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Cristina Matthewman, Tyne W Miller-Fleming, David M Miller, Laura Bianchi
Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca(2+) overload. Mammalian ASIC1a and C. elegans MEC-4(d) neurotoxic channels conduct both Na(+) and Ca(2+) raising the possibility that direct Ca(2+) influx through these channels contributes to the intracellular Ca(2+) overload. However, we showed that homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca(2+) permeable yet it is neurotoxic, suggesting that Na(+) influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca(2+) block in the Xenopus oocytes expression system...
October 19, 2016: American Journal of Physiology. Cell Physiology
David Singer, Jacqueline E McLaughlin, Wendy C Cox
Objective. To assess the multiple mini-interview (MMI) as an admission tool for a satellite campus. Methods. In 2013, the MMI was implemented as part of a new admissions model at the UNC Eshelman School of Pharmacy. From fall 2013 to spring 2015, 73 candidates were interviewed by 15 raters on the satellite campus in Asheville, North Carolina. A many-facet Rasch measurement (MFRM) with three facets was used to determine the variance in candidate ratings attributable to rater severity, candidate ability, and station difficulty...
September 25, 2016: American Journal of Pharmaceutical Education
Claudia Manzoni, Adamantios Mamais, Dorien A Roosen, Sybille Dihanich, Marc P M Soutar, Helene Plun-Favreau, Rina Bandopadhyay, John Hardy, Sharon A Tooze, Mark R Cookson, Patrick A Lewis
Leucine rich repeat kinase 2 is a complex enzyme with both kinase and GTPase activities, closely linked to the pathogenesis of several human disorders including Parkinson's disease, Crohn's disease, leprosy and cancer. LRRK2 has been implicated in numerous cellular processes; however its physiological function remains unclear. Recent reports suggest that LRRK2 can act to regulate the cellular catabolic process of macroautophagy, although the precise mechanism whereby this occurs has not been identified. To investigate the signalling events through which LRRK2 acts to influence macroautophagy, the mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) and Beclin-1/phosphatidylinositol 3-kinase (PI3K) pathways were evaluated in astrocytic cell models in the presence and absence of LRRK2 kinase inhibitors...
October 12, 2016: Scientific Reports
Vanaja-Krishna Naik, Caroline-Annette Jacob, Deepavalli-Arumuga Nainar
BACKGROUND: The purpose of this descriptive study was to observe the distribution of four different classes of non-carious cervical root surface discrepancies in teeth with gingival recession. Additionally to explore the different treatment modalities in the literature for each of these defects. MATERIAL AND METHODS: A total of 150 subjects with at least one labial gingival recession were included in the study. 1400 teeth were evaluated using 2.5 X magnification loupes and UNC -15 probe for the presence of the cemento-enamel junction and step like defects according to Pini-Prato's classification: A-, identifiable CEJ without defect; A+, identifiable CEJ with defect; B-, unidentifiable CEJ without defect, B+, unidentifiable CEJ with defect...
October 2016: Journal of Clinical and Experimental Dentistry
Qianqian Zhao, Zhaopeng Wang, Zhaoxia Wang, Licun Wu, Weidong Zhang
Aspirin is known to have inhibitory effects on growth development in various types of tumor. In previous studies, it was observed to inhibit angiogenesis by downregulating the expression of vascular endothelial growth factor-A (VEGF-A). In the present study, murine H22 hepatocarcinoma and S180 sarcoma models were used to ascertain whether aspirin could inhibit angiogenesis and promote autophagy in tumors. Tumor-bearing mice were randomly divided into four groups with 10 mice per group: i) no treatment; ii) low-dose aspirin (100 mg/kg); iii) high-dose aspirin (400 mg/kg); iv) everolimus group (4 mg/kg)...
October 2016: Oncology Letters
Courtney R Bone, Yu-Tai Chang, Natalie E Cain, Shaun P Murphy, Daniel A Starr
Cellular migrations through constricted spaces are a critical aspect of many developmental and disease processes including hematopoiesis, inflammation, and metastasis. A limiting factor in these events is nuclear deformation. Here, we establish an in vivo model where nuclei can be visualized while moving through constrictions and use it to elucidate mechanisms for nuclear migration. C. elegans hypodermal P-cell larval nuclei traverse a narrow space about 5% their width. This constriction is blocked by fibrous organelles, structures connecting the muscles to cuticle through P cells...
