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https://www.readbyqxmd.com/read/28726994/cell-biology-symposium-practical-application-of-the-basic-aspects-of-glut4-membrane-trafficking-and-insulin-signaling-on-issues-related-to-animal-agriculture
#1
S B Smith
Because of the relatively short lifespans of beef cattle, membrane trafficking in relation to inflammation is not considered important unless it overtly affects productivity. However, glucose uptake and utilization is important for adipose tissue development in beef cattle, and increasing glucose utilization in intramuscular adipose tissue can increase carcass quality. Research from the 1980s demonstrated a lack of insulin sensitivity in isolated bovine adipocytes and adipose tissue explants incubated in vitro...
May 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28724750/disruption-of-a-structurally-important-extracellular-element-in-the-glycine-receptor-leads-to-decreased-synaptic-integration-and-signaling-resulting-in-severe-startle-disease
#2
Natascha Schaefer, Alexandra Berger, Johannes van Brederode, Fang Zheng, Yan Zhang, Sophie Leacock, Laura Littau, Sibylle Jablonka, Sony Malhotra, Maya Topf, Friederike Winter, Daria Davydova, Joseph W Lynch, Christopher J Paige, Christian Alzheimer, Robert J Harvey, Carmen Villmann
Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorder. We found that lack of synaptic integration of GlyRs, together with disrupted receptor function is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant shaky, caused by a missense mutation Q177K located in the extracellular β8-β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8-β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in cys-loop receptors...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28724635/heterodimers-of-the-transcriptional-factors-nfatc3-and-fosb-mediate-tissue-factor-expression-for-15-s-hydroxyeicosatetraenoic-acid-induced-monocyte-trafficking
#3
Sivareddy Kotla, Nikhlesh K Singh, Daniel Kirchhofer, Gadiparthi N Rao
Tissue factor (TF) is expressed in vascular and nonvascular tissues and functions in several pathways, including embryonic development, inflammation, and cell migration. Many risk factors for atherosclerosis, including hypertension, diabetes, obesity, and smoking, increase TF expression. To better understand the TF-related mechanisms in atherosclerosis, here we investigated the role of 12/15-lipoxygenase (12/15-LOX) in TF expression. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), the major product of human 15-LOXs 1 and 2, induced TF expression and activity in a time-dependent manner in the human monocytic cell line THP1...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#4
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28723133/label-free-nanopore-biosensor-for-rapid-and-highly-sensitive-cocaine-detection-in-complex-biological-fluids
#5
Sana Rauf, Ling Zhang, Asghar Ali, Yang Liu, Jinghong Li
Detection of very low amounts of illicit drugs such as cocaine in clinical fluids like serum continues to be important for many areas in the fight against drug trafficking. Herein, we constructed a label-free nanopore biosensor for rapid and highly sensitive detection of cocaine in human serum and saliva samples based on target-induced strand release strategy. In this bioassay, an aptamer for cocaine was prehybridized with a short complementary DNA. Owing to cocaine specific binding with aptamer, the short DNA strand was displaced from aptamer and translocation of this output DNA through α-hemolysin nanopore generated distinct spike-like current blockages...
February 24, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722539/an-autophagy-driven-pathway-of-atp-secretion-supports-the-aggressive-phenotype-of-braf-v600e-inhibitor-resistant-metastatic-melanoma-cells
#6
Shaun Martin, Aleksandra M Dudek-Peric, Abhishek D Garg, Heleen Roose, Seyma Demirsoy, Sofie Van Eygen, Freya Mertens, Peter Vangheluwe, Hugo Vankelecom, Patrizia Agostinis
The ingrained capacity of melanoma cells to rapidly evolve towards an aggressive phenotype is manifested by their increased ability to develop drug-resistance, evident in the case of vemurafenib, a therapeutic-agent targeting BRAF(V600E). Previous studies indicated a tight correlation between heightened melanoma-associated macroautophagy/autophagy and acquired Vemurafenib resistance. However, how this vesicular trafficking pathway supports Vemurafenib resistance remains unclear. Here, using isogenic human and murine melanoma cell lines of Vemurafenib-resistant and patient-derived melanoma cells with primary resistance to the BRAF(V600E) inhibitor, we found that the enhanced migration and invasion of the resistant melanoma cells correlated with an enhanced autophagic capacity and autophagosome-mediated secretion of ATP...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28721844/cd81-large-extracellular-loop-containing-fusion-proteins-with-a-dominant-negative-effect-on-hcv-cell-spread-and-replication
#7
Boyan Grigorov, Jennifer Molle, Eric Rubinstein, Fabien Zoulim, Birke Bartosch
The roles of CD81 in the hepatitis C virus (HCV) life cycle are multiple but remain ill characterized. CD81 is known to interact with the HCV glycoproteins as an attachment factor. It also has an important role in the post-attachment entry process. Its interaction with claudin-1, for example, is vital for viral uptake and trafficking. Furthermore, CD81 and its role in membrane organization and trafficking are thought to play a pivotal role in HCV replication. Some of these functions are particularly limited to human CD81; others can be substituted with CD81 molecules from other species...
