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https://www.readbyqxmd.com/read/28634550/sortilin-related-receptor-expression-in-human-neural-stem-cells-derived-from-alzheimer-s-disease-patients-carrying-the-apoe-epsilon-4-allele
#1
Alen Zollo, Zoe Allen, Helle F Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J Maier, Carmela Matrone
Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28634242/type-ii-secretion-substrates-of-legionella-pneumophila-translocate-out-of-the-pathogen-occupied-vacuole-via-a-semipermeable-membrane
#2
Hilary K Truchan, Harry D Christman, Richard C White, Nakisha S Rutledge, Nicholas P Cianciotto
Legionella pneumophila replicates in macrophages in a host-derived phagosome, termed the Legionella-containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM). Translocation is detected as early as 10 h postinoculation (p...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28631186/association-between-epidermal-growth-factor-receptor-amplification-and-adp-ribosylation-factor-1-methylation-in-human-glioblastoma
#3
Concha López-Ginés, Lara Navarro, Lisandra Muñoz-Hidalgo, Enrique Buso, José Manuel Morales, Rosario Gil-Benso, Mariela Gregori-Romero, Javier Megías, Pedro Roldán, Remedios Segura-Sabater, José Manuel Almerich-Silla, Daniel Monleón, Miguel Cerdá-Nicolás
PURPOSE: Glioblastoma (GB) is the most frequent and most malignant primary brain tumor in adults. Previously, it has been found that both genetic and epigenetic factors may play critical roles in its etiology and prognosis. In addition, it has been found that the epidermal growth factor receptor gene (EGFR) is frequently over-expressed and amplified in primary GBs. Here, we assessed the promoter methylation status of 10 genes relevant to GB and explored associations between these findings and the EGFR gene amplification status...
June 19, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28630007/rna-localization-making-its-way-to-the-center-stage
#4
REVIEW
Ashley Chin, Eric Lécuyer
Cells are highly organized entities that rely on intricate addressing mechanisms to sort their constituent molecules to precise subcellular locations. These processes are crucial for cells to maintain their proper organization and carry out specialized functions in the body, while genetic perturbations that clog up these addressing systems can contribute to disease aetiology. The trafficking of RNA molecules represents an important layer in the control of cellular organization, a process that is both highly prevalent and for which features of the regulatory machineries have been deeply conserved evolutionarily...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28626835/disrupted-er-to-golgi-trafficking-underlies-anti-hiv-drugs-and-alcohol-induced-cellular-stress-and-hepatic-injury
#5
Hui Han, Yuxin He, Jay Hu, Rhema Lau, Harrison Lee, Cheng Ji
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti-human immunodeficiency virus (HIV) drugs and alcohol-induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir-boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes...
April 2017: Hepatol Commun
https://www.readbyqxmd.com/read/28626344/increased-transendothelial-transport-of-ccl3-is-insufficient-to-drive-immune-cell-transmigration-through-the-blood-brain-barrier-under-inflammatory-conditions-in-vitro
#6
Maxime De Laere, Carmelita Sousa, Megha Meena, Roeland Buckinx, Jean-Pierre Timmermans, Zwi Berneman, Nathalie Cools
Many neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we implemented and validated a blood-brain barrier (BBB) model to study chemokine secretion, chemokine transport, and leukocyte trafficking in vitro. In a coculture model consisting of a human cerebral microvascular endothelial cell line and human astrocytes, proinflammatory stimulation downregulated the expression of tight junction proteins, while the expression of adhesion molecules and chemokines was upregulated...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28626029/a-homozygous-founder-mutation-in-trappc6b-associates-with-a-neurodevelopmental-disorder-characterised-by-microcephaly-epilepsy-and-autistic-features
#7
Isaac Marin-Valencia, Gaia Novarino, Anide Johansen, Basak Rosti, Mahmoud Y Issa, Damir Musaev, Gifty Bhat, Eric Scott, Jennifer L Silhavy, Valentina Stanley, Rasim O Rosti, Jeremy W Gleeson, Farhad B Imam, Maha S Zaki, Joseph G Gleeson
BACKGROUND: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human disease, however, has not been fully established, and their functions remain uncertain. OBJECTIVE: We aimed to expand the range of neurodevelopmental disorders associated with mutations in TRAPP subunits by exome sequencing of consanguineous families...
June 16, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28626000/baiap3-a-c2-domain-containing-munc13-protein-controls-the-fate-of-dense-core-vesicles-in-neuroendocrine-cells
#8
Xingmin Zhang, Shan Jiang, Kelly A Mitok, Lingjun Li, Alan D Attie, Thomas F J Martin
Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide-sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain-containing proteins are known to regulate Ca(2+)-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 domain-containing proteins by RNA interference in neuroendocrine cells. 40 genes were identified, including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles...
