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  Subjects -> SCIENCES: COMPREHENSIVE WORKS (Total: 426 journals)
Showing 1 - 200 of 265 Journals sorted alphabetically
AAS Open Research     Open Access  
ABC Journal of Advanced Research     Open Access  
Accountability in Research: Policies and Quality Assurance     Hybrid Journal   (Followers: 17)
Acta Materialia Transilvanica     Open Access  
Acta Nova     Open Access  
Acta Scientifica Malaysia     Open Access  
Acta Scientifica Naturalis     Open Access   (Followers: 2)
Adıyaman University Journal of Science     Open Access  
Advanced Science     Open Access   (Followers: 11)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 3)
Advanced Theory and Simulations     Hybrid Journal   (Followers: 2)
Advances in Research     Open Access  
Advances in Science and Technology     Full-text available via subscription   (Followers: 16)
African Journal of Science, Technology, Innovation and Development     Hybrid Journal   (Followers: 7)
Afrique Science : Revue Internationale des Sciences et Technologie     Open Access   (Followers: 4)
AFRREV STECH : An International Journal of Science and Technology     Open Access   (Followers: 2)
American Academic & Scholarly Research Journal     Open Access   (Followers: 4)
American Journal of Applied Sciences     Open Access   (Followers: 21)
American Journal of Humanities and Social Sciences     Open Access   (Followers: 10)
American Scientist     Full-text available via subscription   (Followers: 12)
ANALES de la Universidad Central del Ecuador     Open Access   (Followers: 1)
Anales del Instituto de la Patagonia     Open Access  
Applied Mathematics and Nonlinear Sciences     Open Access  
Apuntes de Ciencia & Sociedad     Open Access  
Arab Journal of Basic and Applied Sciences     Open Access  
Arabian Journal for Science and Engineering     Hybrid Journal   (Followers: 1)
Archives Internationales d'Histoire des Sciences     Partially Free   (Followers: 5)
Archives of Current Research International     Open Access  
ARO. The Scientific Journal of Koya University     Open Access  
ARPHA Conference Abstracts     Open Access   (Followers: 1)
ARPHA Proceedings     Open Access  
ArtefaCToS : Revista de estudios sobre la ciencia y la tecnología     Open Access  
Asian Journal of Advanced Research and Reports     Open Access   (Followers: 1)
Asian Journal of Applied Science and Engineering     Open Access  
Asian Journal of Scientific Research     Open Access   (Followers: 2)
Asian Journal of Technology Innovation     Hybrid Journal   (Followers: 5)
Australian Field Ornithology     Full-text available via subscription   (Followers: 2)
Australian Journal of Social Issues     Hybrid Journal   (Followers: 7)
Avrasya Terim Dergisi     Open Access  
Bangladesh Journal of Scientific Research     Open Access  
Beni-Suef University Journal of Basic and Applied Sciences     Open Access  
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10)
Berkeley Scientific Journal     Full-text available via subscription  
BIBECHANA     Open Access  
BibNum     Open Access  
Bilge International Journal of Science and Technology Research     Open Access   (Followers: 1)
Bioethics Research Notes     Full-text available via subscription   (Followers: 16)
BJHS Themes     Open Access  
Black Sea Journal of Engineering and Science     Open Access  
Borneo Journal of Resource Science and Technology     Open Access  
Bulletin de la Société Royale des Sciences de Liège     Open Access  
Bulletin of the National Research Centre     Open Access  
Butlletí de la Institució Catalana d'Història Natural     Open Access  
Central European Journal of Clinical Research     Open Access  
Chain Reaction     Full-text available via subscription  
Ciencia Amazónica (Iquitos)     Open Access  
Ciencia en Desarrollo     Open Access  
Ciencia en su PC     Open Access   (Followers: 1)
Ciencia Ergo Sum     Open Access  
Ciência ET Praxis     Open Access  
Ciencia y Tecnología     Open Access  
Ciencias Holguin     Open Access   (Followers: 1)
CienciaUAT     Open Access  
Citizen Science : Theory and Practice     Open Access   (Followers: 1)
Communications Faculty of Sciences University of Ankara Series A2-A3 Physical Sciences and Engineering     Open Access  
Communications in Applied Sciences     Open Access  
Comunicata Scientiae     Open Access  
ConCiencia     Open Access  
Conference Papers in Science     Open Access  
Configurations     Full-text available via subscription   (Followers: 11)
COSMOS     Hybrid Journal   (Followers: 1)
Crea Ciencia Revista Científica     Open Access  
Cuadernos de Investigación UNED     Open Access  
Current Issues in Criminal Justice     Hybrid Journal   (Followers: 14)
Current Research in Geoscience     Open Access   (Followers: 6)
Dalat University Journal of Science     Open Access  
Data     Open Access   (Followers: 4)
Data Curation Profiles Directory     Open Access   (Followers: 4)
Dhaka University Journal of Science     Open Access  
Dharmakarya     Open Access  
Diálogos Interdisciplinares     Open Access  
Digithum     Open Access   (Followers: 2)
Discover Sustainability     Open Access   (Followers: 2)
Einstein (São Paulo)     Open Access  
Ekaia : EHUko Zientzia eta Teknologia aldizkaria     Open Access  
Elkawnie : Journal of Islamic Science and Technology     Open Access  
Emergent Scientist     Open Access  
Enhancing Learning in the Social Sciences     Open Access   (Followers: 6)
Enseñanza de las Ciencias : Revista de Investigación y Experiencias Didácticas     Open Access  
Entramado     Open Access  
Entre Ciencia e Ingeniería     Open Access  
Epiphany     Open Access   (Followers: 1)
Estação Científica (UNIFAP)     Open Access  
Ethiopian Journal of Education and Sciences     Open Access   (Followers: 5)
Ethiopian Journal of Science and Technology     Open Access  
Ethiopian Journal of Sciences and Sustainable Development     Open Access  
European Online Journal of Natural and Social Sciences     Open Access   (Followers: 4)
European Scientific Journal     Open Access   (Followers: 2)
Evidência - Ciência e Biotecnologia - Interdisciplinar     Open Access  
Exchanges : the Warwick Research Journal     Open Access   (Followers: 1)
Experimental Results     Open Access  
Extensionismo, Innovación y Transferencia Tecnológica     Open Access  
