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https://www.readbyqxmd.com/read/28930676/localized-phosphorylation-of-a-kinesin-1-adaptor-by-a-capsid-associated-kinase-regulates-hiv-1-motility-and-uncoating
#1
Viacheslav Malikov, Mojgan H Naghavi
Although microtubule motors mediate intracellular virus transport, the underlying interactions and control mechanisms remain poorly defined. This is particularly true for HIV-1 cores, which undergo complex, interconnected processes of cytosolic transport, reverse transcription, and uncoating of the capsid shell. Although kinesins have been implicated in regulating these events, curiously, there are no direct kinesin-core interactions. We recently showed that the capsid-associated kinesin-1 adaptor protein, fasciculation and elongation protein zeta-1 (FEZ1), regulates HIV-1 trafficking...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930490/tezacaftor-ivacaftor-in-subjects-with-cystic-fibrosis-and-f508del-f508del-cftr-or-f508del-g551d-cftr
#2
Scott H Donaldson, Joseph M Pilewski, Matthias Griese, Jon Cooke, Lakshmi Viswanathan, Elizabeth Tullis, Jane C Davies, Julie A Lekstrom-Himes, Linda T Wang
RATIONALE: Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. OBJECTIVES: To evaluate safety and efficacy of tezacaftor monotherapy and tezacaftor/ivacaftor combination therapy in subjects with CF homozygous for F508del or compound heterozygous for F508del and G551D...
September 20, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28929029/association-of-rs1801157-single-nucleotide-polymorphism-of-cxcl12-gene-in-breast-cancer-in-pakistan-and-in-silico-expression-analysis-of-cxcl12-cxcr4-associated-biological-regulatory-network
#3
Samra Khalid, Rumeza Hanif
BACKGROUND: C-X-C chemokine ligand 12 (CXCL12) has important implications in breast cancer (BC) pathogenesis. It is selectively expressed on B and T lymphocytes and is involved in hematopoiesis, thymocyte trafficking, stem cell motility, neovascularization, and tumorigenesis. The single nucleotide polymorphism (SNP) rs1801157 of CXCL12 gene has been found to be associated with higher risk of BC. METHODS: Our study focuses on the genotypic and allelic distribution of SNP (rs1801157; G/A) in Pakistani population as well as its association with the clinico-pathological features...
2017: PeerJ
https://www.readbyqxmd.com/read/28928743/the-toll-for-trafficking-toll-like-receptor-7-delivery-to-the-endosome
#4
REVIEW
Carlene Petes, Natalya Odoardi, Katrina Gee
Toll-like receptor (TLR)-7 is an endosomal innate immune sensor capable of detecting single-stranded ribonucleic acid. TLR7-mediated induction of type I interferon and other inflammatory cytokine production is important in antiviral immune responses. Furthermore, altered TLR7 expression levels are implicated in various autoimmune disorders, indicating a key role for this receptor in modulating inflammation. This review is focused on the regulation of TLR7 expression and localization compared to that of the other endosomal TLRs: TLR3, 8, and 9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928208/picornaviruses-and-apoptosis-subversion-of-cell-death
#5
REVIEW
Sarah N Croft, Erin J Walker, Reena Ghildyal
Infected cells can undergo apoptosis as a protective response to viral infection, thereby limiting viral infection. As viruses require a viable cell for replication, the death of the cell limits cellular functions that are required for virus replication and propagation. Picornaviruses are single-stranded RNA viruses that modify the host cell apoptotic response, probably in order to promote viral replication, largely as a function of the viral proteases 2A, 3C, and 3CD. These proteases are essential for viral polyprotein processing and also cleave cellular proteins...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28928065/molecular-cloning-and-biophysical-characterization-of-cxcl3-chemokine
#6
Khushboo Gulati, Krishnakant Gangele, Nipanshu Agarwal, Minal Jamsandekar, Dinesh Kumar, Krishna Mohan Poluri
CXCL3 is a neutrophil activating chemokine that belongs to GRO subfamily of CXC chemokines. GRO chemokine family comprises of three chemokines GRO α (CXCL1), GROβ (CXCL2), and GRO γ (CXCL3) that arose as a result of gene duplication events during the course of chemokine evolution. Studies reported that the primary sequences of GRO chemokines are highly similar, but performs several protein specific functions in addition to their common property of neutrophil trafficking. However, the molecular basis for their differential functions has not well understood...
