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https://www.readbyqxmd.com/read/28340354/mechanism-of-substrate-translocation-in-an-alternating-access-transporter
#1
Naomi R Latorraca, Nathan M Fastman, A J Venkatakrishnan, Wolf B Frommer, Ron O Dror, Liang Feng
Transporters shuttle molecules across cell membranes by alternating among distinct conformational states. Fundamental questions remain about how transporters transition between states and how such structural rearrangements regulate substrate translocation. Here, we capture the translocation process by crystallography and unguided molecular dynamics simulations, providing an atomic-level description of alternating access transport. Simulations of a SWEET-family transporter initiated from an outward-open, glucose-bound structure reported here spontaneously adopt occluded and inward-open conformations...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340339/targeted-apoptosis-of-senescent-cells-restores-tissue-homeostasis-in-response-to-chemotoxicity-and-aging
#2
Marjolein P Baar, Renata M C Brandt, Diana A Putavet, Julian D D Klein, Kasper W J Derks, Benjamin R M Bourgeois, Sarah Stryeck, Yvonne Rijksen, Hester van Willigenburg, Danny A Feijtel, Ingrid van der Pluijm, Jeroen Essers, Wiggert A van Cappellen, Wilfred F van IJcken, Adriaan B Houtsmuller, Joris Pothof, Ron W F de Bruin, Tobias Madl, Jan H J Hoeijmakers, Judith Campisi, Peter L J de Keizer
The accumulation of irreparable cellular damage restricts healthspan after acute stress or natural aging. Senescent cells are thought to impair tissue function, and their genetic clearance can delay features of aging. Identifying how senescent cells avoid apoptosis allows for the prospective design of anti-senescence compounds to address whether homeostasis can also be restored. Here, we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340077/idiopathic-non-lupus-full-house-nephropathy-is-associated-with-poor-renal-outcome
#3
Emilie C Rijnink, Y K Onno Teng, Tineke Kraaij, Ron Wolterbeek, Jan A Bruijn, Ingeborg M Bajema
Background.: Full-house immunofluorescence in combination with various histopathologic lesions in the renal biopsies of patients without overt systemic lupus erythematosus (SLE) poses a diagnostic challenge. In this setting, the biopsy findings are sometimes termed non-lupus 'full-house nephropathy' (FHN). It is presently unknown whether idiopathic non-lupus FHN is clinicopathologically and prognostically distinct from lupus FHN. Methods.: We included non-lupus FHN patients and lupus FHN controls (four or more American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) who were biopsied between 1968 and 2014 at the Leiden University Medical Centre...
March 13, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28340053/does-the-regulatory-environment-for-e-cigarettes-influence-the-effectiveness-of-e-cigarettes-for-smoking-cessation-longitudinal-findings-from-the-itc-four-country-survey
#4
Hua-Hie Yong, Sara C Hitchman, K Michael Cummings, Ron Borland, Shannon M L Gravely, Ann McNeill, Geoffrey T Fong
Introduction: To date, no studies have explored how different regulatory environments may influence the effectiveness of ECs as a smoking cessation aid. Objective: This study compares the real-world effectiveness of adult smokers using ECs for quitting compared with quitting unassisted or quitting with NRT and/or prescription medications in two countries with restrictive policies towards ECs (i.e., Canada and Australia) versus two countries with less restrictive policies (i...
March 4, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28339299/the-10th-gcc-closed-forum-rejected-data-gcp-in-bioanalysis-extract-stability-bav-processed-batch-acceptance-matrix-stability-critical-reagents-eln-and-data-integrity-and-counteracting-fraud
#5
Stephanie Cape, Rafiq Islam, Corey Nehls, John Allinson, Afshin Safavi, Patrick Bennett, James Hulse, Chris Beaver, Masood Khan, Shane Karnik, Maria Cruz Caturla, Steve Lowes, Adriana Iordachescu, Luigi Silvestro, Rabab Tayyem, Ron Shoup, Stephanie Mowery, Anahita Keyhani, Andrea Wakefield, Yinghe Li, Jennifer Zimmer, Javier Torres, Philippe Couerbe, Ardeshir Khadang, James Bourdage, Nicola Hughes, Kayode Awaiye, Brent Matthews, Saadya Fatmi, Rhonda Johnson, Christina Satterwhite, Mathilde Yu, Jenny Lin, Laura Cojocaru, Michele Fiscella, Eric Thomas, Kai Kurylak, John Kamerud, Zhongping John Lin, Wei Garofolo, Natasha Savoie, Mike Buonarati, Nadine Boudreau, Clark Williard, Yansheng Liu, Dominic Warrino, Prashant Kale, Neil Adcock, Radha Shekar, Edward O'Connor, Hanna Ritzen, Christina Sanchez, Roger Hayes, Mohammed Bouhajib, Simona Rizea Savu, Bruce Stouffer, Edward Tabler, Jing Tu, Chad Briscoe, Barry van der Strate, Paul Rhyne, Phyllis Conliffe, Ira DuBey, Jim Yamashita, Daniel Tang, Elizabeth Groeber, Jenifer Vija, Michele Malone, Mohamed Osman
The 10th Global CRO Council (GCC) Closed Forum was held in Orlando, FL, USA on 18 April 2016. In attendance were decision makers from international CRO member companies offering bioanalytical services. The objective of this meeting was for GCC members to meet and discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at this closed forum included reporting data from failed method validation runs, GCP for clinical sample bioanalysis, extracted sample stability, biomarker assay validation, processed batch acceptance criteria, electronic laboratory notebooks and data integrity, Health Canada's Notice regarding replicates in matrix stability evaluations, critical reagents and regulatory approaches to counteract fraud...
