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https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#1
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most- and 55 of No-DILI-concern)...
April 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28437468/role-of-cleavage-at-the-core-e1-junction-of-hepatitis-c-virus-polyprotein-in-viral-morphogenesis
#2
Véronique Pène, Matthieu Lemasson, Francis Harper, Gérard Pierron, Arielle R Rosenberg
In hepatitis C virus (HCV) polyprotein sequence, core protein terminates with E1 envelope signal peptide. Cleavage by signal peptidase (SP) separates E1 from the complete form of core protein, anchored in the endoplasmic reticulum (ER) membrane by the signal peptide. Subsequent cleavage of the signal peptide by signal-peptide peptidase (SPP) releases the mature form of core protein, which preferentially relocates to lipid droplets. Both of these cleavages are required for the HCV infectious cycle, supporting the idea that HCV assembly begins at the surface of lipid droplets, yet SPP-catalyzed cleavage is dispensable for initiation of budding in the ER...
2017: PloS One
https://www.readbyqxmd.com/read/28437463/relationship-of-the-crebc-two-component-regulatory-system-and-inner-membrane-protein-cred-with-swimming-motility-in-stenotrophomonas-maltophilia
#3
Hsin-Hui Huang, Wei-Ching Chen, Cheng-Wen Lin, Yi-Tsung Lin, Hsiao-Chen Ning, Yi-Chih Chang, Tsuey-Ching Yang
The CreBC two-component system (TCS) is a conserved regulatory system found in Escherichia coli, Aeromonas spp., Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. In this study, we determined how CreBC TCS regulates secreted protease activities and swimming motility using creB, creC, and creBC in-frame deletion mutants (KJΔCreB, KJΔCreC, and KJΔBC) of S. maltophilia KJ. Compared to wild-type KJ, KJΔCreB had a comparable secreted protease activity; however, the secreted protease activities were obviously reduced in KJΔCreC and KJΔBC, suggesting that CreC works together with another unidentified response regulator (not CreB) to regulate secreted protease activity...
2017: PloS One
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#4
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28437139/protection-against-common-bean-rust-conferred-by-a-gene-silencing-method
#5
Bret Cooper, Kimberly B Campbell
Rust disease of the dry bean plant, Phaseolus vulgaris, is caused by the fungus Uromyces appendiculatus. The fungus acquires its nutrients and energy from bean leaves using a specialized cell structure, the haustorium, through which it secretes effector proteins that contribute to pathogenicity by defeating the plant immune system. Candidate effectors have been identified by DNA sequencing and motif analysis, and some candidates have been observed in infected leaves by mass spectrometry. To assess their roles in pathogenicity, we have inserted small fragments of genes for five candidates into bean pod mottle virus...
April 24, 2017: Phytopathology
https://www.readbyqxmd.com/read/28436958/local-clearance-of-senescent-cells-attenuates-the-development-of-post-traumatic-osteoarthritis-and-creates-a-pro-regenerative-environment
#6
Ok Hee Jeon, Chaekyu Kim, Remi-Martin Laberge, Marco Demaria, Sona Rathod, Alain P Vasserot, Jae Wook Chung, Do Hun Kim, Yan Poon, Nathaniel David, Darren J Baker, Jan M van Deursen, Judith Campisi, Jennifer H Elisseeff
Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP). Removal of SnCs delays several pathologies and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability. Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery, yet their role in disease pathogenesis is unknown...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#7
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436943/transient-cell-specific-exo70a1-activity-in-the-casp-domain-and-casparian-strip-localization
#8
Lothar Kalmbach, Kian Hématy, Damien De Bellis, Marie Barberon, Satoshi Fujita, Robertas Ursache, Jean Daraspe, Niko Geldner
In a striking case of evolutionary convergence, polarized cell layers with ring-like diffusion barriers have evolved in both plant and animal lineages independently. In plants, ring-like Casparian strips become localized by the CASPARIAN STRIP MEMBRANE DOMAIN PROTEINS (CASPs). The mechanism of this striking localization, however, has remained enigmatic. Here we present a genetic screen aimed at isolating determinants of CASP localization. One of the mutants, lord of the rings 2 (lotr2)/exo70a1, displays dramatic de-localization of CASPs into randomly localized microdomains...