Facets     Open Access  
Fides et Ratio : Revista de Difusión Cultural y Científica     Open Access  
Fırat University Turkish Journal of Science & Technology     Open Access  
Fontanus     Open Access  
Forensic Science Policy & Management: An International Journal     Hybrid Journal   (Followers: 238)
Frontiers for Young Minds     Open Access  
Frontiers in Climate     Open Access   (Followers: 3)
Frontiers in Science     Open Access   (Followers: 1)
Fundamental Research     Open Access   (Followers: 4)
Futures & Foresight Science     Hybrid Journal   (Followers: 2)
Gaudium Sciendi     Open Access  
Gazi University Journal of Science     Open Access  
Ghana Studies     Full-text available via subscription   (Followers: 14)
Global Journal of Pure and Applied Sciences     Full-text available via subscription  
Global Journal of Science Frontier Research     Open Access   (Followers: 1)
Globe, The     Full-text available via subscription   (Followers: 3)
HardwareX     Open Access  
Heidelberger Jahrbücher Online     Open Access  
Heliyon     Open Access  
Himalayan Journal of Science and Technology     Open Access  
History of Science and Technology     Open Access   (Followers: 1)
Hoosier Science Teacher     Open Access  
Impact     Open Access   (Followers: 1)
Indian Journal of History of Science     Hybrid Journal  
Indonesian Journal of Fundamental Sciences     Open Access  
Indonesian Journal of Science and Mathematics Education     Open Access   (Followers: 1)
Indonesian Journal of Science and Technology     Open Access  
Ingenieria y Ciencia     Open Access   (Followers: 1)
Innovare : Revista de ciencia y tecnología     Open Access  
Integrated Research Advances     Open Access  
Interciencia     Open Access  
Interface Focus     Full-text available via subscription  
International Annals of Science     Open Access  
International Archives of Science and Technology     Open Access  
International Journal of Academic Research in Business, Arts & Science     Open Access  
International Journal of Advanced Multidisciplinary Research and Review     Open Access  
International Journal of Applied Science     Open Access  
International Journal of Basic and Applied Sciences     Open Access   (Followers: 1)
International Journal of Computational and Experimental Science and Engineering (IJCESEN)     Open Access  
International Journal of Culture and Modernity     Open Access  
International Journal of Engineering, Science and Technology     Open Access  
International Journal of Engineering, Technology and Natural Sciences     Open Access  
International Journal of Innovation and Applied Studies     Open Access   (Followers: 3)
International Journal of Innovative Research and Scientific Studies     Open Access   (Followers: 1)
International Journal of Network Science     Hybrid Journal   (Followers: 3)
International Journal of Recent Contributions from Engineering, Science & IT     Open Access  
International Journal of Research in Science     Open Access   (Followers: 1)
International Journal of Science & Emerging Technologies     Open Access   (Followers: 1)
International Journal of Social Sciences and Management     Open Access   (Followers: 2)
International Journal of Technology Policy and Law     Hybrid Journal   (Followers: 6)
International Letters of Social and Humanistic Sciences     Open Access  
International Scientific and Vocational Studies Journal     Open Access  
InterSciencePlace     Open Access  
Investiga : TEC     Open Access  
Investigación Joven     Open Access  
Investigacion y Ciencia     Open Access   (Followers: 1)
Iranian Journal of Science and Technology, Transactions A : Science     Hybrid Journal  
iScience     Open Access   (Followers: 1)
Issues in Science & Technology     Free   (Followers: 7)
Ithaca : Viaggio nella Scienza     Open Access  
Jaunujų mokslininkų darbai     Open Access  
Journal de la Recherche Scientifique de l'Universite de Lome     Full-text available via subscription  
Journal of Chromatography & Separation Techniques     Open Access   (Followers: 10)
Journal of Advanced Research     Open Access   (Followers: 2)
Journal of Al-Qadisiyah for Pure Science     Open Access  
Journal of Alasmarya University     Open Access  
Journal of Analytical Science & Technology     Open Access   (Followers: 4)
Journal of Applied Science and Technology     Full-text available via subscription   (Followers: 1)
Journal of Applied Sciences and Environmental Management     Open Access   (Followers: 1)
Journal of Big History     Open Access   (Followers: 3)
Journal of Composites Science     Open Access   (Followers: 3)
Journal of Deliberative Mechanisms in Science     Open Access  
Journal of Diversity Management     Open Access   (Followers: 4)
Journal of Indian Council of Philosophical Research     Hybrid Journal  
Journal of Institute of Science and Technology     Open Access  
Journal of Integrated Science and Technology     Open Access  
Journal of Kerbala University     Open Access  
Journal of King Saud University - Science     Open Access  
Journal of Mathematical and Fundamental Sciences     Open Access  
Journal of Natural Sciences and Mathematics Research     Open Access  
Journal of Natural Sciences Research     Open Access   (Followers: 1)
Journal of Negative and No Positive Results     Open Access  
Journal of Responsible Technology     Open Access  
Journal of Science (JSc)     Open Access  
Journal of Science and Engineering     Open Access  
Journal of Science and Technology     Open Access   (Followers: 2)
Journal of Science and Technology     Open Access   (Followers: 1)
Journal of Science and Technology (Ghana)     Open Access   (Followers: 3)
Journal of Science and Technology Policy Management     Hybrid Journal   (Followers: 1)
Journal of Science Foundation     Open Access   (Followers: 1)
Journal of Science of the University of Kelaniya Sri Lanka     Open Access  
Journal of Scientific Research     Open Access  
Journal of Scientific Research and Reports     Open Access  
Journal of Scientometric Research     Open Access   (Followers: 19)
Journal of Shanghai Jiaotong University (Science)     Hybrid Journal  
Journal of Social Science Research     Open Access   (Followers: 2)
Journal of Taibah University for Science     Open Access  
Journal of the Asiatic Society of Bangladesh, Science     Open Access  

