogen species to eliminate cancerous cells via multiple mechanisms of action. While plasma is currently regarded as a local therapy, it can also modulate the mechanisms of cell-to-cell and cell-to-ECM communication, which could facilitate the propagation of its effect in tissue and distant sites. However, it is still largely unknown how the physical interactions occurring between cells and/or the ECM in the tumour microenvironment affect the plasma therapy outcome. In this review, we discuss the effect of plasma on cell-to-cell and cell-to-ECM communication in the context of the tumour microenvironment and suggest new avenues of research to advance our knowledge in the field. Furthermore, we revise the relevant state-of-the-art in three-dimensional in vitro models that could be used to analyse cell-to-cell and cell-to-ECM communication and further strengthen our understanding of the effect of plasma in solid tumours.
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Garcia-Dominguez, Amabel, Alvaro Rodríguez-Prieto, Jorge Ayllón, Juan Claver, Juan Rodríguez-Hernández, and Ana Maria Camacho. "The Effect of Design and Fabrication Parameters on the Mechanical Properties of 3D Re-Entrant Honeycomb Auxetic Structures." Key Engineering Materials 958 (October 5, 2023): 131–38. http://dx.doi.org/10.4028/p-ur2mqn.
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In recent years, the potential of application of auxetic structures, with negative Poisson's ratio, is gaining interest due to the increasingly widespread use of additive manufacturing. Additive technologies allow the manufacture of lightweight and complex shapes, and among them, auxetic cellular three-dimensional structures stand out for their unique behavior and with applications of interest in fields such as aerospace, medical or construction engineering. In the present work, 3D re-entrant honeycomb auxetic structures are designed and manufactured with Stereolithography (SLA) and Fused Filament Fabrication (FFF) with different geometrical parameters to analyse their impact in the mechanical behaviour of these complex structures. To this aim, an Ultimaker S5 and a Formlabs Form3 printer, respectively, have been used. Design variations are approached considering the following parameters: the length of the vertical strut (H), the length of the re-entrant strut (L), the re-entrant angle between the re-entrant and the vertical strut (θ) and the diameter of the struts cross sections (d). The designed structures shape behavior is evaluated with mechanical tests including compression tests and digital image correlation technique, and numerical simulations, The results show that lower Poisson ratio’s values are identified with slimmer profiles and with higher effective lengths and, therefore, corresponds to slender struts. On the other hand, lower angles between vertical and oblique struts show lower Poisson ratios, associated to the load distribution and its effect on the structure’s node displacements.
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Domsicova, Michaela, Jana Korcekova, Alexandra Poturnayova, and Albert Breier. "New Insights into Aptamers: An Alternative to Antibodies in the Detection of Molecular Biomarkers." International Journal of Molecular Sciences 25, no. 13 (June 21, 2024): 6833. http://dx.doi.org/10.3390/ijms25136833.
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Aptamers are short oligonucleotides with single-stranded regions or peptides that recently started to transform the field of diagnostics. Their unique ability to bind to specific target molecules with high affinity and specificity is at least comparable to many traditional biorecognition elements. Aptamers are synthetically produced, with a compact size that facilitates deeper tissue penetration and improved cellular targeting. Furthermore, they can be easily modified with various labels or functional groups, tailoring them for diverse applications. Even more uniquely, aptamers can be regenerated after use, making aptasensors a cost-effective and sustainable alternative compared to disposable biosensors. This review delves into the inherent properties of aptamers that make them advantageous in established diagnostic methods. Furthermore, we will examine some of the limitations of aptamers, such as the need to engage in bioinformatics procedures in order to understand the relationship between the structure of the aptamer and its binding abilities. The objective is to develop a targeted design for specific targets. We analyse the process of aptamer selection and design by exploring the current landscape of aptamer utilisation across various industries. Here, we illuminate the potential advantages and applications of aptamers in a range of diagnostic techniques, with a specific focus on quartz crystal microbalance (QCM) aptasensors and their integration into the well-established ELISA method. This review serves as a comprehensive resource, summarising the latest knowledge and applications of aptamers, particularly highlighting their potential to revolutionise diagnostic approaches.
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Morgan, V., and W. Macafee. "Household and family size and structure in County Antrim in the mid-nineteenth century." Continuity and Change 2, no. 3 (December 1987): 455–76. http://dx.doi.org/10.1017/s0268416000000734.
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Une analyse informatique des Relevés des Recenseurs résultant du recensement de l'lrlande en 1851, pour certaines parties du Comté d'Antrim, suggère que la grandeur des mènages et des families était légèrement plus élevée qu'en Angleterre pour la même période, mais qu' il existait des variations considérables selon les localités. Un rapport étroit entre la taille des ménages et le statut socio-économique semble être confirmé par l'étude des trés grands et des trés petits ménages. Les parents résidents n'appartenant pas à la cellule familiale à deux génêrations ont été dénombrés parmi un quart et un tiers de tous les ménages et il existait des omestiques logés chez les families dans un tiers des ménages au maximum.
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Debry, Laura, and Marjolijn Debulpaep. "Assurer une nouvelle vie pour le carton de tapisserie de Pieter Coecke van Aelst." Studia Bruxellae N° 11, no. 1 (August 24, 2019): 275–96. http://dx.doi.org/10.3917/stud.011.0275.
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Le Musée de la Ville de Bruxelles souhaite améliorer les conditions d’exposition du carton de tapisserie de Pieter Coecke van Aelst après sa restauration. La cellule de conservation préventive de l’IRPA y a mené, de concert avec le personnel, une analyse des risques et le relevé des mesures nécessaires (lumière, climat, poussières, vibrations) afin d’assurer les meilleures conditions de conservation et d’exposition de l’œuvre après sa restauration. Le carton de tapisserie a pu ainsi être exposé dans une vitrine adaptée et un environnement sécurisé assurant une protection optimale face aux agents de détérioration menaçant sa stabilité, ses composants et sa valeur esthétique. L’article recense les risques, les relevés des mesures et des recommandations. Il reprend la démarche suivie entre les différents acteurs soucieux d’offrir au public une rencontre avec le carton en garantissant sa préservation dans le futur.
