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https://www.readbyqxmd.com/read/28607161/uncharacterized-bacterial-structures-revealed-by-electron-cryotomography
#1
Megan J Dobro, Catherine M Oikonomou, Aidan Piper, John Cohen, Kylie Guo, Taylor Jensen, Jahan Tadayon, Joseph Donermeyer, Yeram Park, Benjamin A Solis, Andreas Kjær, Andrew I Jewett, Alasdair W McDowall, Songye Chen, Yi-Wei Chang, Jian Shi, Poorna Subramanian, Cristina V Iancu, Zhuo Li, Ariane Briegel, Elitza I Tocheva, Martin Pilhofer, Grant J Jensen
Electron cryotomography (ECT) can reveal the native structure and arrangement of macromolecular complexes inside intact cells. This technique has greatly advanced our understanding of the ultrastructure of bacterial cells. Rather than undifferentiated bags of enzymes, we now view bacteria as structurally complex assemblies of macromolecular machines. To date, our group has applied ECT to nearly 90 different bacterial species, collecting more than 15,000 cryotomograms. In addition to known structures, we have observed several, to our knowledge, uncharacterized features in these tomograms...
June 12, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28604124/test-systems-in-drug-discovery-for-hazard-identification-and-risk-assessment-of-human-drug-induced-liver-injury
#2
Richard J Weaver, Catherine Betts, Eric A G Blomme, Helga H J Gerets, Klaus Gjervig Jensen, Philip G Hewitt, Satu Juhila, Gilles Labbe, Michael J Liguori, Natalie Mesens, Monday O Ogese, Mikael Persson, Jan Snoeys, James L Stevens, Tracy Walker, B Kevin Park
Introduction The liver is an important target for drug-induced toxicities. Early detection of hepatotoxic drugs requires use of well-characterized test systems, yet current knowledge, gaps and limitations of tests employed remains an important issue for drug development. Areas Covered The current state of the science, understanding and application of test systems in use for the detection of drug-induced cytotoxicity, mitochondrial toxicity, cholestasis and inflammation is summarized. The test systems highlighted herein cover mostly in vitro and some in vivo models and endpoint measurements used in the assessment of small molecule toxic liabilities...
June 12, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28603714/defining-disease-diagnosis-and-translational-medicine-within-a-homeostatic-perturbation-paradigm-the-national-institutes-of-health-undiagnosed-diseases-program-experience
#3
Timothy Gall, Elise Valkanas, Christofer Bello, Thomas Markello, Christopher Adams, William P Bone, Alexander J Brandt, Jennifer M Brazill, Lynn Carmichael, Mariska Davids, Joie Davis, Zoraida Diaz-Perez, David Draper, Jeremy Elson, Elise D Flynn, Rena Godfrey, Catherine Groden, Cheng-Kang Hsieh, Roxanne Fischer, Gretchen A Golas, Jessica Guzman, Yan Huang, Megan S Kane, Elizabeth Lee, Chong Li, Amanda E Links, Valerie Maduro, May Christine V Malicdan, Fayeza S Malik, Michele Nehrebecky, Joun Park, Paul Pemberton, Katherine Schaffer, Dimitre Simeonov, Murat Sincan, Damian Smedley, Zaheer Valivullah, Colleen Wahl, Nicole Washington, Lynne A Wolfe, Karen Xu, Yi Zhu, William A Gahl, Cynthia J Tifft, Camillo Toro, David R Adams, Miao He, Peter N Robinson, Melissa A Haendel, R Grace Zhai, Cornelius F Boerkoel
Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype-phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philosophical bases, methodologies, and processes implemented by the NIH UDP...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28601623/the-role-of-neighborhood-economic-context-on-physical-activity-among-children-evidence-from-the-geographic-research-on-wellbeing-grow-study
#4
Yeonwoo Kim, Catherine Cubbin
Less than half of young children in the U.S. meet physical activity recommendations. While neighborhood economic context has been shown to be associated with physical activity, it is unknown whether this association varies according to family economic context. This study thus investigates whether neighborhood economic context, measured by poverty concentration and income inequality, are associated with physical activity among poor and non-poor children using data from the Geographic Research on Wellbeing study, California, 2012-2013 (N=2670)...
