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https://www.readbyqxmd.com/read/26700819/adipocytes-promote-prostate-cancer-stem-cell-self-renewal-through-amplification-of-the-cholecystokinin-autocrine-loop
#1
Kai-Dun Tang, Ji Liu, Lidija Jovanovic, Jiyuan An, Michelle M Hill, Ian Vela, Terence Kin-Wah Lee, Stephanie Ma, Colleen Nelson, Pamela J Russell, Judith A Clements, Ming-Tat Ling
Obesity has long been linked with prostate cancer progression, although the underlying mechanism is still largely unknown. Here, we report that adipocytes promote the enrichment of prostate cancer stem cells (CSCs) through a vicious cycle of autocrine amplification. In the presence of adipocytes, prostate cancer cells actively secrete the peptide hormone cholecystokinin (CCK), which not only stimulates prostate CSC self-renewal, but also induces cathepsin B (CTSB) production of the adipocytes. In return, CTSB facilitates further CCK secretion by the cancer cells...
January 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26687033/linking-a-genome-wide-association-study-signal-to-a-lrrk2-coding-variant-in-parkinson-s-disease
#2
Jia Nee Foo, Sun Ju Chung, Louis C Tan, Herty Liany, Ho-Sung Ryu, Myunghee Hong, Tat Hung Koh, Ishak D Irwan, Wing-Lok Au, Kumar-M Prakash, Tin Aung, Ching-Yu Cheng, Siow-Ann Chong, Chiea Chuen Khor, Jimmy Lee, E-Shyong Tai, Eranga N Vithana, Tien-Yin Wong, Kyuyoung Song, Jianjun Liu, Eng-King Tan
BACKGROUND: Genome-wide association studies have identified several loci associated with Parkinson's disease (PD). Whole-exome sequencing detects rare coding variants, but their links with PD genome-wide association study loci are unknown. Our objective was to investigate whether nonsynonymous variants in LRRK2 can explain associations at the PD-associated locus tagged by rs1994090. METHODS: We sequenced all coding exons of LRRK2 in 453 East Asian samples and evaluated linkage disequilibrium between each nonsynonymous variant and rs1994090...
April 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/26661213/efficacy-of-the-psd95-inhibitor-tat-nr2b9c-in-mice-requires-dose-translation-between-species
#3
Lucy M Teves, Hong Cui, Michael Tymianski
Tat-NR2B9c, a clinical-stage stroke neuroprotectant validated in rats and primates, was recently deemed ineffective in mice. To evaluate this discrepancy, we conducted studies in mice subjected to temporary middle cerebral artery occlusion (tMCAO) for either 30 or 60 min according to the established principles for dose-translation between species. Tat-NR2B9c treatment reduced infarct volume by by 24.5% (p = 0.49) and 26.0% (p = 0.03) for 30 and 60 min tMCAO, respectively, at the rat-equivalent dose of 10 nMole/g, but not at the previously reported 3 nMole/g in mice...
March 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/26655174/hiv-1-tat-biosensor-current-development-and-trends-for-early-detection-strategies
#4
REVIEW
M F Fatin, A R Ruslinda, M K Md Arshad, K K Tee, R M Ayub, U Hashim, A Kamarulzaman, Subash C B Gopinath
Human immunodeficiency virus (HIV) has infected almost 35 million people worldwide. Various tests have been developed to detect the presence of HIV during the early stages of the disease in order to reduce the risk of transmission to other humans. The HIV-1 Tat protein is one of the proteins present in HIV that are released abundantly approximately 2-4 weeks after infection. In this review, we have outlined various strategies for detecting the Tat protein, which helps transcribe the virus and enhances replication...
April 15, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/26647222/endocrine-disrupting-effects-of-pesticides-through-interference-with-human-glucocorticoid-receptor
#5
Jianyun Zhang, Jing Zhang, Rui Liu, Jay Gan, Jing Liu, Weiping Liu
Many pesticides have been identified as endocrine-disrupting chemicals (EDCs) due to their ability to bind sex-steroid hormone receptors. However, little attention has been paid to the ability of pesticides to interfere with other steroid hormone receptors such as glucocorticoid receptor (GR) that plays a critical role in metabolic, endocrine, immune, and nervous systems. In this study, the glucocorticoidic and antiglucocorticoidic effects of 34 pesticides on human GR were investigated using luciferase reporter gene assay...
