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https://www.readbyqxmd.com/read/28087624/tissue-specific-regulation-of-alternative-polyadenylation-represses-expression-of-neuronal-ankyrin-isoform-in-c-elegans-epidermal-development
#1
Fei Chen, Andrew D Chisholm, Yishi Jin
Differential mRNA polyadenylation plays an important role in shaping the neuronal transcriptome. In C. elegans, several ankyrin isoforms are produced from the unc-44 locus through alternative polyadenylation. Here, we identify a key role for an intronic polyadenylation site (PAS) in temporal- and tissue-specific regulation of UNC-44/ankyrin isoforms. Removing an intronic PAS results in ectopic expression of the neuronal ankyrin isoform in non-neural tissues. This mis-expression underlies epidermal developmental defects in mutants of the conserved tumor suppressor death-associated protein kinase, dapk-1 We previously reported that the use of this intronic PAS depends on the nuclear polyadenylation factor SYDN-1, which inhibits the RNA polymerase II CTD phosphatase SSUP-72...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28076439/predictors-of-student-productivity-in-biomedical-graduate-school-applications
#2
Joshua D Hall, Anna B O'Connell, Jeanette G Cook
Many US biomedical PhD programs receive more applications for admissions than they can accept each year, necessitating a selective admissions process. Typical selection criteria include standardized test scores, undergraduate grade point average, letters of recommendation, a resume and/or personal statement highlighting relevant research or professional experience, and feedback from interviews with training faculty. Admissions decisions are often founded on assumptions that these application components correlate with research success in graduate school, but these assumptions have not been rigorously tested...
2017: PloS One
https://www.readbyqxmd.com/read/28073914/serine-threonine-kinase-unc-51-like-kinase-1-ulk1-phosphorylates-the-co-chaperone-cdc37-and-thereby-disrupts-the-stability-of-cdc37-client-proteins
#3
Ran Li, Fengjie Yuan, Wan Fu, Luyao Zhang, Nan Zhang, Yanan Wang, Ke Ma, Xue Li, Lina Wang, Wei-Guo Zhu, Ying Zhao
The serine/threonine kinase Unc-51 like kinase-1 (Ulk1) is thought to be essential for induction of autophagy, an intracellular bulk degradation process that is activated by various stresses. Although several proteins have been suggested as Ulk1 substrates during autophagic process, it still remains largely unknown about Ulk1's physiological substrates. Here, by performing in vitro and in vivo phosphorylation assay, we report that the co-chaperone cell division cycle protein 37 (Cdc37) is an Ulk1 substrate...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28068334/two-paralogous-tetraspanins-tsp-12-and-tsp-14-function-with-the-adam10-metalloprotease-sup-17-to-promote-bmp-signaling-in-caenorhabditis-elegans
#4
Lin Wang, Zhiyu Liu, Herong Shi, Jun Liu
The highly conserved bone morphogenetic protein (BMP) signaling pathway regulates many developmental and homeostatic processes. While the core components of the BMP pathway have been well studied, much research is needed for understanding the mechanisms involved in the precise spatiotemporal control of BMP signaling in vivo. Here, we provide evidence that two paralogous and evolutionarily conserved tetraspanins, TSP-12 and TSP-14, function redundantly to promote BMP signaling in C. elegans. We further show that the ADAM10 (a disintegrin and metalloprotease 10) ortholog SUP-17 also functions to promote BMP signaling, and that TSP-12 can bind to and promote the cell surface localization of SUP-17...
January 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28059583/mir7-3hg-a-myc-dependent-modulator-of-cell-proliferation-inhibits-autophagy-by-a-regulatory-loop-involving-ambra1
#5
Mariacristina Capizzi, Flavie Strappazzon, Valentina Cianfanelli, Elena Papaleo, Francesco Cecconi
Macroautophagy/autophagy is a tightly regulated intracellular catabolic pathway involving the lysosomal degradation of cytoplasmic organelles and proteins to be recycled into metabolic precursors. AMBRA1 (autophagy and beclin 1 regulator 1) has a central role in the autophagy signaling network; it acts upstream of MTORC1-dependent autophagy by stabilizing the kinase ULK1 (unc-51 like autophagy activating kinase 1) and by favoring autophagosome core complex formation. AMBRA1 also regulates the cell cycle by modulating the activity of the phosphatase PPP2/PP2A (protein phosphatase 2) and degradation of MYC...
