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https://www.readbyqxmd.com/read/29925901/gitelman-s-syndrome-characterization-of-a-novel-c-1181g-a-point-mutation-and-functional-classification-of-the-known-mutations
#1
Verdiana Ravarotto, Johannes Loffing, Dominique Loffing-Cueni, Michèle Heidemeyer, Elisa Pagnin, Lorenzo A Calò, Gian Paolo Rossi
We have investigated the mechanisms by which a novel missense point mutation (c.1181G>A) found in two sisters causes Gitelman's syndrome by impairing the sodium chloride co-transporter (NCC, encoded by SLC12A3 gene) function. The cDNA and in vitro transcribed mRNA of either wild-type or mutated SLC12A3 were transfected into HEK293 cells and injected into Xenopus laevis oocytes, respectively. The expression, maturation, trafficking, and function of the mutated and wild-type NCC were assessed by Western blotting, immunohistochemistry and 22 Na+ uptake studies...
June 20, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29925353/bibliometric-analysis-of-global-migration-health-research-in-peer-reviewed-literature-2000-2016
#2
Waleed M Sweileh, Kolitha Wickramage, Kevin Pottie, Charles Hui, Bayard Roberts, Ansam F Sawalha, Saed H Zyoud
BACKGROUND: The health of migrants has become an important issue in global health and foreign policy. Assessing the current status of research activity and identifying gaps in global migration health (GMH) is an important step in mapping the evidence-base and on advocating health needs of migrants and mobile populations. The aim of this study was to analyze globally published peer-reviewed literature in GMH. METHODS: A bibliometric analysis methodology was used...
June 20, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29924990/hif1%C3%AE-deletion-limits-tissue-regeneration-via-aberrant-b-cell-accumulation-in-experimental-pancreatitis
#3
Kyoung Eun Lee, Michelle Spata, Richard Maduka, Robert H Vonderheide, M Celeste Simon
Pancreatitis is an inflammatory disease of the exocrine pancreas and ranks among the most common gastrointestinal disorders. Inflamed tissues frequently experience conditions of insufficient oxygen availability, or hypoxia. Here, we demonstrate that hypoxia and consequent stabilization of the hypoxia-inducible factor 1α (HIF1α) transcription factor occur in murine and human pancreatitis. Mice lacking pancreas-specific HIF1α expression display markedly impaired pancreatic regeneration following cerulein-induced pancreatitis, which is associated with excessive intrapancreatic B cell accumulation...
June 19, 2018: Cell Reports
https://www.readbyqxmd.com/read/29920219/cilia-protein-ift88-regulates-extracellular-protease-activity-by-optimizing-lrp-1-mediated-endocytosis
#4
Clarissa R Coveney, Isabella Collins, Megan Mc Fie, Anastasios Chanalaris, Kazuhiro Yamamoto, Angus K T Wann
Matrix protease activity is fundamental to developmental tissue patterning and remains influential in adult homeostasis. In cartilage, the principal matrix proteoglycan is aggrecan, the protease-mediated catabolism of which defines arthritis; however, the pathophysiologic mechanisms that drive aberrant aggrecanolytic activity remain unclear. Human ciliopathies exhibit altered matrix, which has been proposed to be the result of dysregulated hedgehog signaling that is tuned within the primary cilium. Here, we report that disruption of intraflagellar transport protein 88 (IFT88), a core ciliary trafficking protein, increases chondrocyte aggrecanase activity in vitro...
June 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29916852/epithelial-sodium-channel-biogenesis-and-quality-control-in-the-early-secretory-pathway
#5
Teresa M Buck, Jeffrey L Brodsky
PURPOSE OF REVIEW: The epithelial sodium channel, ENaC, is responsible for Na reabsorption in several epithelia and is composed of homologous α, β, and γ subunits. Here, we will explore the differential regulation of ENaC subunits during biogenesis in the early secretory pathway. RECENT FINDINGS: ENaC subunits are subject to numerous posttranslational modifications, including glycosylation, protease activation, disulfide bond formation, palmitoylation, and glycosylation, each of which modulate channel function...