September 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28928015/dendritic-homeostasis-disruption-in-a-novel-frontotemporal-dementia-mouse-model-expressing-cytoplasmic-fused-in-sarcoma
#7
Gen Shiihashi, Daisuke Ito, Itaru Arai, Yuki Kobayashi, Kanehiro Hayashi, Shintaro Otsuka, Kazunori Nakajima, Michisuke Yuzaki, Shigeyoshi Itohara, Norihiro Suzuki
Cytoplasmic aggregation of fused in sarcoma (FUS) is detected in brain regions affected by amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which compose the disease spectrum, FUS proteinopathy. To understand the pathomechanism of ALS-FTD-associated FUS, we examined the behavior and cellular properties of an ALS mouse model overexpressing FUS with nuclear localization signal deletion. Mutant FUS transgenic mice showed hyperactivity, social interactional deficits, and impaired fear memory retrieval, all of which are compatible with FTD phenotypes...
September 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28927690/forensic-drug-intelligence-and-the-rise-of-cryptomarkets-part-i-studying-the-australian-virtual-market
#8
Julian Broséus, Marie Morelato, Mark Tahtouh, Claude Roux
Analysing and understanding cryptomarkets is essential to become proactive in the fight against the illicit drug trade. Such a research seeks to combine a diversity of indicators related to the virtual (darknet markets) and physical (the traditional "offline" market) aspects of the illicit drug trade to provide information on the distribution and consumption as well as to assess similarities/differences between the virtual and physical markets. This study analysed data that had previously been collected on cryptomarkets from December 2013 to March 2015...
September 12, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28927260/the-roles-of-the-snare-protein-sed5-in-autophagy-in-saccharomyces-cerevisiae
#9
Shenshen Zou, Dan Sun, Yongheng Liang
Autophagy is a degradation pathway in eukaryotic cells in which aging proteins and organelles are sequestered into double-membrane vesicles, termed autophagosomes, which fuse with vacuoles to hydrolyze cargo. The key step in autophagy is the formation of autophagosomes, which requires different kinds of vesicles, including COPII vesicles and Atg9- containing vesicles, to transport lipid double-membranes to the phagophore assembly site (PAS). In yeast, the cis-Golgi localized t-SNARE protein Sed5 plays a role in endoplasmic reticulum (ER)-Golgi and intra-Golgi vesicular transport...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28927258/a-proteomics-based-approach-reveals-differential-regulation-of-visceral-adipose-tissue-proteins-between-metabolically-healthy-and-unhealthy-obese-patients
#10
Assim A Alfadda, Afshan Masood, Mohammed Y Al-Naami, Pierre Chaurand, Hicham Benabdelkamel
Obesity and the metabolic disorders that constitute metabolic syndrome are a primary cause of morbidity and mortality in the world. Nonetheless, the changes in the proteins and the underlying molecular pathways involved in the relevant pathogenesis are poorly understood.In this study a proteomic analysis of the visceral adipose tissue isolated from metabolically healthy and unhealthy obese patients was used to identify presence of altered pathway(s) leading to metabolic dysfunction. Samples were obtained from 18 obese patients undergoing bariatric surgery and were subdivided into two groups based on the presence or absence of comorbidities as defined by the International Diabetes Federation...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28926780/validation-of-a-standard-forensic-anthropology-examination-protocol-by-measurement-of-applicability-and-reliability-on-exhumed-and-archive-samples-of-known-biological-attribution
#11
Raffaela Arrabaça Francisco, Martin Paul Evison, Moacyr Lobo da Costa Junior, Teresa Cristina Pantozzi Silveira, José Marcelo Secchieri, Marco Aurelio Guimarães
Forensic anthropology makes an important contribution to human identification and assessment of the causes and mechanisms of death and body disposal in criminal and civil investigations, including those related to atrocity, disaster and trafficking victim identification. The methods used are comparative, relying on assignment of questioned material to categories observed in standard reference material of known attribution. Reference collections typically originate in Europe and North America, and are not necessarily representative of contemporary global populations...
