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https://www.readbyqxmd.com/read/29351849/the-dfm1-derlin-is-required-for-erad-retrotranslocation-of-integral-membrane-proteins
#1
Sonya Neal, Philipp A Jaeger, Sascha H Duttke, Christopher K Benner, Christopher Glass, Trey Ideker, Randolph Hampton
Endoplasmic reticulum (ER)-associated degradation (ERAD) removes misfolded proteins from the ER membrane and lumen by the ubiquitin-proteasome pathway. Retrotranslocation of ubiquitinated substrates to the cytosol is a universal feature of ERAD that requires the Cdc48 AAA-ATPase. Despite intense efforts, the mechanism of ER exit, particularly for integral membrane (ERAD-M) substrates, has remained unclear. Using a self-ubiquitinating substrate (SUS), which undergoes normal retrotranslocation independently of known ERAD factors, and the new SPOCK (single plate orf compendium kit) micro-library to query all yeast genes, we found the rhomboid derlin Dfm1 was required for retrotranslocation of both HRD and DOA ERAD pathway integral membrane substrates...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29345841/effects-of-high-impact-exercise-on-the-physical-properties-of-bones-of-ovariectomized-rats-fed-to-a-high-protein-diet
#2
Roberta Carminati Shimano, Gabriela Rezende Yanagihara, Ana Paula Macedo, Jessica Suzuki Yamanaka, Antônio Carlos Shimano, João Manuel R S Tavares, João Paulo Mardegan Issa
The aim of this study was to evaluate the effects of high-impact physical exercise as a prophylactic and therapeutic means in osteopenic bones of rats submitted to ovariectomy and protein diet intake. A total of 64 Wistar rats were divided into eight groups (n=8 each), being: OVX, ovx, standard diet and sedentary; OVXE, ovx, standard diet and jump; OVXP, ovx, high-protein diet and sedentary; and OVXEP, ovx, high-protein diet and jump; SH, sham, standard diet and sedentary; SHE, sham, standard diet and jump; SHP, sham, high-protein diet and sedentary; and SHEP, sham, high-protein-diet and jump...
January 18, 2018: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/29321445/negative-regulation-of-b-cell-responses-and-self-tolerance-to-rna-related-lupus-self-antigen
#3
Takeshi Tsubata
The antibody response to RNA-related antigens such as Sm/RNP requires the endosomal RNA sensor TLR7, and this process is crucial in the development of systemic lupus erythematosus at least in animal models. The inhibitory B cell receptor CD72 is unique because it recognizes Sm/RNP and specifically inhibits the activation of Sm/RNP-reactive B cells by activating SH2-containing protein tyrosine phosphatase 1 (SHP-1). In the normal immune system, Sm/RNP-reactive B cells are tolerized by a unique mechanism that probably involves SHP-1...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29318096/a-two-photon-ratiometric-fluorescent-probe-for-imaging-of-hydrogen-peroxide-levels-in-rat-organ-tissues
#4
Chang Su Lim, Myoung Ki Cho, Mi Yeon Park, Hwan Myung Kim
Hydrogen peroxide (H2O2) is important in the regulation of a variety of biological processes and is involved in various diseases. Quantitative measurement of H2O2 levels at the subcellular level is important for understanding its positive and negative effects on biological processes. Herein, a two-photon ratiometric fluorescent probe (SHP-Cyto) with a boronate-based carbamate leaving group as the H2O2 reactive trigger and 6-(benzo[d]thiazol-2'-yl)-2-(N,N-dimethylamino) naphthalene (BTDAN) as the fluorophore was synthesized and examined for its ability to detect cytosolic H2O2 in situ...