June 18, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29915698/structural-insights-and-characterization-of-human-npas4-protein
#6
Ammad Fahim, Zaira Rehman, Muhammad Faraz Bhatti, Amjad Ali, Nasar Virk, Amir Rashid, Rehan Zafar Paracha
Npas4 is an activity dependent transcription factor which is responsible for gearing the expression of target genes involved in neuro-transmission. Despite the importance of Npas4 in many neuronal diseases, the tertiary structure of Npas4 protein along with its physico-chemical properties is limited. In the current study, first we perfomed the phylogenetic analysis of Npas4 and determined the content of hydrophobic, flexible and order-disorder promoting amino acids. The protein binding regions, post-translational modifications and crystallization propensity of Npas4 were predicted through different in-silico methods...
2018: PeerJ
https://www.readbyqxmd.com/read/29915530/-n-glycosylation-regulates-the-trafficking-and-surface-mobility-of-glun3a-containing-nmda-receptors
#7
Kristyna Skrenkova, Sanghyeon Lee, Katarina Lichnerova, Martina Kaniakova, Hana Hansikova, Martin Zapotocky, Young Ho Suh, Martin Horak
N -methyl-D-aspartate receptors (NMDARs) play critical roles in both excitatory neurotransmission and synaptic plasticity. NMDARs containing the nonconventional GluN3A subunit have different functional properties compared to receptors comprised of GluN1/GluN2 subunits. Previous studies showed that GluN1/GluN2 receptors are regulated by N -glycosylation; however, limited information is available regarding the role of N -glycosylation in GluN3A-containing NMDARs. Using a combination of microscopy, biochemistry, and electrophysiology in mammalian cell lines and rat hippocampal neurons, we found that two asparagine residues (N203 and N368) in the GluN1 subunit and three asparagine residues (N145, N264 and N275) in the GluN3A subunit are required for surface delivery of GluN3A-containing NMDARs...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29915039/large-an-intellectual-disability-associated-protein-regulates-ampa-type-glutamate-receptor-trafficking-and-memory
#8
Bo Am Seo, Taesup Cho, Daniel Z Lee, Joong-Jae Lee, Boyoung Lee, Seong-Wook Kim, Hee-Sup Shin, Myoung-Goo Kang
Mutations in the human LARGE gene result in severe intellectual disability and muscular dystrophy. How LARGE mutation leads to intellectual disability, however, is unclear. In our proteomic study, LARGE was found to be a component of the AMPA-type glutamate receptor (AMPA-R) protein complex, a main player for learning and memory in the brain. Here, our functional study of LARGE showed that LARGE at the Golgi apparatus (Golgi) negatively controlled AMPA-R trafficking from the Golgi to the plasma membrane, leading to down-regulated surface and synaptic AMPA-R targeting...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29915023/enhancement-of-peptide-vaccine-immunogenicity-by-increasing-lymphatic-drainage-and-boosting-serum-stability
#9
Kelly D Moynihan, Rebecca L Holden, Naveen K Mehta, Chensu Wang, Mark R Karver, Jens Dinter, Simon Liang, Wuhbet Abraham, Mariane B Melo, Angela Q Zhang, Na Li, Sylvie Le Gall, Bradley Pentelute, Darrell J Irvine
Antitumor T-cell responses have the potential to be curative in cancer patients, but the induction of potent T-cell immunity through vaccination remains a largely unmet goal of immunotherapy. We previously reported that the immunogenicity of peptide vaccines could be increased by maximizing delivery to lymph nodes (LNs), where T-cell responses are generated. This was achieved by conjugating the peptide to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG (DSPE-PEG) to promote albumin binding, which resulted in enhanced lymphatic drainage and improved T-cell responses...
June 18, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29914512/utilization-of-adipocyte-derived-lipids-and-enhanced-intracellular-trafficking-of-fatty-acids-contribute-to-breast-cancer-progression
#10
Dejuan Yang, Yunhai Li, Lei Xing, Yiqing Tan, Jiazheng Sun, Beilei Zeng, Tingxiu Xiang, Jinxiang Tan, Guosheng Ren, Yuanyuan Wang
BACKGROUND: To determine whether adipocyte-derived lipids could be transferred into breast cancer cells and investigate the underlying mechanisms of subsequent lipolysis and fatty acid trafficking in breast cancer cells. METHODS: A Transwell co-culture system was used in which human breast cancer cells were cultured in the absence or presence of differentiated murine 3 T3-L1 adipocytes. Migration/invasion and proliferation abilities were compared between breast cancer cells that were cultivated alone and those co-cultivated with mature adipocytes...
