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https://www.readbyqxmd.com/read/27926996/small-molecule-modulator-of-sigma-2-receptor-is-neuroprotective-and-reduces-cognitive-deficits-and-neuro-inflammation-in-experimental-models-of-alzheimer-s-disease
#1
Bitna Yi, James J Sahn, Pooneh Memar Ardestani, Andrew K Evans, Luisa Scott, Jessica Z Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan Pierce-Shimomura, Stephen F Martin, Mehrdad Shamloo
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R binding ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease (AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca(2+) levels in human SK-N-SH neuroblastoma cells. The Sig2R antagonists SAS-0132 and JVW-1009 are neuroprotective in a C...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926992/inherited-diseases-caused-by-mutations-in-cathepsin-protease-genes
#2
REVIEW
Stephanie Ketterer, Alejandro Gomez-Auli, Larissa E Hillebrand, Agnese Petrera, Anett Ketscher, Thomas Reinheckel
Lysosomal cathepsins are proteolytic enzymes increasingly recognized as prognostic markers and potential therapeutic targets in a variety of diseases. In those conditions the cathepsins are mostly overexpressed, thereby driving the respective pathogenic processes. Although less known, there are also diseases with a genetic deficiency of cathepsins. In fact, nowadays six out of the fifteen human proteases called "cathepsins" have been linked to inherited syndromes. However, only three of these syndromes are typical lysosomal storage diseases, while the others are apparently caused by defective cleavage of specific protein substrates...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926991/human-mitochondrial-nucleases
#3
REVIEW
Francesco Bruni, Robert N Lightowlers, Zofia M Chrzanowska-Lightowlers
Mitochondria are cytosolic organelles that have many essential roles including ATP production via oxidative phosphorylation, apoptosis, iron-sulphur cluster biogenesis, heme and steroid synthesis, calcium homeostasis and regulation of cellular redox state. One of the unique features of these organelles is the presence of an extra-chromosomal mitochondrial genome (mtDNA), together with all the machinery required to replicate and transcribe mtDNA. The accurate maintenance of mitochondrial gene expression is essential for correct organellar metabolism, and is in part dependent on the levels of mtDNA and mt-RNA, which are regulated by balancing synthesis against degradation...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926952/growth-hormone-treatment-increases-plasma-irisin-concentration-in-patients-with-turner-syndrome
#4
B Wikiera, K Zawadzka, Ł Łaczmański, N Słoka, M Bolanowski, A Basiak, A Noczyńska, J Daroszewski
Irisin (Ir) deficiency may be a contributing factor in metabolic disease. This study aimed to investigate the effect of supraphysiological doses of recombinant human growth hormone (rhGH) on Ir plasma concentration in relation to metabolic disorders, including obesity and other components of metabolic syndrome. We studied 36 girls with Turner syndrome (mean age 8.2 years) treated with rhGH (0.05 mg/kg/day). Anthropometric data and fasting blood levels [e. g., Ir, insulin, glucose, glycated hemoglobin (HbA1c), IGF-1, IGFBP-3, cholesterol, insulin resistance (HOMA-IR), and β-cell function (HOMA-β)] were analyzed prior to and following rhGH therapy [mean (SD) follow-up of 1...
December 7, 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27926944/targeting-neutrophils-to-prevent-malaria-associated-acute-lung-injury-acute-respiratory-distress-syndrome-in-mice
#5
Michelle K Sercundes, Luana S Ortolan, Daniela Debone, Paulo V Soeiro-Pereira, Eliane Gomes, Elizabeth H Aitken, Antonio Condino Neto, Momtchilo Russo, Maria R D' Império Lima, José M Alvarez, Silvia Portugal, Claudio R F Marinho, Sabrina Epiphanio
Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926942/actin-related-protein-2-arp2-and-virus-induced-filopodia-facilitate-human-respiratory-syncytial-virus-spread
#6
Masfique Mehedi, Thomas McCarty, Scott E Martin, Cyril Le Nouën, Eugen Buehler, Yu-Chi Chen, Margery Smelkinson, Sundar Ganesan, Elizabeth R Fischer, Linda G Brock, Bo Liang, Shirin Munir, Peter L Collins, Ursula J Buchholz
Human respiratory syncytial virus (RSV) is an enveloped RNA virus that is the most important viral cause of acute pediatric lower respiratory tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement of host factors in the RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen in human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as a host factor involved in RSV infection. ARP2 knockdown did not reduce RSV entry, and did not markedly reduce gene expression during the first 24 hr of infection, but decreased viral gene expression thereafter, an effect that appeared to be due to inhibition of viral spread to neighboring cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926940/inflammasome-independent-nlrp3-restriction-of-a-protective-early-neutrophil-response-to-pulmonary-tularemia
