Read by QxMD icon Read


Jing Sun, Yarong Mu, Yuanyuan Jiang, Ruilong Song, Jianxin Yi, Jingsong Zhou, Jun Sun, Xinan Jiao, Richard A Prinz, Yi Li, Xiulong Xu
Autophagy plays a central role in degrading misfolded proteins such as mutated superoxide dismutase 1 (SOD1), which forms aggregates in motor neurons and is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is activated when UNC-51-like kinase 1 (ULK1) is phosphorylated at S555 and activated by AMP-activated protein kinase (AMPK). Autophagy is suppressed when ULK1 is phosphorylated at S757 by the mechanistic target of rapamycin (mTOR). Whether p70 S6 kinase 1 (S6K1), a serine/threonine kinase downstream of mTOR, can also regulate autophagy remains uncertain...
March 14, 2018: Cell Death & Disease
Jie Hao, Shuangyue Li, Xiaoxia Shi, Zhiqiang Qian, Yijie Sun, Dunjia Wang, Xueying Zhou, Hongxin Qu, Shuhai Hu, Enjun Zuo, Cong Zhang, Liyan Hou, Qingshan Wang, Fengyuan Piao
Chronic exposure to n-hexane, a widely used organic solvent in industry, induces central-peripheral neuropathy, which is mediated by its active metabolite, 2,5-hexanedione (HD). We recently reported that transplantation of bone marrow-mesenchymal stem cells (BMSC) significantly ameliorated HD-induced neuronal damage and motor deficits in rats. However, the mechanisms remain unclear. Here, we reported that inhibition of HD-induced autophagy contributed to BMSC-afforded protection. BMSC transplantation significantly reduced the levels of microtubule-associated protein 1 light chain 3-II (LC3-II) and the degradation of sequestosome-1 (p62) in the spinal cord and sciatic nerve of HD-intoxicated rats...
March 14, 2018: Scientific Reports
Shruti Thapliyal, Amruta Vasudevan, Yongming Dong, Jihong Bai, Sandhya P Koushika, Kavita Babu
The C. elegans ortholog of mammalian calsyntenins, CASY-1, is an evolutionarily conserved type-I transmembrane protein that is highly enriched in the nervous system. Mammalian calsyntenins are strongly expressed at inhibitory synapses, but their role in synapse development and function is still elusive. Here, we report a crucial role for CASY-1 in regulating GABAergic synaptic transmission at the C. elegans neuromuscular junction (NMJ). The shorter isoforms of CASY-1; CASY-1B and CASY-1C, express and function in GABA motor neurons where they regulate GABA neurotransmission...
March 12, 2018: PLoS Genetics
Jane H Brice, Matthew A Psioda, Renee Johnson, Amy Oakley, Julianne M Cyr, Christopher S Cowden, Richard Uribe
BACKGROUND: Accessing the emergency medical services system via 9-1-1 operators is an effective way for patients to seek urgent health care; however, technological advances and telecommunication practices inundate the 9-1-1 and emergency services infrastructure with unintentional calls that delay response efforts to legitimate medical emergencies. OBJECTIVE: To determine whether the change in university-wide dial-out prefix from "9" to "7" reduced unnecessary calls to a 9-1-1 call center...
March 9, 2018: Prehospital Emergency Care
Sofia Golenkina, Vishal Chaturvedi, Robert Saint, Michael J Murray
Netrin receptors of the DCC/NEO/UNC-40/Frazzled family have well established roles in cell migration and axon guidance but can also regulate epithelial features such as adhesion, polarity and adherens junction (AJ) stability. Previously, we have shown that overexpression of Drosophila Frazzled (Fra) in the peripodial epithelium (PE) inhibits wing disc eversion and also generates cellular protrusions typical of motile cells. Here, we tested whether the molecular pathways by which Fra inhibits eversion are distinct from those driving motility...
2018: PloS One
Stanley M Walls, Anthony Cammarato, Dale A Chatfield, Karen Ocorr, Greg L Harris, Rolf Bodmer
Lipotoxic cardiomyopathy (LCM) is characterized by abnormal myocardial accumulation of lipids, including ceramide; however, the contribution of ceramide to the etiology of LCM is unclear. Here, we investigated the association of ceramide metabolism and ceramide-interacting proteins (CIPs) in LCM in the Drosophila heart model. We find that ceramide feeding or ceramide-elevating genetic manipulations are strongly associated with cardiac dilation and defects in contractility. High ceramide-associated LCM is prevented by inhibiting ceramide synthesis, establishing a robust model of direct ceramide-associated LCM, corroborating previous indirect evidence in mammals...
March 6, 2018: Cell Reports
Lan Zhang, Liang Ouyang, Yongzhi Guo, Jin Zhang, Bo Liu
UNC-51-like kinase 1 (ULK1), known as an ortholog of the yeast Atg1, is the serine-threonine kinase and the autophagic initiator in mammals. Accumulating evidence has recently revealed the kinase domain structure of ULK1 and its post-translational modifications, as well as further elucidated its regulatory autophagic pathways and associations with diverse human diseases. Interestingly, a series of small molecules have been recently reported to target ULK1 or ULK1-modulating autophagy, which may provide a clue on exploiting them as novel candidate drugs...