June 18, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29913165/chemical-chaperone-treatment-improves-levels-and-distributions-of-connexins-in-cx50d47a-mouse-lenses
#11
Oscar Jara, Peter J Minogue, Viviana M Berthoud, Eric C Beyer
Mouse Cx50D47A and human Cx50D47N are non-functional connexin mutants that cause dominantly-inherited cataracts. In tissue culture expression experiments, they both exhibit impaired cellular trafficking and gap junction plaque formation. Lenses of mice expressing Cx50D47A have cataracts, reduced size, drastically decreased levels of connexin50, and less severely reduced levels of connexin46. The PERK-dependent pathway of the ER response to misfolded proteins is activated, and they have impaired differentiation with retained cellular organelles...
June 15, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29912026/rights-response-initiative-guiding-human-trafficking-services
#12
Theresa Vietor, Rosanne Hountz
Human trafficking, including both sex and labor trafficking, is a global issue affecting 20.9 million people worldwide. The National Human Trafficking Hotline identified 36,270 cases of human trafficking in the United States since 2007. Human trafficking affects every community in the United States, no matter the size. The Sexual Assault Response Team (SART) is a crisis intervention model that has shown improved outcomes for sexual assault victims. The SART approach can be modeled to develop a regional community response to human trafficking to improve outcomes for these victims...
June 15, 2018: Journal of Forensic Nursing
https://www.readbyqxmd.com/read/29909287/prazosin-induced-lysosomal-tubulation-interferes-with-cytokinesis-and-the-endocytic-sorting-of-the-tumour-antigen-cd98hc
#13
Robert Fuchs, Anika Stracke, Viktoria Holzmann, Gerfried Luschin-Ebengreuth, Nathalie Meier-Allard, Nadine Ebner, Teresa Maria Lassacher, Markus Absenger-Novak, Eleonore Fröhlich, Matthias Schittmayer, Sara Cano Crespo, Manuel Palacin, Beate Rinner, Ruth Birner-Gruenberger
The quinazoline based drug prazosin (PRZ) is a potent inducer of apoptosis in human cancer cells. We recently reported that PRZ enters cells via endocytosis and induces tubulation of the endolysosomal system. In a proteomics approach aimed at identifying potential membrane proteins with binding affinity to quinazolines, we detected the oncoprotein CD98hc. We confirmed shuttling of CD98hc towards lysosomes and upregulation of CD98hc expression in PRZ treated cells. Gene knockout (KO) experiments revealed that endocytosis of PRZ still occurs in the absence of CD98hc - suggesting that PRZ does not enter the cell via CD98hc but misroutes the protein towards tubular lysosomes...
June 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29908209/the-second-generation-thiazolide-haloxanide-is-a-potent-inhibitor-of-avian-influenza-virus-replication
#14
Simone La Frazia, Sara Piacentini, Anna Riccio, Jean Francois Rossignol, M Gabriella Santoro
The emergence of new avian influenza virus (AIV) strains able to infect humans represents a serious threat to global human health. In addition to surveillance and vaccine development, antiviral therapy remains crucial for AIV control; however, the increase in drug-resistant AIV strains underscores the need for novel approaches to anti-influenza chemotherapy. We have previously shown that the thiazolide anti-infective nitazoxanide (NTZ) inhibits influenza A/PuertoRico/8/1934(H1N1) virus replication, and this effect was associated with inhibition of viral hemagglutinin (HA) maturation...
June 13, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29908156/classifying-the-molecular-functions-of-rab-gtpases-in-membrane-trafficking-using-deep-convolutional-neural-networks
#15
Nguyen-Quoc-Khanh Le, Quang-Thai Ho, Yu-Yen Ou
Deep learning has been increasingly used to solve a number of problems with state-of-the-art performance in a wide variety of fields. In biology, deep learning can be applied to reduce feature extraction time and achieve high levels of performance. In our present work, we apply deep learning via two-dimensional convolutional neural networks and position-specific scoring matrices to classify Rab protein molecules, which are main regulators in membrane trafficking for transferring proteins and other macromolecules throughout the cell...
June 13, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29901166/alternative-splicing-variant-of-rhbdd2-is-associated-with-cell-stress-response-and-breast-cancer-progression
#16
Romina Canzoneri, Martín Enrique Rabassa, Agustina Gurruchaga, Valeria Ferretti, Sabina Palma, Marina Isla-Larrain, María Virginia Croce, Ezequiel Lacunza, Martín Carlos Abba
RHBDD2 is an intramembrane pseudoprotease member of the Rhomboid superfamily. Our previous studies in breast and colorectal cancer indicate an association between RHBDD2 overexpression and advanced tumor stages. Two alternative transcriptional variants have been described for RHBDD2, which would be encoding for different RHBDD2 protein isoforms. The expression of these RHBDD2 variants/isoforms and its association with breast cancer was the focus of this study. First, expression of RHBDD2 splicing variants was evaluated in normal and breast tumor samples...
