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https://www.readbyqxmd.com/read/28734204/molecular-dynamics-of-conformation-specific-dopamine-transporter-inhibitor-complexes
#1
Bernandie Jean, Christopher K Surratt, Jeffry D Madura
The recreational psychostimulant cocaine inhibits dopamine reuptake from the synapse, resulting in excessive stimulation of postsynaptic dopamine receptors in brain areas associated with reward and addiction. Cocaine binds to and stabilizes the outward- (extracellular-) facing conformation of the dopamine transporter (DAT) protein, while the low abuse potential DAT inhibitor benztropine prefers the inward- (cytoplasmic-) facing conformation. A correlation has been previously postulated between psychostimulant abuse potential and preference for the outward-facing DAT conformation...
July 11, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28734154/reducing-alcohol-consumption-to-minimize-weight-gain-and-facilitate-smoking-cessation-among-military-beneficiaries
#2
Mark B Sobell, Alan L Peterson, Linda Carter Sobell, Antoinette Brundige, Christopher M Hunter, Christine M Hunter, Jeffrey L Goodie, Sangeeta Agrawal, Ann S Hrysko-Mullen, William C Isler
INTRODUCTION: Smoking cessation-related weight gain can have significant negative health and career consequences for military personnel. Alcohol reduction combined with smoking cessation may decrease weight gain and relapse. METHOD: A randomized clinical trial of military beneficiaries compared a standard smoking cessation (i.e., brief informational) intervention (N=159), with a brief motivational smoking cessation intervention that emphasized reduced drinking to lessen caloric intake and minimize weight gain (N=158)...
June 30, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28734118/the-perniciousness-of-perfectionism-a-meta-analytic-review-of-the-perfectionism-suicide-relationship
#3
Martin M Smith, Simon B Sherry, Samantha Chen, Donald H Saklofske, Christopher Mushquash, Gordon L Flett, Paul L Hewitt
Over 50 years of research implicates perfectionism in suicide. Yet the role of perfectionism in suicide needs clarification due to notable between-study inconsistencies in findings, underpowered studies, and uncertainty whether perfectionism confers risk for suicide. OBJECTIVE: We addressed this by meta-analyzing perfectionism's relationship with suicide ideation and attempts. We also tested whether self-oriented, other-oriented, and socially prescribed perfectionism predicted increased suicide ideation, beyond baseline ideation...
July 22, 2017: Journal of Personality
https://www.readbyqxmd.com/read/28732406/quantifying-deforestation-and-forest-degradation-with-thermal-response
#4
Hua Lin, Yajun Chen, Qinghai Song, Peili Fu, James Cleverly, Vincenzo Magliulo, Beverly E Law, Christopher M Gough, Lukas Hörtnagl, Filippo Di Gennaro, Giorgio Matteucci, Leonardo Montagnani, Pierpaolo Duce, Changliang Shao, Tomomichi Kato, Damien Bonal, Eugénie Paul-Limoges, Jason Beringer, John Grace, Zexin Fan
Deforestation and forest degradation cause the deterioration of resources and ecosystem services. However, there are still no operational indicators to measure forest status, especially for forest degradation. In the present study, we analysed the thermal response number (TRN, calculated by daily total net radiation divided by daily temperature range) of 163 sites including mature forest, disturbed forest, planted forest, shrubland, grassland, savanna vegetation and cropland. TRN generally increased with latitude, however the regression of TRN against latitude differed among vegetation types...
