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Found 35817 matches. Displaying 51-60
Stern SA, Bulik CM
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Alternative Frameworks for Advancing the Study of Eating Disorders

TRENDS IN NEUROSCIENCES 2020 DEC; 43(12):951-959
Eating disorders are life-interrupting psychiatric conditions with high morbidity and mortality, yet the basic mechanisms underlying these conditions are understudied compared with other psychiatric disorders. In this opinion, we suggest that recent knowledge gleaned from genomic and neuroimaging investigations of eating disorders in humans presents a rich opportunity to sharpen animal models of eating disorders and to identify neural mechanisms that contribute to the risk and maintenance of these conditions. Our article reflects the state of the science, with a primary focus on anorexia nervosa (AN) and binge-eating behavior, and encourages further study of all conditions categorized under feeding and eating disorders.
Hunter RG
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Stress, Adaptation, and the Deep Genome: Why Transposons Matter

INTEGRATIVE AND COMPARATIVE BIOLOGY 2020 DEC; 60(6):1495-1505
Stress is a common, if often unpredictable life event. It can be defined from an evolutionary perspective as a force an organism perceives it must adapt to. Thus stress is a useful tool to study adaptation and the adaptive capacity of organisms. The deep genome, long neglected as a pile of "junk" has emerged as a source of regulatory DNA and RNA as well as a potential stockpile of adaptive capacity at the organismal and species levels. Recent work on the regulation of transposable elements (TEs), the principle constituents of the deep genome, by stress has shown that these elements are responsive to host stress and other environmental cues. Further, we have shown that some are likely directly regulated by the glucocorticoid receptor (GR), one of the two major vertebrate stress steroid receptors in a fashion that appears adaptive. On the basis of this and other emerging evidence I argue that the deep genome may represent an adaptive toolkit for organisms to respond to their environments at both individual and evolutionary scales. This argues that genomes may be adapted for what Waddington called "trait adaptability" rather than being purely passive objects of natural selection and single nucleotide level mutation.
Stern SA, Bulik CM
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Alternative Frameworks for Advancing the Study of Eating Disorders

TRENDS IN NEUROSCIENCES 2020 DEC; 43(12):?
Eating disorders are life-interrupting psychiatric conditions with high morbidity and mortality, yet the basic mechanisms underlying these conditions are understudied compared with other psychiatric disorders. In this opinion, we suggest that recent knowledge gleaned from genomic and neuroimaging investigations of eating disorders in humans presents a rich opportunity to sharpen animal models of eating disorders and to identify neural mechanisms that contribute to the risk and maintenance of these conditions. Our article reflects the state of the science, with a primary focus on anorexia nervosa (AN) and binge-eating behavior, and encourages further study of all conditions categorized under feeding and eating disorders.
Schwarz C, Hadjantonakis AK
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Cells under Tension Drive Gastrulation

DEVELOPMENTAL CELL 2020 DEC 21; 55(6):669-670
In this issue of Developmental Cell, Muncie et al. describe the generation of gastrulation-like foci of cells within micropatterned colonies of pluripotent stem cells. This demonstration of mechanosensitive beta-catenin/Wnt-dependent specification of cell fate during gastrulation illustrates the insights gleaned by placing stem cells in embryo-like mechanical environments.
Zhang ML, Vandana JJ, Lacko L, Chen SB
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Modeling cancer progression using human pluripotent stem cell-derived cells and organoids

STEM CELL RESEARCH 2020 DEC; 49(?):? Article 102063
Conventional cancer cell lines and animal models have been mainstays of cancer research. More recently, human pluripotent stem cells (hPSCs) and hPSC-derived organoid technologies, together with genome engineering approaches, have provided a complementary platform to model cancer progression. Here, we review the application of these technologies in cancer modeling with respect to the cell-of-origin, cancer propagation, and metastasis. We further discuss the benefits and challenges accompanying the use of hPSC models for cancer research and discuss their broad applicability in drug discovery, biomarker identification, decoding molecular mechanisms, and the deconstruction of clonal and intra-tumoral heterogeneity. In summary, hPSC-derived organoids provide powerful models to recapitulate the pathogenic states in cancer and to perform drug discovery.
Toubiana J, Levy C, Allali S, Jung C, Leruez-Ville M, Varon E, Bajolle F, Ouldali N, Chareyre J, Bechet S, Elbez A, Casanova JL, Chalumeau M, Cohen R, Cohen JF
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Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020

EUROSURVEILLANCE 2020 DEC 3; 25(48):?
Chu CS, Hellmuth JC, Singh R, Ying HY, Skrabanek L, Teater MR, Doane AS, Elemento O, Melnick AM, Roeder RG
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Unique Immune Cell Coactivators Specify Locus Control Region Function and Cell Stage

MOLECULAR CELL 2020 DEC 3; 80(5):845-861.e10
Locus control region (LCR) functions define cellular identity and have critical roles in diseases such as cancer, although the hierarchy of structural components and associated factors that drive functionality are incompletely understood. Here we show that OCA-B, a B cell-specific coactivator essential for germinal center (GC) formation, forms a ternary complex with the lymphoid-enriched OCT2 and GC-specific MEF2B transcription factors and that this complex occupies and activates an LCR that regulates the BCL6 proto-oncogene and is uniquely required by normal and malignant GC B cells. Mechanistically, through OCA-B-MED1 interactions, this complex is required for Mediator association with the BCL6 promoter. Densely tiled CRISPRi screening indicates that only LCR segments heavily bound by this ternary complex are essential for its function. Our results demonstrate how an intimately linked complex of lineage- and stage-specific factors converges on specific and highly essential enhancer elements to drive the function of a cell-type-defining LCR.
Todor H, Osadnik H, Campbell EA, Myers KS, Li H, Donohue TJ, Gross CA
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Rewiring the specificity of extracytoplasmic function sigma factors