June 14, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29899553/ubxn3b-positively-regulates-sting-mediated-antiviral-immune-responses
#17
Long Yang, Leilei Wang, Harshada Ketkar, Jinzhu Ma, Guang Yang, Shuang Cui, Tingting Geng, Dana G Mordue, Toyoshi Fujimoto, Gong Cheng, Fuping You, Rongtuan Lin, Erol Fikrig, Penghua Wang
The ubiquitin regulatory X domain-containing proteins (UBXNs) are likely involved in diverse biological processes. Their physiological functions, however, remain largely unknown. Here we present physiological evidence that UBXN3B positively regulates stimulator-of-interferon genes (STING) signaling. We employ a tamoxifen-inducible Cre-LoxP approach to generate systemic Ubxn3b knockout in adult mice as the Ubxn3b-null mutation is embryonically lethal. Ubxn3b-/- , like Sting-/- mice, are highly susceptible to lethal herpes simplex virus 1 (HSV-1) and vesicular stomatitis virus (VSV) infection, which is correlated with deficient immune responses when compared to Ubxn3b+/+ littermates...
June 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29899178/detailed-analysis-of-the-interaction-of-yeast-cog-complex
#18
Midori Ishii, Vladimir V Lupashin, Akihiko Nakano
The Golgi apparatus is a central station for protein trafficking in eukaryotic cells. A widely accepted model of protein transport within the Golgi apparatus is cisternal maturation. Each cisterna has specific resident proteins, which are thought to be maintained by COPI-mediated transport. However, the mechanisms underlying specific sorting of these Golgi-resident proteins remain elusive. To obtain a clue to understand the selective sorting of vesicles between the Golgi cisterenae, we investigated the molecular arrangements of the conserved oligomeric Golgi (COG) subunits in yeast cells...
June 14, 2018: Cell Structure and Function
https://www.readbyqxmd.com/read/29897333/itap-a-novel-irhom-interactor-controls-tnf-secretion-by-policing-the-stability-of-irhom-tace
#19
Ioanna Oikonomidi, Emma Burbridge, Miguel Cavadas, Graeme Sullivan, Blanka Collis, Heike Naegele, Danielle Clancy, Jana Brezinova, Tianyi Hu, Andrea Bileck, Christopher Gerner, Alfonso Bolado, Alex von Kriegsheim, Seamus J Martin, Florian Steinberg, Kvido Strisovsky, Colin Adrain
The apical inflammatory cytokine TNF regulates numerous important biological processes including inflammation and cell death, and drives inflammatory diseases. TNF secretion requires TACE (also called ADAM17), which cleaves TNF from its transmembrane tether. The trafficking of TACE to the cell surface, and stimulation of its proteolytic activity, depends on membrane proteins, called iRhoms. To delineate how the TNF/TACE/iRhom axis is regulated, we performed an immunoprecipitation/mass spectrometry screen to identify iRhom-binding proteins...
June 13, 2018: ELife
https://www.readbyqxmd.com/read/29895829/dishevelled-has-a-yap-nuclear-export-function-in-a-tumor-suppressor-context-dependent-manner
#20
Yoonmi Lee, Nam Hee Kim, Eunae Sandra Cho, Ji Hye Yang, Yong Hoon Cha, Hee Eun Kang, Jun Seop Yun, Sue Bean Cho, Seon-Hyeong Lee, Petra Paclikova, Tomasz W Radaszkiewicz, Vitezslav Bryja, Chi Gu Kang, Young Soo Yuk, So Young Cha, Soo-Youl Kim, Hyun Sil Kim, Jong In Yook
Phosphorylation-dependent YAP translocation is a well-known intracellular mechanism of the Hippo pathway; however, the molecular effectors governing YAP cytoplasmic translocation remains undefined. Recent findings indicate that oncogenic YAP paradoxically suppresses Wnt activity. Here, we show that Wnt scaffolding protein Dishevelled (DVL) is responsible for cytosolic translocation of phosphorylated YAP. Mutational inactivation of the nuclear export signal embedded in DVL leads to nuclear YAP retention, with an increase in TEAD transcriptional activity...
June 12, 2018: Nature Communications
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