January 5, 2016: Environmental Science & Technology
https://www.readbyqxmd.com/read/26642755/the-role-of-rice-fields-fish-ponds-and-water-canals-for-transmission-of-fish-borne-zoonotic-trematodes-in-aquaculture-ponds-in-nam-dinh-province-vietnam
#6
Henry Madsen, Bui Thi Dung, Dang Tat The, Nguyen Khue Viet, Anders Dalsgaard, Phan Thi Van
BACKGROUND: Fish-borne zoonotic trematodes (FZT), such as Clonorchis sinensis, Opistorchis viverini (Opisthorchiidae) and intestinal trematodes of the family Heterophyidae, constitute a public health hazard in Vietnam and infections with these trematodes has been linked to consumption of raw or undercooked fish from aquaculture. The FZT transmission pathways, however, are more complicated than just the presence of intermediate snail hosts in aquaculture ponds as ponds may exchange water with surrounding habitats such as rice fields and irrigation canals and thereby these surrounding habitats may be a source of snails and cercariae and contribute to FZT infection in cultured fish...
2015: Parasites & Vectors
https://www.readbyqxmd.com/read/26635073/recombinant-human-prothrombin-medi8111-prevents-bleeding-in-haemophilia-a-and-b-mice
#7
K M Hansson, A Lindblom, M Elg, A Lövgren
BACKGROUND: Haemophilia A and B are treated with FVIII and FIX replacement therapy. Treatment may be complicated by inhibitory antibodies that require bypass therapy such as FEIBA(®) in which prothrombin (FII) is suggested to be the main active component. METHODS: To evaluate the effect of FII on haemophilia recombinant human (rh) FII (MEDI8111) or plasma-derived human FII (pdhFII) was given as single doses to anaesthetized haemophilia A and B mice 3 min before tail transection and rhFVIII or rhFIX was used for comparison...
May 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/26634992/single-particle-dynamic-imaging-and-fe3-sensing-with-bright-carbon-dots-derived-from-bovine-serum-albumin-proteins
#8
Qingxiu Yang, Lin Wei, Xuanfang Zheng, Lehui Xiao
In this work, we demonstrated a convenient and green strategy for the synthesis of highly luminescent and water-soluble carbon dots (Cdots) by carbonizing carbon precursors, i.e., Bovine serum albumin (BSA) nanoparticles, in water solution. Without post surface modification, the as-synthesized Cdots exhibit fluorescence quantum yield (Q.Y.) as high as 34.8% and display superior colloidal stability not only in concentrated salt solutions (e.g. 2 M KCl) but also in a wide range of pH solutions. According to the FT-IR measurements, the Cdots contain many carboxyl groups, providing a versatile route for further chemical and biological functionalization...
December 4, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26608746/hiv-1-tat-protein-enhances-the-intracellular-growth-of-leishmania-amazonensis-via-the-ds-rna-induced-protein-pkr
#9
Áislan de Carvalho Vivarini, Renata de Meirelles Santos Pereira, Victor Barreto-de-Souza, Jairo Ramos Temerozo, Deivid C Soares, Elvira M Saraiva, Alessandra Mattos Saliba, Dumith Chequer Bou-Habib, Ulisses Gazos Lopes
HIV-1 co-infection with human parasitic diseases is a growing public health problem worldwide. Leishmania parasites infect and replicate inside macrophages, thereby subverting host signaling pathways, including the response mediated by PKR. The HIV-1 Tat protein interacts with PKR and plays a pivotal role in HIV-1 replication. This study shows that Tat increases both the expression and activation of PKR in Leishmania-infected macrophages. Importantly, the positive effect of Tat addition on parasite growth was dependent on PKR signaling, as demonstrated in PKR-deficient macrophages or macrophages treated with the PKR inhibitor...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26586575/tripartite-containing-motif-32-modulates-proliferation-of-human-neural-precursor-cells-in-hiv-1-neurodegeneration
#10
M Fatima, R Kumari, J C Schwamborn, A Mahadevan, S K Shankar, R Raja, P Seth
In addition to glial cells, HIV-1 infection occurs in multipotent human neural precursor cells (hNPCs) and induces quiescence in NPCs. HIV-1 infection of the brain alters hNPC stemness, leading to perturbed endogenous neurorestoration of the CNS following brain damage by HIV-1, compounding the severity of dementia in adult neuroAIDS cases. In pediatric neuroAIDS cases, HIV-1 infection of neural stem cell can lead to delayed developmental milestones and impaired cognition. Using primary cultures of human fetal brain-derived hNPCs, we gained novel insights into the role of a neural stem cell determinant, tripartite containing motif 32 (TRIM32), in HIV-1 Tat-induced quiescence of NPCs...
