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Protein restriction

Joana C Silva, Emmanuel Cornillot, Carrie McCracken, Sahar Usmani-Brown, Ankit Dwivedi, Olukemi O Ifeonu, Jonathan Crabtree, Hanzel T Gotia, Azan Z Virji, Christelle Reynes, Jacques Colinge, Vidya Kumar, Lauren Lawres, Joseph E Pazzi, Jozelyn V Pablo, Chris Hung, Jana Brancato, Priti Kumari, Joshua Orvis, Kyle Tretina, Marcus Chibucos, Sandy Ott, Lisa Sadzewicz, Naomi Sengamalay, Amol C Shetty, Qi Su, Luke Tallon, Claire M Fraser, Roger Frutos, Douglas M Molina, Peter J Krause, Choukri Ben Mamoun
Babesia microti, a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite...
October 18, 2016: Scientific Reports
David S Lynch, Wei Jia Zhang, Rahul Lakshmanan, Justin A Kinsella, Günes Altiokka Uzun, Merih Karbay, Zeynep Tüfekçioglu, Hasmet Hanagasi, Georgina Burke, Nicola Foulds, Simon R Hammans, Anupam Bhattacharjee, Heather Wilson, Matthew Adams, Mark Walker, James A R Nicoll, Jeremy Chataway, Nick Fox, Indran Davagnanam, Rahul Phadke, Henry Houlden
Importance: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations...
October 17, 2016: JAMA Neurology
Joanna J Hoppins, David R Gruber, Heather L Miears, Alexey S Kiryutin, Rustem D Kasymov, Darya V Petrova, Anton V Endutkin, Alexander V Popov, Alexandra V Yurkovskaya, Stanislav O Fedechkin, Jacob A Brockerman, Dmitry O Zharkov, Serge L Smirnov
8-oxoguanine is one of the most abundant and impactful oxidative DNA lesions. However, the reasons underlying its effects, especially those not directly explained by the altered base pairing ability, are poorly understood. We report the effect of the lesion on the action of EcoRI, a widely used restriction endonuclease. Introduction of 8-oxoguanine inside, or adjacent to, the GAATTC recognition site embedded within the Drew-Dickerson dodecamer sequence notably reduced the EcoRI activity. Solution NMR revealed that 8-oxoguanine in the DNA duplex causes substantial alterations in the sugar-phosphate backbone conformation, inducing a BI→BII transition...
2016: PloS One
Crystal N Marconett, Beiyun Zhou, Mitsuhiro Sunohara, Tiffany M Pouldar, HongJun Wang, Yixin Liu, Megan E Rieger, Evelyn Tran, Per Flodby, Kimberly D Siegmund, Edward D Crandall, Ite A Laird-Offringa, Zea Borok
Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed lineage tracing studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells...
October 17, 2016: American Journal of Respiratory Cell and Molecular Biology
Roshanak Farhoodi, Bahar Akbal-Delibas, Nurit Haspel
Discriminating native-like structures from false positives with high accuracy is one of the biggest challenges in protein-protein docking. While there is an agreement on the existence of a relationship between various favorable intermolecular interactions (e.g., Van der Waals, electrostatic, and desolvation forces) and the similarity of a conformation to its native structure, the precise nature of this relationship is not known. Existing protein-protein docking methods typically formulate this relationship as a weighted sum of selected terms and calibrate their weights by using a training set to evaluate and rank candidate complexes...
October 17, 2016: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
Alexandra E Paharik, Wilmara Salgado-Pabon, David K Meyerholz, Mark J White, Patrick M Schlievert, Alexander R Horswill
The Spl proteases are a group of six serine proteases that are encoded on the νSaβ pathogenicity island and are unique to Staphylococcus aureus. Despite their interesting biochemistry, their biological substrates and functions in virulence have been difficult to elucidate. We found that an spl operon mutant of the community-associated methicillin-resistant S. aureus USA300 strain LAC induced localized lung damage in a rabbit model of pneumonia, characterized by bronchopneumonia observed histologically. Disease in the mutant-infected rabbits was restricted in distribution compared to that in wild-type USA300-infected rabbits...
