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https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#1
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28212290/defining-clinical-response-criteria-and-early-response-criteria-for-precision-oncology-current-state-of-the-art-and-future-perspectives
#2
Vivek Subbiah, Hubert H Chuang, Dhiraj Gambhire, Kalevi Kairemo
In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016...
February 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/28208656/primetime-for-learning-genes
#3
REVIEW
Joyce Keifer
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28202970/heinrich-events-triggered-by-ocean-forcing-and-modulated-by-isostatic-adjustment
#4
Jeremy N Bassis, Sierra V Petersen, L Mac Cathles
During the last glacial period, the Laurentide Ice Sheet sporadically discharged huge numbers of icebergs through the Hudson Strait into the North Atlantic Ocean, leaving behind distinct layers of ice-rafted debris in the ocean sediments. Perplexingly, these massive discharge events-Heinrich events-occurred during the cold portion of millennial-scale climate oscillations called Dansgaard-Oeschger cycles. This is in contrast to the expectation that ice sheets expand in colder climates and shrink in warmer climates...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28202646/mussel-adhesion-essential-footwork
#5
REVIEW
J Herbert Waite
Robust adhesion to wet, salt-encrusted, corroded and slimy surfaces has been an essential adaptation in the life histories of sessile marine organisms for hundreds of millions of years, but it remains a major impasse for technology. Mussel adhesion has served as one of many model systems providing a fundamental understanding of what is required for attachment to wet surfaces. Most polymer engineers have focused on the use of 3,4-dihydroxyphenyl-l-alanine (Dopa), a peculiar but abundant catecholic amino acid in mussel adhesive proteins...
February 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28197553/the-role-of-sirt1-in-epileptogenesis
#6
Alicia M Hall, Gary P Brennan, Tiffany M Nguyen, Akanksha Singh-Taylor, Hyun-Seung Mun, Mary J Sargious, Tallie Z Baram
The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults, including trauma, stroke, tumors, infections, and long seizures [status epilepticus (SE)], create a neuronal state of increased metabolic demand or decreased energy supply. Neurons express molecules that monitor their metabolic state, including sirtuins (Sirts). Sirtuins deacetylate cytoplasmic proteins and nuclear histones, and their epigenetic modulation of the chromatin governs the expression of many genes, influencing neuronal properties...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28196633/old-and-new-oral-anticoagulants-food-herbal-medicines-and-drug-interactions
#7
REVIEW
Alessandro Di Minno, Beatrice Frigerio, Gaia Spadarella, Alessio Ravani, Daniela Sansaro, Mauro Amato, Joseph P Kitzmiller, Mauro Pepi, Elena Tremoli, Damiano Baldassarre
The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs...
February 5, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28192422/identification-of-quiescent-and-spatially-restricted-mammary-stem-cells-that-are-hormone-responsive
#8
Nai Yang Fu, Anne C Rios, Bhupinder Pal, Charity W Law, Paul Jamieson, Ruijie Liu, François Vaillant, Felicity Jackling, Kevin He Liu, Gordon K Smyth, Geoffrey J Lindeman, Matthew E Ritchie, Jane E Visvader
Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5(+) basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures...
February 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28192107/gastrointestinal-complications-of-obesity
#9
Michael Camilleri, Harmeet Malhi, Andres Acosta
Obesity is usually associated with morbidity related to diabetes mellitus and cardiovascular diseases. However, there are many gastrointestinal and hepatic diseases for which obesity is the direct cause [e.g. non-alcoholic fatty liver diseases (NAFLD)] or is a significant risk factor, such as reflux esophagitis and gallstones. When obesity is a risk factor, it may interact with other mechanisms and result in earlier presentation or complicated diseases. There are increased odds ratios or relative risks of several gastrointestinal complications of obesity: gastroesophageal reflux disease (GERD), erosive esophagitis, Barrett's esophagus, esophageal adenocarcinoma, erosive gastritis, gastric cancer, diarrhea, colonic diverticular disease, polyps, cancer, liver disease including NAFLD, cirrhosis, hepatocellular carcinoma, gallstones, acute pancreatitis, and pancreatic cancer...