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ISSN (Online) 2371-1671
Published by Canadian Science Publishing Homepage  [3 journals]
  • SnRNA sequencing defines signaling by RBC-derived extracellular vesicles
           in the murine heart

    • Authors: Valkov, N; Das, A, Tucker, N. R, Li, G, Salvador, A. M, Chaffin, M. D, Pereira De Oliveira Junior, G, Kur, I, Gokulnath, P, Ziegler, O, Yeri, A, Lu, S, Khamesra, A, Xiao, C, Rodosthenous, R, Srinivasan, S, Toxavidis, V, Tigges, J, Laurent, L. C, Momma, S, Kitchen, R, Ellinor, P, Ghiran, I, Das, S.
      Abstract: Extracellular vesicles (EVs) mediate intercellular signaling by transferring their cargo to recipient cells, but the functional consequences of signaling are not fully appreciated. RBC-derived EVs are abundant in circulation and have been implicated in regulating immune responses. Here, we use a transgenic mouse model for fluorescence-based mapping of RBC-EV recipient cells to assess the role of this intercellular signaling mechanism in heart disease. Using fluorescent-based mapping, we detected an increase in RBC-EV–targeted cardiomyocytes in a murine model of ischemic heart failure. Single cell nuclear RNA sequencing of the heart revealed a complex landscape of cardiac cells targeted by RBC-EVs, with enrichment of genes implicated in cell proliferation and stress signaling pathways compared with non-targeted cells. Correspondingly, cardiomyocytes targeted by RBC-EVs more frequently express cellular markers of DNA synthesis, suggesting the functional significance of EV-mediated signaling. In conclusion, our mouse model for mapping of EV-recipient cells reveals a complex cellular network of RBC-EV–mediated intercellular communication in ischemic heart failure and suggests a functional role for this mode of intercellular signaling.
      Keywords: Methods & Resources, Physiology, Cell Biology
      PubDate: 2021-10-18T11:31:51-07:00
      DOI: 10.26508/lsa.202101048
      Issue No: Vol. 4, No. 12 (2021)
       