September 2016: MSphere
Adriana N Mudryj, Harold M Aukema, Paul Fieldhouse, B Nancy Yu
Poor eating habits among children are associated with negative health outcomes. The objective of this study was to use pulse/soy consumption as an indicator to evaluate the eating profile of young Manitobans. Data from the Canadian Community Health Survey Cycle 2.2 were used for analysis and restricted to Manitoba residents aged 2 to 18 years (n = 1840). Consumers were identified as individuals who reported eating at least 1 pulse/soy product during their recall. On any given day, 8.2% of Manitobans reported consumption of pulses/soy...
July 19, 2016: Canadian Journal of Dietetic Practice and Research
Jeniffer V Quijada, Nicholas Daniel Schmitt, Joseph P Salisbury, Jared R Auclair, Jeffrey Neil Agar
Stable isotope labeling techniques for quantitative top-down proteomics face unique challenges. These include unpre-dictable mass shifts following isotope labeling, which impedes analysis of unknown proteins and complex mixtures; and exponen-tially greater susceptibility to incomplete isotope incorporation, manifesting as broadening of labeled intact protein peaks. Like pop-ular bottom-up isotope labeling techniques, most top-down labeling methods are restricted to defined media/feed as well as amino acid auxotrophic organisms...
October 15, 2016: Analytical Chemistry
Mariko Okamoto, Ai Asamura, Ko Tanaka, Takefumi Soeda, Kyo Watanabe, Hiroyuki Mizuguchi, Teruo Ikeda
Adenovirus (Ad) vectors are widely used in cancer gene therapies. However, compared to human patients, relatively limited information is available on gene transduction efficiency or cell-specific cytotoxicity in canine tumor cells transduced with Ad vectors. Since epidermal growth factor receptor (EGFR) is highly expressed on canine breast tumor cells, we sought to develop an Ad vector based on the RGD fiber-mutant adenovirus vector (AdRGD) that expresses canine caspase 3 under the control of EGFR promoter...
October 16, 2016: Veterinary Research Communications
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD(+)-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways...
October 15, 2016: Aging
A D Vaudo, D Stabler, H M Patch, J F Tooker, C M Grozinger, G A Wright
Bee population declines are linked to reduction of nutritional resources due to land-use intensification, yet we know little about the specific nutritional needs of many bee species. Pollen provides bees their primary source of protein and lipids, but nutritional quality varies widely among host-plant species. Therefore, bees may be adapted to assess resource quality and adjust their foraging behavior to balance nutrition from multiple food sources. We tested the ability of two bumble bee species, Bombus terrestris and B...
October 14, 2016: Journal of Experimental Biology
Huilian Wang, Xi Lu, Xudong Yang, Nan Xu
BACKGROUND: To date, a definite conclusion about efficiency and safety of tenofovir alafenamide for patients with HIV-1 is not available. The aim of the study was to investigate the efficacy and safety of TAF versus TDF in antiretroviral regimens for patients with HIV-1. METHODS: PUBMED, MEDLINE, and EMBASE database were searched in March 2016, with no language restriction, for randomized controlled trials (RCTs). RESULTS: Six RCTs (n = 5888) met entry criteria...
October 2016: Medicine (Baltimore)
Olga Villamar Cruz, Tatiana Y Prudnikova, Daniela Araiza-Olivera, Carlos Perez-Plasencia, Neil Johnson, Andrea J Bernhardy, Michael Slifker, Catherine Renner, Jonathan Chernoff, Luis E Arias-Romero
Cells that are deficient in homologous recombination, such as those that have mutations in any of the Fanconi Anemia (FA)/BRCA genes, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, FA/BRCA-deficient tumors represent a small fraction of breast cancers, which might restrict the therapeutic utility of PARP inhibitor monotherapy. The gene encoding the serine-threonine protein kinase p21-activated kinase 1 (PAK1) is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors...
October 11, 2016: Oncotarget
Gu-Choul Shin, Hong Seok Kang, Ah Ram Lee, Kyun-Hwan Kim
Death receptors of TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) contribute to immune surveillance against virus-infected or transformed cells by promoting apoptosis. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling, leading to persistent infection. Here, we report that hepatitis B virus (HBV) X protein (HBx) restricts TNFSF10 receptor signaling via macroautophagy/autophagy-mediated degradation of TNFRSF10B/DR5, a TNFSF10 death receptor, and thus permits survival of virus-infected cells...