July 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28732215/a-method-for-next-generation-sequencing-of-paired-diagnostic-and-remission-samples-to-detect-mitochondrial-dna-mutations-associated-with-leukemia
#5
Ilaria S Pagani, Chung H Kok, Verity A Saunders, Mark B Van der Hoek, Susan L Heatley, Anthony P Schwarer, Christopher N Hahn, Timothy P Hughes, Deborah L White, David M Ross
Somatic mitochondrial DNA (mtDNA) mutations have been identified in many human cancers, including leukemia. To identify somatic mutations, it is necessary to have a control tissue from the same individual for comparison. When patients with leukemia achieve remission, the remission peripheral blood may be a suitable and easily accessible control tissue, but this approach has not previously been applied to the study of mtDNA mutations. We have developed and validated a next-generation sequencing approach for the identification of leukemia-associated mtDNA mutations in 26 chronic myeloid leukemia patients at diagnosis using either nonhematopoietic or remission blood samples as the control...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28732195/fake-inhibitors-ampk-activation-trumps-inhibition
#6
Christopher G Langendorf, John W Scott, Bruce E Kemp
Protein kinase inhibitors have become increasingly important therapeutic drugs for the treatment of human diseases; however, resistance and off-target effects can limit their use. In this issue of Cell Chemical Biology, Ross et al. (2017) reveal a novel off-target mechanism where the Src kinase inhibitor SU6656 paradoxically primes AMPK for phosphorylation and activation by the upstream kinase LKB1.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28732035/vaccine-induced-immune-responses-against-both-gag-and-env-improve-control-of-simian-immunodeficiency-virus-replication-in-rectally-challenged-rhesus-macaques
#7
Mauricio A Martins, Young C Shin, Lucas Gonzalez-Nieto, Aline Domingues, Martin J Gutman, Helen S Maxwell, Iris Castro, Diogo M Magnani, Michael Ricciardi, Nuria Pedreño-Lopez, Varian Bailey, Dillon Betancourt, John D Altman, Matthias Pauthner, Dennis R Burton, Benjamin von Bredow, David T Evans, Maoli Yuan, Christopher L Parks, Keisuke Ejima, David B Allison, Eva Rakasz, Glen N Barber, Saverio Capuano, Jeffrey D Lifson, Ronald C Desrosiers, David I Watkins
The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4)...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28731986/the-effect-of-sex-on-heart-rate-variability-at-high-altitude
#8
Christopher John Boos, Emma Vincent, Adrian Mellor, John O'Hara, Caroline Newman, Richard Cruttenden, Phylip Scott, Mark Cooke, Jamie Matu, David Richard Woods
There is evidence to suggest that high altitude (HA) exposure leads to a fall in heart rate variability (HRV) that is linked to the development of acute mountain sickness (AMS). The effects of sex on changes in HRV at HA and its relationship to AMS are unknown. METHODS: HRV (5-minute single lead ECG) was measured in 63 healthy adults (41 men and 22 women) aged 18-56 years at sea level (SL) and during a HA trek at 3619m, 4600m and 5140m respectively. The main effects of altitude (SL, 3619, 4600 and 5140m) and sex (men vs women) and their potential interaction were assessed using a Factorial Repeated Measures ANOVA...
July 20, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28731978/differences-in-spatiotemporal-parameters-between-trained-runners-and-untrained-participants
#9
Josué Gómez-Molina, Ana Ogueta-Alday, Christopher Stickley, Jesús Cámara, Jon Cabrejas-Ugartondo, Juan García-López
Gómez-Molina, J, Ogueta-Alday, A, Stickley, C, Tobalina, JC, Cabrejas-Ugartondo, J, and García-López, J. Differences in spatiotemporal parameters between trained runners and untrained participants. J Strength Cond Res 31(8): 2169-2175, 2017-The aim of this study was to compare the spatiotemporal parameters of trained runners and untrained participants with the same foot strike pattern (rearfoot) during running at controlled speeds. Twenty-one participants were classified in 2 groups according to their training experience: Trained (n = 10, amateur runners with long distance training experience) and Untrained (n = 11, healthy untrained participants)...
August 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28731947/early-stage-cancer-in-older-adults-prostate-avoiding-overtreatment-and-undertreatment
#10
Vikram Narayan, Song Jiang, Christopher A Warlick
The diagnosis of prostate cancer in elderly men is likely to increase over the next several decades, owing to changing demographics and a rising population of men older than 65 years. Given the heterogeneity and well-documented challenges in screening, diagnosing, and managing indolent versus aggressive prostate cancer, the geriatric patient population is particularly vulnerable to prostate cancer treatment nuances. Clinicians must become familiar with geriatric assessment tools to better answer life-expectancy questions prior to counseling patients on treatment options...