  • A brain-specific pgc1{alpha} fusion transcript affects gene expression and
           behavioural outcomes in mice

    • Authors: Lozoya, O. A; Xu, F, Grenet, D, Wang, T, Stevanovic, K. D, Cushman, J. D, Hagler, T. B, Gruzdev, A, Jensen, P, Hernandez, B, Riadi, G, Moy, S. S, Santos, J. H, Woychik, R. P.
      Abstract: PGC1α is a transcriptional coactivator in peripheral tissues, but its function in the brain remains poorly understood. Various brain-specific Pgc1α isoforms have been reported in mice and humans, including two fusion transcripts (FTs) with non-coding repetitive sequences, but their function is unknown. The FTs initiate at a simple sequence repeat locus ~570 Kb upstream from the reference promoter; one also includes a portion of a short interspersed nuclear element (SINE). Using publicly available genomics data, here we show that the SINE FT is the predominant form of Pgc1α in neurons. Furthermore, mutation of the SINE in mice leads to altered behavioural phenotypes and significant up-regulation of genes in the female, but not male, cerebellum. Surprisingly, these genes are largely involved in neurotransmission, having poor association with the classical mitochondrial or antioxidant programs. These data expand our knowledge on the role of Pgc1α in neuronal physiology and suggest that different isoforms may have distinct functions. They also highlight the need for further studies before modulating levels of Pgc1α in the brain for therapeutic purposes.
      Keywords: Neuroscience
      PubDate: 2021-10-14T12:12:52-07:00
      DOI: 10.26508/lsa.202101122
      Issue No: Vol. 4, No. 12 (2021)
       
  • Kinomics platform using GBM tissue identifies BTK as being associated with
           higher patient survival

    • Authors: Al Shboul, S; Curran, O. E, Alfaro, J. A, Lickiss, F, Nita, E, Kowalski, J, Naji, F, Nenutil, R, Ball, K. L, Krejcir, R, Vojtesek, B, Hupp, T. R, Brennan, P. M.
      Abstract: Better understanding of GBM signalling networks in-vivo would help develop more physiologically relevant ex vivo models to support therapeutic discovery. A "functional proteomics" screen was undertaken to measure the specific activity of a set of protein kinases in a two-step cell-free biochemical assay to define dominant kinase activities to identify potentially novel drug targets that may have been overlooked in studies interrogating GBM-derived cell lines. A dominant kinase activity derived from the tumour tissue, but not patient-derived GBM stem-like cell lines, was Bruton tyrosine kinase (BTK). We demonstrate that BTK is expressed in more than one cell type within GBM tissue; SOX2-positive cells, CD163-positive cells, CD68-positive cells, and an unidentified cell population which is SOX2-negative CD163-negative and/or CD68-negative. The data provide a strategy to better mimic GBM tissue ex vivo by reconstituting more physiologically heterogeneous cell co-culture models including BTK-positive/negative cancer and immune cells. These data also have implications for the design and/or interpretation of emerging clinical trials using BTK inhibitors because BTK expression within GBM tissue was linked to longer patient survival.
      Keywords: Stem Cells, Cancer
      PubDate: 2021-10-13T09:55:30-07:00
      DOI: 10.26508/lsa.202101054
      Issue No: Vol. 4, No. 12 (2021)
       
  • Non-canonical activation of the ER stress sensor ATF6 by Legionella
           pneumophila effectors

    • Authors: Ibe, N. U; Subramanian, A, Mukherjee, S.
      Abstract: The intracellular bacterial pathogen Legionella pneumophila (L.p.) secretes ~330 effector proteins into the host cell to sculpt an ER-derived replicative niche. We previously reported five L.p. effectors that inhibit IRE1, a key sensor of the homeostatic unfolded protein response (UPR) pathway. In this study, we discovered a subset of L.p. toxins that selectively activate the UPR sensor ATF6, resulting in its cleavage, nuclear translocation, and target gene transcription. In a deviation from the conventional model, this L.p.–dependent activation of ATF6 does not require its transport to the Golgi or its cleavage by the S1P/S2P proteases. We believe that our findings highlight the unique regulatory control that L.p. exerts upon the three UPR sensors and expand the repertoire of bacterial proteins that selectively perturb host homeostatic pathways.
      Keywords: Cell Biology
      PubDate: 2021-10-11T10:26:37-07:00
      DOI: 10.26508/lsa.202101247
      Issue No: Vol. 4, No. 12 (2021)
       