September 7, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28926376/seeking-to-close-the-loopholes-in-transplant-tourism-and-organ-trafficking
#12
Jeremy R Chapman
No abstract text is available yet for this article.
September 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28925387/a-vital-sugar-code-for-ricin-toxicity
#13
Jasmin Taubenschmid, Johannes Stadlmann, Markus Jost, Tove Irene Klokk, Cory D Rillahan, Andreas Leibbrandt, Karl Mechtler, James C Paulson, Julian Jude, Johannes Zuber, Kirsten Sandvig, Ulrich Elling, Thorsten Marquardt, Christian Thiel, Christian Koerner, Josef M Penninger
Ricin is one of the most feared bioweapons in the world due to its extreme toxicity and easy access. Since no antidote exists, it is of paramount importance to identify the pathways underlying ricin toxicity. Here, we demonstrate that the Golgi GDP-fucose transporter Slc35c1 and fucosyltransferase Fut9 are key regulators of ricin toxicity. Genetic and pharmacological inhibition of fucosylation renders diverse cell types resistant to ricin via deregulated intracellular trafficking. Importantly, cells from a patient with SLC35C1 deficiency are also resistant to ricin...
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28924207/novel-ecto-tagged-integrins-reveal-their-trafficking-in-live-cells
#14
Clotilde Huet-Calderwood, Felix Rivera-Molina, Daniel V Iwamoto, Emil B Kromann, Derek Toomre, David A Calderwood
Integrins are abundant heterodimeric cell-surface adhesion receptors essential in multicellular organisms. Integrin function is dynamically modulated by endo-exocytic trafficking, however, major mysteries remain about where, when, and how this occurs in living cells. To address this, here we report the generation of functional recombinant β1 integrins with traceable tags inserted in an extracellular loop. We demonstrate that these 'ecto-tagged' integrins are cell-surface expressed, localize to adhesions, exhibit normal integrin activation, and restore adhesion in β1 integrin knockout fibroblasts...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28924192/short-chain-fatty-acids-ameliorate-immune-mediated-uveitis-partially-by-altering-migration-of-lymphocytes-from-the-intestine
#15
Yukiko K Nakamura, Cathleen Janowitz, Christina Metea, Mark Asquith, Lisa Karstens, James T Rosenbaum, Phoebe Lin
Short chain fatty acids (SCFA) are metabolites of intestinal bacteria resulting from fermentation of dietary fiber. SCFA are protective in various animal models of inflammatory disease. We investigated the effects of exogenous administration of SFCAs, particularly propionate, on uveitis using an inducible model of experimental autoimmune uveitis (EAU). Oral SCFA administration attenuated uveitis severity in a mouse strain-dependent manner through regulatory T cell induction among lymphocytes in the intestinal lamina propria (LPL) and cervical lymph nodes (CLN)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923947/tpc2-polymorphisms-associated-with-a-hair-pigmentation-phenotype-in-humans-result-in-gain-of-channel-function-by-independent-mechanisms
#16
Yu-Kai Chao, Verena Schludi, Cheng-Chang Chen, Elisabeth Butz, O N Phuong Nguyen, Martin Müller, Jens Krüger, Claudia Kammerbauer, Manu Ben-Johny, Angelika M Vollmar, Carola Berking, Martin Biel, Christian A Wahl-Schott, Christian Grimm
