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https://www.readbyqxmd.com/read/28822075/recycling-endosomes-in-human-cytotoxic-t-lymphocytes-constitute-an-auxiliary-intracellular-trafficking-pathway-for-newly-synthesized-perforin
#1
Kelsey Lesteberg, Jordan Orange, George Makedonas
Although cytotoxic T lymphocytes (CTLs) store perforin within cytoplasmic secretory granules for immediate use, perforin is synthesized anew within hours of TCR stimulation. Previously, we observed new perforin protein at an immunologic synapse independent of secretory lysosomes; herein, we aimed to determine how new perforin transits to the synapse if not via lytic granules. We analyzed antigen-specific human CTLs via imaging flow cytometry and high-resolution confocal microscopy, with attention to intracellular trafficking components and new perforin...
August 18, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28819289/escrt-iii-membrane-trafficking-misregulation-contributes-to-fragile-x-syndrome-synaptic-defects
#2
Dominic J Vita, Kendal Broadie
The leading cause of heritable intellectual disability (ID) and autism spectrum disorders (ASD), Fragile X syndrome (FXS), is caused by loss of the mRNA-binding translational suppressor Fragile X Mental Retardation Protein (FMRP). In the Drosophila FXS disease model, we found FMRP binds shrub mRNA (human Chmp4) to repress Shrub expression, causing overexpression during the disease state early-use critical period. The FXS hallmark is synaptic overelaboration causing circuit hyperconnectivity. Testing innervation of a central brain learning/memory center, we found FMRP loss and Shrub overexpression similarly increase connectivity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815213/identification-of-rab18-as-an-essential-host-factor-for-bk-polyomavirus-infection-using-a-whole-genome-rna-interference-screen
#3
Linbo Zhao, Michael J Imperiale
BK polyomavirus (BKPyV) is a human pathogen first isolated in 1971. BKPyV infection is ubiquitous in the human population, with over 80% of adults worldwide being seropositive for BKPyV. BKPyV infection is usually asymptomatic; however, BKPyV reactivation in immunosuppressed transplant patients causes two diseases, polyomavirus-associated nephropathy and hemorrhagic cystitis. To establish a successful infection in host cells, BKPyV must travel in retrograde transport vesicles to reach the nucleus. To make this happen, BKPyV requires the cooperation of host cell proteins...
July 2017: MSphere
https://www.readbyqxmd.com/read/28814519/extracellular-matrix-proteins-mediate-hiv-1-gp120-interactions-with-%C3%AE-4%C3%AE-7
#4
David Plotnik, Wenjin Guo, Brad Cleveland, Priska von Haller, Jimmy K Eng, Miklos Guttman, Kelly K Lee, James Arthos, Shiu-Lok Hu
Gut-homing α4β7(high) CD4(+) T lymphocytes have been shown to be preferentially targeted by Human Immunodeficiency Virus-1 (HIV), and are implicated in HIV pathogenesis. Previous studies demonstrated that HIV envelope protein gp120 binds and signals through α4β7, and that this likely contributes to the infection of α4β7(high) T cells and promotes cell-to-cell virus transmission. Structures within the second variable loop (V2) of gp120, including the tripeptide motif LDV/I, are thought to mediate gp120-α4β7 binding...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28813206/levamisole-in-illicit-trafficking-cocaine-seized-a-one-year-study
#5
Simona Martello, Massimo Pieri, Cristiano Ialongo, Stefano Pignalosa, Gianluca Noce, Francesca Vernich, Carmelo Russo, Federico Mineo, Sergio Bernardini, Luigi Tonino Marsella
Cocaine use is increasing around the world and its purity is frequently altered through dilution, substitution, contamination, and adulteration. Sugars, talc, starch, and carbonates represent the principal diluents of cocaine, while phenacetin, levamisole, caffeine, and lidocaine are its major adulterants in Europe. Levamisole is used because it is an odorless powder, with physical properties similar to cocaine, and it has reasonable cost and availability, being widely used in veterinary medicine. For this study, we analyzed 88 cocaine samples...
August 16, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28812388/silk-nanoparticles-proof-of-lysosomotropic-anticancer-drug-delivery-at-single-cell-resolution
#6
John D Totten, Thidarat Wongpinyochit, F Philipp Seib
Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28811318/the-%C3%AE-cell-assassin-iapp-cytotoxicity
#7
Daniel Raleigh, Xiaoxue Zhang, Benoit Hastoy, Anne Clark
Islet amyloid polypeptide (IAPP) forms cytotoxic oligomers and amyloid fibrils in islets in Type 2 diabetes (T2DM). The causal factors for amyloid formation are largely unknown. Mechanisms of molecular folding and assembly of human IAPP (hIAPP) into β-sheets, oligomers and fibrils have been assessed by detailed biophysical studies of hIAPP and non-fibrillogenic, rodent IAPP (rIAPP); cytotoxicity is associated with the early phases (oligomers/multimers) of fibrillogenesis. Interaction with synthetic membranes promotes β-sheet assembly possibly via a transient α-helical molecular conformation...