May 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/26581162/potent-and-targeted-activation-of-latent-hiv-1-using-the-crispr-dcas9-activator-complex
#11
Sheena M Saayman, Daniel C Lazar, Tristan A Scott, Jonathan R Hart, Mayumi Takahashi, John C Burnett, Vicente Planelles, Kevin V Morris, Marc S Weinberg
HIV-1 provirus integration results in a persistent latently infected reservoir that is recalcitrant to combined antiretroviral therapy (cART) with lifelong treatment being the only option. The "shock and kill" strategy aims to eradicate latent HIV by reactivating proviral gene expression in the context of cART treatment. Gene-specific transcriptional activation can be achieved using the RNA-guided CRISPR-Cas9 system comprising single guide RNAs (sgRNAs) with a nuclease-deficient Cas9 mutant (dCas9) fused to the VP64 transactivation domain (dCas9-VP64)...
March 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/26569339/toll-like-receptor-3-mediates-hiv-1-transactivation-via-nf%C3%AE%C2%BAb-and-jnk-pathways-and-histone-acetylation-but-prolonged-activation-suppresses-tat-and-hiv-1-replication
#12
Biju Bhargavan, Shawna M Woollard, Georgette D Kanmogne
TLR3 has been implicated in the pathogenesis of several viral infections, including SIV- and HIV-1-induced inflammation and AIDS. However the molecular mechanisms of these TLR3-mediated effects are not known, and it is not known whether HIV interacts with cellular TLR3 to affect disease process. Here we investigate the effects of TLR3 ligands on HIV-1 transactivation using both primary human macrophages and cells containing integrated copies of the HIV-1 promoter. We demonstrate that TLR3 activation induced upregulation of transcription factors such as c-Jun, CCAAT/enhancer-binding protein alpha (CEBPA), signal transducer and activator of transcription (STAT)-1, STAT-2, RELB, and nuclear factor kappa-B1 (NFκB1), most of which are known to regulate the HIV promoter activity...
February 2016: Cellular Signalling
https://www.readbyqxmd.com/read/26554585/a-naturally-occurring-rev1-vpu-fusion-gene-does-not-confer-a-fitness-advantage-to-hiv-1
#13
Simon M Langer, Kristina Hopfensperger, Shilpa S Iyer, Edward F Kreider, Gerald H Learn, Lan-Hui Lee, Beatrice H Hahn, Daniel Sauter
BACKGROUND: Pandemic strains of HIV-1 (group M) encode a total of nine structural (gag, pol, env), regulatory (rev, tat) and accessory (vif, vpr, vpu, nef) genes. However, some subtype A and C viruses exhibit an unusual gene arrangement in which the first exon of rev (rev1) and the vpu gene are placed in the same open reading frame. Although this rev1-vpu gene fusion is present in a considerable fraction of HIV-1 strains, its functional significance is unknown. RESULTS: Examining infectious molecular clones (IMCs) of HIV-1 that encode the rev1-vpu polymorphism, we show that a fusion protein is expressed in infected cells...
2015: PloS One
https://www.readbyqxmd.com/read/26542612/pregnancy-diabetes-a-comparison-of-diagnostic-protocols-based-on-point-of-care-routine-and-optimized-laboratory-conditions
#14
COMPARATIVE STUDY
Sjoerd A A van den Berg, Monique J M de Groot, Lorenzo P W Salden, Patrick J G J Draad, Ineke M Dijkstra, Simone Lunshof, Sjoerd W van Thiel, Kristel J M Boonen, Marc H M Thelen
In vitro glycolysis poses a problem during diabetes screening, especially in remote laboratories. Point-of-care analysis (POC) may provide an alternative. We compared POC, routine and STAT analysis and a feasible protocol during glucose tolerance test (GTT) for pregnancy diabetes (GDM) screening. In the routine protocol, heparin tubes were used and turn-around-time (TAT) was unsupervised. In the STAT protocol, tubes were processed immediately. The feasible protocol comprised of citrated tubes with a TAT of 1 hour...
November 6, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26542403/morphine-tolerance-and-physical-dependence-are-altered-in-conditional-hiv-1-tat-transgenic-mice
#15
Sylvia Fitting, David L Stevens, Fayez A Khan, Krista L Scoggins, Rachel M Enga, Patrick M Beardsley, Pamela E Knapp, William L Dewey, Kurt F Hauser
Despite considerable evidence that chronic opiate use selectively affects the pathophysiologic consequences of human immunodeficiency virus type 1 (HIV-1) infection in the nervous system, few studies have examined whether neuro-acquired immune deficiency syndrome (neuroAIDS) might intrinsically alter the pharmacologic responses to chronic opiate exposure. This is an important matter because HIV-1 and opiate abuse are interrelated epidemics, and HIV-1 patients are often prescribed opiates as a treatment of HIV-1-related neuropathic pain...