January 2018: ChemistryOpen
https://www.readbyqxmd.com/read/29298416/prion-like-propagation-of-%C3%AE-synuclein-is-regulated-by-the-fc%C3%AE-riib-shp-1-2-signaling-pathway-in-neurons
#5
Yu Ree Choi, Seon-Heui Cha, Seo-Jun Kang, Jae-Bong Kim, Ilo Jou, Sang Myun Park
Recent evidence of prion-like propagation of α-synuclein (α-syn) into neighboring neurons set up a paradigm to elucidate the mechanism of progression of Parkinson's disease (PD) and to develop therapeutic strategies. Here, we show that FcγRIIB expressed in neurons functions as a receptor for α-syn fibrils and mediates cell-to-cell transmission of α-syn. SHP-1 and 2 are activated downstream by α-syn fibrils through FcγRIIB and play an important role in cell-to-cell transmission of α-syn. Also, taking advantage of a co-culture system, we show that cell-to-cell transmission of α-syn induces intracellular Lewy body-like inclusion body formation and that the FcγRIIB/SHP-1/2 signaling pathway is involved in it...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29291072/multiple-steady-states-and-the-form-of-response-functions-to-antigen-in-a-model-for-the-initiation-of-t-cell-activation
#6
Alan D Rendall, Eduardo D Sontag
The aim of this paper is to study the qualitative behaviour predicted by a mathematical model for the initial stage of T-cell activation. The state variables in the model are the concentrations of phosphorylation states of the T-cell receptor (TCR) complex and the phosphatase SHP-1 in the cell. It is shown that these quantities cannot approach zero and that the model possesses more than one positive steady state for certain values of the parameters. It can also exhibit damped oscillations. It is proved that the chemical concentration which represents the degree of activation of the cell, that of the maximally phosphorylated form of the TCR complex, is, in general, a non-monotone function of the activating signal...
November 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/29288235/ring-finger-protein-6-amplification-activates-jak-stat3-pathway-by-modifying-shp-1-ubiquitylation-and-associates-with-poor-outcome-in-colorectal-cancer
#7
Qian Liang, Dan Ma, Xiaoqiang Zhu, Zhenhua Wang, Tian-Tian Sun, Chaoqin Shen, Tingting Yan, Xianglong Tian, TaChuang Yu, Fangfang Guo, JiaYin Tang, Yanwei Lin, Huimin Chen, Chao Zhou, Zhizheng Ge, Ming Zhong, Jinxian Chen, Qiang Liu, Zheng Wang, Jing-Yuan Fang, Hao-Yan Chen, Jie Hong
Objective The E3 ubiquitin ligase RNF6 (RING-finger protein 6) plays a crucial role in carcinogenesis. However, the copy number and expression of RNF6 were rarely reported in colorectal cancer (CRC). We aimed to explore the mechanical, biological and clinical role of RNF6 in CRC initiation and progression. Design The copy number and expression of RNF6 were analyzed from Tumorscape and The Cancer Genome Atlas (TCGA) datasets. Gene expressions were examined by real time PCR, western blot and immunohistochemical staining...
December 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29288206/il-4-induced-gene-1-a-negative-immune-checkpoint-controlling-b-cell-differentiation-and-activation
#8
Lloyd Bod, Laetitia Douguet, Cédric Auffray, Renée Lengagne, Fériel Bekkat, Elena Rondeau, Valérie Molinier-Frenkel, Flavia Castellano, Yolande Richard, Armelle Prévost-Blondel
Emerging data highlight the crucial role of enzymes involved in amino acid metabolism in immune cell biology. IL-4-induced gene-1 (IL4I1), a secreted l-phenylalanine oxidase expressed by APCs, has been detected in B cells, yet its immunoregulatory role has only been explored on T cells. In this study, we show that IL4I1 regulates multiple steps in B cell physiology. Indeed, IL4I1 knockout mice exhibit an accelerated B cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B cells...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29286073/proteasome-inhibition-protects-against-diet-induced-gallstone-formation-through-modulation-of-cholesterol-and-bile-acid-homeostasis
#9
Eun-Ji Lee, Min Hee Kim, Ye-Ryung Kim, Joo-Won Park, Woo-Jae Park
Gallstone disease is one of the most prevalent and costly gastrointestinal disorders worldwide. Gallstones are formed in the biliary system by cholesterol secretions in bile, which result from excess cholesterol, a deficiency in bile salts or a combination of the two. The present study examined the effects of proteasome inhibition on gallstone formation using the proteasome inhibitors bortezomib (BT) and carfilzomib (CF). C57BL/6J mice were fed a lithogenic diet to generate gallstones and injected with BT or CF for 12 weeks...
December 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29283075/evaluation-of-farnesoid-x-receptor-target-gene-induction-in-human-hepatocytes-amino-acid-conjugation
#10
Jean Simmermacher, Michael Sinz
BACKGROUND: The nuclear hormone receptor, farnesoid X receptor (FXR) regulates the transcription of genes associated with bile acid metabolism and disposition. OBJECTIVE: This study investigates possible changes in the expression of target genes responsible for amino acid conjugation, i.e., bile acid-CoA synthetase (BACS) and bile acid-CoA: amino acid N-acetyltransferase (BAT). These genes have been shown to be inducible by FXR agonists in rat models, however, to date no studies have been conducted in a human hepatocyte model...