June 7, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28591822/neural-sources-and-underlying-mechanisms-of-neural-responses-to-heartbeats-and-their-role-in-bodily-self-consciousness-an-intracranial-eeg-study
#5
Hyeong-Dong Park, Fosco Bernasconi, Roy Salomon, Catherine Tallon-Baudry, Laurent Spinelli, Margitta Seeck, Karl Schaller, Olaf Blanke
Recent research has shown that heartbeat-evoked potentials (HEPs), brain activity in response to heartbeats, are a useful neural measure for investigating the functional role of brain-body interactions in cognitive processes including self-consciousness. In 2 experiments, using intracranial electroencephalography (EEG), we investigated (1) the neural sources of HEPs, (2) the underlying mechanisms for HEP generation, and (3) the functional role of HEPs in bodily self-consciousness. In Experiment-1, we found that shortly after the heartbeat onset, phase distributions across single trials were significantly concentrated in 10% of the recording sites, mainly in the insula and the operculum, but also in other regions including the amygdala and fronto-temporal cortex...
June 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28575357/data-management-and-data-quality-in-perch-a-large-international-case-control-study-of-severe-childhood-pneumonia
#6
Nora L Watson, Christine Prosperi, Amanda J Driscoll, Melissa M Higdon, Daniel E Park, Megan Sanza, Andrea N DeLuca, Juliet O Awori, Doli Goswami, Emily Hammond, Lokman Hossain, Catherine Johnson, Alice Kamau, Locadiah Kuwanda, David P Moore, Omid Neyzari, Uma Onwuchekwa, David Parker, Patranuch Sapchookul, Phil Seidenberg, Arifin Shamsul, Kazungu Siazeele, Prasong Srisaengchai, Mamadou Sylla, Orin S Levine, David R Murdoch, Katherine L O'Brien, Mark Wolff, Maria Deloria Knoll
The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study...
June 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28544750/unexpected-ethical-dilemmas-in-sex-assignment-in-46-xy-dsd-due-to-5-alpha-reductase-type-2-deficiency
#7
Heather M Byers, Lauren H Mohnach, Patricia Y Fechner, Ming Chen, Inas H Thomas, Linda A Ramsdell, Margarett Shnorhavorian, Elizabeth A McCauley, Anne-Marie E Amies Oelschlager, John M Park, David E Sandberg, Margaret P Adam, Catherine E Keegan
Sex assignment at birth remains one of the most clinically challenging and controversial topics in 46,XY disorders of sexual development (DSD). This is particularly challenging in deficiency of 5-alpha reductase type 2 given that external genitalia are typically undervirilized at birth but typically virilize at puberty to a variable degree. Historically, most individuals with 5-alpha reductase deficiency were raised females. However, reports that over half of patients who underwent a virilizing puberty adopted an adult male gender identity have challenged this practice...
May 25, 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/28538734/zika-virus-evolution-and-spread-in-the-americas
#8
Hayden C Metsky, Christian B Matranga, Shirlee Wohl, Stephen F Schaffner, Catherine A Freije, Sarah M Winnicki, Kendra West, James Qu, Mary Lynn Baniecki, Adrianne Gladden-Young, Aaron E Lin, Christopher H Tomkins-Tinch, Simon H Ye, Daniel J Park, Cynthia Y Luo, Kayla G Barnes, Rickey R Shah, Bridget Chak, Giselle Barbosa-Lima, Edson Delatorre, Yasmine R Vieira, Lauren M Paul, Amanda L Tan, Carolyn M Barcellona, Mario C Porcelli, Chalmers Vasquez, Andrew C Cannons, Marshall R Cone, Kelly N Hogan, Edgar W Kopp, Joshua J Anzinger, Kimberly F Garcia, Leda A Parham, Rosa M Gélvez Ramírez, Maria C Miranda Montoya, Diana P Rojas, Catherine M Brown, Scott Hennigan, Brandon Sabina, Sarah Scotland, Karthik Gangavarapu, Nathan D Grubaugh, Glenn Oliveira, Refugio Robles-Sikisaka, Andrew Rambaut, Lee Gehrke, Sandra Smole, M Elizabeth Halloran, Luis Villar, Salim Mattar, Ivette Lorenzana, Jose Cerbino-Neto, Clarissa Valim, Wim Degrave, Patricia T Bozza, Andreas Gnirke, Kristian G Andersen, Sharon Isern, Scott F Michael, Fernando A Bozza, Thiago M L Souza, Irene Bosch, Nathan L Yozwiak, Bronwyn L MacInnis, Pardis C Sabeti
Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28538723/genomic-epidemiology-reveals-multiple-introductions-of-zika-virus-into-the-united-states
#9