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Epp, Robert, Chaim Glück, Nadine Felizitas Binder, Mohamad El Amki, Bruno Weber, Susanne Wegener, Patrick Jenny, and Franca Schmid. "The role of leptomeningeal collaterals in redistributing blood flow during stroke." PLOS Computational Biology 19, no. 10 (October 23, 2023): e1011496. http://dx.doi.org/10.1371/journal.pcbi.1011496.
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Leptomeningeal collaterals (LMCs) connect the main cerebral arteries and provide alternative pathways for blood flow during ischaemic stroke. This is beneficial for reducing infarct size and reperfusion success after treatment. However, a better understanding of how LMCs affect blood flow distribution is indispensable to improve therapeutic strategies. Here, we present a novel in silico approach that incorporates case-specific in vivo data into a computational model to simulate blood flow in large semi-realistic microvascular networks from two different mouse strains, characterised by having many and almost no LMCs between middle and anterior cerebral artery (MCA, ACA) territories. This framework is unique because our simulations are directly aligned with in vivo data. Moreover, it allows us to analyse perfusion characteristics quantitatively across all vessel types and for networks with no, few and many LMCs. We show that the occlusion of the MCA directly caused a redistribution of blood that was characterised by increased flow in LMCs. Interestingly, the improved perfusion of MCA-sided microvessels after dilating LMCs came at the cost of a reduced blood supply in other brain areas. This effect was enhanced in regions close to the watershed line and when the number of LMCs was increased. Additional dilations of surface and penetrating arteries after stroke improved perfusion across the entire vasculature and partially recovered flow in the obstructed region, especially in networks with many LMCs, which further underlines the role of LMCs during stroke.
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Lacoux, C., M. Truchi, J. Fassy, I. Manosalva-Pena, M. Gautier, V. Magnone, K. Lebrigand, et al. "Analyse des longs ARN non codants régulés par l’hypoxie dans les cellules d’adénocarcinome pulmonaire à l’aide d’un crible basé sur l’interférence CRISPR sur cellules uniques." Revue des Maladies Respiratoires 40, no. 2 (February 2023): 122–23. http://dx.doi.org/10.1016/j.rmr.2022.11.029.
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Mathieu, Maxime, Amandine Girousse, and Coralie Sengenès. "Et si l’origine des progéniteurs fibro-adipeux contribuait à leur hétérogénéité dans le muscle ?" médecine/sciences 39 (November 2023): 15–21. http://dx.doi.org/10.1051/medsci/2023129.
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Les progéniteurs fibro-adipogéniques (FAPs), cellules stromales mésenchymateuses (CSMs) résidentes du muscle squelettique, jouent un rôle crucial dans l’homéostasie et la régénération musculaire via leur activité paracrine. Les avancées technologiques récentes dans le domaine du séquençage de l’ARN en cellule unique ont permis la description de l’hétérogénéité de cette population cellulaire. Dans cet article, nous présenterons les différentes sous-populations de FAPs en condition basale, lésionnelle ou de dégénérescence, ainsi que leurs fonctions associées chez la souris et l’homme. Nous discuterons ensuite de l’origine extra-musculaire possible d’une population de FAPs post-lésionnelle. En effet, nos travaux récents démontrent que des CSMs provenant du tissu adipeux et infiltrées dans le muscle pourraient participer à l’hétérogénéité des FAPs.
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Deng, Yanxiang, Amanda Finck, and Rong Fan. "Single-Cell Omics Analyses Enabled by Microchip Technologies." Annual Review of Biomedical Engineering 21, no. 1 (June 4, 2019): 365–93. http://dx.doi.org/10.1146/annurev-bioeng-060418-052538.
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Single-cell omics studies provide unique information regarding cellular heterogeneity at various levels of the molecular biology central dogma. This knowledge facilitates a deeper understanding of how underlying molecular and architectural changes alter cell behavior, development, and disease processes. The emerging microchip-based tools for single-cell omics analysis are enabling the evaluation of cellular omics with high throughput, improved sensitivity, and reduced cost. We review state-of-the-art microchip platforms for profiling genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multi-omics at single-cell resolution. We also discuss the background of and challenges in the analysis of each molecular layer and integration of multiple levels of omics data, as well as how microchip-based methodologies benefit these fields. Additionally, we examine the advantages and limitations of these approaches. Looking forward, we describe additional challenges and future opportunities that will facilitate the improvement and broad adoption of single-cell omics in life science and medicine.
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Tsekhmistrenko, S. I., V. S. Bityutskyy, O. S. Tsekhmistrenko, L. P. Horalskyi, N. O. Tymoshok, and M. Y. Spivak. "Bacterial synthesis of nanoparticles: A green approach." Biosystems Diversity 28, no. 1 (March 2, 2020): 9–17. http://dx.doi.org/10.15421/012002.
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In recent decades, the attention of scientists has been drawn towards nanoparticles (NPs) of metals and metalloids. Traditional methods for the manufacturing of NPs are now being extensively studied. However, disadvantages such as the use of toxic agents and high energy consumption associated with chemical and physical processes impede their continued use in various fields. In this article, we analyse the relevance of the use of living systems and their components for the development of "green" synthesis of nano-objects with exceptional properties and a wide range of applications. The use of nano-biotechnological methods for the synthesis of nanoparticles has the potential of large-scale application and high commercial potential. Bacteria are an extremely convenient target for green nanoparticle synthesis due to their variety and ability to adapt to different environmental conditions. Synthesis of nanoparticles by microorganisms can occur both intracellularly and extracellularly. It is known that individual bacteria are able to bind and concentrate dissolved metal ions and metalloids, thereby detoxifying their environment. There are various bacteria cellular components such as enzymes, proteins, peptides, pigments, which are involved in the formation of nanoparticles. Bio-intensive manufacturing of NPs is environmentally friendly and inexpensive and requires low energy consumption. Some biosynthetic NPs are used as heterogeneous catalysts for environmental restoration, exhibiting higher catalytic efficiency due to their stability and increased biocompatibility. Bacteria used as nanofactories can provide a new approach to the removal of metal or metalloid ions and the production of materials with unique properties. Although a wide range of NPs have been biosynthetic and their synthetic mechanisms have been proposed, some of these mechanisms are not known in detail. This review focuses on the synthesis and catalytic applications of NPs obtained using bacteria. Known mechanisms of bioreduction and prospects for the development of NPs for catalytic applications are discussed.