October 14, 2016: Autophagy
Roi Isaac, Ido Goldstein, Noa Furth, Neta Zilber, Sarina Streim, Sigalit Boura-Halfon, Eytan Elhanany, Varda Rotter, Moshe Oren, Yehiel Zick
Earlier reported small interfering RNA (siRNA) high-throughput screens, identified seven-transmembrane superfamily member 3 (TM7SF3) as a novel inhibitor of pancreatic β-cell death. Here we show that TM7SF3 maintains protein homeostasis and promotes cell survival through attenuation of ER stress. Overexpression of TM7SF3 inhibits caspase 3/7 activation. In contrast, siRNA-mediated silencing of TM7SF3 accelerates ER stress and activation of the unfolded protein response (UPR). This involves inhibitory phosphorylation of eukaryotic translation initiation factor 2α activity and increased expression of activating transcription factor-3 (ATF3), ATF4 and C/EBP homologous protein, followed by induction of apoptosis...
October 14, 2016: Cell Death and Differentiation
Juan Wu, Junfeng Zhang, Qinhong Cao, Junqin Wang, Zhen Zhan, Zhong Li
BACKGROUND: Secreted frizzled-related protein 1 (sFRP1), a negative regulator of the Wnt signaling pathway, is frequently inactivated in human gastric cancer. Genetic variants in the 3' untranslated region (UTR) of the gene may influence the strength of miRNA binding and the regulation of mRNA transcription, affecting the individual's cancer risk. This study aims to investigate the impact of variants in the 3' UTR of sFRP1 on the gastric cancer susceptibility in a Chinese population. PATIENTS AND METHODS: The association between 2 sFRP1 gene variation loci (rs1127379 and rs10088390) with minor allele frequency more than 0...
October 10, 2016: International Journal of Biological Markers
Martin S Weiß, Ioannis V Pavlidis, Paul Spurr, Steven P Hanlon, Beat Wirz, Hans Iding, Uwe T Bornscheuer
Application of amine transaminases (ATAs) for stereoselective amination of prochiral ketones represents an environmentally benign and economically attractive alternative to transition metal catalyzed asymmetric synthesis. However, the restrictive substrate scope has limited the conversion typically to non-sterically demanding scaffolds. Recently, we reported on the identification and design of fold class I ATAs that effect a highly selective asymmetric synthesis of a set of chiral aromatic bulky amines from the corresponding ketone precursors in high yield...
October 14, 2016: Organic & Biomolecular Chemistry
Carlos Henrique Tomich de Paula da Silva, Carlton Anthony Taft
The knowledge of the bioactive conformation for an active hit is relevant because of the easier interpretation and the general quality of the recognition models of protein and ligand. With the aim of investigating potential bioactive conformations without previous structural knowledge of the molecular target, we present herewith a 'protocol' that could be used which includes generation of low-energy conformations, calculations of tridimensional descriptors and investigation of structural similarity via principal component analysis...
October 14, 2016: Journal of Biomolecular Structure & Dynamics
Amy M Lange, Ekaterina S Altynova, Giang N Nguyen, Denise E Sabatino
Factor VIII (FVIII) is a large glycoprotein that is challenging to express both in vitro and in vivo. Several studies suggest that high levels of FVIII expression can lead to cellular stress. After gene transfer, transgene expression is restricted to a subset of cells and the increased FVIII load per cell may impact activation of the unfolded protein response. We sought to determine whether increased FVIII expression in mice after adeno-associated viral liver gene transfer would affect the unfolded protein response and/or immune response to the transgene...
2016: Molecular Therapy. Methods & Clinical Development
Donna Arvans, Yong-Chul Jung, Dionysios Antonopoulos, Jason Koval, Ignacio Granja, Mohamed Bashir, Eltayeb Karrar, Jayanta Roy-Chowdhury, Mark Musch, John Asplin, Eugene Chang, Hatim Hassan
Hyperoxaluria is a major risk factor for kidney stones and has no specific therapy, although Oxalobacter formigenes colonization is associated with reduced stone risk. O. formigenes interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion, via an unknown secretagogue. The difficulties in sustaining O. formigenes colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of O...
October 13, 2016: Journal of the American Society of Nephrology: JASN
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