June 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28624967/routes-and-machinery-of-primary-cilium-biogenesis
#9
REVIEW
Miguel Bernabé-Rubio, Miguel A Alonso
Primary cilia are solitary, microtubule-based protrusions of the cell surface that play fundamental roles as photosensors, mechanosensors and biochemical sensors. Primary cilia dysfunction results in a long list of developmental and degenerative disorders that combine to give rise to a large spectrum of human diseases affecting almost any major body organ. Depending on the cell type, primary ciliogenesis is initiated intracellularly, as in fibroblasts, or at the cell surface, as in renal polarized epithelial cells...
June 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28622814/identifying-treating-and-advocating-for-human-trafficking-victims-a-key-role-for-psychiatric-inpatient-units
#10
EDITORIAL
Phuong T Nguyen, John H Coverdale, Mollie R Gordon
No abstract text is available yet for this article.
May 2017: General Hospital Psychiatry
https://www.readbyqxmd.com/read/28620321/treating-posttraumatic-stress-disorder-in-female-victims-of-trafficking-using-narrative-exposure-therapy-a-retrospective-audit
#11
Katy Robjant, Jackie Roberts, Cornelius Katona
BACKGROUND: Human trafficking is a form of modern slavery that involves the forced movement of people internally within countries, or externally across borders. Victims who are trafficked for sexual exploitation are subject to repeated, multiple trauma, and high rates of mental health problems including posttraumatic stress disorder (PTSD) have been found. Narrative exposure therapy (NET) is an evidence-based treatment for PTSD. METHODS: In this retrospective audit, we record the results of NET to treat 10 women who had been trafficked for sexual exploitation who were diagnosed with PTSD...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28620028/the-secret-life-of-kinases-insights-into-non-catalytic-signalling-functions-from-pseudokinases
#12
REVIEW
Annette V Jacobsen, James M Murphy
Over the past decade, our understanding of the mechanisms by which pseudokinases, which comprise ∼10% of the human and mouse kinomes, mediate signal transduction has advanced rapidly with increasing structural, biochemical, cellular and genetic studies. Pseudokinases are the catalytically defective counterparts of conventional, active protein kinases and have been attributed functions as protein interaction domains acting variously as allosteric modulators of conventional protein kinases and other enzymes, as regulators of protein trafficking or localisation, as hubs to nucleate assembly of signalling complexes, and as transmembrane effectors of such functions...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28618839/sphingosine-kinase-and-sphingosine-1-phosphate-in-liver-pathobiology
#13
Timothy Rohrbach, Michael Maceyka, Sarah Spiegel
Over 20 years ago, sphingosine-1-phosphate (S1P) was discovered to be a bioactive signaling molecule. Subsequent studies later identified two related kinases, sphingosine kinase 1 and 2, which are responsible for the phosphorylation of sphingosine to S1P. Many stimuli increase sphingosine kinase activity and S1P production and secretion. Outside the cell, S1P can bind to and activate five S1P-specific G protein-coupled receptors (S1PR1-5) to regulate many important cellular and physiological processes in an autocrine or paracrine manner...
June 15, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28617998/schwann-cell-specific-deletion-of-the-endosomal-pi-3-kinase-vps34-leads-to-delayed-radial-sorting-of-axons-arrested-myelination-and-abnormal-erbb2-erbb3-tyrosine-kinase-signaling
#14
Anne M Logan, Anna E Mammel, Danielle C Robinson, Andrea L Chin, Alec F Condon, Fred L Robinson
The PI 3-kinase Vps34 (Pik3c3) synthesizes phosphatidylinositol 3-phosphate (PI3P), a lipid critical for both endosomal membrane traffic and macroautophagy. Human genetics have implicated PI3P dysregulation, and endosomal trafficking in general, as a recurring cause of demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy. Here, we investigated the role of Vps34, and PI3P, in mouse Schwann cells by selectively deleting Vps34 in this cell type. Vps34-Schwann cell knockout (Vps34(SCKO) ) mice show severe hypomyelination in peripheral nerves...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28615248/the-transcriptome-of-the-didelphis-virginiana-opossum-kidney-ok-proximal-tubule-cell-line
#15
Megan L Eshbach, Rahil Sethi, Raghunandan Avula, Janette Lamb, Deborah J Hollingshead, David N Finegold, Joseph Locker, Uma R Chandran, Ora A Weisz
The OK cell line derived from kidney of a female opossum Didelphis virginiana has proven to be a useful model in which to investigate the unique regulation of ion transport and membrane trafficking mechanisms in the proximal tubule (PT). Sequence data and comparison of the transcriptome of this cell line to eutherian mammal PTs would further broaden the utility of this culture model. However, genomic sequence for Didelphis virginiana is not available and although a draft genome sequence for the opossum Monodelphis domestica (sequenced in 2012 by the Broad Institute) exists, transcripts sequenced from both species show significant divergence...