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Besley, Caroline Mary, Eleni Kotsiou, Robert Petty, Ajanthah Sangaralingum, Rifca Le Dieu, John G. Gribben, and Jeff K. Davies. "Lenalidomide Enhances Human Alloresponses By Increasing Proliferation of Effector Memory CD8 T Cells with Enhanced Polyfunctional Effector Capacity and a Unique Gene Expression Profile." Blood 124, no. 21 (December 6, 2014): 1103. http://dx.doi.org/10.1182/blood.v124.21.1103.1103.
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Abstract Introduction IMiDs like lenalidomide have immunostimulatory effects and therefore the potential to reduce relapse after allogeneic haematopoietic cell transplant (AHCT) by increasing graft-versus-tumour (GvT) effects. However, early clinical experience using IMiDs after AHCT has been limited by induction of graft-versus-host disease (GvHD). Although lenalidomide has been shown to augment mitogen-stimulated T cell responses, the effects of this drug on T cell alloresponses that mediate both GvT and GvHD have not been well defined. Better understanding of the immune mechanisms involved would facilitate tracking and manipulation of lenalidomide-potentiated alloresponses and could reveal ways to use the drug to maximise GvT without excess GvHD. Therefore we used an HLA-mismatched in vitro model to analyse in depth the effects of lenalidomide on functional human T cell alloresponses. Materials and Methods We cocultured CFSE-labelled PBMC from healthy donors with irradiated allogeneic PBMC in the presence of 1μM lenalidomide, vehicle control or following pre-incubation with 1μM lenalidomide for 24 hours. Functional alloresponses were quantified after 7-9 days of allo-coculture by flow cytometry. In addition, allo-coculture responders were flow-sorted into alloproliferative or non-proliferative fractions and extracted RNA used for gene expression profiling. Results Addition of lenalidomide to allo-cocultures increased the total number of responder cells (p<0.001) due primarily to increased proliferation (74% median increase) of allospecific responder CD8 (alloCD8) T cells (p<0.001). Proliferation kinetic analysis showed that lenalidomide did not increase the number of cell divisions of alloCD8 cells, but increased the CD8 allospecific precursor frequency within the responder cell pool (from a median of 2.6% to 10%, p<0.001) consistent with lowering the activation threshold of alloCD8 cells. A significant enrichment for effector memory phenotype was observed in these cells (median 48% increased to 59%, p<0.001). Addition of lenalidomide to allo-cocultures also increased the proportion of alloCD8 cells secreting TNF-α, IFN-γ and expressing CD107a, as well as polyfunctional effector cells (Fig. 1A). Although lenalidomide did not increase proliferation of CD4 cells, TNF-α production by proliferative CD4 T cells was increased suggesting they may contribute indirectly to CD8 alloresponses. Pre-treatment of stimulators, responders or both prior to allo-coculture did not result in increased alloCD8 proliferation, indicating that the drug must be present in the co-culture to exert an effect. Finally to assess whether lenalidomide exerted effects via potentiation of intrinsic alloproliferative pathways or by qualitatively different pathways we performed gene expression profiling of CD8 T cells sorted from allo-cocultures. As expected, alloCD8 cells from untreated allo-cocultures demonstrated >2-fold altered expression of >500 genes mostly associated with DNA synthesis and cellular proliferation when compared to non-proliferative CD8 cells. Lenalidomide-treated alloCD8 cells showed further increases in expression of many of these genes; however treatment also resulted in significant changes in expression of additional genes in alloCD8 cells compared to untreated alloCD8 cells (Fig 1B). These included >8 fold increases in expression of genes reported to potentiate T cell immune responses in other settings including PFKFB4,Pirin, and SOCS2 (part of the E3 ubiquitin ligase complex with cereblon), and >5 fold decreases in genes which can suppress T cell activation and memory differentiation including FAIM3 and PMCH. Conclusion We have shown for the first time that lenalidomide potentiates human alloresponses primarily by increasing alloproliferation of effector memory CD8 T cells. This likely results from altered expression of (i) multiple genes common to the intrinsic CD8 alloproliferative response and (ii) additional genes involved in the control of T cell activation and differentiation specific to lenalidomide-potentiated CD8 alloresponses. Furthermore treatment enhances the functional capacity of these cells by conferring greater polyfunctional effector potential. These findings could enable tracking of CD8 alloresponses induced by lenalidomide after AHCT and could inform novel clinical strategies for the use of the drug to augment GvT effects. Figure 1 Figure 1. Disclosures Gribben: Celgene: Research Funding; Pharmacyclics: Honoraria; Roche: Honoraria.
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Rapoport *, Benoît. "Famille nucléaire et accueil de parents dans les ménages urbains au Gabon." Cahiers québécois de démographie 31, no. 1 (November 28, 2002): 151–82. http://dx.doi.org/10.7202/000427ar.