August 15, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28808969/methods-of-assessing-sting-activation-and-trafficking
#8
Vladislav Pokatayev, Nan Yan
The signaling adapter protein STING is crucial for the host immune response to cytosolic DNA and cyclic dinucleotides. Under basal conditions, STING resides on the endoplasmic reticulum (ER ) , but upon activation, it traffics through secretory pathway to cytoplasmic vesicles, where STING activates downstream immune signaling. Classical STING activation and trafficking are triggered by binding of cyclic dinucleotide ligands. STING signaling can also be activated by gain-of-function mutations that lead to constitutive trafficking of STING...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28806752/the-escrt-iii-pathway-facilitates-cardiomyocyte-release-of-cbin1-containing-microparticles
#9
Bing Xu, Ying Fu, Yan Liu, Sosse Agvanian, Robert C Wirka, Rachel Baum, Kang Zhou, Robin M Shaw, TingTing Hong
Microparticles (MPs) are cell-cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold- generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus...
August 14, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28801409/what-is-the-prevalence-of-and-associations-with-forced-labour-experiences-among-male-migrants-from-dolakha-nepal-findings-from-a-cross-sectional-study-of-returnee-migrants
#10
Joelle Mak, Tanya Abramsky, Bandita Sijapati, Ligia Kiss, Cathy Zimmerman
OBJECTIVES: Growing numbers of people are migrating outside their country for work, and many experience precarious conditions, which have been linked to poor physical and mental health. While international dialogue on human trafficking, forced labour and slavery increases, prevalence data of such experiences remain limited. METHODS: Men from Dolakha, Nepal, who had ever migrated outside of Nepal for work were interviewed on their experiences, from predeparture to return (n=194)...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28801230/a-mitochondrial-proteomics-view-of-complex-i-deficiency-in-candida-albicans
#11
Xiaodong She, Pengyi Zhang, Ying Gao, Lulu Zhang, Qiong Wang, Hui Chen, Richard Calderone, Weida Liu, Dongmei Li
Proteomic analyses were carried out on isolated mitochondrial samples of C. albicans from gene-deleted mutants (nuo1Δ, nuo2Δ and goa1Δ) as well as the parental strain in order to better understand the contribution of these three fungal-specific mitochondrial ETC complex I (CI) subunits to cellular activities. Herein, we identify 2333 putative proteins from four strains, in which a total of 663 proteins (28.5%) are putatively located in mitochondria. Comparison of protein abundances between mutants and the parental strain reveal 146 differentially-expressed proteins, of which 78 are decreased and 68 are increased in at least one mutant...
August 8, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28800810/international-emergency-psychiatry-challenges-disaster-medicine-war-human-trafficking-displaced-persons
#12
REVIEW
Michael Jaung, Suni Jani, Sophia Banu, Joy M Mackey
Mental health disorders are a major cause of morbidity and a growing burden in low-income and middle-income countries; but there is little existing literature on the detailed epidemiology, diagnosis, and treatment in low-resource settings. Special situations with vulnerable populations, such as those created by international humanitarian emergencies, refugees or internally displaced people, and victims of human trafficking, are increasing in prevalence. These victims are often resettled in developed countries and come to the emergency department seeking care...
September 2017: Psychiatric Clinics of North America
https://www.readbyqxmd.com/read/28800156/quantitative-dextran-trafficking-to-the-coxiella-burnetii-parasitophorous-vacuole
#13
Seth Winfree, Stacey D Gilk
The gram-negative bacterium Coxiella burnetii causes human Q fever, a disease characterized by a debilitating flu-like illness in acute cases and endocarditis in chronic patients. An obligate intracellular pathogen, Coxiella burnetii survives within a large, lysosome-like vacuole inside the host cell. A unique feature of the Coxiella parasitophorous vacuole (PV) is high levels of fusion with the host endocytic pathway, with PV-endosome fusion critical for Coxiella survival within the host cell. This unit describes quantitating PV-endosome fusion by measuring delivery of the fluid phase endosome marker dextran to the PV using live cell imaging...
August 11, 2017: Current Protocols in Microbiology
https://www.readbyqxmd.com/read/28799850/a-qualitative-study-exploring-factors-associated-with-pap-test-use-among-north-korean-refugees
#14
Kyounghae Kim, Soohyun Kim, Yoonkyung Chung
Lack of medical care in North Korea and vulnerability to human trafficking during their migration increase risks of cervical cancer among North Korean refugees. To better understand factors influencing Pap test use, we conducted a qualitative study of 8 North Korean refugees in South Korea. Individual barriers were limited knowledge, lack of perceived need for preventive services, and concerns about costs. Environmental facilitators included having female providers, receiving family support, and free screenings...