April 24, 2017: Nature Plants
https://www.readbyqxmd.com/read/28436939/an-inflammatory-bowel-disease-risk-variant-in-inava-decreases-pattern-recognition-receptor-induced-outcomes
#9
Jie Yan, Matija Hedl, Clara Abraham
Inflammatory bowel disease (IBD) is characterized by dysregulation in both cytokines and responses to intestinal microbes, and proper regulation of pattern recognition receptor (PRR) signaling is critical for intestinal immune homeostasis. Altered functions for the IBD risk locus containing rs7554511, which encompasses the C1orf106 gene (recently named INAVA), and roles for the protein encoded by the INAVA gene are unknown. Here, we investigated the role of INAVA and INAVA genotype in regulating PRR-initiated outcomes in primary human cells...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28436760/diabetes-management-by-probiotics-current-knowledge-and-future-pespective
#10
Aziz Homayouni-Rad, Ahmad-Reza Soroush, Leila Khalili, Leila Norouzi-Panahi, Zahra Kasaie, Hanieh-Sadat Ejtahed
Diabetes mellitus, a multifactorial disorder, is related to the intestinal microbiota via numerous molecular mechanisms. The vast increase in the prevalence of diabetes and its associated complications requires a natural and safe solution. There is a growing evidence of gut microbiota effi ciency in improving insulin resistance, impaired insulin secretion, and metabolic complications in diabetic patients. Probiotics are defi ned as live microorganisms that, when ingested in adequate amounts, exert health benefi ts to the host...
April 24, 2017: International Journal for Vitamin and Nutrition Research. Journal International de Vitaminologie et de Nutrition
https://www.readbyqxmd.com/read/28436493/an-attenuated-mycobacterium-tuberculosis-clinical-strain-with-a-defect-in-esx-1-secretion-induces-minimal-host-immune-responses-and-pathology
#11
Helena Strand Clemmensen, Niels Peter Hell Knudsen, Erik Michael Rasmussen, Jessica Winkler, Ida Rosenkrands, Ahmad Ahmad, Troels Lillebaek, David R Sherman, Peter Lawætz Andersen, Claus Aagaard
Although Mycobacterium tuberculosis (M.tb) DK9897 is an attenuated strain, it was isolated from a patient with extrapulmonary tuberculosis and vaccination with a subunit vaccine (H56) induced poor protection against it. Both attenuation and lack of protection are because M.tb DK9897 cannot secrete the EsxA virulence factor nor induce a host response against it. Genome sequencing identified a frameshift mutation in the eccCa1 gene. Since the encoded EccCa1 protein provides energy for ESX-1 secretion, it suggested a defect in the ESX-1 type VII secretion system...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436309/corticotropin-releasing-hormone-binding-protein-and-stress-from-invertebrates-to-humans
#12
Kyle D Ketchesin, Gwen S Stinnett, Audrey F Seasholtz
Corticotropin-releasing hormone (CRH) is a key regulator of the stress response. This peptide controls the hypothalamic-pituitary adrenal (HPA) axis as well as a variety of behavioral and autonomic stress responses via the two CRH receptors, CRH-R1 and CRH-R2. The CRH system also includes an evolutionarily conserved CRH-binding protein (CRH-BP), a secreted glycoprotein that binds CRH with subnanomolar affinity to modulate CRH receptor activity. In this review, we discuss the current literature on CRH-BP and stress across multiple species, from insects to humans...
April 23, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28436203/endoplasmic-reticulum-proteostasis-impairment-in-aging
#13
REVIEW
Gabriela Martínez, Claudia Duran-Aniotz, Felipe Cabral-Miranda, Juan P Vivar, Claudio Hetz
Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking, secretion, and their degradation. A reduction in the buffering capacity of the proteostasis network during aging may increase the risk to undergo neurodegeneration by enhancing the accumulation of misfolded proteins. As almost one-third of the proteome is synthetized at the endoplasmic reticulum (ER), maintenance of its proper function is fundamental to sustain neuronal function...
April 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28436089/a-novel-dense-granule-protein-gra41-regulates-timing-of-egress-and-calcium-sensitivity-in-toxoplasma-gondii
#14
Kaice A LaFavers, Karla M Márquez-Nogueras, Isabelle Coppens, Silvia N J Moreno, Gustavo Arrizabalaga
Toxoplasma gondii is an obligate intracellular apicomplexan parasite with high seroprevalence in humans. Repeated lytic cycles of invasion, replication and egress drive both the propagation and the virulence of this parasite. Key steps in this cycle, including invasion and egress, depend on tightly regulated calcium fluxes and, while many of the calcium-dependent effectors have been identified, the factors that detect and regulate the calcium fluxes are mostly unknown. To address this knowledge gap, we used a forward genetic approach to isolate mutants resistant to extracellular exposure to the calcium ionophore A23187...