July 18, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28720068/inhibitory-effect-of-par-4-combined-with-cisplatin-on-human-wilms-tumor-cells
#8
Jun Wang, Yunjie Li, Fangfang Ma, Huifeng Zhou, Rong Ding, Binbin Lu, Li Zou, Junxia Li, Rugang Lu
Wilms' tumor is associated with a high treatment success rate, but there is still a risk of recurrence. Cisplatin, which is one of the chemotherapeutic agents used for its treatment, is associated with a very high rate of resistance. Par-4 (prostate apoptosis response 4) is a tumor suppressor, which is capable of sensitizing tumor cells to chemotherapy. Therefore, the aim of this study was to determine whether combined treatment with Par-4 and cisplatin is effective for inhibiting growth of Wilms' tumor. Wilms' tumor and control cell samples were collected and analyzed by immunofluorescence assay and immunohistochemistry...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28719054/evolutionary-cell-biology-of-proteins-from-protists-to-humans-and-plants
#9
REVIEW
Helmut Plattner
During evolution, the cell as a fine-tuned machine had to undergo permanent adjustments to match changes in its environment, while "closed for repair work" was not possible. Evolution from protists (protozoa and unicellular algae) to multicellular organisms may have occurred in basically two lineages, Unikonta and Bikonta, culminating in mammals and angiosperms (flowering plants), respectively. Unicellular models for unikont evolution are myxamoebae (Dictyostelium) and increasingly also choanoflagellates, whereas, for bikonts, ciliates are preferred models...
July 18, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28717161/development-and-characterization-of-a-novel-prox1-egfp-lymphatic-and-schlemm-s-canal-reporter-rat
#10
Eunson Jung, Daniel Gardner, Dongwon Choi, Eunkyung Park, Young Jin Seong, Sara Yang, Jorge Castorena-Gonzalez, Antoine Louveau, Zhao Zhou, Gene K Lee, David P Perrault, Sunju Lee, Maxwell Johnson, George Daghlian, Maria Lee, Yeo Jin Hong, Yukinari Kato, Jonathan Kipnis, Michael J Davis, Alex K Wong, Young-Kwon Hong
The lymphatic system plays a key role in tissue fluid homeostasis, immune cell trafficking, and fat absorption. We previously reported a bacterial artificial chromosome (BAC)-based lymphatic reporter mouse, where EGFP is expressed under the regulation of the Prox1 promoter. This reporter line has been widely used to conveniently visualize lymphatic vessels and other Prox1-expressing tissues such as Schlemm's canal. However, mice have a number of experimental limitations due to small body size. By comparison, laboratory rats are larger in size and more closely model the metabolic, physiological, and surgical aspects of humans...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715456/the-trypanosoma-brucei-dihydroxyacetonephosphate-acyltransferase-tbdat-is-dispensable-for-normal-growth-but-important-for-synthesis-of-ether-glycerophospholipids
#11
Rachel Zufferey, Karim Pirani, Melanie Cheung-See-Kit, Sungsu Lee, Tyler A Williams, Daniel G Chen, Md Faruk Hossain
Glycerophospholipids are the most abundant constituents of biological membranes in Trypanosoma brucei, which causes sleeping sickness in humans and nagana in cattle. They are essential cellular components that fulfill various important functions beyond their structural role in biological membranes such as in signal transduction, regulation of membrane trafficking or control of cell cycle progression. Our previous studies have established that the glycerol-3-phosphate acyltransferase TbGAT is dispensable for growth, viability, and ester lipid biosynthesis suggesting the existence of another initial acyltransferase(s)...
2017: PloS One
https://www.readbyqxmd.com/read/28713781/the-metalloprotease-mpr1-engages-annexina2-to-promote-the-transcytosis-of-fungal-cells-across-the-blood-brain-barrier
#12
Sarisa Na Pombejra, Michelle Salemi, Brett S Phinney, Angie Gelli
Eukaryotic pathogens display multiple mechanisms for breaching the blood-brain barrier (BBB) and invading the central nervous system (CNS). Of the fungal spp., that cause disease in mammals, only some cross brain microvascular endothelial cells which constitute the BBB, and invade the brain. Cryptococcus neoformans, the leading cause of fungal meningoencephalitis, crosses the BBB directly by transcytosis or by co-opting monocytes. We previously determined that Mpr1, a secreted fungal metalloprotease, facilitates association of fungal cells to brain microvascular endothelial cells and we confirmed that the sole expression of CnMPR1 endowed S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28712489/plant-made-virus-like-particles-bearing-influenza-hemagglutinin-ha-recapitulate-early-interactions-of-native-influenza-virions-with-human-monocytes-macrophages
#13
Alexander I Makarkov, Sabrina Chierzi, Stéphane Pillet, Keith K Murai, Nathalie Landry, Brian J Ward
INTRODUCTION: Plant-made virus-like particles (VLP) bearing influenza virus hemagglutinins (HA) are novel vaccine candidates that induce cross-reactive humoral and poly-functional T cell responses. To better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of VLPs bearing either H1 (A/California/07/2009 (H1N1)) or H5 (A/Indonesia/05/2005 (H5N1)) with a human monocytoid cell line (U-937 cells) and human monocyte-derived macrophages (MDMs) as model antigen-presenting cells (APC)...