March 24, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28334770/smokers-perceptions-of-sources-of-advice-about-quitting-findings-from-the-australian-arm-of-the-itc-4-country-survey
#6
James Balmford, Ron Borland
Smokers are exposed to advice about quitting from numerous sources. Within the 2013 ITC 4-Country Survey, 1211 Australian smokers or recent ex-smokers rated the perceived importance of eight sources of advice, categorized into evidence-based, non evidence-based, personal experience and vicarious experience (two items each), and also rated their intention to quit, nicotine dependence, use of quit medication, health concerns and harm beliefs. The eight items were all positively correlated. Respondents who placed greater importance on their experiences (either personal or vicarious) were more likely to agree that the evidence for smoking-related harm is exaggerated, and although not more likely to intend to quit overall, these responses were most strongly related to quit intention...
February 27, 2017: Health Education Research
https://www.readbyqxmd.com/read/28334598/tir-axons-apart-unpredicted-nadase-controls-axonal-degeneration
#7
Ron Goldner, Avraham Yaron
SARM1 is a key regulator of axonal degeneration. However, SARM1 mechanism of action is not clear. In this issue of Neuron, Essuman et al. (2017) reveal an intrinsic NADase activity in the SARM1-TIR domain that is required for axonal degeneration.
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28334165/ctsge-clustering-subgroups-of-expression-data
#8
Michal Sharabi-Schwager, Etti Or, Ron Ophir
Summary: A prerequisite to clustering noisy data, such as gene-expression data, is the filtering step. As an alternative to this step, the ctsGE R-package applies a sorting step in which all of the data are divided into small groups. The groups are divided according to how the time points are related to the time-series median. Then clustering is performed separately on each group. Thus, the clustering is done in two steps. First, an expression index (i.e., a sequence of 1, -1, and 0) is defined and genes with the same index are grouped together, and then each group of genes is clustered by k-means to create subgroups...
March 3, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28332939/pediatric-asthma-hospitalizations-among-urban-minority-children-and-the-continuity-of-primary-care
#9
Levon H Utidjian, Alexander G Fiks, A Russell Localio, Lihai Song, Mark J Ramos, Ron Keren, Louis M Bell, Robert W Grundmeier
OBJECTIVE: To examine the effect of ambulatory health care processes on asthma hospitalizations. METHODS: A retrospective cohort study using electronic health records was completed. Patients aged 2-18 years receiving health care from 1 of 5 urban practices between Jan 1, 2004 and Dec 31, 2008 with asthma documented on their problem list were included. Independent variables were modifiable health care processes in the primary care setting: (1) use of asthma controller medications; (2) regular assessment of asthma symptoms; (3) use of spirometry; (4) provision of individualized asthma care plans; (5) timely influenza vaccination; (6) access to primary healthcare; and (7) use of pay for performance physician incentives...
February 25, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28332246/weight-management-in-adults-with-intellectual-and-developmental-disabilities-a-randomized-controlled-trial-of-two-dietary-approaches
#10
Lauren T Ptomey, Richard R Saunders, Muriel Saunders, Richard A Washburn, Matthew S Mayo, Debra K Sullivan, Cheryl A Gibson, Jeannine R Goetz, Jeff J Honas, Erik A Willis, Jessica C Danon, Ron Krebill, Joseph E Donnelly
BACKGROUND: The prevalence of obesity among individuals with intellectual and developmental disabilities (IDD) is equal to or greater than the general population. METHODS: Overweight/obese adults (BMI ≥25 kg/m(2) ) with mild-to-moderate intellectual and developmental disabilities were randomized to an enhanced stop light diet (eSLD = SLD + portion-controlled meals, n = 78) or a conventional diet (CD, n = 72) for an 18 months trial (6 months weight loss, 12 months maintenance)...