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RésuméPour analyser le phénomène d’accueil de parents dans les ménages africains librevillois et port-gentillais (Gabon), nous utilisons ici une enquête budget et consommation réalisée en 1994. Nous montrons que la population se regroupe en ménages de taille relativement importante, habituellement construits autour d’une seule source de revenu, et que les structures complexes sont très rares. La cellule familiale nucléaire ne représente que les trois quarts des membres du ménage, mais le ménage n’est élargi qu’aux frères, aux soeurs et à leurs enfants. Ces accueillis sont généralement moins âgés que le chef de ménage. Les jeunes accueillis sont généralement scolarisés, et les plus âgés sont souvent inactifs. Une analyse multivariée indique que ce sont essentiellement les caractéristiques observables du chef de ménage, du ménage nucléaire et du logement qui déterminent l’accueil et que, une fois ces facteurs pris en compte, le revenu, soit n’a plus d’effet, soit a un effet négatif, sur la décision d’accueil et le nombre de parents hébergés.
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Eidinejad, Zahra, Reza Saadati, and Dušan D. Repovš. "Mittag-Leffler Stability and Attractiveness of Pseudo Almost Periodic Solutions for Delayed Cellular Neural Networks." Journal of Function Spaces 2022 (October 11, 2022): 1–15. http://dx.doi.org/10.1155/2022/3186963.
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We consider a class of nonautonomous cellular neural networks (CNNs) with mixed delays, to study the solutions of these systems which are type pseudo almost periodicity. Using general measure theory and the Mittag-Leffler function, we obtain the existence of unique solutions for cellular neural equations and investigate the Mittag-Leffler stability and attractiveness of pseudo almost periodic functions. We also present numerical examples to illustrate the application of our results.
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Hisamatsu, Daisuke, Akari Ikeda, Lisa Ito, Yasushi Matsushita, Makoto Hiki, Hirotake Mori, Yoko Tabe, Toshio Naito, and Chihiro Akazawa. "Longitudinal Analyses after COVID-19 Recovery or Prolonged Infection Reveal Unique Immunological Signatures after Repeated Vaccinations." Vaccines 10, no. 11 (October 28, 2022): 1815. http://dx.doi.org/10.3390/vaccines10111815.
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To develop preventive and therapeutic measures against coronavirus disease 2019, the complete characterization of immune response and sustained immune activation following viral infection and vaccination are critical. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals. We evaluated the serum levels of 29 cytokines and their correlation with neutralizing antibody titer. We investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants, and in vaccinated individuals. Longitudinal correlation analyses revealed that post-vaccination neutralizing potential was more strongly associated with various serum cytokine levels in recovered patients than in naïve individuals. We found that IL-10, CCL2, CXCL10, and IL-12p40 are candidate biomarkers of serum-neutralizing antibody titer after the vaccination of recovered individuals. We found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for 1 year. Thus, distinct immune responses occur depending on the viral strain and clinical history, suggesting that therapeutic options should be selected on a case-by-case basis. Candidate biomarkers that correlate with repeated vaccination may support the efficacy and safety evaluation systems of mRNA vaccines and lead to the development of novel vaccine strategies.
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Jouanno, Aubrie. "Un mandat de surveillance étendu. Une analyse des effets de la pauvreté sur la surexposition au signalement à la maternité et à l’école." Revue française des affaires sociales, no. 3 (December 5, 2023): 49–72. http://dx.doi.org/10.3917/rfas.233.0049.
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Depuis les années 1980, la politique de protection de l’enfance s’est orientée vers le repérage des situations de maltraitance par des campagnes de sensibilisation et le développement de nouveaux canaux d’interpellation des pouvoirs publics. À partir d’une enquête quantitative et qualitative reposant sur l’ensemble des informations préoccupantes (IP) et signalements transmis aux services de protection de l’enfance parisiens entre 2017 et 2020 (n = 19 599) et la lecture de dossiers de la Cellule de recueil des informations préoccupantes de Paris (n = 66), cet article montre que l’élargissement du repérage des enfants en danger a participé à renforcer la vigilance autour des familles les plus pauvres. Alors que les travaux de Delphine Serre ont mis en évidence l’encadrement spécifique de la parentalité auquel les familles assistées sont soumises (Serre, 2009), cet article montre que la massification de l’encadrement sanitaire des grossesses d’une part et de la scolarisation d’autre part ont participé, quant à eux, à imposer des attentes sociales fortes autour de l’enfant auxquelles certaines familles pauvres peinent à répondre.
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Serek-Heuberger, Justyna, Cédric F. V. Hobel, Stanislaw Dunin-Horkawicz, Beate Rockel, Jörg Martin, and Andrei N. Lupas. "Two unique membrane-bound AAA proteins from Sulfolobus solfataricus." Biochemical Society Transactions 37, no. 1 (January 20, 2009): 118–22. http://dx.doi.org/10.1042/bst0370118.
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Thermoacidophilic crenarchaea of the genus Sulfolobus contain six AAA (ATPase associated with various cellular activities) proteins, including a proteasome-associated ATPase, a Vps4 (vacuolar protein sorting 4) homologue, and two Cdc48 (cell-division cycle 48)-like proteins. The last two AAA proteins are deeply branching divergent members of this family without close relatives outside the Sulfolobales. Both proteins have two nucleotide-binding domains and, unlike other members of the family, they seem to lack folded N-terminal domains. Instead, they contain N-terminal extensions of approx. 50 residues, which are predicted to be unstructured, except for a single transmembrane helix. We have analysed the two proteins, MBA (membrane-bound AAA) 1 and MBA2, by computational and experimental means. They appear to be monophyletic and to share a common ancestor with the Cdc48 clade. Both are membrane-bound and active as nucleotidases upon heterologous expression in Escherichia coli. They form ring complexes, which are stable after solubilization in a mild detergent and whose formation is dependent on the presence of the N-terminal extensions.
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BOMBERT, C., M. CHAUFER, J. BOISSIER, and L. RICHECŒUR. "Opération « Serval » : intérêt du « Patient evacuation coordination cell »." Médecine et Armées Vol. 43 No. 4, Volume 43, Numéro 4 (October 1, 2015): 325–29. http://dx.doi.org/10.17184/eac.6893.
