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https://www.readbyqxmd.com/read/28642249/unc-cancer-center-director-to-lead-nci
#1
(no author information available yet)
President Donald Trump has selected Norman "Ned" Sharpless, MD, director of the University of North Carolina Lineberger Comprehensive Cancer Center, to lead the NCI. The news was met with widespread approval among cancer researchers, who view Sharpless as a strong communicator who can ably represent the needs of the cancer community in the face of proposed funding cuts.
June 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28628528/increased-persistence-of-initial-treatment-for-hiv-infection-with-modern-antiretroviral-therapy
#2
Thibaut Davy-Mendez, Joseph J Eron, Oksana Zakharova, David A Wohl, Sonia Napravnik
BACKGROUND: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic response to initial ART according to the class of anchor agent used. SETTING: An observational clinical cohort study in the Southeastern United States. METHODS: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28624033/house-staff-led-interdisciplinary-morbidity-and-mortality-conference-promotes-systematic-improvement
#3
Christopher J Tignanelli, Genevieve G R Embree, Amir Barzin
BACKGROUND: Improvements in patient safety are critical to improving clinical outcomes. We present a resident-led interdisciplinary morbidity and mortality (M&M) conference utilizing postconference task forces to identify unique system issues, classify key contributors to interdisciplinary complications, and implement systems solutions. The conference also served to facilitate resident involvement in quality improvement projects. MATERIALS AND METHODS: Members of the UNC Housestaff Council designed and implemented a hospital-wide M&M conference...
June 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28617448/diminishing-effectiveness-of-long-term-maintenance-topical-steroid-therapy-in-ppi-non-responsive-eosinophilic-esophagitis
#4
Swathi Eluri, Thomas M Runge, Jason Hansen, Bharati Kochar, Craig C Reed, Benjamin S Robey, John T Woosley, Nicholas J Shaheen, Evan S Dellon
OBJECTIVES: While topical corticosteroids are first-line therapy for eosinophilic esophagitis (EoE), the data regarding long-term effectiveness are lacking. We aimed to determine long-term histologic and endoscopic outcomes of maintenance therapy in EoE steroid responders. METHODS: We performed a retrospective study of adults with EoE at UNC Hospitals who had initial histologic response (<15 eos/hpf) after 8 weeks of topical steroids, and maintained on therapy...
June 15, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28596978/multiple-roles-of-ulk4-in-neurogenesis-and-brain-function
#5
Min Liu, Ping Xu, Timothy O'Brien, Sanbing Shen
Neurogenesis is essential for proper brain formation and function, and abnormal neural proliferation is an underlying neuropathology of many brain disorders. Recent advances on adult neurogenesis demonstrate that neural stem cells (NSCs) at the subventricular zone (SVZ) are largely derived during mid-embryonic neurogenesis from a subset of cells, which slow down in their pace of cell division,(1) become quiescent cells and can be reactivated in need.(2) The NSCs at birth constitute the stem cell pool for both postnatal oligodendrogenesis(3) and adult neurogenesis...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28596808/saturated-hydrogen-saline-ameliorates-lipopolysaccharide-induced-acute-lung-injury-by-reducing-excessive-autophagy
#6
Yiming Liu, Jin Zhang
The pathogenesis of acute lung injury (ALI) induced by lipopolysaccharide (LPS) involves excessive pulmonary inflammation and oxidative stress. In turn, autophagy is associated with inflammatory diseases and organ dysfunction, and studies have demonstrated that LPS treatment may trigger autophagy. Thus, excessive autophagy may stimulate the strong inflammatory response observed in the development of LPS-induced ALI. Saturated hydrogen saline may alleviate LPS-induced ALI by inhibiting autophagy, however its underlying mechanisms of action remain unknown...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28592648/allelic-variation-in-the-toll-like-receptor-adaptor-protein-ticam2-contributes-to-sars-coronavirus-pathogenesis-in-mice
#7
Lisa E Gralinski, Vineet D Menachery, Andrew P Morgan, Allison L Totura, Anne Beall, Jacob Kocher, Jessica Plante, D Corinne Harrison-Shostak, Alexandra Schäfer, Fernando Pardo-Manuel de Villena, Martin T Ferris, Ralph S Baric
Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV...
June 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28592645/inbred-strain-variant-database-isvdb-a-repository-for-probabilistically-informed-sequence-differences-among-the-collaborative-cross-strains-and-their-founders
#8
Daniel Oreper, Yanwei Cai, Lisa M Tarantino, Fernando Pardo-Manuel de Villena, William Valdar
The Collaborative Cross (CC) is a panel of recently established multiparental recombinant inbred mouse strains. For the CC, as for any multiparental population (MPP), effective experimental design and analysis benefit from detailed knowledge of the genetic differences between strains. Such differences can be directly determined by sequencing, but until now whole-genome sequencing was not publicly available for individual CC strains. An alternative and complementary approach is to infer genetic differences by combining two pieces of information: probabilistic estimates of the CC haplotype mosaic from a custom genotyping array, and probabilistic variant calls from sequencing of the CC founders...