Two-pore channels (TPCs) are endolysosomal cation channels. Two members exist in humans, TPC1 and TPC2. Functional roles associated with the ubiquitously expressed TPCs include VEGF-induced neoangiogenesis, LDL-cholesterol trafficking and degradation, physical endurance under fasting conditions, autophagy regulation, the acrosome reaction in sperm, cancer cell migration, and intracellular trafficking of pathogens such as Ebola virus or bacterial toxins (e.g., cholera toxin). In a genome-wide association study for variants associated with human pigmentation characteristics two coding variants of TPC2, rs35264875 (encoding M484L) and rs3829241 (encoding G734E), have been found to be associated with a shift from brown to blond hair color...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923922/trkb-neurotrophic-activities-are-blocked-by-%C3%AE-synuclein-triggering-dopaminergic-cell-death-in-parkinson-s-disease
#17
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Matthew J Benskey, Xuebing Cao, Jun Xu, Yi E Sun, Keqiang Ye
BDNF/TrkB neurotrophic signaling is essential for dopaminergic neuronal survival, and the activities are reduced in the substantial nigra (SN) of Parkinson's disease (PD). However, whether α-Syn (alpha-synuclein) aggregation, a hallmark in the remaining SN neurons in PD, accounts for the neurotrophic inhibition remains elusive. Here we show that α-Syn selectively interacts with TrkB receptors and inhibits BDNF/TrkB signaling, leading to dopaminergic neuronal death. α-Syn binds to the kinase domain on TrkB, which is negatively regulated by BDNF or Fyn tyrosine kinase...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923919/multiple-interactions-between-an-arf-gef-complex-and-charged-lipids-determine-activation-kinetics-on-the-membrane
#18
Deepti Karandur, Agata Nawrotek, John Kuriyan, Jacqueline Cherfils
Lipidated small GTPases and their regulators need to bind to membranes to propagate actions in the cell, but an integrated understanding of how the lipid bilayer exerts its effect has remained elusive. Here we focused on ADP ribosylation factor (Arf) GTPases, which orchestrate a variety of regulatory functions in lipid and membrane trafficking, and their activation by the guanine-nucleotide exchange factor (GEF) Brag2, which controls integrin endocytosis and cell adhesion and is impaired in cancer and developmental diseases...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923836/dna-pk-plays-a-central-role-in-transformation-of-breast-epithelial-cells-following-alkylation-damage
#19
Libi Anandi, Vaishali Chakravarty, K A Ashiq, Satish Bodakuntla, Mayurika Lahiri
DNA alkylating agents form the first line of cancer chemotherapy. They not only kill cells but also behave as potential carcinogens. MNU, a DNA methylating agent is well known to induce mammary tumours in rodents. However, the mechanism of tumorigenesis is not well understood. Our study reports a novel role played by DNA-PK in methylation damage-induced transformation using three dimensional breast acinar cultures. Here, we report that exposure of breast epithelial cells to MNU led to their inhibition to polarise at the basolateral domain, increased dispersal of Golgi at the apical domain, induction of EMT-like phenotype as well as invasion...
September 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28923791/gja1-20k-arranges-actin-to-guide-cx43-delivery-to-cardiac-intercalated-discs
#20
Wassim A Basheer, Shaohua Xiao, Irina Epifantseva, Ying Fu, Andre G Kleber, TingTing Hong, Robin M Shaw
Rationale: Delivery of connexin 43 (Cx43) to the intercalated disc is a continuous and rapid process critical for intercellular coupling. By a pathway of targeted delivery involving microtubule highways, vesicles of Cx43 hemichannels are efficiently trafficked to adherens junctions at intercalated discs. It has also been identified that actin provides rest stops for Cx43 forward trafficking, and that Cx43 has a 20kDa internally translated small C-terminus isoform (GJA1-20k) which is required for full-length Cx43 trafficking, but by an unknown mechanism...
September 18, 2017: Circulation Research
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