Nathan D Grubaugh, Jason T Ladner, Moritz U G Kraemer, Gytis Dudas, Amanda L Tan, Karthik Gangavarapu, Michael R Wiley, Stephen White, Julien Thézé, Diogo M Magnani, Karla Prieto, Daniel Reyes, Andrea M Bingham, Lauren M Paul, Refugio Robles-Sikisaka, Glenn Oliveira, Darryl Pronty, Carolyn M Barcellona, Hayden C Metsky, Mary Lynn Baniecki, Kayla G Barnes, Bridget Chak, Catherine A Freije, Adrianne Gladden-Young, Andreas Gnirke, Cynthia Luo, Bronwyn MacInnis, Christian B Matranga, Daniel J Park, James Qu, Stephen F Schaffner, Christopher Tomkins-Tinch, Kendra L West, Sarah M Winnicki, Shirlee Wohl, Nathan L Yozwiak, Joshua Quick, Joseph R Fauver, Kamran Khan, Shannon E Brent, Robert C Reiner, Paola N Lichtenberger, Michael J Ricciardi, Varian K Bailey, David I Watkins, Marshall R Cone, Edgar W Kopp, Kelly N Hogan, Andrew C Cannons, Reynald Jean, Andrew J Monaghan, Robert F Garry, Nicholas J Loman, Nuno R Faria, Mario C Porcelli, Chalmers Vasquez, Elyse R Nagle, Derek A T Cummings, Danielle Stanek, Andrew Rambaut, Mariano Sanchez-Lockhart, Pardis C Sabeti, Leah D Gillis, Scott F Michael, Trevor Bedford, Oliver G Pybus, Sharon Isern, Gustavo Palacios, Kristian G Andersen
Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28538439/nonlinear-imputation-of-pao2-fio2-from-spo2-fio2-among-mechanically-ventilated-patients-in-the-icu-a-prospective-observational-study
#10
Samuel M Brown, Abhijit Duggal, Peter C Hou, Mark Tidswell, Akram Khan, Matthew Exline, Pauline K Park, David A Schoenfeld, Ming Liu, Colin K Grissom, Marc Moss, Todd W Rice, Catherine L Hough, Emanuel Rivers, B Taylor Thompson, Roy G Brower
OBJECTIVES: In the contemporary ICU, mechanically ventilated patients may not have arterial blood gas measurements available at relevant timepoints. Severity criteria often depend on arterial blood gas results. Retrospective studies suggest that nonlinear imputation of PaO2/FIO2 from SpO2/FIO2 is accurate, but this has not been established prospectively among mechanically ventilated ICU patients. The objective was to validate the superiority of nonlinear imputation of PaO2/FIO2 among mechanically ventilated patients and understand what factors influence the accuracy of imputation...
May 22, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28528810/titration-of-intravenous-oxytocin-infusion-for-postdate-induction-of-labor-across-body-mass-index-groups
#11
Angela B Maeder, Susan C Vonderheid, Chang G Park, Aleeca F Bell, Barbara L McFarlin, Catherine Vincent, C Sue Carter
OBJECTIVE: To evaluate whether oxytocin titration for postdate labor induction differs among women who are normal weight, overweight, and obese and whether length of labor and birth method differ by oxytocin titration and body mass index (BMI). DESIGN: Retrospective cohort study. SETTING: U.S. university-affiliated hospital. PARTICIPANTS: Of 280 eligible women, 21 were normal weight, 134 were overweight, and 125 were obese at labor admission...
May 18, 2017: Journal of Obstetric, Gynecologic, and Neonatal Nursing: JOGNN
https://www.readbyqxmd.com/read/28524161/efficacy-of-anti-pd-1-therapy-in-patients-with-melanoma-brain-metastases
#12
Sagun Parakh, John J Park, Shehara Mendis, Rajat Rai, Wen Xu, Serigne Lo, Martin Drummond, Catherine Rowe, Annie Wong, Grant McArthur, Andrew Haydon, Miles C Andrews, Jonathan Cebon, Alex Guminski, Richard F Kefford, Georgina V Long, Alexander M Menzies, Oliver Klein, Matteo S Carlino
BACKGROUND: There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic. METHOD: We retrospectively assessed pts with melanoma BM treated with PD-1 antibodies, nivolumab and pembrolizumab. Clinicopathologic and treatment parameters were collected and outcomes determined for intracranial (IC) response rate (RR) using a modified RECIST criteria, with up to five IC target lesions used to determine IC response, disease control rate (DCR) and progression-free survival (PFS)...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28490664/inhibiting-the-oncogenic-translation-program-is-an-effective-therapeutic-strategy-in-multiple-myeloma
#13
Salomon Manier, Daisy Huynh, Yu J Shen, Jia Zhou, Timur Yusufzai, Karma Z Salem, Richard Y Ebright, Jiantao Shi, Jihye Park, Siobhan V Glavey, William G Devine, Chia-Jen Liu, Xavier Leleu, Bruno Quesnel, Catherine Roche-Lestienne, John K Snyder, Lauren E Brown, Nathanael Gray, James Bradner, Luke Whitesell, John A Porco, Irene M Ghobrial
Multiple myeloma (MM) is a frequently incurable hematological cancer in which overactivity of MYC plays a central role, notably through up-regulation of ribosome biogenesis and translation. To better understand the oncogenic program driven by MYC and investigate its potential as a therapeutic target, we screened a chemically diverse small-molecule library for anti-MM activity. The most potent hits identified were rocaglate scaffold inhibitors of translation initiation. Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven transcriptional program by CMLD010509, the most promising rocaglate...