#7
Sivakumar Periasamy, Hongnga T Le, Ellen B Duffy, Heather Chin, Jonathan A Harton
Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft challenge, more mature myeloid cells are elicited and are protective. In addition, inflammasome-dependent IL-1β and IL-18 are important for protection. As Nlrp3 appears dispensable for resistance to infection with Francisella novicida, we considered its role during infection with the virulent Type A strain SchuS4 and the attenuated Type B live vaccine strain LVS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926938/uncovering-the-pathogenic-landscape-of-helminth-opisthorchis-viverrini-infections-a-cross-sectional-study-on-contributions-of-physical-and-social-environment-and-healthcare-interventions
#8
Xueyuan Ong, Yi-Chen Wang, Paiboon Sithithaworn, Jutamas Namsanor, David Taylor, Luxana Laithavewat
BACKGROUND: Helminth infections have proven recalcitrant to control by chemotherapy in many parts of Southeast Asia and indeed farther afield. This study isolates and examines the influence of different aspects of the physical and social environment, and uneven intervention effort contributing to the pathogenic landscape of human Opisthorchis viverrini infections. METHODOLOGY: A cross-sectional survey, involving 632 participants, was conducted in four villages in northeast Thailand to examine the impact on prevalence and parasite burden of the reservoir dam environment, socio-economic, demographic, and behavioral factors, and health center intervention efforts...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926937/intensive-circulation-of-japanese-encephalitis-virus-in-peri-urban-sentinel-pigs-near-phnom-penh-cambodia
#9
Julien Cappelle, Veasna Duong, Long Pring, Lida Kong, Maud Yakovleff, Didot Budi Prasetyo, Borin Peng, Rithy Choeung, Raphaël Duboz, Sivuth Ong, San Sorn, Philippe Dussart, Arnaud Tarantola, Philippe Buchy, Véronique Chevalier
Despite the increased use of vaccination in several Asian countries, Japanese Encephalitis (JE) remains the most important cause of viral encephalitis in Asia in humans with an estimated 68,000 cases annually. Considered a rural disease occurring mainly in paddy-field dominated landscapes where pigs are amplifying hosts, JE may nevertheless circulate in a wider range of environment given the diversity of its potential hosts and vectors. The main objective of this study was to assess the intensity of JE transmission to pigs in a peri-urban environment in the outskirt of Phnom Penh, Cambodia...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926936/scaling-properties-of-dimensionality-reduction-for-neural-populations-and-network-models
#10
Ryan C Williamson, Benjamin R Cowley, Ashok Litwin-Kumar, Brent Doiron, Adam Kohn, Matthew A Smith, Byron M Yu
Recent studies have applied dimensionality reduction methods to understand how the multi-dimensional structure of neural population activity gives rise to brain function. It is unclear, however, how the results obtained from dimensionality reduction generalize to recordings with larger numbers of neurons and trials or how these results relate to the underlying network structure. We address these questions by applying factor analysis to recordings in the visual cortex of non-human primates and to spiking network models that self-generate irregular activity through a balance of excitation and inhibition...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27926935/serological-and-virological-evidence-of-crimean-congo-haemorrhagic-fever-virus-circulation-in-the-human-population-of-borno-state-northeastern-nigeria
#11
David N Bukbuk, Stuart D Dowall, Kuiama Lewandowski, Andrew Bosworth, Saka S Baba, Anitha Varghese, Robert J Watson, Andrew Bell, Barry Atkinson, Roger Hewson
BACKGROUND: Despite several studies on the seroprevalence of antibodies against Crimean-Congo Haemorrhagic Fever virus (CCHFV) from humans and cattle in Nigeria, detailed investigation looking at IgG and IgM have not been reported. Additionally, there have been no confirmed cases of human CCHFV infection reported from Nigeria. PRINCIPAL FINDINGS: Samples from sera (n = 1189) collected from four Local Government Areas in Borno State (Askira/Uba, Damboa, Jere and Maiduguri) were assessed for the presence of IgG and IgM antibodies...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926934/public-health-interventions-for-aedes-control-in-the-time-of-zikavirus-a-meta-review-on-effectiveness-of-vector-control-strategies
#12
Maha Bouzid, Julii Brainard, Lee Hooper, Paul R Hunter
BACKGROUND: There is renewed interest in effective measures to control Zika and dengue vectors. A synthesis of published literature with a focus on the quality of evidence is warranted to determine the effectiveness of vector control strategies. METHODOLOGY: We conducted a meta-review assessing the effectiveness of any Aedes control measure. We searched Scopus and Medline for relevant reviews through to May 2016. Titles, abstracts and full texts were assessed independently for inclusion by two authors...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#13
