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https://www.readbyqxmd.com/read/28535179/reduced-frequency-of-cells-latently-infected-with-replication-competent-hiv-1-in-virally-suppressed-individuals-living-in-rakai-uganda
#1
Jessica L Prodger, Jun Lai, Steven J Reynolds, Jeanne C Keruly, Richard D Moore, Jingo Kasule, Taddeo Kityamuweesi, Paul Buule, David Serwadda, Martha Nason, Adam A Capoferri, Stephen F Porcella, Robert F Siliciano, Andrew D Redd, Janet D Siliciano, Thomas C Quinn
Background: HIV-1 persists in latently infected resting CD4+ T cells (rCD4), posing a major barrier to curing HIV-1 infection. Previous studies have quantified this pool of latently infected cells in Americans; however, no study has quantified this reservoir in sub-Saharan Africans, who make up the largest population of HIV-1-infected individuals globally. Methods: Peripheral blood was collected from 70 virally suppressed HIV-1-infected individuals from Rakai District, Uganda, who had initiated antiretroviral therapy (ART) during chronic infection...
May 23, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28534873/molecular-indicators-of-stress-induced-neuroinflammation-in-a-mouse-model-simulating-features-of-post-traumatic-stress-disorder
#2
S Muhie, A Gautam, N Chakraborty, A Hoke, J Meyerhoff, R Hammamieh, M Jett
A social-stress mouse model was used to simulate features of post-traumatic stress disorder (PTSD). The model involved exposure of an intruder (male C57BL/6) mouse to a resident aggressor (male SJL) mouse for 5 or 10 consecutive days. Transcriptome changes in brain regions (hippocampus, amygdala, medial prefrontal cortex and hemibrain), blood and spleen as well as epigenome changes in the hemibrain were assayed after 1- and 10-day intervals following the 5-day trauma or after 1- and 42-day intervals following the 10-day trauma...
May 23, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28533135/enhanced-local-disorder-in-a-clinically-elusive-von-willebrand-factor-provokes-high-affinity-platelet-clumping
#3
Alexander Tischer, Venkata R Machha, Juan P Frontroth, Maria A Brehm, Tobias Obser, Reinhard Schneppenheim, Leland Mayne, S Walter Englander, Matthew Auton
Mutation of the cysteines forming the disulfide loop of the platelet GPIbα adhesive A1 domain of von Willebrand factor causes quantitative VWF deficiencies in the blood and von Willebrand disease. We report two cases of transient severe thrombocytopenia induced by DDAVP-treatment. Cys1272Trp and Cys1458Tyr mutations identified by genetic sequencing implicate an abnormal gain-of-function phenotype, evidenced by thrombocytopenia, that quickly relapses back to normal platelet counts and deficient plasma VWF. Using surface plasmon resonance, analytical rheology, and hydrogen-deuterium exchange mass spectrometry (HXMS), we decipher mechanisms of A1-GPIbα mediated platelet adhesion and resolve dynamic secondary structure elements that regulate the binding pathway...
May 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28527385/pharmacokinetic-analyses-using-absorption-kinetics-in-low-alcohol-dose-cases-of-drunken-driving
#4
Ayako Himemiya-Hakucho, Tatsuya Fujimiya
In Japan, low-alcohol dose cases of drunken driving, where drivers drink just before getting behind the wheel, are increasing for expert witnesses since the penalties for drunken driving have become stricter. Widmark's equation has generally been used for the pharmacokinetic analysis of blood alcohol concentration, which encompasses the one-compartment model with zero-order elimination kinetics but ignores absorption kinetics. We therefore propose that the formula might not be applicable to the analysis of low-alcohol dose cases of drunken driving because the issue is focused on the absorption phase...