  • Set4 regulates stress response genes and coordinates histone deacetylases
           within yeast subtelomeres

    • Authors: Jethmalani, Y; Tran, K, Negesse, M. Y, Sun, W, Ramos, M, Jaiswal, D, Jezek, M, Amos, S, Garcia, E. J, Park, D, Green, E. M.
      Abstract: The yeast chromatin protein Set4 is a member of the Set3-subfamily of SET domain proteins which play critical roles in the regulation of gene expression in diverse developmental and environmental contexts. We previously reported that Set4 promotes survival during oxidative stress and regulates expression of stress response genes via stress-dependent chromatin localization. In this study, global gene expression analysis and investigation of histone modification status identified a role for Set4 in maintaining gene repressive mechanisms within yeast subtelomeres under both normal and stress conditions. We show that Set4 works in a partially overlapping pathway to the SIR complex and the histone deacetylase Rpd3 to maintain proper levels of histone acetylation and expression of stress response genes encoded in subtelomeres. This role for Set4 is particularly critical for cells under hypoxic conditions, where the loss of Set4 decreases cell fitness and cell wall integrity. These findings uncover a new regulator of subtelomeric chromatin that is key to stress defense pathways and demonstrate a function for Set4 in regulating repressive, heterochromatin-like environments.
      Keywords: Chromatin & Epigenetics
      PubDate: 2021-10-08T10:25:13-07:00
      DOI: 10.26508/lsa.202101126
      Issue No: Vol. 4, No. 12 (2021)
       
  • Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA
           damage repair

    • Authors: Tang, J; Casey, P. J, Wang, M.
      Abstract: DNA damage is a double-edged sword for cancer cells. On the one hand, DNA damage–induced genomic instability contributes to cancer development; on the other hand, accumulating damage compromises proliferation and survival of cancer cells. Understanding the key regulators of DNA damage repair machinery would benefit the development of cancer therapies that induce DNA damage and apoptosis. In this study, we found that isoprenylcysteine carboxylmethyltransferase (ICMT), a posttranslational modification enzyme, plays an important role in DNA damage repair. We found that ICMT suppression consistently reduces the activity of MAPK signaling, which compromises the expression of key proteins in the DNA damage repair machinery. The ensuing accumulation of DNA damage leads to cell cycle arrest and apoptosis in multiple breast cancer cells. Interestingly, these observations are more pronounced in cells grown under anchorage-independent conditions or grown in vivo. Consistent with the negative impact on DNA repair, ICMT inhibition transforms the cancer cells into a "BRCA-like" state, hence sensitizing cancer cells to the treatment of PARP inhibitor and other DNA damage–inducing agents.
      Keywords: Cancer, Cell Biology
      PubDate: 2021-10-05T08:42:02-07:00
      DOI: 10.26508/lsa.202101144
      Issue No: Vol. 4, No. 12 (2021)
       
  • Loss of Resf1 reduces the efficiency of embryonic stem cell self-renewal
           and germline entry

    • Authors: Vojtek, M; Chambers, I.
      Abstract: Retroelement silencing factor 1 (RESF1) interacts with the key regulators of mouse embryonic stem cells (ESCs) OCT4 and NANOG, and its absence results in sterility of mice. However, the function of RESF1 in ESCs and germline specification is poorly understood. In this study, we used Resf1 knockout cell lines to determine the requirements of RESF1 for ESC self-renewal and for in vitro specification of ESCs into primordial germ cell-like cells (PGCLCs). We found that deletion of Resf1 in ESCs cultured in serum and LIF reduces self-renewal potential, whereas episomal expression of RESF1 has a modest positive effect on ESC self-renewal. In addition, RESF1 is not required for the capacity of NANOG and its downstream target ESRRB to drive self-renewal in the absence of LIF. However, Resf1 deletion reduces the efficiency of PGCLC differentiation in vitro. These results identify Resf1 as a novel player in the regulation of pluripotent stem cells and germ cell specification.
      Keywords: Stem Cells, Cell Biology, Development
      PubDate: 2021-10-04T11:15:12-07:00
      DOI: 10.26508/lsa.202101190
      Issue No: Vol. 4, No. 12 (2021)
       
  • Engineered RNA biosensors enable ultrasensitive SARS-CoV-2 detection in a
           simple color and luminescence assay