August 11, 2017: Health Care for Women International
https://www.readbyqxmd.com/read/28796316/effects-of-tocilizumab-on-neutrophil-function-and-kinetics
#15
Laurence S C Lok, Neda Farahi, Jatinder K Juss, Chrystalla Loutsios, Chandra K Solanki, A Michael Peters, Francis Donaldson, Benjamin Porter-Brown, Edwin R Chilvers
BACKGROUND: Decreases in circulating neutrophils (polymorphonuclear leukocytes, PMNs) have been reported in patients treated with the anti-interleukin-6 receptor (IL-6R) antibody tocilizumab (TCZ); the mechanism for this is unclear. We hypothesize that TCZ reduces circulating neutrophils by affecting margination and / or bone marrow trafficking without affecting neutrophil function or apoptosis. MATERIALS AND METHODS: 18 healthy subjects were randomized to single intravenous dose of TCZ 8 mg/kg (n = 12) or placebo (n = 6) on day 0...
August 10, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28795723/intracellular-iron-and-heme-trafficking-and-metabolism-in-developing-erythroblasts
#16
Martin D Kafina, Barry H Paw
Vertebrate red blood cells (RBCs) arise from erythroblasts in the human bone marrow through a process known as erythropoiesis. Iron uptake is a crucial hallmark, essential for heme biosynthesis in the differentiating erythroblasts, which are dedicated to producing hemoglobin. Erythropoiesis is facilitated by a network of intracellular transport proteins, chaperones, and circulating hormones. Intracellular iron is targeted to the mitochondria for incorporation into a porphyrin ring to form heme and cytosolic iron-sulfur proteins, including Iron Regulatory Protein 1 (IRP1)...
August 10, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28792385/health-providers-helping-to-disrupt-human-trafficking
#17
EDITORIAL
The Lancet
No abstract text is available yet for this article.
August 5, 2017: Lancet
https://www.readbyqxmd.com/read/28783704/constitutive-resistance-to-viral-infection-in-human-cd141-dendritic-cells
#18
Aymeric Silvin, Chun I Yu, Xavier Lahaye, Francesco Imperatore, Jean-Baptiste Brault, Sylvain Cardinaud, Christian Becker, Wing-Hong Kwan, Cécile Conrad, Mathieu Maurin, Christel Goudot, Santy Marques-Ladeira, Yuanyuan Wang, Virginia Pascual, Esperanza Anguiano, Randy A Albrecht, Matteo Iannacone, Adolfo García-Sastre, Bruno Goud, Marc Dalod, Arnaud Moris, Miriam Merad, A Karolina Palucka, Nicolas Manel
Dendritic cells (DCs) are critical for the launching of protective T cell immunity in response to viral infection. Viruses can directly infect DCs, thereby compromising their viability and suppressing their ability to activate immune responses. How DC function is maintained in light of this paradox is not understood. By analyzing the susceptibility of primary human DC subsets to viral infections, we report that CD141(+) DCs have an innate resistance to infection by a broad range of enveloped viruses, including HIV and influenza virus...
July 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783139/antipsychotic-induced-hdac2-transcription-via-nf-%C3%AE%C2%BAb-leads-to-synaptic-and-cognitive-side-effects
#19
Daisuke Ibi, Mario de la Fuente Revenga, Nebojsa Kezunovic, Carolina Muguruza, Justin M Saunders, Supriya A Gaitonde, José L Moreno, Maryum K Ijaz, Vishaka Santosh, Alexey Kozlenkov, Terrell Holloway, Jeremy Seto, Aintzane García-Bea, Mitsumasa Kurita, Grace E Mosley, Yan Jiang, Daniel J Christoffel, Luis F Callado, Scott J Russo, Stella Dracheva, Juan F López-Giménez, Yongchao Ge, Carlos R Escalante, J Javier Meana, Schahram Akbarian, George W Huntley, Javier González-Maeso
Antipsychotic drugs remain the standard for schizophrenia treatment. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic medications leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition remain to be elucidated. Here we demonstrate that chronic antipsychotic drug exposure increases nuclear translocation of NF-κB in both mouse and human frontal cortex, a trafficking event triggered via 5-HT2A-receptor-dependent downregulation of the NF-κB repressor IκBα...
August 7, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28777934/mutations-in-trappc12-manifest-in-progressive-childhood-encephalopathy-and-golgi-dysfunction
#20
Miroslav P Milev, Megan E Grout, Djenann Saint-Dic, Yong-Han Hank Cheng, Ian A Glass, Christopher J Hale, David S Hanna, Michael O Dorschner, Keshika Prematilake, Avraham Shaag, Orly Elpeleg, Michael Sacher, Dan Doherty, Simon Edvardson
Progressive childhood encephalopathy is an etiologically heterogeneous condition characterized by progressive central nervous system dysfunction in association with a broad range of morbidity and mortality. The causes of encephalopathy can be either non-genetic or genetic. Identifying the genetic causes and dissecting the underlying mechanisms are critical to understanding brain development and improving treatments. Here, we report that variants in TRAPPC12 result in progressive childhood encephalopathy. Three individuals from two unrelated families have either a homozygous deleterious variant (c...
August 3, 2017: American Journal of Human Genetics
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