May 5, 2017: Legal Medicine
https://www.readbyqxmd.com/read/28524818/fluorescence-lifetime-imaging-microscopy-reveals-rerouting-of-snare-trafficking-driving-dendritic-cell-activation
#5
Daniëlle Rianne José Verboogen, Natalia González Mancha, Martin Ter Beest, Geert van den Bogaart
SNARE proteins play a crucial role in intracellular trafficking by catalyzing membrane fusion, but assigning SNAREs to specific intracellular transport routes is challenging with current techniques. We developed a novel Förster resonance energy transfer-fluorescence lifetime imaging microscopy (FRET-FLIM)-based technique allowing visualization of real-time local interactions of fluorescently tagged SNARE proteins in live cells. We used FRET-FLIM to delineate the trafficking steps underlying the release of the inflammatory cytokine interleukin-6 (IL-6) from human blood-derived dendritic cells...
May 19, 2017: ELife
https://www.readbyqxmd.com/read/28524734/capillary-microsampling-in-nonclinical-safety-assessment-practical-sampling-and-bioanalysis-from-a-cro-perspective
#6
David Coleman, Graeme Smith, Rachel Lawrence, Deborah McManus, Sunetha Diaram, Joanna Edwards
Microsampling has the 3R benefits of refining blood collection techniques while reducing the number of animals required for rodent safety assessment studies. There are significant scientific benefits of correlating study findings with systemic exposure and consequently, there is an industry drive to utilize microsampling in regulatory toxicology studies. This article will focus on capillary microsampling and will discuss the initial considerations before using capillary microsampling, study design and some practicalities of sample collection...
May 19, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28524002/mirna-expression-in-bladder-cancer-and-their-potential-role-in-clinical-practice
#7
Ana Blanca, Liang Cheng, Rodolfo Montironi, Holger Moch, Francesco Massari, Michelangelo Fiorentino, Maria Rosaria Raspollini, Marina Scarpelli, Antonio Lopez-Beltran
To date more than 3000 miRNA sequences have been described in humans and reg¬istered at miRBase since their discovery. However, the functions of only a few of these miRNAs have been experimentally determined using deep sequencing technology. Aberrant miRNA expression has been associated with differentiation, invasion and metastasis in several cancers. In this context, recent reports have suggested that miRNAs play important roles in the regulation of target genes by binding to complementary regions of messenger transcripts to repress their translation or regulate degradation...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28523567/peripheral-viral-challenge-triggers-hippocampal-production-of-inflammatory-proteins
#8
Tiffany Petrisko, Gregory Konat
Peripheral viral infections increase seizure propensity and intensity in susceptible individuals. We have modeled this comorbidity by demonstrating that intraperitoneal (ip) injection of the conventional viral mimetic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to seizures induced by kainic acid (KA). At the molecular level, the hippocampus, which is the ictal site of KA-induced seizures, exhibits upregulated expression of messages encoding several inflammatory genes. Here, we profiled temporal expression of these genes at the protein level...