    • Authors: Chakravarthy, A; Nandakumar, A, George, G, Ranganathan, S, Umashankar, S, Shettigar, N, Palakodeti, D, Gulyani, A, Ramesh, A.
      Abstract: The continued resurgence of the COVID-19 pandemic with multiple variants underlines the need for diagnostics that are adaptable to the virus. We have developed toehold RNA–based sensors across the SARS-CoV-2 genome for direct and ultrasensitive detection of the virus and its prominent variants. Here, isothermal amplification of a fragment of SARS-CoV-2 RNA coupled with activation of our biosensors leads to a conformational switch in the sensor. This leads to translation of a reporter protein, for example, LacZ or nano-lantern that is easily detected using color/luminescence. By optimizing RNA amplification and biosensor design, we have generated a highly sensitive diagnostic assay that is capable of detecting as low as 100 copies of viral RNA with development of bright color. This is easily visualized by the human eye and quantifiable using spectrophotometry. Finally, this PHAsed NASBA-Translation Optical Method (PHANTOM) using our engineered RNA biosensors efficiently detects viral RNA in patient samples. This work presents a powerful and universally accessible strategy for detecting COVID-19 and variants. This strategy is adaptable to further viral evolution and brings RNA bioengineering center-stage.
      Keywords: Molecular Biology, Molecular Diagnostics & Diagnostic Imaging
      PubDate: 2021-09-30T08:44:21-07:00
      DOI: 10.26508/lsa.202101213
      Issue No: Vol. 4, No. 12 (2021)
       
  • Gut microbiota-derived short-chain fatty acids protect against the
           progression of endometriosis

    • Authors: Chadchan, S. B; Popli, P, Ambati, C. R, Tycksen, E, Han, S. J, Bulun, S. E, Putluri, N, Biest, S. W, Kommagani, R.
      Abstract: Worldwide, ~196 million are afflicted with endometriosis, a painful disease in which endometrial tissue implants and proliferates on abdominal peritoneal surfaces. Theories on the origin of endometriosis remained inconclusive. Whereas up to 90% of women experience retrograde menstruation, only 10% develop endometriosis, suggesting that factors that alter peritoneal environment might contribute to endometriosis. Herein, we report that whereas some gut bacteria promote endometriosis, others protect against endometriosis by fermenting fiber to produce short-chain fatty acids. Specifically, we found that altered gut microbiota drives endometriotic lesion growth and feces from mice with endometriosis contained less of short-chain fatty acid and n-butyrate than feces from mice without endometriosis. Treatment with n-butyrate reduced growth of both mouse endometriotic lesions and human endometriotic lesions in a pre-clinical mouse model. Mechanistic studies revealed that n-butyrate inhibited human endometriotic cell survival and lesion growth through G-protein–coupled receptors, histone deacetylases, and a GTPase activating protein, RAP1GAP. Our findings will enable future studies aimed at developing diagnostic tests, gut bacteria metabolites and treatment strategies, dietary supplements, n-butyrate analogs, or probiotics for endometriosis.
      Keywords: Microbiology, Virology & Host Pathogen Interaction, Molecular Biology, Cell Biology
      PubDate: 2021-09-30T08:44:21-07:00
      DOI: 10.26508/lsa.202101224
      Issue No: Vol. 4, No. 12 (2021)
       
  • The DREAM complex represses growth in response to DNA damage in
           Arabidopsis

    • Authors: Lang, L; Pettko-Szandtner, A, Tuncay Elbası, H, Takatsuka, H, Nomoto, Y, Zaki, A, Dorokhov, S, De Jaeger, G, Eeckhout, D, Ito, M, Magyar, Z, Bögre, L, Heese, M, Schnittger, A.
      Abstract: The DNA of all organisms is constantly damaged by physiological processes and environmental conditions. Upon persistent damage, plant growth and cell proliferation are reduced. Based on previous findings that RBR1, the only Arabidopsis homolog of the mammalian tumor suppressor gene retinoblastoma, plays a key role in the DNA damage response in plants, we unravel here the network of RBR1 interactors under DNA stress conditions. This led to the identification of homologs of every DREAM component in Arabidopsis, including previously not recognized homologs of LIN52. Interestingly, we also discovered NAC044, a mediator of DNA damage response in plants and close homolog of the major DNA damage regulator SOG1, to directly interact with RBR1 and the DREAM component LIN37B. Consistently, not only mutants in NAC044 but also the double mutant of the two LIN37 homologs and mutants for the DREAM component E2FB showed reduced sensitivities to DNA-damaging conditions. Our work indicates the existence of multiple DREAM complexes that work in conjunction with NAC044 to mediate growth arrest after DNA damage.
      Keywords: Molecular Biology, Plant Science, Cell Biology
      PubDate: 2021-09-28T11:10:19-07:00
      DOI: 10.26508/lsa.202101141
      Issue No: Vol. 4, No. 12 (2021)
       
  • Activation of mitochondrial unfolded protein response protects against
           multiple exogenous stressors