January 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28056346/diversification-of-c-%C3%A2-elegans-motor-neuron-identity-via-selective-effector-gene-repression
#6
Sze Yen Kerk, Paschalis Kratsios, Michael Hart, Romulo Mourao, Oliver Hobert
A common organizational feature of nervous systems is the existence of groups of neurons that share common traits but can be divided into individual subtypes based on anatomical or molecular features. We elucidate the mechanistic basis of neuronal diversification processes in the context of C.elegans ventral cord motor neurons that share common traits that are directly activated by the terminal selector UNC-3. Diversification of motor neurons into different classes, each characterized by unique patterns of effector gene expression, is controlled by distinct combinations of phylogenetically conserved, class-specific transcriptional repressors...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28056033/fiji-macro-3d-art-veselect-3d-automated-reconstruction-tool-for-vesicle-structures-of-electron-tomograms
#7
Kristin Verena Kaltdorf, Katja Schulze, Frederik Helmprobst, Philip Kollmannsberger, Thomas Dandekar, Christian Stigloher
Automatic image reconstruction is critical to cope with steadily increasing data from advanced microscopy. We describe here the Fiji macro 3D ART VeSElecT which we developed to study synaptic vesicles in electron tomograms. We apply this tool to quantify vesicle properties (i) in embryonic Danio rerio 4 and 8 days past fertilization (dpf) and (ii) to compare Caenorhabditis elegans N2 neuromuscular junctions (NMJ) wild-type and its septin mutant (unc-59(e261)). We demonstrate development-specific and mutant-specific changes in synaptic vesicle pools in both models...
January 5, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28047658/we-fg-bra-05-potential-clinical-benefit-of-linac-flattening-filter-free-fff-mode-improvement-of-treatment-therapeutic-ratio
#8
S Chang, J Rivera, H Tian, A Price, C Santos, Y Zhang
PURPOSE: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045544/chembench-a-publicly-accessible-integrated-cheminformatics-portal
#9
Stephen Joseph Capuzzi, Ian Sang-June Kim, Wai In Lam, Thomas E Thornton, Eugene N Muratov, Diane Pozefsky, Alexander Tropsha
The enormous increase in the amount of publicly available chemical genomics data and the growing emphasis on data sharing and open science mandates that cheminformaticians make their models publicly available for broad use by the scientific community. Chembench is one of the first publicly-accessible, integrated cheminformatics Web portals. It has been extensively used by researchers from different fields for curation, visualization, analysis, and modeling of chemogenomics data. Since its launch in 2008, Chembench has been accessed more than 1 million times by more than 5K users from a total of 98 countries...
January 3, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28040740/the-role-of-the-unc-82-protein-kinase-in-organizing-myosin-filaments-in-striated-muscle-of-caenorhabditis-elegans
#10
NaTasha R Schiller, Christopher D Duchesneau, Latrisha S Lane, April R Reedy, Emily R Manzon, Pamela E Hoppe
We study the mechanisms that guide the formation and maintenance of the highly-ordered actin-myosin cytoskeleton in striated muscle. The UNC-82 kinase of Caenorhabditis elegans is orthologous to mammalian kinases ARK5/NUAK1 and SNARK/NUAK2. UNC-82 localizes to the M-line and is required for proper organization of thick filaments, but its substrate and mechanism of action are unknown. Antibody staining of three mutants with missense mutations in the UNC-82 catalytic domain revealed muscle structure that is less disorganized than in the null unc-82(0), but which contained distinctive ectopic accumulations not found in unc-82(0) These accumulations contain paramyosin and myosin B, but lack myosin A and myosin A-associated proteins as well as proteins of the integrin-associated complex...