July 2017: Cancer Journal
https://www.readbyqxmd.com/read/28731931/renal-function-and-its-association-with-blood-pressure-in-middle-eastern-immigrants-and-native-swedes
#11
Christopher Nilsson, Anders Christensson, Peter M Nilsson, Louise Bennet
BACKGROUND: Iraqi-born immigrants residing in Sweden are at high risk for type 2 diabetes, obesity and hyperlipidemia compared with native Swedes. Paradoxically, hypertension is less prevalent in this immigrant population. The aim of this study was to investigate differences in renal function and further if differences in blood pressure (BP) levels were associated with differences across ethnicities in renal function as a possible explanation to the paradox. METHODS: A population-based, cross-sectional study of men and women, born in Iraq or Sweden, aged 30-75 years was conducted in Malmö, Sweden, from 2010 to 2012...
July 20, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28731910/new-answers-to-old-conundrums-what-antibodies-exosomes-and-inflammasomes-bring-to-the-conversation-canadian-national-transplant-research-program-international-summit-report
#12
Mélanie Dieudé, Lori J West, Daniel A Muruve, Lakshman Gunaratman, Thalachallour Mohanakumar, Emmanuel Zorn, Christopher W Cairo, Darren H Freed, Kirk R Schultz, Robert L Fairchild, Marie-Josée Hébert
Antibody-mediated injury is a major cause of allograft dysfunction and loss. Antibodies to ABH(O) blood group antigens are classical mediators of ABO-incompatible (ABOi) graft rejection, while donor-specific anti-HLA antibodies and, more recently, autoantibodies are appreciated as important contributors to allograft inflammation and dysfunction. In August 2016, the International Summit of the Canadian National Transplant Research Program focused on recent advances in the field of antibody-mediated rejection...
July 21, 2017: Transplantation
https://www.readbyqxmd.com/read/28731851/the-frequency-of-occurrence-of-fish-shaped-red-blood-cells-in-different-haematologic-disorders
#13
Christoph Robier, Carolin Körber, Franz Quehenberger, Manfred Neubauer, Albert Wölfler
BACKGROUND: Red blood cells (RBC) resembling the silhouette of a fish are rarely observed in peripheral blood (PB) smears. In this study, we determined the frequency of occurrence of fish-shaped RBC in different haematologic diseases. METHODS: We examined PB smears of patients with iron deficiency anaemia (IDA) (n=23), β-thalassaemia minor (BTM) (n=30), sickle cell disease (SCD) (n=7), autoimmune haemolytic anaemia (AIHA) (n=13), microangiopathic haemolytic anaemia (MAHA) (n=11), hereditary sphaerocytosis (HS) (n=4), hereditary elliptocytosis (HE) (n=3), vitamin B12 and folate deficiency (n=15), anaemia in liver disease (LD) (n=17), myelodysplastic syndrome (MDS) (n=15), acute myeloid leukaemia (AML) (n=29), chronic myeloid leukaemia (CML) (n=18), primary myelofibrosis (PMF) (n=12), chronic myelo-monocytic leukaemia (CMML) (n=15) and 21 healthy controls by light microscopy for the occurrence of fish-shaped erythrocytes...
July 21, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28731828/geographical-variation-in-community-divergence-insights-from-tropical-forest-monodominance-by-ectomycorrhizal-trees
#14
Tadashi Fukami, Mifuyu Nakajima, Claire Fortunel, Paul V A Fine, Christopher Baraloto, Sabrina E Russo, Kabir G Peay
Convergence occurs in both species traits and community structure, but how convergence at the two scales influences each other remains unclear. To address this question, we focus on tropical forest monodominance, in which a single, often ectomycorrhizal (EM) tree species occasionally dominates forest stands within a landscape otherwise characterized by diverse communities of arbuscular mycorrhizal (AM) trees. Such monodominance is a striking potential example of community divergence resulting in alternative stable states...
August 2017: American Naturalist
https://www.readbyqxmd.com/read/28731801/diversification-of-trait-combinations-in-coevolving-plant-and-insect-lineages
#15
John N Thompson, Christopher Schwind, Magne Friberg
Closely related species often have similar traits and sometimes interact with the same species. A crucial problem in evolutionary ecology is therefore to understand how coevolving species diverge when they interact with a set of closely related species from another lineage rather than with a single species. We evaluated geographic differences in the floral morphology of all woodland star plant species (Lithophragma, Saxifragaceae) that are pollinated by Greya (Prodoxidae) moths. Flowers of each woodland star species differed depending on whether plants interact locally with one, two, or no pollinating moth species...