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Projetée trois semaines après le lancement de l’opération, la cellule de coordination et d’évacuation de blessés est un maillon incontournable du soutien santé du théâtre. L’immensité du territoire malien, l’entrée en premier, mais également la dureté des combats associée à une rusticité des conditions de vie, ont constitué autant de défis pour le personnel du Service de santé des armées projeté sur place. Le flux des blessés dans les premières semaines, le faible nombre de vecteurs aériens et le point unique d’évacuation vers la métropole ont bien démontré l’impérieuse nécessité d’une régulation des demandes d’évacuation médicale associée à un suivi des patients en temps réel. Nous proposons de décrire cet outil projeté pour la deuxième fois sur un théâtre et qui fait partie intégrante de la chaîne du soutien médical en opération extérieure mais aussi de la chaîne de conduite des opérations.
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Crampsie, Shauna, Ilon Liu, Lucia Lisa Petrilli, Alan Mackay, Giulio Spinozzi, Yura Grabovska, Olivia A. Hack, et al. "HGG-17. SINGLE-CELL AND SPATIAL ANALYSES DECIPHER THE UNIQUE INVASIVE GROWTH PATTERN OF GLIOMATOSIS CEREBRI." Neuro-Oncology 25, Supplement_1 (June 1, 2023): i42—i43. http://dx.doi.org/10.1093/neuonc/noad073.166.
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Abstract Gliomatosis cerebri (GC) is a rare, lethal glioma that is radiologically diagnosed and characterised by its diffuse infiltration throughout the cerebral lobes of the brain. It is no longer recognised as a separate entity by the WHO classification, but its growth pattern and invasive phenotype differ from other types of glioma. In order to understand what underlies this unique presentation, we sought to unravel these complex tumours in children through single cell and spatial approaches. 26 paediatric cases (1.3-19 years, median=11.3) were collected for DNA methylation, whole exome sequencing and single cell RNA-sequencing. Of these, 16 cases were used for Imaging Mass Cytometry (IMC). 5 patient-derived cell lines were used to model migration and invasion in vitro, whereby we have also been able to explore gene expression differences associated with the invading cells by RNAseq. We analyzed the transcriptional landscape of all 26 GC patients at single-cell resolution, and identified shared tumor cellular programs of glial and neuronal lineage. We observed notable heterogeneity of neuronal lineage tumor cells that were composed of different states, such as metabolic active and synaptogenic states. We described tumor cell states associated with higher invasivity, as corroborated from integrated analysis with our in vitro invasion-associated gene expression profiles. Next, we stratified all tumors by their DNA methylation profiles, and defined 16 archetypal GC cases, for which we show specific transcriptional features. Furthermore, we analyzed multiple regions of interest within FFPE patient tissue sections by IMC and demonstrate spatial patterns in the interaction between the tumour and normal brain tissue interface, and inter-regional heterogeneity for stem, invasive and proliferative markers. Together, we dissect the characteristic invasive phenotype of GC at multiple molecular, spatial and functional layers, thereby providing the basis for modelling and therapeutic avenues much needed for this lethal disease.
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Jehel, L., N. Howard, M. Pradem, Y. Simchowitz, Y. Robert, and A. Messiah. "Prendre en compte la dimension transculturelle dans l’évaluation du risque suicidaire et du psychotraumatisme." European Psychiatry 30, S2 (November 2015): S79. http://dx.doi.org/10.1016/j.eurpsy.2015.09.357.
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La situation de la Guyane-Française, département français d’Amérique, est un exemple fort de l’exigence de prendre en compte les paramètres transculturels pour comprendre et agir sur la prévention du suicide. On distingue, dans cette région, la population vivant sur le littoral ayant accès aux principales ressources et la population vivant dans les communes de l’intérieur. En effet, les peuples de la Guyane sont irrégulièrement répartis sur 84 000 km2. Certains villages sont éloignés des structures de soins et de santé parfois de plusieurs jours de pirogues. Les dernières études de l’OMS démontrent que les risques du suicide croissent avec l’éloignement des centres urbanisés. La population résidant sur les deux fleuves de la Guyane et à l’Intérieur (espace forestier amazonien) présente une vulnérabilité au suicide supérieure à tous les autres segments de la société guyanaise et française. Ces suicides sont essentiellement le fait de jeunes. La question du suicide chez les populations autochtones de la Guyane révèle un mal être profond qui dépasse la simple conception médicopsychologique du risque de passage à l’acte. Les causes de ce phénomène sont pluridimensionnelles et regroupent entre autres des facteurs psychologiques, sociaux, anthropologiques, écologiques et politiques. Si les passages à l’acte sont dans la majorité des cas liés à une consommation excessive d’alcool et déclenchés par des motifs au premier abord anodins (différends familiaux, obstacle à l’achat de produits de consommation), ils résultent plutôt de la manifestation extrême d’un mal-être bien plus profond. Pertes de repères liés à la modification brutale des modes de vie, déstructuration de la cellule familiale, inactivité en particulier chez les jeunes, échecs scolaires, absence de perspectives d’avenir et isolement sont des motifs qui peuvent expliquer le comportement suicidaire. Un partenaire majeur dans cette réflexion est le CCPAB (Conseil consultatif des populations amérindiennes et Bushininge de Guyane), instance auprès de la future collectivité unique, siégeant à la Préfecture, spécifique aux DOM, qui fait du suicide des autochtones un axe prioritaire de lutte. C’est une démarche intégrative de ces dimensions pour une évaluation globale avec des outils spécifiques que nous construisons au sein de l’équipe Inserm (Ipsom) à laquelle est adossée la CeRMEPI (cellule régionale pour le mieux être des populations de l’intérieur) créée par le préfet. Cette prise en charge holistique permettra d’aider le travail plus spécifiquement médical de prévention et de soins qui est actuellement effectué par les services de psychiatrie de Guyane grâce aux équipes mobiles et à la CUMP (cellule d’urgence médicopsychologique).