June 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28582503/hugin-hi-c-unifying-genomic-interrogator
#9
Joshua S Martin, Zheng Xu, Alex P Reiner, Karen L Mohlke, Patrick Sullivan, Bing Ren, Ming Hu, Yun Li
Motivation: High throughput chromatin conformation capture (3C) technologies, such as Hi-C and ChIA-PET, have the potential to elucidate the functional roles of non-coding variants. However, most of published genome-wide unbiased chromatin organization studies have used cultured cell lines, limiting their generalizability. Results: We developed a web browser, HUGIn, to visualize Hi-C data generated from 21 human primary tissues and cell lines. HUGIn enables assessment of chromatin contacts both constitutive across and specific to tissue(s) and/or cell line(s) at any genomic loci, including GWAS SNPs, eQTLs and cis-regulatory elements, facilitating the understanding of both GWAS and eQTLs results and functional genomics data...
June 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28576866/heat-induced-calcium-leakage-causes-mitochondrial-damage-in-caenorhabditis-elegans-body-wall-muscles
#10
Kenta Momma, Takashi Homma, Ruri Isaka, Surabhi Sudevan, Atsushi Higashitani
Acute onset of organ failure in heatstroke is triggered by rhabdomyolysis of skeletal muscle. To gain insight into heat-induced muscle breakdown, we investigated alterations of Ca(2+) homeostasis and mitochondrial morphology in vivo in body-wall muscles of Caenorhabditis elegans exposed to elevated temperature. Heat stress for 3h at 35°C increased the concentration of free cytosolic Ca(2+), and led to mitochondrial fragmentation and subsequent dysfunction in the muscle cells. A similar mitochondrial fragmentation phenotype is induced in the absence of heat stress by treatment with a calcium ionophore, ionomycin...
June 1, 2017: Genetics
https://www.readbyqxmd.com/read/28569731/-%C3%B6-%C3%AF-%C3%B6-%C3%AF
#11
EDITORIAL
Howard A Rockman
L'dor vador, transliterated from the Hebrew above, is an ancient concept in Judaic scripture meaning "from generation to generation," which is now generally interpreted to mean that we have a responsibility to pass on teachings to future generations. It has been 5 years that I have been at the helm of the Duke-UNC Editorial Board of the Journal of Clinical Investigation and have had the privilege of publishing scientific knowledge that will be passed on to generations of future scientists. Now, with the selection of Dr...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28567145/applicability-of-the-moyers-probability-tables-in-adolescents-with-different-facial-biotypes
#12
Jorge J Pavani Carrillo, Maria C Rubial, Cristina Albornoz, Silvina Villalba, Patricia Damiani, Marta Rugani de Cravero
INTRODUCTION: The Moyers' probability tables are used in mixed dentition analysis to estimate the extent of space required for the alignment of canines and premolars, by correlating the mesiodistal size of lower incisors with the size of permanent canines and premolars. OBJECTIVE: This study intended to evaluate the applicability of the Moyer's probability tables for predicting the mesiodistal space needed for the correct location of premolars and permanent canines non-erupted, in adolescents of the city of Cordoba, Argentina, who show different facial biotypes...
2017: Open Dentistry Journal
https://www.readbyqxmd.com/read/28560556/shear-stress-induces-phenotypic-modulation-of-vascular-smooth-muscle-cells-via-ampk-mtor-ulk1-mediated-autophagy
#13
Liqian Sun, Manman Zhao, Aihua Liu, Ming Lv, Jingbo Zhang, Youxiang Li, Xinjian Yang, Zhongxue Wu
Phenotypic modulation of vascular smooth muscle cells (VSMCs) is involved in the pathophysiological processes of the intracranial aneurysms (IAs). Although shear stress has been implicated in the proliferation, migration, and phenotypic conversion of VSMCs, the molecular mechanisms underlying these events are currently unknown. In this study, we investigated whether shear stress(SS)-induced VSMC phenotypic modulation was mediated by autophagy involved in adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) pathway...
May 30, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28553505/discovery-of-a-small-molecule-targeting-ulk1-modulated-cell-death-of-triple-negative-breast-cancer-in-vitro-and-in-vivo
#14
Lan Zhang, Leilei Fu, Shouyue Zhang, Jin Zhang, Yuqian Zhao, Yaxin Zheng, Gu He, Shengyong Yang, Liang Ouyang, Bo Liu
UNC-51-like kinase 1 (ULK1) is well-known to initiate autophagy, and the downregulation of ULK1 has been found in most breast cancer tissues. Thus, the activation of ULK1-modulated autophagy could be a promising strategy for breast cancer therapy. In this study, we found that ULK1 was remarkably downregulated in breast cancer tissue samples by The Cancer Genome Atlas (TCGA) analysis and tissue microarray (TMA) analysis, especially in triple negative breast cancer (TNBC). To design a ULK1 agonist, we integrated in silico screening and chemical synthesis to acquire a series of small molecule candidates...