July 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28710278/phosphorylation-of-human-aquaporin-2-aqp2-allosterically-controls-its-interaction-with-the-lysosomal-trafficking-protein-lip5
#14
Jennifer Virginia Roche, Sabeen Survery, Stefan Kreida, Veronika Nesverova, Henry Ampah-Korsah, Maria Gourdon, Peter M T Deen, Susanna Toernroth-Horsefield
The interaction between the renal water channel aquaporin-2 (AQP2) and the lysosomal trafficking regulator-interacting protein LIP5 targets AQP2 to multivesicular bodies and facilitates lysosomal degradation. This interaction is part of a process which controls AQP2 apical membrane abundance in a vasopressin-dependent manner, allowing for urine volume adjustment. Vasopressin regulates phosphorylation at four sites within the AQP2 C-terminus (S256, S261, S264, T269), of which S256 is crucial and sufficient for AQP2 translocation from storage vesicles to the apical membrane...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28708859/interleukin-17a-induced-production-of-acute-serum-amyloid-a-by-keratinocytes-contributes-to-psoriasis-pathogenesis
#15
Elodie Couderc, Franck Morel, Pierre Levillain, Amandine Buffière-Morgado, Magalie Camus, Camille Paquier, Charles Bodet, Jean-François Jégou, Mathilde Pohin, Laure Favot, Martine Garcia, Vincent Huguier, Jiad Mcheik, Corinne Lacombe, Hans Yssel, Gérard Guillet, François-Xavier Bernard, Jean-Claude Lecron
BACKGROUND: Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 activated by proinflammatory cytokines. OBJECTIVES: We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation...
2017: PloS One
https://www.readbyqxmd.com/read/28705375/regulation-of-expression-and-trafficking-of-perforin-2-by-lps-and-tnf-%C3%AE
#16
Peng Xiong, Motoaki Shiratsuchi, Takamitsu Matsushima, Jiyuan Liao, Emi Tanaka, Yasuhiro Nakashima, Ryoichi Takayanagi, Yoshihiro Ogawa
Perforin-2 is constitutively expressed in macrophages that are required for bacterial control. In this study, we found that perforin-2 is expressed in human macrophages with two isoforms: full-length perforin-2a and a splice variant, perforin-2b. Two isoforms show different subcellular distributions. Perforin-2a was predominantly localized to the membrane of endosome-like vesicles by a C-terminal transmembrane domain. In contrast, the short isoform perforin-2b lacking the transmembrane domain failed to localize to the membrane of vesicles...
July 8, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28701417/protein-trafficking-in-the-mitochondrial-intermembrane-space-mechanisms-and-links-to-human-disease
#17
REVIEW
Lisa MacPherson, Kostas Tokatlidis
Mitochondria fulfill a diverse range of functions in cells including oxygen metabolism, homeostasis of inorganic ions and execution of apoptosis. Biogenesis of mitochondria relies on protein import pathways that are ensured by dedicated multiprotein translocase complexes localized in all sub-compartments of these organelles. The key components and pathways involved in protein targeting and assembly have been characterized in great detail over the last three decades. This includes the oxidative folding machinery in the intermembrane space, which contributes to the redox-dependent control of proteostasis...
July 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28700649/autophagy-mediates-cell-cycle-response-by-regulating-nucleocytoplasmic-transport-of-pax6-in-limbal-stem-cells-under-ultraviolet-a-stress
#18
Maria Laggner, Andreas Pollreisz, Gerald Schmidinger, Ursula Schmidt-Erfurth, Ying-Ting Chen
Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28698599/genes-and-molecular-pathways-underpinning-ciliopathies
#19
REVIEW
Jeremy F Reiter, Michel R Leroux
Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped us to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling...
July 12, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28698062/the-clandestine-multiple-graves-in-malaysia-the-first-mass-identification-operation-of-human-skeletal-remains
#20
Mohd Suhani Mohd Noor, Lay See Khoo, Wan Zafirah Zamaliana Alias, Ahmad Hafizam Hasmi, Mohamad Azaini Ibrahim, Mohd Shah Mahmood
The first ever mass identification operation of skeletal remains conducted for the clandestine graves in Malaysia consisted of 165 individuals unearthed from 28 human trafficking transit camps located in Wang Kelian, along the Thai-Malaysia border. A DVI response was triggered in which expert teams comprising of pathologists, anthropologists, odontologists, radiologists and DNA experts were gathered at the identified operation centre. The Department of Forensic Medicine, Hospital Sultanah Bahiyah, Alor Star, Kedah, located approximately 75km away from Wang Kelian, was temporarily converted into a victim identification centre (VIC) as it is the nearest available forensic facility to the mass grave site...
May 27, 2017: Forensic Science International
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