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Neri, Paola, Pierfrancesco Tassone, Masood A. Shammas, Daniel R. Carrasco, Renate Burger, Constantine S. Mitsdiades, Simona Blotta, et al. "Novel Model To Evaluate Changes in Gene Expression Profile of Myeloma Cells In Vivo Following Interaction with Human BM Microenvironment." Blood 106, no. 11 (November 16, 2005): 2490. http://dx.doi.org/10.1182/blood.v106.11.2490.2490.
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Abstract Multiple Myeloma (MM) cells interact with bone marrow (BM) microenvironment leading to induction of adhesion-mediated and cytokine mediated cell signalling which plays a critical role in promoting MM cell growth, survival, migration and development of drug resistance. We have previously evaluated gene expression changes following interaction between MM cells and BM stromal cells in vitro. However, the interaction between MM cells and microenvironment cells within the bone marrow is unique and its understanding is critical in evaluating effects of novel agents. We here describe a unique model that allows us to analyse in vivo expression changes in MM cells within the human BM milieu; and present preliminary results of expression changes following these in vivo interactions. In this model, BM stromal and IL-6-dependent human MM cell line INA-6 tranduced with GFP (green fluorescent protein) was injected in human fetal bone chip transplanted into SCID mice (SCID-hu mice). The MM cells were allowed to interact with the bone marrow for variable length of time, the bone chip was then retrieved, cells flashed out and GFP+ MM cells were separated by flow cytometry. The GFP negative fraction, containing stromal elements was also separated. Similar flow isolation process was used on INA-6GFP+ cells cultured in vitro and used as control. Total RNA was isolated from these cells and gene expression profile analyzed using the HG-U133 array chip (Affimetrix). We report that interaction between INA-6 cells and the BM microenvironment in vivo induced significant changes in expression profile. In particular, we observed up-regulation of genes implicated in regulation of cell proliferation (RGS 1 and 2, FOS, FOSB, S100A4); DNA transcription (AP1, SWI/SNF related member 1); chromosome organization (Histone1, 2 and 3); cellular trafficking and transport (ARFGEF2, Aquarin 3 and ATPase 4B); and signal transduction (Chemokine ligand 2, 3 and 15, Chemokine receptor 1, 2 and 4, Dual specificity phosphatase 1 and 4, Protein tyrosine phosphatase 1, PIP5-kinase 1A and ZAP70). We also observed down-regulation of genes involved in apoptosis (BCL2-interacting killer, APC, E1A binding protein p300, Fas-associated via death domain, Caspase-activated Dnase, Raf1); and cell-cell adhesion molecules (Cadherin 15, Leupakin, Neurekin, CD44, ICAM2 and PECAM-1a). Although some similarities were observed in gene profile changes following in vitro and in vivo interaction with microenvironment cells, differences were also found. We are now evaluating the effects of interaction on expression profile of stromal cells as well as duration of interaction. Taken together these data confirm the ability of BM microenvironment to modulate gene expression profile of the MM cells in vivo to mediate the MM cell growth, survival and migration. This model now provides us with an opportunity to study effects of novel agents on MM cells expression profile in vivo to pre-clinically characterize their activity.
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MAUGEY, B., G. LAGARDE, M. FLUSIN, M. LACQUEMENT, C. PAUGAM, and G. HEREDIA. "Bilan de l’année d’activité 2008-2009 de la cellule de régulation médicale de Kaboul (Med RC C)." Médecine et Armées Vol. 39 No. 4, Volume 39, Numéro 4 (October 1, 2011): 347–58. http://dx.doi.org/10.17184/eac.6570.
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La cellule de régulation médicale franco-allemande (MEdical Regulation Command Capital/Med RC C) organise et conduit les évacuations médicales (MEDEVAC) au Régional Command Capital (RC C) de Kaboul au sein de la Force internationale d’assistance à la sécurité (FIAS/ISAF) de l’Organisation du traité de l’Atlantique Nord (OTAN) en Afghanistan. Le Med RC C est chargé de coordonner l’ensemble des MEDEVAC dans la région de Kaboul ou en provenance des quatre autres régions d’Afghanistan (RC N, RC E, RC S, RC W). La mission prioritaire est la relève en urgence des blessés de toutes origines en zone hostile (MEDEVAC primaire/Forward MEDEVAC). Mais le pilotage des transferts des blessés en provenance des différents centres de soins du pays vers Kaboul (MEDEVAC secondaire/Tactical MEDEVAC) reste le travail de fond du Med RC C. L’étude est une analyse d’une année d’activité du Med RC C entre août 2008 et juillet 2009, période au cours de laquelle 80 MEDEVAC primaires au bénéfice de 134 blessés (dont 69 français), et 320 MEDEVAC secondaires pour 333 patients (dont 33 français) ont été conduites. L’important soutien santé à la population afghane mérite d’être rapporté (40 % de l’activité totale s’applique aux blessés civils dont 16 % aux enfants). L’état de guerre du théâtre afghan oblige la pratique d’une régulation des blessés particulière. L’activité du Med RC C est un exemple de coopération internationale qui exploite la complémentarité des moyens opérationnels engagés.
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Lamini N'Soundhat, NE, R. Bileckot, G. Ndziessi, M. Diafouka, and H. Ntsiba. "Facteurs associés à la survenue des arthrites au cours de l’infection par le virus de l’immunodéficience humaine." Rhumatologie Africaine Francophone 1, no. 2 (August 31, 2021): 11–16. http://dx.doi.org/10.62455/raf.v1i2.4.