December 27, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29280057/effects-of-sleeve-gastrectomy-on-nonalcoholic-fatty-liver-disease-in-an-obese-rat-model
#11
Kiminori Watanabe, Masayuki Ohta, Hiroomi Takayama, Kazuhiro Tada, Yuki Shitomi, Takahide Kawasaki, Yuichiro Kawano, Yuichi Endo, Yukio Iwashita, Masafumi Inomata
BACKGROUND/AIM: Laparoscopic sleeve gastrectomy (SG) is an increasingly used bariatric surgery, which is reported to be effective for nonalcoholic fatty liver disease (NAFLD). Recently, activation of farnesoid X receptor (FXR), which is a nuclear receptor of bile acid (BA), was reported to contribute to the resolution of NAFLD. However, it is unclear whether SG has an effect on expression of FXR in the liver. We aimed to investigate the expression of FXR and its related factors in the liver after SG and to clarify the relationship between changes in FXR expression and NAFLD in an obese rat model...
December 26, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/29249757/-familial-summer-type-hypersensitivity-pneumonitis-induced-in-summer-and-winter-at-the-work-place
#12
Toshihisa Ishikawa, Tsutomu Kawasaki, Kazuhiro Shimaya, Yukiko Abe, Yuki Kata, Kaori Okayasu, Koji Unoura, Yoichi Nakamura
We report two family members, a 64-year-old woman (patient 1) and her 37-year-old son (patient 2) diagnosed with summer-type hypersensitivity pneumonitis (SHP). Both patients had high serum titers of anti-Trichosporon asahii antibody. The patients lived in the same house and worked in the same barbershop. Patient 1 was diagnosed with SHP in the summer, and she reacted positively to the provocation test at the work place, but not in the house. Patient 2 was diagnosed with SHP in the winter. Generally, SHP develops and is diagnosed in the summer...
2017: Arerugī, [Allergy]
https://www.readbyqxmd.com/read/29247647/moesin-and-myosin-iia-modulate-phagolysosomal-biogenesis-in-macrophages
#13
Carolina P Gomez, Albert Descoteaux
Biogenesis of phagolysosomes is central to the elimination of pathogens by macrophages. We previously showed that Src homology region 2 domain-containing phosphatase 1 (SHP-1) participates in the regulation of phagosome maturation. Through proteomics, we identified moesin and the non-muscle myosin-IIA as proteins interacting with SHP-1 during phagocytosis. Silencing of either moesin or myosin IIA with small interfering RNA inhibited phagosomal acidification and recruitment of LAMP-1. Moreover, the intraphagosomal oxidative burst was impaired in the absence of either SHP-1 or myosin IIA but not moesin...
December 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29243851/alterations-in-gene-expression-in-vitamin-d-deficiency-down-regulation-of-liver-cyp7a1-and-renal-oat3-in-mice
#14
Holly P Quach, Keumhan Noh, Stacie Y Hoi, Adrie Bruinsma, Geny M M Groothuis, Albert P Li, Edwin C Y Chow, K Sandy Pang
The vitamin D-deficient model, established in C57BL/6 mouse after 8-week feeding of vitamin D-deficient diets in absence or presence of added calcium, was found associated with elevated levels of plasma parathyroid hormone (PTH) and plasma and liver cholesterol, and reduction in cholesterol 7α-hydroxylase (Cyp7a1, rate-limiting enzyme for cholesterol metabolism) and renal Oat3 mRNA/protein expression levels. There was, however, no change in plasma calcium and phosphate levels. Appraisal of the liver revealed up-regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D-deficiency...
December 15, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29235014/increased-bile-acid-signals-after-duodenal-jejunal-bypass-improve-non-alcoholic-steatohepatitis-nash-in-a-rodent-model-of-diet-induced-nash
#15
Takahiro Tsuchiya, Takeshi Naitoh, Munenori Nagao, Naoki Tanaka, Kazuhiro Watanabe, Hirofumi Imoto, Tomohiro Miyachi, Fuyuhiko Motoi, Michiaki Unno
BACKGROUND: The increasing incidence of non-alcoholic steatohepatitis (NASH) has resulted in it becoming a common cause of liver-related mortality; however, no efficient treatment has been established. It has been reported that bariatric surgery improves metabolic comorbidities, such as diabetes mellitus and NASH. Although the mechanism is unclear, it is thought that the changes in bile acid (BA) signaling via its nuclear receptor, farnesoid X receptor (FXR), produce various metabolic effects...