    • Authors: Soo, S. K; Traa, A, Rudich, P. D, Mistry, M, Van Raamsdonk, J. M.
      Abstract: The mitochondrial unfolded protein response (mitoUPR) is an evolutionarily conserved pathway that responds to mitochondria insults through transcriptional changes, mediated by the transcription factor ATFS-1/ATF-5, which acts to restore mitochondrial homeostasis. In this work, we characterized the role of ATFS-1 in responding to organismal stress. We found that activation of ATFS-1 is sufficient to cause up-regulation of genes involved in multiple stress response pathways including the DAF-16–mediated stress response pathway, the cytosolic unfolded protein response, the endoplasmic reticulum unfolded protein response, the SKN-1–mediated oxidative stress response pathway, the HIF-1-mediated hypoxia response pathway, the p38-mediated innate immune response pathway, and antioxidant genes. Constitutive activation of ATFS-1 increases resistance to multiple acute exogenous stressors, whereas disruption of atfs-1 decreases stress resistance. Although ATFS-1–dependent genes are up-regulated in multiple long-lived mutants, constitutive activation of ATFS-1 decreases lifespan in wild-type animals. Overall, our work demonstrates that ATFS-1 serves a vital role in organismal survival of acute stressors through its ability to activate multiple stress response pathways but that chronic ATFS-1 activation is detrimental for longevity.
      Keywords: Aging, Genetics, Gene Therapy & Genetic Disease, Cell Biology
      PubDate: 2021-09-28T11:10:19-07:00
      DOI: 10.26508/lsa.202101182
      Issue No: Vol. 4, No. 12 (2021)
       
  • Functional and metabolic fitness of human CD4+ T lymphocytes during
           metabolic stress

    • Authors: Holthaus, L; Sharma, V, Brandt, D, Ziegler, A.-G, Jastroch, M, Bonifacio, E.
      Abstract: Human CD4+ T cells are essential mediators of immune responses. By altering the mitochondrial and metabolic states, we defined metabolic requirements of human CD4+ T cells for in vitro activation, expansion, and effector function. T-cell activation and proliferation were reduced by inhibiting oxidative phosphorylation, whereas early cytokine production was maintained by either OXPHOS or glycolytic activity. Glucose deprivation in the presence of mild mitochondrial stress markedly reduced all three T-cell functions, contrasting the exposure to resveratrol, an antioxidant and sirtuin-1 activator, which specifically inhibited cytokine production and T-cell proliferation, but not T-cell activation. Conditions that inhibited T-cell activation were associated with the down-regulation of 2',5'-oligoadenylate synthetase genes via interferon response pathways. Our findings indicate that T-cell function is grossly impaired by stressors combined with nutrient deprivation, suggesting that correcting nutrient availability, metabolic stress, and/or the function of T cells in these conditions will improve the efficacy of T-cell–based therapies.
      Keywords: Immunology
      PubDate: 2021-09-27T11:00:42-07:00
      DOI: 10.26508/lsa.202101013
      Issue No: Vol. 4, No. 12 (2021)
       
  • MKP-1 modulates ubiquitination/phosphorylation of TLR signaling

    • Authors: Talreja, J; Bauerfeld, C, Wang, X, Hafner, M, Liu, Y, Samavati, L.
      Abstract: Ubiquitination and phosphorylation are reversible posttranslational protein modifications regulating physiological and pathological processes. MAPK phosphatase (MKP)-1 regulates innate and adaptive immunity. The multifaceted roles of MKP-1 were attributed to dephosphorylation of p38 and JNK MAPKs. We show that the lack of MKP-1 modulates the landscape of ubiquitin ligases and deubiquitinase enzymes (DUBs). MKP-1–/– showed an aberrant regulation of several DUBs and increased expression of proteins and genes involved in IL-1/TLR signaling upstream of MAPK, including IL-1R1, IRAK1, TRAF6, phosphorylated TAK1, and an increased K63 polyubiquitination on TRAF6. Increased K63 polyubiquitination on TRAF6 was associated with an enhanced phosphorylated form of A20. Among abundant DUBs, ubiquitin-specific protease-13 (USP13), which cleaves polyubiquitin-chains on client proteins, was substantially enhanced in murine MKP-1–deficient BMDMs. An inhibitor of USP13 decreased the K63 polyubiquitination on TRAF6, TAK1 phosphorylation, IL-1β, and TNF-α induction in response to LPS in BMDMs. Our data show for the first time that MKP-1 modulates the ligase activity of TRAF6 through modulation of specific DUBs.
      Keywords: Immunology
      PubDate: 2021-09-27T11:00:42-07:00
      DOI: 10.26508/lsa.202101137
      Issue No: Vol. 4, No. 12 (2021)
       