May 18, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28522896/shear-stress-counteracts-endothelial-cx3cl1-induction-and-monocytic-cell-adhesion
#9
Aaron Babendreyer, Lisa Molls, Daniela Dreymueller, Stefan Uhlig, Andreas Ludwig
Flow conditions critically regulate endothelial cell functions in the vasculature. Reduced shear stress resulting from disturbed blood flow can drive the development of vascular inflammatory lesions. On endothelial cells, the transmembrane chemokine CX3CL1/fractalkine promotes vascular inflammation by functioning as a surface-expressed adhesion molecule and by becoming released as soluble chemoattractant for monocytic cells expressing the receptor CX3CR1. Here, we report that endothelial cells from human artery, vein, or microvasculature constitutively express CX3CL1 when cultured under static conditions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28515334/central-acting-therapeutics-alleviate-respiratory-weakness-caused-by-heart-failure-induced-ventilatory-overdrive
#10
Andrew J Foster, Mathew J Platt, Jason S Huber, Ashley L Eadie, Alicia M Arkell, Nadya Romanova, David C Wright, Todd E Gillis, Coral L Murrant, Keith R Brunt, Jeremy A Simpson
Diaphragmatic weakness is a feature of heart failure (HF) associated with dyspnea and exertional fatigue. Most studies have focused on advanced stages of HF, leaving the cause unresolved. The long-standing theory is that pulmonary edema imposes a mechanical stress, resulting in diaphragmatic remodeling, but stable HF patients rarely exhibit pulmonary edema. We investigated how diaphragmatic weakness develops in two mouse models of pressure overload-induced HF. As in HF patients, both models had increased eupneic respiratory pressures and ventilatory drive...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28514936/evaluation-of-an-indirect-oscillometric-blood-pressure-monitor-in-anaesthetised-dogs-at-three-different-anatomical-locations
#11
M Fujiyama, H Sano, J P Chambers, M Gieseg
AIMS: To evaluate the agreement between invasive and non-invasive measurements of blood pressure (BP) using an oscillometer (PetTrust) at three different anatomical locations in anaesthetised dogs under different haemodynamic conditions. METHODS: Eight adult Greyhounds weighing 23.5-36.5 kg were anaesthetised with isoflurane and positioned in dorsal recumbency. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) were measured invasively via a dorsal pedal artery and non-invasively using the oscillometer with cuffs placed above the carpus, above the tarsus and around the tail base...
July 2017: New Zealand Veterinary Journal
https://www.readbyqxmd.com/read/28513058/pro-myogenic-and-low-oxygen-culture-increases-expression-of-contractile-smooth-muscle-markers-in-human-fibroblasts
#12
Matija Veber, David Dolivo, Marsha Rolle, Tanja Dominko
Smooth muscle cells are essential for tissue engineering strategies to fabricate organs such as blood vessels, esophagus, and bladder, and to create disease models of these systems. In order for such therapies and models to be feasible, smooth muscle cells must be sourced effectively to enable production of large numbers of functional cells. In vitro, smooth muscle cells divide slowly and demonstrate short proliferative lifespans compared to other types of cells including stem cells and fibroblasts, limiting the number of cells that can be derived from expansion in culture of a primary isolation...
May 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28512447/low-dose-pulsatile-interleukin-6-as-a-treatment-option-for-diabetic-peripheral-neuropathy
#13
REVIEW
April Ann Cox, Yves Sagot, Gael Hedou, Christina Grek, Travis Wilkes, Aaron I Vinik, Gautam Ghatnekar
Diabetic peripheral neuropathy (DPN) remains one of the most common and serious complications of diabetes. Currently, pharmacological agents are limited to treating the pain associated with DPN, and do not address the underlying pathological mechanisms driving nerve damage, thus leaving a significant unmet medical need. Interestingly, research conducted using exercise as a treatment for DPN has revealed interleukin-6 (IL-6) signaling to be associated with many positive benefits such as enhanced blood flow and lipid metabolism, decreased chronic inflammation, and peripheral nerve fiber regeneration...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28511848/intense-resistance-exercise-increases-peripheral-brain-derived-neurotrophic-factor
#14
Kieran J Marston, Michael J Newton, Belinda M Brown, Stephanie R Rainey-Smith, Sabine Bird, Ralph N Martins, Jeremiah J Peiffer
OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been shown to increase in an intensity dependent manner in response to aerobic exercise. However, previous research investigating the use of resistance exercise to increase BDNF levels has been less conclusive, likely due to the low intensity nature of traditional resistance exercise programs. This study examined the influence of acute resistance exercise to-fatigue on serum BDNF levels and blood lactate. DESIGN: Acute crossover study...