December 30, 2016: Genetics
https://www.readbyqxmd.com/read/28031243/caenorhabditis-elegans-male-copulation-circuitry-incorporates-sex-shared-defecation-components-to-promote-intromission-and-sperm-transfer
#11
Brigitte LeBoeuf, L Rene Garcia
Sexual dimorphism can be achieved using a variety of mechanisms, including sex-specific circuits and sex-specific function of shared circuits, though how these work together to produce sexually dimorphic behaviors require further investigation. Here, we explore how components of the sex-shared defecation circuitry are incorporated into the sex-specific male mating circuitry in Caenorhabditis elegans to produce successful copulation. Using behavioral studies, calcium imaging, and genetic manipulation, we show that aspects of the defecation system are co-opted by the male copulatory circuitry to facilitate intromission and ejaculation...
December 27, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28025121/tris-1-3-dichloro-2-propyl-phosphate-induces-apoptosis-and-autophagy-in-sh-sy5y-cells-involvement-of-ros-mediated-ampk-mtor-ulk1-pathways
#12
Ruiwen Li, Peijiang Zhou, Yongyong Guo, Jae-Seong Lee, Bingsheng Zhou
Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in the environment and biota. Recent studies have shown that TDCIPP has neurotoxic effects. We hypothesized that the neurotoxicity might occur via the induction of the apoptosis and autophagy pathways. In the present study, we investigated TDCIPP-induced apoptotic death and autophagy in SH-SY5Y cells. Treatment with TDCIPP induced increased reactive oxygen species (ROS) generation and cell apoptosis, as well as autophagy...
December 23, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28011640/regulation-of-ulk1-expression-and-autophagy-by-stat1
#13
Alexander A Goldberg, Bernard Nkengfac, Anthony M J Sanchez, Nikolay Moroz, Salman T Qureshi, Antonis E Koromilas, Shuo Wang, Yan Burelle, Sabah N Hussain, Arnold S Kristof
Autophagy involves the lysosomal degradation of cytoplasmic contents for regeneration of anabolic substrates during nutritional or inflammatory stress. Its initiation occurs rapidly after inactivation of the protein- kinase 'mammalian target of rapamycin' (mTOR; or 'mechanistic target of rapamycin', MTOR), leading to de-phosphorylation of Unc-51-like kinase 1 (ULK1) and autophagosome formation. Recent studies indicate that mTOR can, in parallel, regulate the activity of stress transcription factors, including 'signal transducer and activator of transcription-1' (STAT1)...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28011637/tribbles-pseudokinase-3-induces-both-apoptosis-and-autophagy-in-amyloid-%C3%AE-induced-neuronal-death
#14
Suraiya Saleem, Subhas Chandra Biswas
Amyloid-β (Aβ) induced neuron death is considered central to the pathogenesis of Alzheimer disease (AD). Among several death modalities, autophagy and apoptosis play important roles in Aβ-induced neuron death suggesting that there may be regulatory mechanisms that initiate both cell death pathways. However, molecules that govern both pathways have not been identified. Here, we report that, upon Aβ treatment, tribbles pseudokinase 3 (TRIB3, an ortholog of Drosophila Tribbles), is upregulated in neurons, both in vivo and in vitro...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27993786/defcom-analysis-and-modeling-of-transcription-factor-binding-sites-using-a-motif-centric-genomic-footprinter
#15
Bryan Quach, Terrence S Furey
MOTIVATION: Identifying the locations of transcription factor binding sites is critical for understanding how gene transcription is regulated across different cell types and conditions. Chromatin accessibility experiments such as DNaseI sequencing (DNase-seq) and Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) produce genome-wide data that include distinct "footprint" patterns at binding sites. Nearly all existing computational methods to detect footprints from these data assume that footprint signals are highly homogeneous across footprint sites...