February 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28191936/development-of-fluorophore-labeled-thailanstatin-antibody-drug-conjugates-for-cellular-trafficking-studies
#10
Chethana Kulkarni, James E Finley, Andrew J Bessire, Xiaotian Zhong, Sylvia Musto, Edmund Idris Graziani
As the antibody-drug conjugate (ADC) field grows increasingly important for cancer treatment, it is vital for researchers to establish a firm understanding of how ADCs function at the molecular level. To gain insight into ADC uptake, trafficking, and catabolism-processes that are critical to ADC efficacy and toxicity-imaging studies have been performed with fluorophore-labeled conjugates. However, such labels may alter the properties and behavior of the ADC under investigation. As an alternative approach, we present here the development of a "clickable" ADC bearing an azide-functionalized linker-payload (LP) poised for "click" reaction with alkyne fluorophores; the azide group represents a significantly smaller structural perturbation to the LP than most fluorophores...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28188998/midwives-experiences-of-working-in-an-obstetric-high-dependency-unit-a-qualitative-study
#11
Isabelle J Eadie, Nicolette F Sheridan
OBJECTIVES: to understand the challenges experienced by midwives providing obstetric high dependency care and identify the training they perceive is needed for work in an obstetric high dependency unit. DESIGN: sixteen midwives who worked in the obstetric high dependency unit participated in one of three focus groups. Focus groups lasted 60-90minutes and were conducted in the workplace and facilitated by author (IE). Data were digitally recorded, transcribed and analysed manually by author (IE), specifically using a 'codebook' model to generate codes, categories and themes...
January 21, 2017: Midwifery
https://www.readbyqxmd.com/read/28187950/advancing-nmda-receptor-physiology-by-integrating-multiple-approaches
#12
REVIEW
Huan-Xiang Zhou, Lonnie P Wollmuth
NMDA receptors (NMDARs) are ion channels activated by the excitatory neurotransmitter glutamate and are essential to all aspects of brain function, including learning and memory formation. Missense mutations distributed throughout NMDAR subunits have been associated with an array of neurological disorders. Recent structural, functional, and computational studies have generated many insights into the activation process connecting glutamate binding to ion-channel opening, which is central to NMDAR physiology and pathophysiology...
February 7, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28171830/a-review-on-antioxidant-potential-of-bioactive-heterocycle-benzofuran-natural-and-synthetic-derivatives
#13
REVIEW
Karam Chand, Rajeshwari, Asha Hiremathad, Mahak Singh, M Amelia Santos, Rangappa S Keri
The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. In this context, oxygen heterocycles exhibit diverse biological and pharmacological activities due in part to the similarities with many natural and synthetic molecules with known biological activity. Among oxygen containing heterocycles, benzofuran (synthetic and natural isolated) and its derivatives have attracted medicinal chemists and pharmacologists due to their pronounced biological activities and their potential applications as pharmacological agents such as antioxidant, antitumor, antiplatelet, antimalarial, antiinflammatory, antidepressant and anticonvulsant properties...
November 18, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28165368/reducing-low-birth-weight-among-african-americans-in-the-midwest-a-look-at-how-faith-based-organizations-are-poised-to-inform-and-influence-health-communication-on-the-developmental-origins-of-health-and-disease-dohad
#14
Crystal Y Lumpkins, Jarron M Saint Onge
Low birth weight (LBW) rates remain the highest among African Americans despite public health efforts to address these disparities; with some of the highest racial disparities in the Midwest (Kansas). The Developmental Origins of Health and Disease (DOHaD) perspective offers an explanation for how LBW contributes to racial health disparities among African Americans and informs a community directed health communication framework for creating sustainable programs to address these disparities. Trusted community organizations such as faith-based organizations are well situated to explain health communication gaps that may occur over the life course...
February 4, 2017: Healthcare (Basel, Switzerland)
https://www.readbyqxmd.com/read/28162229/the-increased-transforming-growth-factor-%C3%AE-signaling-induced-by-diabetes-protects-retinal-vessels
#15
Zeina Dagher, Chiara Gerhardinger, Joseph Vaz, Michael Goodridge, Francesco Tecilazich, Mara Lorenzi
The roles of transforming growth factor (TGF)-β in extracellular matrix production and vascular remodeling, coupled with increased TGF-β expression and signaling in diabetes, suggest TGF-β as an important contributor to the microangiopathy of diabetic retinopathy and nephropathy. To investigate whether increased TGF-β signaling could be a therapeutic target for preventing retinopathy, we used a pharmacologic approach (SM16, a selective inhibitor of the type 1 TGF-β receptor activin receptor-like kinase 5, orally active) to inhibit the increased, but not the basal, Tgf-β signaling in retinal vessels of diabetic rats...