January 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/26524629/deciphering-structure-activity-relationships-in-a-series-of-tat-tar-inhibitors
#16
Lise Pascale, Alejandro López González, Audrey Di Giorgio, Marc Gaysinski, Jordi Teixido Closa, Roger Estrada Tejedor, Stéphane Azoulay, Nadia Patino
A series of pentameric "Polyamide Amino Acids" (PAAs) compounds derived from the same trimeric precursor have been synthesized and investigated as HIV TAR RNA ligands, in the absence and in the presence of a Tat fragment. All PAAs bind TAR with similar sub-micromolar affinities but their ability to compete efficiently with the Tat fragment strongly differs, IC50 ranging from 35 nM to >2 μM. While NMR and CD studies reveal that all PAA interact with TAR at the same site and induce globally the same RNA conformational change upon binding, a comparative thermodynamic study of PAA/TAR equilibria highlights distinct TAR binding modes for Tat competitor and non-competitor PAAs...
November 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/26501780/hiv-1-transgenic-rats-display-an-increase-in-3-h-dopamine-uptake-in-the-prefrontal-cortex-and-striatum
#17
Jun Zhu, Yaxia Yuan, Narasimha M Midde, Adrian M Gomez, Wei-Lun Sun, Pamela M Quizon, Chang-Guo Zhan
HIV viral proteins within the central nervous system are associated with the development of neurocognitive impairments in HIV-infected individuals. Dopamine transporter (DAT)-mediated dopamine transport is critical for normal dopamine homeostasis. Abnormal dopaminergic transmission has been implicated as a risk determinant of HIV-induced neurocognitive impairments. Our published work has demonstrated that transactivator of transcription (Tat)-induced inhibition of DAT is mediated by allosteric binding site(s) on DAT, not the interaction with the dopamine uptake site...
June 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/26499464/construction-of-a-novel-twin-arginine-translocation-tat-dependent-type-expression-vector-for-secretory-production-of-heterologous-proteins-in-corynebacterium-glutamicum
#18
Lirong Zhang, Huimin Jia, Daqing Xu
Corynebacterium glutamicum is recognized as a favorable host for the secretory production of heterologous proteins. However, there are few secretion-type expression vectors available for protein production in C. glutamicum. In this study, we constructed a shuttle expression vector pAU3, which harbors the strong promoter tac-M for constitutive gene transcription, the consensus RBS sequence for protein translation, and the strong cgR_0949 signal sequence for protein secretion via the Tat pathway in C. glutamicum...
November 2015: Plasmid
https://www.readbyqxmd.com/read/26492372/development-of-a-neuroprotective-peptide-that-preserves-survival-pathways-by-preventing-kidins220-arms-calpain-processing-induced-by-excitotoxicity
#19
A Gamir-Morralla, C López-Menéndez, S Ayuso-Dolado, G S Tejeda, J Montaner, A Rosell, T Iglesias, M Díaz-Guerra
Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), has a central role in the coordination of receptor crosstalk and the integration of signaling pathways essential for neuronal differentiation, survival and function. This protein is a shared downstream effector for neurotrophin- and ephrin-receptors signaling that also interacts with the N-methyl-d-aspartate type of glutamate receptors (NMDARs). Failures in neurotrophic support and glutamate signaling are involved in pathologies related to excitotoxicity and/or neurodegeneration, where different components of these dynamic protein complexes result altered by a combination of mechanisms...
2015: Cell Death & Disease
https://www.readbyqxmd.com/read/26486246/detection-of-prothrombotic-state-in-ischemic-stroke-by-monitoring-plasma-molecular-markers
#20
M Nagayama, Y Shinohara, T Nagayama
The feasibility of using recently developed coagulation-fibrinolysis markers to detect hemostatic alteration in acute ischemic stroke was examined to see whether they may be employed as predictors of recurrence. We measured serially the plasma thrombin-antithrombin III complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC) and D-dimer in patients with ischemic stroke (53 acute, 102 chronic) and 37 normal control subjects. In the acute stage, TAT and D-dimer were significantly increased in both atherothrombotic and lacunar stroke...
1994: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
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