April 24, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28436005/fast-and-reliable-strain-characterization-of-streptomyces-lividans-through-micro-scale-cultivation
#15
Joachim Koepff, Matthias Keller, C Konstantinos Tsolis, Tobias Busche, Christian Rückert, Mohamed B Hamed, Jozef Anné, Joern Kalinowski, Wolfgang Wiechert, Anastassios Economou, Marco Oldiges
Filamentous organisms of the genus Streptomyces play an important role in industrial production processes, due to their extensive secondary metabolism variability, as well as their ability to secrete efficiently large amounts of (heterologous) proteins. While genetic engineering tools are available to rapidly build up large strain libraries, the subsequent strain screening and bioprocess development still constitutes a bottleneck. This is due to the lack of reliable parallelized and accelerated cultivation techniques for morphologically challenging organisms...
April 24, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28436002/characterization-of-the-chondrocyte-secretome-in-photoclickable-poly-ethylene-glycol-hydrogels
#16
Margaret C Schneider, Christopher A Barnes, Stephanie J Bryant
Poly(ethylene glycol) (PEG) hydrogels are highly tunable platforms that are promising cell delivery vehicles for chondrocytes and cartilage tissue engineering. In addition to characterizing the type of extracellular matrix (ECM) that forms, understanding the types of proteins that are secreted by encapsulated cells may be important. Thus, the objectives for this study were to characterize the secretome of chondrocytes encapsulated in PEG hydrogels and determine whether the secretome varies as a function of hydrogel stiffness and culture condition...
April 24, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28435976/-role-of-igg-plasma-cells-in-the-change-of-protein-c-system-in-ulcerative-colitis
#17
Xu-Hong Lin, Jun-Ling Guo, Yu-Qing Wen, Yu-Xia Li, Dan-Dan Wei, Rui-Lin Yang, Xiao-Yun Mu, Hui-Chao Wang
The present study is designed to explore the role of plasma cells in the change of protein C system (PCS) in ulcerative colitis (UC). Dextran sulfate sodium (DSS, 4% in concentration) was used to induce mouse UC model. The plasma cells and the type of immune complex in colon were observed by immunofluorescence. The amount and type of plasma cells separated from colonic mucosal lamina propria were detected by flow cytometry using anti-CD54(+)CD38(+) and IgA/M/G antibodies, respectively. After stimulation of macrophages by IgG type immune complex, TNF-α and IL-6 levels were evaluated by ELISA...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28435841/evading-plant-immunity-feedback-control-of-the-t3ss-in-pseudomonas-syringae
#18
COMMENT
Christopher Waite, Jörg Schumacher, Milija Jovanovic, Mark Bennett, Martin Buck
Microbes are responsible for over 10% of the global yield losses in staple crops such as wheat, rice, and maize. Understanding the decision-making strategies that enable bacterial plant pathogens to evade the host immune system and cause disease is essential for managing their ever growing threat to food security. Many utilise the needle-like type III secretion system (T3SS) to suppress plant immunity, by injecting effector proteins that inhibit eukaryotic signalling pathways into the host cell cytoplasm. Plants can in turn evolve resistance to specific pathogens via recognition and blocking of the T3SS effectors, so leading to an ongoing co-evolutionary 'arms race' between pathogen and host pairs...
March 17, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28435837/staphylococcus-aureus-type-i-signal-peptidase-essential-or-not-essential-that-s-the-question
#19
COMMENT
Wouter L Hazenbos, Elizabeth Skippington, Man-Wah Tan
Secretion of proteins into the extracellular environment is crucial for the normal physiology and virulence of pathogenic bacteria. Type I signal peptidase (SPase I) mediates the final step of bacterial secretion, by cleaving proteins at their signal peptide once they are translocated by the Sec or twin-arginine (Tat) translocon. SPase I has long been thought to be essential for viability in multiple bacterial pathogens. Challenging this view, we and others have recently created Staphylococcus aureus bacteria lacking the SPase I SpsB that are viable and able to grow in vitro when over-expressing a native gene cassette encoding for a putative ABC transporter...
March 17, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28435518/sparc-overexpression-alters-microrna-expression-profiles-involved-in-tumor-progression
#20
Bhavesh K Ahir, Nasya M Elias, Sajani S Lakka
Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth in vitro and in vivo and also alters chemo sensitivity. MicroRNAs are a class of post-transcriptional gene regulators with critical functions in tumor progression. In addition, microRNA (miRNA) expression changes are also involved in chemo-resistance...
January 2017: Genes & Cancer
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