February 1, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28161702/the-course-and-impact-of-poststroke-insomnia-in-stroke-survivors-aged-18-to-65-years-results-from-the-psychosocial-outcomes-in-stroke-poise-study%C3%A2
#16
Nick Glozier, Tom J Moullaali, Børge Sivertsen, Dukyeon Kim, Gillian Mead, Stephen Jan, Qiang Li, Maree L Hackett
BACKGROUND: Insomnia symptoms are common in the population and have negative psychosocial and functional sequelae. There are no prospective studies of the course of such symptoms and their impact, if any, in stroke survivors. This prospective cohort study investigated insomnia after stroke in working-age adults and evaluated its impact on psychological and functional outcomes over the subsequent year. METHODS: We prospectively recruited 441 young (<65 years) consecutive stroke survivors from 20 public hospitals in the New South Wales Stroke Service network...
February 3, 2017: Cerebrovascular Diseases Extra
https://www.readbyqxmd.com/read/28160786/advancing-health-equity-for-lesbian-gay-bisexual-and-transgender-lgbt-people-through-sexual-health-education-and-lgbt-affirming-health-care-environments
#17
Alex S Keuroghlian, Kevin L Ard, Harvey J Makadon
Lesbian, gay, bisexual and transgender (LGBT) people face pervasive health disparities and barriers to high-quality care. Adequate LGBT sexual health education for emerging health professionals is currently lacking. Clinical training programs and healthcare organisations are well poised to start addressing these disparities and affirming LGBT patients through curricula designed to cultivate core competencies in LBGT health as well as health care environments that welcome, include and protect LGBT patients, students and staff...
February 6, 2017: Sexual Health
https://www.readbyqxmd.com/read/28154873/a-low-cost-smartphone-based-platform-for-highly-sensitive-point-of-care-testing-with-persistent-luminescent-phosphors
#18
Andrew S Paterson, Balakrishnan Raja, Vinay Mandadi, Blane Townsend, Miles Lee, Alex Buell, Binh Vu, Jakoah Brgoch, Richard C Willson
Through their computational power and connectivity, smartphones are poised to rapidly expand telemedicine and transform healthcare by enabling better personal health monitoring and rapid diagnostics. Recently, a variety of platforms have been developed to enable smartphone-based point-of-care testing using imaging-based readout with the smartphone camera as the detector. Fluorescent reporters have been shown to improve the sensitivity of assays over colorimetric labels, but fluorescence readout necessitates incorporating optical hardware into the detection system, adding to the cost and complexity of the device...
February 3, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28150777/pathologically-expanded-peripheral-t-helper-cell-subset-drives-b-cells-in-rheumatoid-arthritis
#19
Deepak A Rao, Michael F Gurish, Jennifer L Marshall, Kamil Slowikowski, Chamith Y Fonseka, Yanyan Liu, Laura T Donlin, Lauren A Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C Teslovich, Michael E Weinblatt, Elena M Massarotti, Jonathan S Coblyn, Simon M Helfgott, Yvonne C Lee, Derrick J Todd, Vivian P Bykerk, Susan M Goodman, Alessandra B Pernis, Lionel B Ivashkiv, Elizabeth W Karlson, Peter A Nigrovic, Andrew Filer, Christopher D Buckley, James A Lederer, Soumya Raychaudhuri, Michael B Brenner
CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis...
1, 2017: Nature
https://www.readbyqxmd.com/read/28148652/calcium-signals-drive-cell-shape-changes-during-zebrafish-midbrain-hindbrain-boundary-formation
#20
Srishti U Sahu, Mike R Visetsouk, Ryan J Garde, Leah Hennes, Constance Kwas, Jennifer H Gutzman
One of the first morphogenetic events in the vertebrate brain is the formation of the highly conserved midbrain-hindbrain boundary (MHB). Specific cell shape changes occur at the point of deepest constriction of the MHB, the midbrain-hindbrain boundary constriction (MHBC), and are critical for proper MHB formation. These cell shape changes are controlled by non-muscle myosin II (NMII) motor proteins which are tightly regulated via the phosphorylation of their associated myosin regulatory light chains (MRLC)...
February 1, 2017: Molecular Biology of the Cell
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