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926930/cytomegalovirus-specific-il-10-producing-cd4-t-cells-are-governed-by-type-i-ifn-induced-il-27-and-promote-virus-persistence
#14
Mathew Clement, Morgan Marsden, Maria A Stacey, Juneid Abdul-Karim, Silvia Gimeno Brias, Diana Costa Bento, Martin J Scurr, Peter Ghazal, Casey T Weaver, Gianluca Carlesso, Simon Clare, Simon A Jones, Andrew Godkin, Gareth W Jones, Ian R Humphreys
CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926929/functional-and-evolutionary-analyses-identify-proteolysis-as-a-general-mechanism-for-nlrp1-inflammasome-activation
#15
Joseph Chavarría-Smith, Patrick S Mitchell, Alvin M Ho, Matthew D Daugherty, Russell E Vance
Inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the Caspase-1 protease. Human NLRP1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. Recently, specific variants of mouse and rat NLRP1 were found to be activated upon N-terminal cleavage by the anthrax lethal factor protease. However, agonists for other NLRP1 variants, including human NLRP1, are not known, and it remains unclear if they are also activated by proteolysis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926928/an-interactome-centered-protein-discovery-approach-reveals-novel-components-involved-in-mitosome-function-and-homeostasis-in-giardia-lamblia
#16
Samuel Rout, Jon Paulin Zumthor, Elisabeth M Schraner, Carmen Faso, Adrian B Hehl
Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926927/male-circumcision-and-the-epidemic-emergence-of-hiv-2-in-west-africa
#17
João Dinis Sousa, Marina Padrão Temudo, Barry Stephen Hewlett, Ricardo Jorge Camacho, Viktor Müller, Anne-Mieke Vandamme
BACKGROUND: Epidemic HIV-2 (groups A and B) emerged in humans circa 1930-40. Its closest ancestors are SIVsmm infecting sooty mangabeys from southwestern Côte d'Ivoire. The earliest large-scale serological surveys of HIV-2 in West Africa (1985-91) show a patchy spread. Côte d'Ivoire and Guinea-Bissau had the highest prevalence rates by then, and phylogeographical analysis suggests they were the earliest epicenters. Wars and parenteral transmission have been hypothesized to have promoted HIV-2 spread...
2016: PloS One
https://www.readbyqxmd.com/read/27926925/dengue-in-the-middle-east-and-north-africa-a-systematic-review
#18
John M Humphrey, Natalie B Cleton, Chantal B E M Reusken, Marshall J Glesby, Marion P G Koopmans, Laith J Abu-Raddad
BACKGROUND: Dengue virus (DENV) infection is widespread and its disease burden has increased in past decades. However, little is known about the epidemiology of dengue in the Middle East and North Africa (MENA). METHODOLOGY / PRINCIPAL FINDINGS: Following Cochrane Collaboration guidelines and reporting our findings following PRISMA guidelines, we systematically reviewed available records across MENA describing dengue occurrence in humans (prevalence studies, incidence studies, and outbreak reports), occurrence of suitable vectors (Aedes aegypti and Aedes albopictus), and DENV vector infection rates...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926917/implementation-of-syndromic-surveillance-systems-in-two-rural-villages-in-senegal
#19
Cédric Abat, Philippe Colson, Hervé Chaudet, Jean-Marc Rolain, Hubert Bassene, Aldiouma Diallo, Oleg Mediannikov, Florence Fenollar, Didier Raoult, Cheikh Sokhna
Infectious diseases still represent a major challenge for humanity. In this context, their surveillance is critical. From 2010 to 2016, two Point-Of-Care (POC) laboratories have been successfully implemented in the rural Saloum region of Senegal. In parallel, a homemade syndromic surveillance system called EPIMIC was implemented to monitor infectious diseases using data produced by the POC laboratory of the Timone hospital in Marseille, France. The aim of this study is to describe the steps necessary for implementing EPIMIC using data routinely produced by two POC laboratories (POC-L) established in rural Senegal villages...
December 7, 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926905/sildenafil-in-pregnancy-a-systematic-review-of-maternal-tolerance-and-obstetric-and-perinatal-outcomes
#20
Liam Dunn, Ristan Greer, Vicki Flenady, Sailesh Kumar
INTRODUCTION: This systematic review evaluates maternal tolerance and obstetric and perinatal outcomes following sildenafil citrate (SC) use in human pregnancy. DATA SOURCES: Scopus, PubMed, Cochrane Library, Web of Science, Embase, and Google Scholar were searched. Relevant full-text studies including case series and reports in English were included. Publications were excluded if the pregnancy was terminated or if SC was used only at conception. RESULTS: Sixteen studies were included (n = 165)...
December 8, 2016: Fetal Diagnosis and Therapy
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