April 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28537930/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#15
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516065/mir-142-5p-disrupts-neuronal-morphogenesis-underlying-porcine-hemagglutinating-encephalomyelitis-virus-infection-by-targeting-ulk1
#16
Zi Li, Yungang Lan, Kui Zhao, Xiaoling Lv, Ning Ding, Huijun Lu, Jing Zhang, Huiqing Yue, Junchao Shi, Deguang Song, Feng Gao, Wenqi He
Porcine hemagglutinating encephalomyelitis virus (PHEV) invades the central nervous system (CNS) and causes neurodegenerative disease in suckling piglets, but the understanding of its neuropathogenicity for neurological dysfunction remains limited. Here, we report that miR-142-5p is localized to neurons and negatively regulates neuronal morphogenesis in porcine hemagglutinating encephalomyelitis (PHE). This phenotype was mediated by miR-142-5p inhibition of an mRNA encoding unc-51-like-kinase1 (Ulk1), which controls axon outgrowth and dendrite formation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28498429/sbi0206965-a-novel-inhibitor-of-ulk1-suppresses-non-small-cell-lung-cancer-cell-growth-by-modulating-both-autophagy-and-apoptosis-pathways
#17
Fang Tang, Pengchao Hu, Zetian Yang, Chao Xue, Jun Gong, Shaoxing Sun, Liu Shi, Shimin Zhang, Zhenzhen Li, Chunxu Yang, Junhong Zhang, Conghua Xie
Lung cancer is a major public health problem worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently sparked great interest, and it is thought to participate in a variety of diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a serine/threonine kinase, plays a central role in the autophagy pathway. However, the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with prognosis in lung cancer patients...
May 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28487481/functional-genomics-in-brugia-malayi-reveal-diverse-muscle-nachrs-and-differences-between-cholinergic-anthelmintics
#18
Saurabh Verma, Sudhanva Srinivas Kashyap, Alan Patrick Robertson, Richard John Martin
Many techniques for studying functional genomics of important target sites of anthelmintics have been restricted to Caenorhabditis elegans because they have failed when applied to animal parasites. To overcome these limitations, we have focused our research on the human nematode parasite Brugia malayi, which causes elephantiasis. Here, we combine single-cell PCR, whole muscle cell patch clamp, motility phenotyping (Worminator), and dsRNA for RNAi for functional genomic studies that have revealed, in vivo, four different muscle nAChRs (M-, L-, P-, and N-)...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28484969/autophagy-activation-alleviates-amyloid-%C3%AE-induced-oxidative-stress-apoptosis-and-neurotoxicity-in-human-neuroblastoma-sh-sy5y-cells
#19
Abhishek Kumar Singh, Akalabya Bissoyi, Mahendra Pratap Kashyap, Pradeep Kumar Patra, Syed Ibrahim Rizvi
Autophagy is an evolutionary conserved catabolic process that ensures continuous removal of damaged cell organelles and long-lived protein aggregates to maintain cellular homeostasis. Although autophagy has been implicated in amyloid-β (Aβ) production and deposition, its role in pathogenesis of Alzheimer's disease remains elusive. Thus, the present study was undertaken to assess the cytoprotective and neuroprotective potential of autophagy on Aβ-induced oxidative stress, apoptosis and neurotoxicity in human neuroblastoma SH-SY5Y cells...
May 8, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28477408/autoinhibition-of-munc18-1-modulates-synaptobrevin-binding-and-helps-to-enable-munc13-dependent-regulation-of-membrane-fusion
#20
Ewa Sitarska, Junjie Xu, Seungmee Park, Xiaoxia Liu, Bradley Quade, Karolina Stepien, Kyoko Sugita, Chad A Brautigam, Shuzo Sugita, Josep Rizo
Munc18-1 orchestrates SNARE complex assembly together with Munc13-1 to mediate neurotransmitter release. Munc18-1 binds to synaptobrevin, but the relevance of this interaction and its relation to Munc13 function are unclear. NMR experiments now show that Munc18-1 binds specifically and non-specifically to synaptobrevin. Specific binding is inhibited by a L348R mutation in Munc18-1 and enhanced by a D326K mutation designed to disrupt the 'furled conformation' of a Munc18-1 loop. Correspondingly, the activity of Munc18-1 in reconstitution assays that require Munc18-1 and Munc13-1 for membrane fusion is stimulated by the D326K mutation and inhibited by the L348R mutation...
May 6, 2017: ELife
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