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Introduction: déterminer les facteurs associés à la survenue des arthrites au cours de l’infection à VIH.Matériels et méthodes: étude cas-témoins réalisée au Centre de traitement ambulatoire de Brazzaville, des patients vivants avec le VIH. Le groupe de cas était constitué de 106 patients ayant une arthrite, parmi 1681 patients suivis de 2006 à 2010. Le groupe témoin de 106 patients appariés selon l’âge et le sexe a été constitué grâce au programme Visual Basic Macro Excel (version 11.1). La force d’association a été mesurée par le calcul des odds ratios bruts en analyse univariée et pour les odds ratios ajustés en analyse multivariée.Résultats: la fréquence des arthrites au cours du VIH était de 6%. L’âge moyen des cas était de 45+/- 11,35 ans (extrêmes: 17-72 ans) et celui des témoins était de 39,25±10,97 ans (extrêmes:16-59 ans). Dans les 2 groupes les femmes étaient deux fois plus atteintes que les hommes (sex ratio: 0,5). Les facteurs associés de survenue d’arthrite étaient : l’appartenance à la classe B3 et C3 (OR=10,63 ; IC=5,58-19,31), un taux de CD4 inférieur à 200 cellules/mm3 (OR=2.11 ; IC= 1.63-3.48) et une charge virale détectable (OR=11.14 ; IC=2.79-19.38). La différence entre les deux groupes était statistiquement significative (p=0.001). L’association de ces facteurs accroissait le risque de survenue d’arthrites (OR=15.95 ; IC=6.38-38.86).Conclusion: l’appartenance à la classe B3 et C3, un taux de CD4 bas inférieur à 200 cellule/mm3 et une charge virale détectable étaient les facteurs associés à la survenue d’arthrites.
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Jost, François. "Oz, la prison et l’art de la fugue." Cinémas 23, no. 2-3 (April 18, 2013): 145–74. http://dx.doi.org/10.7202/1015188ar.
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La sérieOzmet en scène un prisonnier, Augustus Hill, dans une sorte de cage transparente, s’adressant au téléspectateur au début, à la fin et au coeur de chaque épisode. À première vue, il est hors-diégèse et ses propos entretiennent une relation sémantique avec l’épisode. En réalité, cette « cellule narrative » est à la fois un espace immune et un sas entre le monde extérieur et la prison, puis entre le monde des morts et le monde des vivants. L’auteur du présent article étudie d’abord les multiples variations des interventions de Hill, tant d’un point de vue iconique que plastique. Si celles-ci sont l’objet d’une constante re-création, paradoxalement, elles ont une fonction rhétorique qui n’est pas loin de caractériser les séries américaines en tant qu’elles sont américaines, et qui trouve ses racines dans une tradition littéraire anglo-saxonne, celle ducommonplace book. La particularité d’Ozest de construire sa narration sur la pierre angulaire de l’intimité télévisuelle : le regard-caméra. Par cette analyse, l’auteur cherche à montrer que, pour comprendre les séries comme des objets télévisuels, il faut les remettre dans leur contexte et examiner leur finalité, soit leur diffusion programmée sur un média qui accompagne le téléspectateur dans sa temporalité.
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Chacon-Barahona, Jonathan A., Jeffrey P. MacKeigan, and Nathan J. Lanning. "Unique Metabolic Contexts Sensitize Cancer Cells and Discriminate between Glycolytic Tumor Types." Cancers 15, no. 4 (February 11, 2023): 1158. http://dx.doi.org/10.3390/cancers15041158.
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Cancer cells utilize variable metabolic programs in order to maintain homeostasis in response to environmental challenges. To interrogate cancer cell reliance on glycolytic programs under different nutrient availabilities, we analyzed a gene panel containing all glycolytic genes as well as pathways associated with glycolysis. Using this gene panel, we analyzed the impact of an siRNA library on cellular viability in cells containing only glucose or only pyruvate as the major bioenergetic nutrient source. From these panels, we aimed to identify genes that elicited conserved and glycolysis-dependent changes in cellular bioenergetics across glycolysis-promoting and OXPHOS-promoting conditions. To further characterize gene sets within this panel and identify similarities and differences amongst glycolytic tumor RNA-seq profiles across a pan-cancer cohort, we then used unsupervised statistical classification of RNA-seq profiles for glycolytic cancers and non-glycolytic cancer types. Here, Kidney renal clear cell carcinoma (KIRC); Head and Neck squamous cell carcinoma (HNSC); and Lung squamous cell carcinoma (LUSC) defined the glycolytic cancer group, while Prostate adenocarcinoma (PRAD), Thyroid carcinoma (THCA), and Thymoma (THYM) defined the non-glycolytic cancer group. These groups were defined based on glycolysis scoring from previous studies, where KIRC, HNSC, and LUSC had the highest glycolysis scores, meanwhile, PRAD, THCA, and THYM had the lowest. Collectively, these results aimed to identify multi-omic profiles across cancer types with demonstrated variably glycolytic rates. Our analyses provide further support for strategies aiming to classify tumors by metabolic phenotypes in order to therapeutically target tumor-specific vulnerabilities.
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Jiang, Rong-San, Wan-Chun Huang, and Kai-Li Liang. "Characteristics of Sinus Fungus Ball: A Unique Form of Rhinosinusitis." Clinical Medicine Insights: Ear, Nose and Throat 11 (January 2018): 117955061879225. http://dx.doi.org/10.1177/1179550618792254.
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Objective: The purpose of this study was to investigate the characteristics of this unique form of rhinosinusitis. Methods: Ninety-one patients with sinus fungus balls were evaluated for clinical characteristics. Nasal tissues obtained from 38 patients with sinus fungus ball, along with 26 controls were used for histopathological, cytokines/chemokines, western blotting, and genetic analyses. Results: Patients with fungus balls had significantly more females and their age was older. The presentation of fungus ball was predominantly unilateral (97.8%). Thirty-three patients (36.3%) had risk factors for fungal infection. Macrophage and neutrophil dominated cellular infiltration was found in nasal tissues of fungus ball patients. A tendency of reduced tight junction staining (e-cadherin) and protein expression was found. Interleukin 8 (IL8) and granulocyte colony stimulating factor (G-CSF) significantly increased in sinus fungus ball tissue homogenates when compared with those from controls. Higher prevalence of a single single nucleotide polymorphism (SNP) with E-cadherin was found in the patients with fungus ball. Conclusions: We found that patients with sinus fungus ball had robust immune responses, allowing recruitment and activation of macrophages and neutrophils. However, patients with sinus fungus ball could have genetic or acquired weakness in immunity. The fungal hyphae were localized and accumulated within single sinus instead of being eradicated by host.