  • ATAD2 controls chromatin-bound HIRA turnover

    • Authors: Wang, T; Perazza, D, Boussouar, F, Cattaneo, M, Bougdour, A, Chuffart, F, Barral, S, Vargas, A, Liakopoulou, A, Puthier, D, Bargier, L, Morozumi, Y, Jamshidikia, M, Garcia-Saez, I, Petosa, C, Rousseaux, S, Verdel, A, Khochbin, S.
      Abstract: Taking advantage of the evolutionary conserved nature of ATAD2, we report here a series of parallel functional studies in human, mouse, and Schizosaccharomyces pombe to investigate ATAD2’s conserved functions. In S. pombe, the deletion of ATAD2 ortholog, abo1, leads to a dramatic decrease in cell growth, with the appearance of suppressor clones recovering normal growth. The identification of the corresponding suppressor mutations revealed a strong genetic interaction between Abo1 and the histone chaperone HIRA. In human cancer cell lines and in mouse embryonic stem cells, we observed that the KO of ATAD2 leads to an accumulation of HIRA. A ChIP-seq mapping of nucleosome-bound HIRA and FACT in Atad2 KO mouse ES cells demonstrated that both chaperones are trapped on nucleosomes at the transcription start sites of active genes, resulting in the abnormal presence of a chaperone-bound nucleosome on the TSS-associated nucleosome-free regions. Overall, these data highlight an important layer of regulation of chromatin dynamics ensuring the turnover of histone-bound chaperones.
      Keywords: Chromatin & Epigenetics
      PubDate: 2021-09-27T11:00:42-07:00
      DOI: 10.26508/lsa.202101151
      Issue No: Vol. 4, No. 12 (2021)
       
  • OrtSuite: from genomes to prediction of microbial interactions within
           targeted ecosystem processes

    • Authors: Saraiva, J. P; Bartholomäus, A, Kallies, R, Gomes, M, Bicalho, M, Coelho Kasmanas, J, Vogt, C, Chatzinotas, A, Stadler, P, Dias, O, Nunes da Rocha, U.
      Abstract: The high complexity found in microbial communities makes the identification of microbial interactions challenging. To address this challenge, we present OrtSuite, a flexible workflow to predict putative microbial interactions based on genomic content of microbial communities and targeted to specific ecosystem processes. The pipeline is composed of three user-friendly bash commands. OrtSuite combines ortholog clustering with genome annotation strategies limited to user-defined sets of functions allowing for hypothesis-driven data analysis such as assessing microbial interactions in specific ecosystems. OrtSuite matched, on average, 96% of experimentally verified KEGG orthologs involved in benzoate degradation in a known group of benzoate degraders. We evaluated the identification of putative synergistic species interactions using the sequenced genomes of an independent study that had previously proposed potential species interactions in benzoate degradation. OrtSuite is an easy-to-use workflow that allows for rapid functional annotation based on a user-curated database and can easily be extended to ecosystem processes where connections between genes and reactions are known. OrtSuite is an open-source software available at https://github.com/mdsufz/OrtSuite.
      Keywords: Genomics & Functional Genomics, Systems & Computational Biology, Ecology
      PubDate: 2021-09-27T11:00:42-07:00
      DOI: 10.26508/lsa.202101167
      Issue No: Vol. 4, No. 12 (2021)
       
  • Gradual compaction of the central spindle decreases its dynamicity in PRC1
           and EB1 gene-edited cells

    • Authors: Asthana, J; Cade, N. I, Normanno, D, Lim, W. M, Surrey, T.
      Abstract: During mitosis, the spindle undergoes morphological and dynamic changes. It reorganizes at the onset of the anaphase when the antiparallel bundler PRC1 accumulates and recruits central spindle proteins to the midzone. Little is known about how the dynamic properties of the central spindle change during its morphological changes in human cells. Using gene editing, we generated human cells that express from their endogenous locus fluorescent PRC1 and EB1 to quantify their native spindle distribution and binding/unbinding turnover. EB1 plus end tracking revealed a general slowdown of microtubule growth, whereas PRC1, similar to its yeast orthologue Ase1, binds increasingly strongly to compacting antiparallel microtubule overlaps. KIF4A and CLASP1 bind more dynamically to the central spindle, but also show slowing down turnover. These results show that the central spindle gradually becomes more stable during mitosis, in agreement with a recent "bundling, sliding, and compaction" model of antiparallel midzone bundle formation in the central spindle during late mitosis.
      Keywords: Cell Biology
      PubDate: 2021-09-27T11:00:42-07:00
      DOI: 10.26508/lsa.202101222
      Issue No: Vol. 4, No. 12 (2021)
       
 
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