October 3, 2016: Development
Chuncheng Liu, Jessica Mao, Terrence Wong, Weiming Tang, Lai Sze Tso, Songyuan Tang, Ye Zhang, Wei Zhang, Yilu Qin, Zihuang Chen, Wei Ma, Dianming Kang, Haochu Li, Meizhen Liao, Katie Mollan, Michael Hudgens, Barry Bayus, Shujie Huang, Bin Yang, Chongyi Wei, Joseph D Tucker
INTRODUCTION: Crowdsourcing has been used to spur innovation and increase community engagement in public health programmes. Crowdsourcing is the process of giving individual tasks to a large group, often involving open contests and enabled through multisectoral partnerships. Here we describe one crowdsourced video intervention in which a video promoting condom use is produced through an open contest. The aim of this study is to determine whether a crowdsourced intervention is as effective as a social marketing intervention in promoting condom use among high-risk men who have sex with men (MSM) and transgender male-to-female (TG) in China...
October 3, 2016: BMJ Open
Hong-Yi Zhang, Ya-Dong Ma, Ye Zhang, Jie Cui, Zi-Ming Wang
AIM: To evaluate the expression levels and prognostic significance of autophagy-related markers, UNC-51-like kinase1 (ULK1), Beclin1, microtubule-associated protein light chain 3 (LC3), autophagy-related gene 5 (ATG5) and mitochondrion-associated autophagy inhibitor, LRPPRC, in patients with metastatic prostate cancer (PCa) after androgen deprivation therapy (ADT). METHODS: Expressions of ULK1, Beclin1, LC3, ATG5 and LRPPRC were assessed by immunohistochemical examination in 198 patients with metastatic PCa who were receiving ADT (goserelin and bicalutamide)...
September 27, 2016: Journal of Clinical Pathology
A Franchi, M Cubilla, H A Guidobaldi, A A Bravo, L C Giojalas
STUDY QUESTION: Does the rapid transit through the uterine environment modulate the sperm physiological state? SUMMARY ANSWER: The uterosome-like vesicles (ULV) secreted by endometrial epithelial cells (EEC) in vitro are able to fuse with human spermatozoa, prompting their fertilising capacity. WHAT IS KNOWN ALREADY: Early studies suggest that sperm capacitation begins in the uterus and ends in the oviduct, and that a synergistic effect of both female organs may accelerate this process...
September 27, 2016: Molecular Human Reproduction
Bing Lang, Lei Zhang, Guanyu Jiang, Ling Hu, Wei Lan, Lei Zhao, Irene Hunter, Michal Pruski, Ning-Ning Song, Ying Huang, Ling Zhang, David St Clair, Colin D McCaig, Yu-Qiang Ding
Schizophrenia is a debilitating familial neuropsychiatric disorder which affects 1% of people worldwide. Although the heritability for schizophrenia approaches 80% only a small proportion of the overall genetic risk has been accounted for, and to date only a limited number of genetic loci have been definitively implicated. We have identified recently through genetic and in vitro functional studies, a novel serine/threonine kinase gene, unc-51-like kinase 4 (ULK4), as a rare risk factor for major mental disorders including schizophrenia...
September 27, 2016: Scientific Reports
Monica G Risley, Stephanie P Kelly, Kailiang Jia, Brock Grill, Ken Dawson-Scully
The microscopic nematode Caenorhabditis elegans has emerged as a valuable model for understanding the molecular and cellular basis of neurological disorders. The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide-array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C...
2016: PloS One
Cynthia L Gay, Sarah J Willis, Anna B Cope, JoAnn D Kuruc, Kara S Mcgee, Joe Sebastian, Amanda M Crooks, Mehri S Mckellar, David M Margolis, Susan A Fiscus, Charles B Hicks, Guido Ferrari, Joseph J Eron
BACKGROUND: Updated guidelines recommend immediate antiretroviral treatment (ART) during acute HIV infection (AHI), but efficacy data on regimens during AHI are limited. METHODS: We provide final data on a prospective, single-arm 96-week open label study of once daily emtricitabine/tenofovir/efavirenz initiated during AHI. The primary endpoint was the proportion of responders with HIV RNA <200 copies/mL by week 24. We examined time-to-viral-suppression, retention and CD8 cell activation through week 96 in relation to baseline characteristics...
September 20, 2016: AIDS
Abhishek Kumar Singh, Mahendra Pratap Kashyap, Vinay Kumar Tripathi, Sandeep Singh, Geetika Garg, Syed Ibrahim Rizvi
Autophagy is a catabolic process involved in the continuous removal of toxic protein aggregates and cellular organelles to maintain the homeostasis and functional integrity of cells. The mechanistic understanding of autophagy mediated neuroprotection during the development of neurodegenerative disorders remains elusive. Here, we investigated the potential role of rapamycin-induced activation of autophagy and PI3K/Akt1/mTOR/CREB pathway(s) in the neuroprotection of amyloid-beta (Aβ1-42)-insulted hippocampal neurons in rat model of Alzheimer's disease (AD) like phenotypes...