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Khan, Zia A., Juan M. Melero-Martin, Xiao Wu, Sailaja Paruchuri, Elisa Boscolo, John B. Mulliken, and Joyce Bischoff. "Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin." Blood 108, no. 3 (August 1, 2006): 915–21. http://dx.doi.org/10.1182/blood-2006-03-006478.
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Abstract Infantile hemangiomas are composed of endothelial cells (ECs), endothelial progenitor cells (EPCs), as well as perivascular and hematopoietic cells. Our hypothesis is that hemangioma-derived EPCs (HemEPCs) differentiate into the mature ECs that comprise the major compartment of the tumor. To test this, we isolated EPCs (CD133+/Ulex europeus– I+) and mature ECs (CD133–/Ulex europeus–I+) from proliferating hemangiomas and used a previously described property of hemangioma-derived ECs (HemECs), enhanced migratory activity in response to the angiogenesis inhibitor endostatin, to determine if HemEPCs share this abnormal behavior. Umbilical cord blood–derived EPCs (cbEPCs) were analyzed in parallel as a normal control. Our results show that HemEPCs, HemECs, and cbEPCs exhibit increased adhesion, migration, and proliferation in response to endostatin. This angiogenic response to endostatin was consistently expressed by HemEPCs over several weeks in culture, whereas HemECs and cbEPCs shifted toward the mature endothelial response to endostatin. Similar mRNA-expression patterns among HemEPCs, HemECs, and cbEPCs, revealed by microarray analyses, provided further indication of an EPC phenotype. This is the first demonstration that human EPCs, isolated from blood or from a proliferating hemangioma, are stimulated by an angiogenesis inhibitor. These findings suggest that EPCs respond differently from mature ECs when exposed to angiogenic or antiangiogenic signals.
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Raja, Sripriya, and Bennett Van Houten. "The Multiple Cellular Roles of SMUG1 in Genome Maintenance and Cancer." International Journal of Molecular Sciences 22, no. 4 (February 17, 2021): 1981. http://dx.doi.org/10.3390/ijms22041981.
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Single-strand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2′-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase: SMUG1 has a unique helical wedge that influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.
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Pryce, Rhys, Kristopher Azarm, Ilona Rissanen, Karl Harlos, Thomas A. Bowden, and Benhur Lee. "A key region of molecular specificity orchestrates unique ephrin-B1 utilization by Cedar virus." Life Science Alliance 3, no. 1 (December 20, 2019): e201900578. http://dx.doi.org/10.26508/lsa.201900578.
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The emergent zoonotic henipaviruses, Hendra, and Nipah are responsible for frequent and fatal disease outbreaks in domestic animals and humans. Specificity of henipavirus attachment glycoproteins (G) for highly species-conserved ephrin ligands underpins their broad host range and is associated with systemic and neurological disease pathologies. Here, we demonstrate that Cedar virus (CedV)—a related henipavirus that is ostensibly nonpathogenic—possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3. Uniquely among known henipaviruses, CedV can use ephrin-B1 for cellular entry. Structural analyses of CedV-G reveal a key region of molecular specificity that directs ephrin-B1 utilization, while preserving a universal mode of ephrin-B2 recognition. The structural and functional insights presented uncover diversity within the known henipavirus receptor repertoire and suggest that only modest structural changes may be required to modulate receptor specificities within this group of lethal human pathogens.
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Saul, Dominik, and Robyn Laura Kosinsky. "Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations." Cells 10, no. 11 (November 11, 2021): 3126. http://dx.doi.org/10.3390/cells10113126.
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The human aging process is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Despite their potential correlation, the relationship between cancer- and ageing-related transcriptional changes is largely unknown. In this study, we aimed to analyze aging-associated transcriptional patterns in publicly available bulk mRNA-seq and single-cell RNA-seq (scRNA-seq) datasets for chronic myelogenous leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC), and pancreatic ductal adenocarcinoma (PDAC). Indeed, we detected that various aging/senescence-induced genes (ASIGs) were upregulated in malignant diseases compared to healthy control samples. To elucidate the importance of ASIGs during cell development, pseudotime analyses were performed, which revealed a late enrichment of distinct cancer-specific ASIG signatures. Notably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. While only minor correlations were detected between ASIGs and transcriptome-wide changes in PDAC, a high proportion of ASIGs was induced in CML, CRC, HCC, and LC samples. These unique cellular subpopulations could serve as a basis for future studies on the role of aging and senescence in human malignancies.
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Hammond, Timothy, Patricia Allen, and Holly Birdsall. "Effects of Space Flight on Mouse Liver versus Kidney: Gene Pathway Analyses." International Journal of Molecular Sciences 19, no. 12 (December 18, 2018): 4106. http://dx.doi.org/10.3390/ijms19124106.
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Understanding genome wide, tissue-specific, and spaceflight-induced changes in gene expression is critical to develop effective countermeasures. Transcriptome analysis has been performed on diverse tissues harvested from animals flown in space, but not the kidney. We determined the genome wide gene expression using a gene array analysis of kidney and liver tissue from mice flown in space for 12 days versus ground based control animals. By comparing the transcriptome of liver and kidney from animals flown in space versus ground control animals, we tested a unique hypothesis: Are there common gene expression pathways activated in multiple tissue types in response to spaceflight stimuli? Although there were tissue-specific changes, both liver and kidney overexpressed genes in the same four areas: (a) cellular responses to peptides, hormones, and nitrogen/organonitrogen compounds; (b) apoptosis and cell death; (c) fat cell differentiation and (d) negative regulation of protein kinase.