August 2017: American Naturalist
https://www.readbyqxmd.com/read/28731778/a-pharmacologic-algorithm-for-youth-who-are-at-high-risk-for-bipolar-disorder
#16
Christopher D Schneck, Kiki D Chang, Manpreet K Singh, Melissa P DelBello, David J Miklowitz
OBJECTIVE: Depression and brief periods of manic symptoms are linked to a significant risk of progression to bipolar disorder (BD) in children who have a first-degree relative with BD I or II. However, little evidence exists to guide the pharmacologic management of children with these high-risk phenotypes. We propose a pharmacological treatment algorithm for high-risk youth and present results on its use in a study of children with a first-degree relative with BD. METHODS: Subjects were 40 youth (mean 12...
July 21, 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28731777/induction-and-maintenance-adjuvant-mitomycin-c-topical-therapy-for-upper-tract-urothelial-carcinoma-tolerability-and-intermediate-term-outcomes
#17
Michael Metcalfe, Gavin Wagenheim, Lianchun Xiao, John Papadopoulos, Neema Navai, John W Davis, Jose A Karam, Ashish M Kamat, Christopher G Wood, Colin P Dinney, Surena F Matin
PURPOSE: Endoscopic management of upper tract urothelial carcinoma (UTUC) is associated with higher recurrences, which could be reduced by application of topical therapy. Adjuvant induction Bacillus Calmette-Guerin has shown inferior outcomes for UTUC compared to bladder cancer, and maintenance regimens for UTUC are unexplored. We report on the efficacy, safety, and tolerability of Mitomycin C (MMC) induction and maintenance adjuvant topical therapy for UTUC. MATERIALS AND METHODS: Patients with UTUC who received adjuvant topical therapy after complete endoscopic control of Ta/T1 tumors were retrospectively reviewed...
July 21, 2017: Journal of Endourology
https://www.readbyqxmd.com/read/28731719/discovery-structure-activity-relationship-and-binding-mode-of-imidazo-1-2-a-pyridine-series-of-autotaxin-inhibitors
#18
Agnès Joncour, Nicolas Desroy, Christopher Housseman, Xavier Bock, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Christophe Peixoto, Denis Annoot, Luce Lepissier, Jörg Heiermann, Willem Jan Hengeveld, Gregor Pilzak, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, René Galien, Christelle David, Nele Vandervoort, Thierry Christophe, Katja Conrath, Mia Jans, Alexandre Wohlkonig, Robert Touitou, Damien Fleury, Lionel Vercheval, Patrick Mollat, Nicolas Triballeau, Ellen Van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases and inflammation among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high throughput screening (HTS). A co-crystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site...
July 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28731677/an-evaluation-of-optimal-pegylation-strategies-for-maximizing-the-lymphatic-exposure-and-antiviral-activity-of-interferon-after-subcutaneous-administration
#19
Linda J Chan, Orlagh M Feeney, Nathania J Leong, Victoria M Mcleod, Christopher J H Porter, Charlotte C Williams, Lisa M Kaminskas
Interferon α2 is an antiviral/antiproliferative protein that is currently used to treat hepatitis C infections and several forms of cancer. Two PEGylated variants of interferon α2 (containing 12 and 40 kDa PEGs) are currently marketed and display longer plasma circulation times than unmodified interferon. With increasing realization that the lymphatic system plays an important role in the extrahepatic replication of the hepatitis C virus and in the metastatic dissemination of cancers, this study sought to evaluate PEGylation strategies to optimally enhance the antiviral activity and plasma and lymphatic exposure of interferon after subcutaneous administration in rats...
July 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28731570/susceptibility-weighted-imaging-and-quantitative-susceptibility-mapping-of-the-cerebral-vasculature-using-ferumoxytol
#20
Saifeng Liu, Jean-Christophe Brisset, Jiani Hu, E Mark Haacke, Yulin Ge
PURPOSE: To demonstrate the potential of imaging cerebral arteries and veins with ferumoxytol using susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: The relationships between ferumoxytol concentration and the apparent susceptibility at 1.5T, 3T, and 7T were determined using phantom data; the ability of visualizing subvoxel vessels was evaluated using simulations; and the feasibility of using ferumoxytol to enhance the visibility of small vessels was confirmed in three healthy volunteers at 7T(with doses 1 mg/kg to 4 mg/kg)...
July 21, 2017: Journal of Magnetic Resonance Imaging: JMRI
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