December 19, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27974481/unc-84-linc-ing-chromosome-movement-and-double-strand-break-repair
#16
Nicola Silva, Verena Jantsch
Assaults to our DNA take place at a high frequency and are incompatible with life. In this issue, Lawrence et al. (2016. J. Cell Biol https://doi.org/10.1083/jcb.201604112) demonstrate that a novel complex links the nucleus with cytoplasmic microtubules for the promotion of DNA repair by homologous recombination.
December 19, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27968910/spatiotemporal-clusters-of-primary-and-secondary-syphilis-cases-in-south-china-an-observational-study
#17
Ngai Sze Wong, Shujie Huang, Lei Chen, Peizhen Zhao, Joseph D Tucker, Li Gang Yang, Beng Tin Goh, Heping Zheng, Bin Yang
BACKGROUND: Although the overall rate of newly reported primary and secondary syphilis cases in Guangdong Province has been decreasing since 2011, incidence in some cities has increased. Location-based intervention is needed for effective resource allocation. We aimed to understand the geographical variations of syphilis epidemiology and detect possible outbreaks and epidemics at county level by spatiotemporal analyses. METHODS: In this observational study, we collected demographics, residential location, syphilis staging and diagnosis date of all reported primary and secondary syphilis cases in patients diagnosed and living in 21 cities, which were further subcategorised into 126 smaller counties, in Guangdong Province, China, from 2014 to mid-2015...
October 2016: Lancet
https://www.readbyqxmd.com/read/27968894/hiv-self-testing-among-high-risk-men-who-have-sex-with-men-in-china-a-cross-sectional-study
#18
Yilu Qin, Fengying Liu, Weiming Tang, Songyuan Tang, Chuncheng Liu, Jessica Mao, Chongyi Wei, Joseph Tucker
BACKGROUND: HIV self-testing holds great promise for reaching high-risk key populations who do not access facility-based services, but it has rarely been evaluated outside of structured research settings. HIV self-testing is a process by which a person takes and interprets a test. We aimed to characterise implementation of unsupervised HIV self-testing among men who have sex with men (MSM) in China. METHODS: We undertook a nationwide online survey of MSM in November, 2015, in China...
October 2016: Lancet
https://www.readbyqxmd.com/read/27968892/hiv-and-syphilis-among-men-who-have-sex-with-men-and-transgender-individuals-in-china-a-scoping-review
#19
Songyuan Tang, Weiming Tang, Kathrine Meyers, Polin Chan, Zhongdan Chen, Joseph D Tucker
BACKGROUND: HIV and syphilis epidemics in men who have sex with men (MSM) continue to grow in China, despite considerable government attention. We did a literature review to synthesise key features of the HIV and syphilis epidemics and responses among MSM and transgender individuals in China. Our goal was to inform evidence-based recommendations for policy makers and program managers. METHODS: We searched Medline, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang using the terms "MSM", "transgender", "meta-analysis", "review", and "China" for articles published in the last six years...
October 2016: Lancet
https://www.readbyqxmd.com/read/27968891/crowdsourcing-health-communication-about-condom-use-in-men-who-have-sex-with-men-in-china-a-randomised-controlled-trial
#20
Weiming Tang, Jessica Mao, Chuncheng Liu, Katie Mollan, Haochu Li, Terrence Wong, Ye Zhang, Songyuan Tang, Michael Hudgens, Yilu Qin, Baoli Ma, Meizhen Liao, Bin Yang, Wei Ma, Dianmin Kang, Chongyi Wei, Joseph D Tucker
BACKGROUND: The Chinese government now encourages innovation, and more specifically, crowdsourcing. Crowdsourcing, the process of shifting individual tasks to a large group, might reimagine health communication, making it more people-centred. We aimed to compare the effectiveness of a crowdsourced versus social marketing condom promotion video to promote condom use. METHODS: A non-inferiority randomised controlled trial was conducted in November 2015 in China. Men who have sex with men (MSM) aged 16 years or older who reported having had sexual contact without use of a condom in the preceding 3 months were recruited through a nationwide MSM website...
October 2016: Lancet
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