March 23, 2017: Journal of Applied Research in Intellectual Disabilities: JARID
https://www.readbyqxmd.com/read/28328615/patient-reported-experience-of-diagnosis-management-and-burden-of-neuroendocrine-tumors-results-from-a-large-patient-survey-in-the-united-states
#11
Edward M Wolin, John Leyden, Grace Goldstein, Teodora Kolarova, Ron Hollander, Richard R P Warner
OBJECTIVES: The aim of this survey was to examine the experience of patients with neuroendocrine tumors (NETs) to raise awareness of the NET-related burden and identify unmet needs. Here, we report data from patients in the United States. METHODS: Patients with NETs participated in a 25-minute anonymous survey, conducted primarily online from February to May 2014. Survey questions captured information on sociodemographics, clinical characteristics, NET diagnostic experience, disease impact/management, interaction with medical teams, and NETs knowledge/awareness...
March 21, 2017: Pancreas
https://www.readbyqxmd.com/read/28328563/patients-without-intraoperative-neuromonitoring-ionm-alerts-during-veptr-implantation-did-not-sustain-neurological-injury-during-subsequent-routine-expansions-a-retrospective-multicenter-cohort-study
#12
Jaren LaGreca, Tara Flynn, Patrick J Cahill, Amer Samdani, Michael G Vitale, Ron El-Hawary, John T Smith, Jonathan H Phillips, John M Flynn, Michael Glotzbecker, Sumeet Garg
BACKGROUND: The purpose of this study was to determine the rate of intraoperative neurological monitoring (IONM) alerts and neurological injury during vertical expandable prosthetic titanium rib (VEPTR) treatment and evaluate the utility of IONM during VEPTR expansion procedures in patients who have not previously had neurological injury or IONM alerts. METHODS: After institutional review board approval, VEPTR procedures and IONM records were reviewed at 17 institutions for patients treated with VEPTR from 2005 to 2011...
March 21, 2017: Journal of Pediatric Orthopedics
https://www.readbyqxmd.com/read/28328307/a-comment-on-wong-and-waite-elder-mistreatment-predicts-later-physical-and-psychological-health-results-from-a-national-longitudinal-study-jean-issue-29-1-pp-15-42
#13
Ron Acierno
Wong and Waite present a longitudinal study of elder abuse and its effects. However, they contend that their data do not support the protective effects of social support, a finding in contrast with virtually all existing research on the topic. Closer inspection of their variables indicates that they misclassify "elder abuse" insofar as their results are actually in terms of only one type of elder abuse, psychological abuse, ignoring physical and sexual abuse, and they define "elder abuse" using only one question: "Is there anyone who insults you or puts you down?" Finally, they measure social support with the single item "if they generally feel they can open up to, and rely on, these significant others...
March 22, 2017: Journal of Elder Abuse & Neglect
https://www.readbyqxmd.com/read/28328243/factors-associated-with-bleeding-and-thrombosis-in-children-receiving-extracorporeal-membrane-oxygenation-ecmo
#14
Heidi J Dalton, Ron Reeder, Pamela Garcia-Filion, Richard Holubkov, Robert A Berg, Athena Zuppa, Frank W Moler, Thomas Shanley, Murray M Pollack, Christopher Newth, John Berger, David Wessel, Joseph Carcillo, Michael Bell, Sabrina Heidemann, Kathleen L Meert, Richard Harrison, Allan Doctor, Robert F Tamburro, J Michael Dean, Tammara Jenkins, Carol Nicholson
RATIONALE: Extracorporeal membrane oxygenation (ECMO) is employed for respiratory and cardiac failure in children but is complicated by bleeding and thrombosis. OBJECTIVES: (1) Measure the incidence of bleeding (blood loss requiring transfusion or intracranial hemorrhage) and thrombosis during ECMO support; (2) identify factors associated with these complications; and (3) determine the impact of these complications on patient outcome. METHODS: Prospective, observational cohort study in pediatric, cardiac, and neonatal intensive care units in eight hospitals from December 2012 to September 2014...
March 22, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28326538/integrating-lipid-storage-into-general-representations-of-fish-energetics
#15
Benjamin T Martin, Ron Heintz, Eric M Danner, Roger M Nisbet
1.Fish, even of the same species, can exhibit substantial variation in energy density (energy per unit wet weight). Most of this variation is due to differences in the amount of storage lipids. In addition to their importance as energy reserves for reproduction and for survival during unfavorable conditions, the accumulation of lipids represents a large energetic flux for many species, so figuring out how this energy flux is integrated with other major energy fluxes (growth, reproduction) is critical for any general theory of organismal energetics...