June 14, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28613117/heavy-subunit-of-cell-surface-gal-galnac-lectin-hgl-undergoes-degradation-via-endo-lysosomal-compartments-in-entamoeba-histolytica
#16
Kuldeep Verma, Sunando Datta
The human gut parasite Entamoeba histolytica uses a multifunctional virulence factor, Hgl, a cell surface transmembrane receptor subunit of Gal/GalNAc lectin that contributes to adhesion, invasion, cytotoxicity and immune response in the host. At present, the physiological importance of Hgl receptor is mostly known for pathogenicity of E. histolytica. However, the molecular mechanisms of Hgl trafficking events and their association with the intracellular membrane transport machinery are largely unknown. We employed biochemical and microscopy-based assays to understand the Hgl trafficking in the amoebic trophozoites...
June 14, 2017: Small GTPases
https://www.readbyqxmd.com/read/28611252/the-primary-enveloped-virion-of-herpes-simplex-virus-1-its-role-in-nuclear-egress
#17
William W Newcomb, Juan Fontana, Dennis C Winkler, Naiqian Cheng, J Bernard Heymann, Alasdair C Steven
Many viruses migrate between different cellular compartments for successive stages of assembly. The HSV-1 capsid assembles in the nucleus and then transfers into the cytoplasm. First, the capsid buds through the inner nuclear membrane, becoming coated with nuclear egress complex (NEC) protein. This yields a primary enveloped virion (PEV) whose envelope fuses with the outer nuclear membrane, releasing the capsid into the cytoplasm. We investigated the associated molecular mechanisms by isolating PEVs from US3-null-infected cells and imaging them by cryo-electron microscopy and tomography...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28608535/discovery-and-characterization-of-two-novel-cb1-receptor-splice-variants-with-modified-n-termini-in-mouse
#18
Sabine Ruehle, James Wager-Miller, Alex Straiker, Jill Farnsworth, Michelle N Murphy, Sebastian Loch, Krisztina Monory, Ken Mackie, Beat Lutz
Numerous studies have been carried out in the mouse model, investigating the role of the CB1 cannabinoid receptor. However, mouse CB1 (mCB1) receptor differs from human CB1 (hCB1) receptor in 13 amino acid residues. Two splice variants, hCB1a and hCB1b, diverging in their amino-termini, have been reported to be unique for hCB1 and, via different signaling properties, contribute to CB1 receptor physiology and pathophysiology. We hypothesized that splice variants also exist for the mCB1 receptor and have different signaling properties...
June 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28607619/molecular-mechanisms-underlying-the-pilsicainide-induced-stabilization-of-herg-proteins-in-transfected-mammalian-cells
#19
Takeshi Onohara, Ichiro Hisatome, Yasutaka Kurata, Peili Li, Tomomi Notsu, Kumi Morikawa, Naoyuki Otani, Akio Yoshida, Kazuhiko Iitsuka, Masaru Kato, Junichiro Miake, Haruaki Ninomiya, Katsumi Higaki, Yasuaki Shirayoshi, Takashi Nishihara, Toshiyuki Itoh, Yoshinobu Nakamura, Motonobu Nishimura
BACKGROUND: Pilsicainide, classified as a relatively selective Na(+) channel blocker, also has an inhibitory action on the rapidly-activating delayed-rectifier K(+) current (IKr ) through human ether-a-go-go-related gene (hERG) channels. We studied the effects of chronic exposure to pilsicainide on the expression of wild-type (WT) hERG proteins and WT-hERG channel currents, as well as on the expression of mutant hERG proteins, in a heterologous expression system. METHODS: HEK293 cells stably expressing WT or mutant hERG proteins were subjected to Western blotting, immunofluorescence microscopy and patch-clamp experiments...
June 2017: Journal of Arrhythmia
https://www.readbyqxmd.com/read/28603639/folding-correction-of-abc-transporter-abcb1-by-pharmacological-chaperones-a-mechanistic-concept
#20
Matthias Spork, Muhammad Imran Sohail, Diethart Schmid, Gerhard F Ecker, Michael Freissmuth, Peter Chiba, Thomas Stockner
Point mutations of ATP-binding cassette (ABC) proteins are a common cause of human diseases. Available crystal structures indicate a similarity in the architecture of several members of this protein family. Their molecular architecture makes these proteins vulnerable to mutation, when critical structural elements are affected. The latter preferentially involve the two transmembrane domain (TMD)/nucleotide-binding domain (NBD) interfaces (transmission interfaces), formation of which requires engagement of coupling helices of intracellular loops with NBDs...
June 2017: Pharmacology Research & Perspectives
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