March 21, 2017: Journal of Science and Medicine in Sport
https://www.readbyqxmd.com/read/28511572/mtor-drives-cerebral-blood-flow-and-memory-deficits-in-ldlr-mice-modeling-atherosclerosis-and-vascular-cognitive-impairment
#15
Jordan B Jahrling, Ai-Ling Lin, Nicholas DeRosa, Stacy A Hussong, Candice E Van Skike, Milena Girotti, Martin Javors, Qingwei Zhao, Leigh Ann Maslin, Reto Asmis, Veronica Galvan
We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28511292/gut-inflammation-in-hla-b27-transgenic-rats-alters-the-monocyte-compartment-and-its-osteoclastogenic-potential
#16
Cecilia Ansalone, Lotta Utriainen, Simon Milling, Carl S Goodyear
Objective To investigate the relationship between intestinal inflammation and the central and peripheral innate immune system, in the pathogenesis of HLA-B27 associated spondyloarthritis. Methods The myeloid compartment of the bone marrow and blood of HLA-B27 transgenic (B27), control HLA-B7 transgenic (B7), and non-transgenic rats were evaluated by flow cytometry. Plasma from rats were assessed by ELISA for CCL2 and IL-1α levels. Rats were treated for 4 weeks with antibiotics and the blood and bone marrow myeloid compartments were evaluated by flow cytometry...
May 16, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28510599/selective-inhibition-of-brain-endothelial-rho-kinase-2-provides-optimal-protection-of-an-in-vitro-blood-brain-barrier-from-tissue-type-plasminogen-activator-and-plasmin
#17
Be'eri Niego, Natasha Lee, Pia Larsson, T Michael De Silva, Amanda E-Ling Au, Fiona McCutcheon, Robert L Medcalf
Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model...
2017: PloS One
https://www.readbyqxmd.com/read/28508896/obesity-related-cpg-methylation-cg07814318-of-kruppel-like-factor-13-klf13-gene-with-childhood-obesity-and-its-cis-methylation-quantitative-loci
#18
In-Uk Koh, Hye-Ja Lee, Joo-Yeon Hwang, Nak-Hyun Choi, Suman Lee
The cg07814318 hypermethylation of Kruppel-like factor 13 (KLF13) gene has been reported for its relevancy with Body Mass Index (BMI) from European origin. We explored the cg07814318 methylation and its cis-meQTL (cis-methylation quantitative loci) of KLF13 from a childhood obesity cohort. The cg07814318 methylation in blood was significantly associated with obesity and correlated with several obesity-related physical and biochemical traits. We examined the same loci from purified three human cell types (n = 47), i...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28503991/platelet-concentrates-modulate-myeloid-dendritic-cell-immune-responses
#19
Katrina K Ki, Helen M Faddy, Robert L Flower, Melinda M Dean
Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) following platelet transfusion are largely undefined. To determine the potential for platelet concentrates (PC) to modulate responses of crucial immune regulatory cells, a human in vitro whole blood model of transfusion was established. Maturation and activation of human myeloid dendritic cells (mDC) and the specialized subset blood DC antigen (BDCA)3(+) DC were assessed following exposure to buffy-coat derived PC at day (D)2 (fresh) and D5 (date-of-expiry)...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28503326/incomplete-paraplegia-caused-by-extramedullary-hematopoiesis-in-a-patient-with-thalassemia-intermedia
#20
Nurhasyimah Hisamud-Din, Nadia Mohd Mustafah, Aishah Ahmad Fauzi, Natiara Mohamad Hashim
INTRODUCTION: Extramedullary hematopoiesis (EMH) is the production of blood cell precursors outside the bone marrow that occur in various hematological diseases. In patients with thalassemia intermedia, ineffective erythropoiesis drives compensatory EMH in the liver, pancreas, pleura, spleen, ribs and spine. CASE PRESENTATION: We describe a patient with thalassemia intermedia who presented with acute neurological symptoms caused by paraspinal EMH, which responded well to combination therapy of steroid, hypertransfusion, laminectomy and excision of pseudotumor and hydroxyurea therapy to boost the formation of fetal haemoglobin...
2017: Spinal Cord Series and Cases
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