March 6, 2018: Journal of Medicinal Chemistry
Zhiheng Huang, Xiaoyan Huang, Qian Wang, Ruizhi Jiang, Guangda Sun, Yiming Xu, Qinan Wu
Positive regulation of autophagy by Euryale ferox Salisb (ES) leads to antidepressant effects. This study focused on the potential antidepressant mechanisms induced by the petroleum ether fraction of ES (ES-PE) in the chronically unpredictable mild stress (CUMS) mouse model. Deficits in the sucrose preference test, open field test, tail suspension test, and forced swim test were observed following CUMS, and were reversed following ES-PE administration. Contrary to the expression of mammalian target of rapamycin, autophagy was decreased after establishment of the CUMS model...
March 6, 2018: IUBMB Life
Haowen Liu, Lei Li, Wei Wang, Jihong Gong, Xiaofei Yang, Zhitao Hu
The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca2+ channels in triggering spontaneous release at cholinergic and GABAergic synapses. Recordings of the miniature excitatory/inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) showed that UNC-2/CaV2 and EGL-19/CaV1 channels are the two major triggers for spontaneous release...
February 27, 2018: Cell Reports
Courtney E Boen, David A Barrow, Jeannette T Bensen, Laura Farnan, Adrian Gerstel, Laura H Hendrix, Yang Claire Yang
BACKGROUND: Social stressors such as social relationship deficits have been increasingly linked to chronic disease outcomes, including cancer. However, critical gaps exist in our understanding of the nature and strength of such links, as well as the underlying biological mechanisms relating social relationships to cancer progression and survival. METHODS: Utilizing novel questionnaire and biomarker data from the UNC Health Registry/Cancer Survivorship Cohort (HR/CSC), the present study examines the associations between diverse measures of social support and mortality risk among individuals with cancer (N=1,004)...
February 23, 2018: Cancer Epidemiology, Biomarkers & Prevention
Morgan L Trepte, Jessica J Auten, Stephen M Clark, Hendrik W van Deventer
Hyperleukocytosis occurs in 15-20% of all newly diagnosed acute myeloid leukemia patients and requires emergent treatment with leukapheresis or hydroxyurea when accompanied by signs or symptoms of leukostasis. Currently, there is no standardized hydroxyurea dosing strategy, although usual dosing ranges from 50 to 150 mg/kg/day, and prescribing patterns vary significantly among oncologists and institutions. In addition to other hematologic and dermatologic toxicities, the use of hydroxyurea may be associated with significant mucositis and mucositis-related pain...
January 1, 2018: Journal of Oncology Pharmacy Practice
Peter Weinberg, Matthew Berkseth, David Zarkower, Oliver Hobert
Nervous systems display intriguing patterns of sexual dimorphisms across the animal kingdom, but the mechanisms that generate such dimorphisms remain poorly characterized. In the nematode Caenorhabditis elegans, a number of neurons present in both sexes are synaptically connected to one another in a sexually dimorphic manner as a result of sex-specific synaptic pruning and maintenance [1-3]. We define here a mechanism for the male-specific maintenance of the synaptic connections of the phasmid sensory neuron PHB and its male-specific target, the sex-shared AVG interneuron...
February 2, 2018: Current Biology: CB
Clothilde Esteve, Ludmila Francescatto, Perciliz L Tan, Aurélie Bourchany, Cécile De Leusse, Evelyne Marinier, Arnaud Blanchard, Patrice Bourgeois, Céline Brochier-Armanet, Ange-Line Bruel, Arnauld Delarue, Yannis Duffourd, Emmanuelle Ecochard-Dugelay, Géraldine Hery, Frédéric Huet, Philippe Gauchez, Emmanuel Gonzales, Catherine Guettier-Bouttier, Mina Komuta, Caroline Lacoste, Raphaelle Maudinas, Karin Mazodier, Yves Rimet, Jean-Baptiste Rivière, Bertrand Roquelaure, Sabine Sigaudy, Xavier Stephenne, Christel Thauvin-Robinet, Julien Thevenon, Jacques Sarles, Nicolas Levy, Catherine Badens, Olivier Goulet, Jean-Pierre Hugot, Nicholas Katsanis, Laurence Faivre, Alexandre Fabre
Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function...
February 1, 2018: American Journal of Human Genetics
Eugene Urrutia, Hao Chen, Zilu Zhou, Nancy R Zhang, Yuchao Jiang
Summary: Copy number variation is an important and abundant source of variation in the human genome, which has been associated with a number of diseases, especially cancer. Massively parallel next-generation sequencing allows copy number profiling with fine resolution. Such efforts, however, have met with mixed successes, with setbacks arising partly from the lack of reliable analytical methods to meet the diverse and unique challenges arising from the myriad experimental designs and study goals in genetic studies...