March 22, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28323992/quantification-of-thyroid-cancer-and-multinodular-goiter-risk-in-the-dicer1-syndrome-a-family-based-cohort-study
#16
Nicholas E Khan, Andrew J Bauer, Kris Ann P Schultz, Leslie Doros, Rosamma M Decastro, Alexander Ling, Maya B Lodish, Laura A Harney, Ron G Kase, Ann G Carr, Christopher T Rossi, Amanda Field, Anne K Harris, Gretchen M Williams, Louis P Dehner, Yoav H Messinger, D Ashley Hill, Douglas R Stewart
Context: The risk of thyroid cancer and multinodular goiter (MNG) in the DICER1 syndrome, a rare tumor-predisposition disorder, is unknown. Objective: To quantify the risk of thyroid cancer and MNG in individuals with the DICER1 syndrome. Design: Family-based cohort study. Setting: National Institutes of Health (NIH) Clinical Center (CC). Participants: The National Cancer Institute DICER1 syndrome cohort consisted of 145 individuals with a DICER1 germline mutation and 135 family controls from 48 families...
February 2, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323965/long-acting-ctp-modified-hgh-mod-4023-results-of-a-safety-and-dose-finding-study-in-ghd-children
#17
Nataliya Zelinska, Violeta Iotova, Julia Skorodok, Oleg Malievsky, Valentina Peterkova, Lubov Samsonova, Ron G Rosenfeld, Zvi Zadik, Michal Jaron-Mendelson, Ronit Koren, Leanne Amitzi, Dmitri Raduk, Oren Hershkovitz, Gili Hart
Context: Daily injections are required for growth hormone replacement therapy, which may cause low compliance as a result of inconvenience and distress in patients. Objective: CTP-modified human growth hormone (MOD-4023) is developed for once-a-week dosing regimen in GH-deficient (GHD) adults and children. The present trial was a safety and dose-finding study for weekly MOD-4023 in GHD children. Design: a multi-center, open-label, randomized, controlled Phase 2 study in children with GHD, evaluating the safety, tolerability, PK/PD and efficacy of 3 different weekly MOD-4023 doses, compared to daily r-hGH...
January 31, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28322768/unintended-pregnancies-among-women-serving-in-the-israeli-military
#18
Misgav Rottenstreich, Limor Loitner, Shir Dar, Ron Kedem, Noam Smorgick, Zvi Vaknin
OBJECTIVE: To identify the prevalence of and variables associated with unintended pregnancy among young, unmarried women serving in the Israeli military. STUDY DESIGN: A retrospective cohort study of unmarried women drafted by the Israeli military between 2013 and 2015 at the age of 18years. We used multivariable logistic regression to examine associations between unintended pregnancy and women's education, IQ, immigration status, country of origin, neighborhood socioeconomic status, and history of psychiatric illness...
March 16, 2017: Contraception
https://www.readbyqxmd.com/read/28321275/features-of-hepatocellular-carcinoma-in-hispanics-differ-from-african-americans-and-non-hispanic-whites
#19
Neeta K Venepalli, Mary V Modayil, Stephanie A Berg, Tad D Nair, Mayur Parepally, Priyanka Rajaram, Ron C Gaba, James T Bui, Yue Huang, Scott J Cotler
AIM: To compare features of hepatocellular carcinoma (HCC) in Hispanics to those of African Americans and Whites. METHODS: Patients treated for HCC at an urban tertiary medical center from 2005 to 2011 were identified from a tumor registry. Data were collected retrospectively, including demographics, comorbidities, liver disease characteristics, tumor parameters, treatment, and survival (OS) outcomes. OS analyses were performed using Kaplan-Meier method. RESULTS: One hundred and ninety-five patients with HCC were identified: 80...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28320945/three-dimensional-culture-system-identifies-a-new-mode-of-cetuximab-resistance-and-disease-relevant-genes-in-colorectal-cancer
#20
Cunxi Li, Bhuminder Singh, Ramona Graves-Deal, Haiting Ma, Alina Starchenko, William H Fry, Yuanyuan Lu, Yang Wang, Galina Bogatcheva, Mohseen P Khan, Ginger L Milne, Shilin Zhao, Gregory Daniel Ayers, Nenggan Li, Huaying Hu, Mary Kay Washington, Timothy J Yeatman, Oliver G McDonald, Qi Liu, Robert J Coffey
We previously reported that single cells from a human colorectal cancer (CRC) cell line (HCA-7) formed either hollow single-layered polarized cysts or solid spiky masses when plated in 3D in type-I collagen. To begin in-depth analyses into whether clonal cysts and spiky masses possessed divergent properties, individual colonies of each morphology were isolated and expanded. The lines thus derived faithfully retained their parental cystic and spiky morphologies and were termed CC (cystic) and SC (spiky), respectively...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
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