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2020 DEC 29; 117(52):33496-33506
Bacterial genomes are being sequenced at an exponentially increasing rate, but our inability to decipher their transcriptional wiring limits our ability to derive new biology from these sequences. De novo determination of regulatory interactions requires accurate prediction of regulators' DNA binding and precise determination of biologically significant binding sites. Here we address these challenges by solving the DNA-specificity code of extracytoplasmic function sigma factors (ECF sigma s), a major family of bacterial regulators, and determining their putative regulons. We generated an aligned collection of ECF sigma s and their promoters by leveraging the autoregulatory nature of ECF sigma s as a means of promoter discovery and analyzed it to identify and characterize the conserved amino acid-nucleotide interactions that determine promoter specificity. This enabled de novo prediction of ECF sigma specificity, which we combined with a statistically rigorous phylogenetic footprinting pipeline based on precomputed orthologs to predict the direct targets of similar to 67% of ECF sigma s. This global survey indicated that some ECF sigma s are conserved global regulators controlling many genes throughout the genome, which are important under many conditions, while others are local regulators, controlling a few closely linked genes in response to specific stimuli in select species. This analysis reveals important organizing principles of bacterial gene regulation and presents a conceptual and computational framework for deciphering gene regulatory networks.
Basrur NS, De Obaldia ME, Morita T, Herre M, von Heynitz RK, Tsitohay YN, Vosshall LB
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Fruitless mutant male mosquitoes gain attraction to human odor

ELIFE 2020 DEC 7; 9(?):? Article e63982
The Aedesaegypti mosquito shows extreme sexual dimorphism in feeding. Only females are attracted to and obtain a blood-meal from humans, which they use to stimulate egg production. The fruitless gene is sex-specifically spliced and encodes a BTB zinc-finger transcription factor proposed to be a master regulator of male courtship and mating behavior across insects. We generated fruitless mutant mosquitoes and showed that males failed to mate, confirming the ancestral function of this gene in male sexual behavior. Remarkably, fruitless males also gain strong attraction to a live human host, a behavior that wild-type males never display, suggesting that male mosquitoes possess the central or peripheral neural circuits required to host-seek and that removing fruitless reveals this latent behavior in males. Our results highlight an unexpected repurposing of a master regulator of male-specific sexual behavior to control one module of female-specific blood-feeding behavior in a deadly vector of infectious diseases.
Collier AD, Khalizova N, Chang GQ, Min S, Campbell S, Gulati G, Leibowitz SF
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Involvement of Cxcl12a/Cxcr4b Chemokine System in Mediating the Stimulatory Effect of Embryonic Ethanol Exposure on Neuronal Density in Zebrafish Hypothalamus

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 2020 DEC; 44(12):2519-2535
Background Embryonic exposure to ethanol (EtOH) produces marked disturbances in neuronal development and alcohol-related behaviors, with low-moderate EtOH doses stimulating neurogenesis without producing apoptosis and high doses having major cytotoxic effects while causing gross morphological abnormalities. With the pro-inflammatory chemokine system, Cxcl12, and its main receptor Cxcr4, known to promote processes of neurogenesis, we examined here this neuroimmune system in the embryonic hypothalamus to test directly if it mediates the stimulatory effects low-moderate EtOH doses have on neuronal development. Methods We used the zebrafish (Danio rerio) model, which develops externally and allows one to investigate the developing brain in vivo with precise control of dose and timing of EtOH delivery in the absence of maternal influence. Zebrafish were exposed to low-moderate EtOH doses (0.1, 0.25, 0.5% v/v), specifically during a period of peak hypothalamic development from 22 to 24 hours postfertilization, and in some tests were pretreated from 2 to 22 hpf with the Cxcr4 receptor antagonist, AMD3100. Measurements in the hypothalamus at 26 hpf were taken of cxcl12a and cxcr4b transcription, signaling, and neuronal density using qRT-PCR, RNAscope, and live imaging of transgenic zebrafish. Results Embryonic EtOH exposure, particularly at the 0.5% dose, significantly increased levels of cxcl12a and cxcr4b mRNA in whole embryos, number of cxcl12a and cxcr4b transcripts in developing hypothalamus, and internalization of Cxcr4b receptors in hypothalamic cells. Embryonic EtOH also caused an increase in the number of hypothalamic neurons and coexpression of cxcl12a and cxcr4b transcripts within these neurons. Each of these stimulatory effects of EtOH in the embryo was blocked by pretreatment with the Cxcr4 antagonist AMD3100. Conclusions These results provide clear evidence that EtOH's stimulatory effects at low-moderate doses on the number of hypothalamic neurons early in development are mediated, in part, by increased transcription and intracellular activation of this chemokine system, likely due to autocrine signaling of Cxcl12a at its Cxcr4b receptor within the neurons.