February 5, 2018: Bioinformatics
Doris Hellerschmied, Max Roessler, Anita Lehner, Linn Gazda, Karel Stejskal, Richard Imre, Karl Mechtler, Alexander Dammermann, Tim Clausen
Muscle development requires the coordinated activities of specific protein folding and degradation factors. UFD-2, a U-box ubiquitin ligase, has been reported to play a central role in this orchestra regulating the myosin chaperone UNC-45. Here, we apply an integrative in vitro and in vivo approach to delineate the substrate-targeting mechanism of UFD-2 and elucidate its distinct mechanistic features as an E3/E4 enzyme. Using Caenorhabditis elegans as model system, we demonstrate that UFD-2 is not regulating the protein levels of UNC-45 in muscle cells, but rather shows the characteristic properties of a bona fide E3 ligase involved in protein quality control...
February 2, 2018: Nature Communications
Liling Zheng, Sihuang Lin, Chengyu Lv
MiRNA is a class of small non-coding RNA which has an important effect on posttranscriptional gene regulation. It can regulate the expression of the target gene at the mRNA level and further influence the protein level of the target gene. We found that ULK1 may be the target gene of miR-26a-5p, and ULK1 (unc-51 like autophagy activating kinase 1) is a key component in autophagy pathway. In this study, we overexpressed miR-26a-5p by transfecting miR-26a-5p mimic into cells and simultaneously inhibited miR-26a-5p by transfecting miR-26a-5p inhibitor into cells...
February 1, 2018: Scientific Reports
Min Liu, Marie Fitzgibbon, Yanqin Wang, Jamie Reilly, Xiaohong Qian, Timothy O'Brien, Steve Clapcote, Sanbing Shen, Michelle Roche
Excitation/inhibition imbalance has been proposed as a fundamental mechanism in the pathogenesis of neuropsychiatric and neurodevelopmental disorders, in which copy number variations of the Unc-51 like kinase 4 (ULK4) gene encoding a putative Serine/Threonine kinase have been reported in approximately 1/1000 of patients suffering pleiotropic clinical conditions of schizophrenia, depression, autistic spectrum disorder (ASD), developmental delay, language delay, intellectual disability, or behavioral disorder...
February 2, 2018: Translational Psychiatry
Sarah K Nordquist, Sofia R Smith, Jonathan T Pierce
Individuals with Down syndrome have neurological and muscle impairments due to an additional copy of the human 21st chromosome (HSA21). Only a few of ~200 HSA21 genes encoding protein have been linked to specific Down syndrome phenotypes, while the remainder are understudied. To identify poorly characterized HSA21 genes required for nervous system function, we studied behavioral phenotypes caused by loss-of-function mutations in conserved HSA21 orthologs in the nematode Caenorhabditis elegans We identified ten HSA21 orthologs that are required for neuromuscular behaviors: cle-1 (COL18A1), cysl-2 (CBS), dnsn-1 (DONSON), eva-1 (EVA1C), mtq-2 (N6ATM1), ncam-1 (NCAM2), pad-2 (POFUT2), pdxk-1 (PDXK), rnt-1 (RUNX1), and unc-26 (SYNJ1)...
January 24, 2018: G3: Genes—Genomes—Genetics
Melanie Abongwa, Djordje S Marjanovic, James G Tipton, Fudan Zheng, Richard J Martin, Sasa M Trailovic, Alan P Robertson
Zolvix® is a recently introduced anthelmintic drench containing monepantel as the active ingredient. Monepantel is a positive allosteric modulator of DEG-3/DES-2 type nicotinic acetylcholine receptors (nAChRs) in several nematode species. The drug has been reported to produce hypercontraction of Caenorhabditis elegans and Haemonchus contortus somatic muscle. We investigated the effects of monepantel on nAChRs from Ascaris suum and Oesophagostomum dentatum heterologously expressed in Xenopus laevis oocytes...
December 16, 2017: International Journal for Parasitology, Drugs and Drug Resistance
Shangbang Gao, Sihui Asuka Guan, Anthony D Fouad, Jun Meng, Taizo Kawano, Yung-Chi Huang, Yi Li, Salvador Alcaire, Wesley Hung, Yangning Lu, Yingchuan Billy Qi, Yishi Jin, Mark Alkema, Christopher Fang-Yen, Mei Zhen
Cell- or network-driven oscillators underlie motor rhythmicity. The identity of C. elegans oscillators remains unknown. Through cell ablation, electrophysiology, and calcium imaging, we show: (1) forward and backward locomotion is driven by different oscillators; (2) the cholinergic and excitatory A-class motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive backward locomotion in the absence of premotor interneurons; (3) the UNC-2 P/Q/N high-voltage-activated calcium current underlies A motor neuron's oscillation; (4) descending premotor interneurons AVA, via an evolutionarily conserved, mixed gap junction and chemical synapse configuration, exert state-dependent inhibition and potentiation of A motor neuron's intrinsic activity to regulate backward locomotion...
January 23, 2018: ELife
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"