December 12, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/29226620/comparative-potency-of-obeticholic-acid-and-natural-bile-acids-on-fxr-in-hepatic-and-intestinal-in%C3%A2-vitro-cell-models
#16
Yuanyuan Zhang, Carl LaCerte, Sanjay Kansra, Jonathan P Jackson, Kenneth R Brouwer, Jeffrey E Edwards
Obeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating FXR-mediated mechanisms in a physiologically relevant in vitro cell system, Sandwich-cultured Transporter Certified ™ human primary hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in combination with OCA in SCHH...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29220323/grasp-performance-of-a-soft-synergy-based-prosthetic-hand-a-pilot-study
#17
Alycia S Gailey, Sasha Blue Godfrey, Ryan E Breighner, Karen L Andrews, Kristin D Zhao, Antonio Bicchi, Marco Santello
Current prosthetic hands are frequently rejected in part due to limited functionality and versatility. We assessed the feasibility of a novel prosthetic hand, the SoftHand Pro (SHP), whose design combines soft robotics and hand postural synergies. Able-bodied subjects ( ) tracked cursor motion by opening and closing the SHP and performed a grasp-lift-hold-release (GLHR) task with a sensorized cylindrical object of variable weight. The SHP control was driven by electromyographic (EMG) signals from two antagonistic muscles...
December 2017: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/29218329/high-mobility-group-protein-2-regulated-by-microrna-127-and-small-heterodimer-partner-modulates-pluripotency-of-mouse-embryonic-stem-cells-and-liver-tumor-initiating-cells
#18
Yulan Zhao, Zhihong Yang, Jianguo Wu, Raymond Wu, Santosh K Keshipeddy, Dennis Wright, Li Wang
High-mobility-group protein 2 (HMGB2) expression is upregulated in human liver cancer. However, little is known about its regulatory function. Here we establish HMGB2 as a new modulator of the pluripotency of mouse embryonic stem cells (ESCs). Similar to OCT4 and SOX2, HMGB2 protein is highly expressed in undifferentiated CGR8 cells, whereas it undergoes rapid decline during embryonic body (EB) formation. HMGB2 interacts with OCT4, increases protein expression of OCT4 and SOX2, and enhances their transcriptional activities...
October 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29216714/fabrication-of-hyperbranched-block-statistical-copolymer-based-prodrug-with-dual-sensitivities-for-controlled-release
#19
Luping Zheng, Yunfei Wang, Xianshuo Zhang, Liwei Ma, Baoyan Wang, Xiangling Ji, Hua Wei
Dendrimer with hyperbranched structure and multivalent surface is regarded as one of the most promising candidates close to the ideal drug delivery systems, but the clinical translation and scale-up production of dendrimer has been hampered significantly by the synthetic difficulties. Therefore there is considerable scope for the development of novel hyperbranched polymer that can not only address the drawbacks of dendrimer but maintain its advantages. The reversible addition-fragmentation chain transfer self-condensing vinyl polymerization (RAFT-SCVP) technique has enabled facile preparation of segmented hyperbranched polymer (SHP) by using chain transfer monomer (CTM)-based double-head agent during the past decade...
December 7, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29216638/microrna-122-inhibits-lipid-droplet-formation-and-hepatic-triglyceride-accumulation-via-yin-yang-1
#20
Guo-Yi Wu, Chen Rui, Ji-Qiao Chen, Eiketsu Sho, Shan-Shan Zhan, Xian-Wen Yuan, Yi-Tao Ding
BACKGROUND/AIMS: An increase in intracellular lipid droplet formation and hepatic triglyceride (TG) content usually results in nonalcoholic fatty liver disease. However, the mechanisms underlying the regulation of hepatic TG homeostasis remain unclear. METHODS: Oil red O staining and TG measurement were performed to determine the lipid content. miRNA expression was evaluated by quantitative PCR. A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1) by microRNA (miR)-122...
2017: Cellular Physiology and Biochemistry
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