September 22, 2016: Molecular Neurobiology
Jennica Siddle, Sue Tolleson-Rinehart, Jane Brice
INTRODUCTION: In the domestic response to the outbreak of Ebola virus disease from 2013 to 2015, many US hospitals developed and implemented specialized training programs to care for patients with Ebola. This research reports on the effects of targeted training on Emergency Department (ED) staff's Ebola-related perceptions and attitudes. METHODS: One hundred fifty-nine members of the UNC Health Care System ED staff participated in a voluntary cross-sectional, anonymous Web survey administered using a one-time "post then pre" design...
2016: American Journal of Disaster Medicine
Sukriti Krishan, Des R Richardson, Sumit Sahni
Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor that monitors ATP levels. There is also evidence that AMPK has onco-suppressive properties. Iron plays a crucial role in cellular energy transducing pathways and tumor cell proliferation. Therefore, metals (e.g., iron) could play an important role in the regulation of AMPK-dependent pathways. Hence, this investigation examined the effect of the iron and copper chelator and potent anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), on the AMPK-mediated pathway...
September 15, 2016: Biochimica et Biophysica Acta
Ammar Kurdi, Mireille De Doncker, Arthur Leloup, Hugo Neels, Jean-Pierre Timmermans, Katrien Lemmens, Sandra Apers, Guido R Y De Meyer, Wim Martinet
BACKGROUND AND PURPOSE: Everolimus is an allosteric inhibitor of the mechanistic target of rapamycin complex 1 (mTORC1) widely known for its potent autophagy stimulating properties. Because everolimus shows poor solubility and stability in aqueous solutions, long-term in vivo administration in preclinical models is challenging. The aim of the present study was to evaluate the effects of short-term and long-term everolimus administration on mTORC1 inhibition and autophagy induction in mice...
September 16, 2016: British Journal of Pharmacology
Richard F Campbell, Walter W Walthall
Gene regulatory networks orchestrate the assembly of functionally related cells within a cellular network. Subtle differences often exist among functionally related cells within such networks. How differences are created among cells with similar functions has been difficult to determine due to the complexity of both the gene and the cellular networks. In Caenorhabditis elegans, the DD and VD motor neurons compose a cross-inhibitory, GABAergic network that coordinates dorsal and ventral muscle contractions during locomotion...
September 12, 2016: Developmental Biology
Spencer W Lindgren, Katie Kwaschyn, Ellen Roberts, Jan Busby-Whitehead, Lori A Evarts, Tiffany Shubert
INTRODUCTION: Falls among persons over 60 present significant risks for serious injury or debility. Falls place burdens on Emergency Medical Services (EMS), hospitals, and the adults themselves. Recognizing a need to provide interventions to minimize risk, Orange County Emergency Services (OCES), the Orange County Department on Aging (OCDoA), and the University of North Carolina at Chapel Hill (UNC) partnered to create the Stay Up and Active Program (SUAA). The purpose of this study was to determine if SUAA was a feasible program to implement in the community...
2016: Frontiers in Public Health
Zuhair S Natto, Majdi Aladmawy, Heba K Alshaeri, Mohammed Alasqah, Athena Papas
OBJECTIVE: To investigate possible correlations of clinical attachment level and pocket depth with number of medications in elderly individuals. METHODS: Intra-oral examinations for 139 patients visiting Tufts dental clinic were done. Periodontal assessments were performed with a manual UNC-15 periodontal probe to measure probing depth (PD) and clinical attachment level (CAL) at 6 sites. Complete lists of patients' medications were obtained during the examinations...
March 2016: Ghana Medical Journal
Shreesh Raj Sammi, Shalini Trivedi, Srikanta Kumar Rath, Abhishek Nagar, Sudeep Tandon, Alok Kalra, Rakesh Pandey
Cholinergic dysfunction is manifested in a plethora of neurodegenerative and psychiatric disorders such as Alzheimer's, Parkinson's, and Huntington's diseases. The extent of cholinergic affliction is maximum in Alzheimer's disease which is a progressive neurodegenerative disorder involving death of cholinergic neurons. To this date, the therapeutic management of cholinergic dysfunction is limited to provide symptomatic relief through the use of acetylcholinesterase (Ache) inhibitors only. The present study elaborates the potential of thyme oil and its individual components in curtailing cholinergic deficits...
September 6, 2016: Molecular Neurobiology
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