May 10, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28482936/a-comparison-of-immersive-virtual-reality-with-traditional-neuropsychological-measures-in-the-assessment-of-executive-functions
#14
Sophie Melissa Clare Davison, Catherine Deeprose, Sylvia Terbeck
OBJECTIVE: This study investigated immersive virtual reality (IVR), as a novel technique to test executive function of healthy younger and older adults. We predicted IVR tasks to have greater predictive power than traditional measures when assessing age-related cognitive functioning due to the real-world validity of the tasks. METHODS: Participants (n=40) completed the Stroop colour-word test and the trail-making test (TMT) as traditional and commonly used assessments of executive functioning...
May 9, 2017: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/28482159/cascading-effects-of-nanoparticle-coatings-surface-functionalization-dictates-the-assemblage-of-complexed-proteins-and-subsequent-interaction-with-model-cell-membranes
#15
Eric S Melby, Samuel E Lohse, Ji Eun Park, Ariane M Vartanian, Rebecca A Putans, Hannah B Abbott, Robert J Hamers, Catherine J Murphy, Joel A Pedersen
Interactions of functionalized nanomaterials with biological membranes are expected to be governed by not only nanoparticle physiochemical properties, but also coatings or "coronas" of biomacromolecules acquired after emersion in biological fluids. Here, we prepared a library of 4-5 nm gold nanoparticles (AuNPs) coated with either ω-functionalized thiols or polyelectrolyte wrappings to examine the influence of surface functional groups on the assemblage of proteins complexing the nanoparticles and its subsequent impact on attachment to model biological membranes...
May 8, 2017: ACS Nano
https://www.readbyqxmd.com/read/28469563/the-role-of-associative-cortices-and-hippocampus-during-movement-perturbations
#16
Matthew S D Kerr, Pierre Sacré, Kevin Kahn, Hyun-Joo Park, Mathew Johnson, James Lee, Susan Thompson, Juan Bulacio, Jaes Jones, Jorge González-Martínez, Catherine Liégeois-Chauvel, Sridevi V Sarma, John T Gale
Although motor control has been extensively studied, most research involving neural recordings has focused on primary motor cortex, pre-motor cortex, supplementary motor area, and cerebellum. These regions are involved during normal movements, however, associative cortices and hippocampus are also likely involved during perturbed movements as one must detect the unexpected disturbance, inhibit the previous motor plan, and create a new plan to compensate. Minimal data is available on these brain regions during such "robust" movements...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28444390/characterisation-of-drug-specific-signalling-between-primary-human-hepatocytes-and-immune-cells
#17
Monday O Ogese, Lee Faulkner, Roz E Jenkins, Neil S French, Ian M Copple, Daniel J Antoine, Mohamed Elmasry, Hasan Malik, Christopher E Goldring, B Kevin Park, Catherine Betts, Dean J Naisbitt
It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO)...
April 21, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28438497/theory-of-planned-behavior-constructs-associated-with-nurses-pain-assessment-and-pro-re-nata-prn-opioid-analgesic-administration-a-cross-sectional-study
#18
Phichpraorn Youngcharoen, Catherine Vincent, Chang G Park
Little theory-based research has been performed to better understand nurses' perceptions of pain management. Framed by the theory of planned behavior, the aims of the study were to describe nurses' beliefs (behavioral, normative, and control) about pain management for hospitalized elderly patients with postoperative pain; to present an item analysis for beliefs, attitudes, perceived norms, perceived behavioral control, intentions, and behaviors (measured in case study vignettes) for nurses (a) with different durations of nursing experience, (b) working in university, public health, and military hospitals, and (c) who either had or had not received pain management training in the past six months; and to compare differences in the constructs across these three groups...
April 21, 2017: Pain Management Nursing: Official Journal of the American Society of Pain Management Nurses
https://www.readbyqxmd.com/read/28412764/how-networks-of-informal-trails-cause-landscape-level-damage-to-vegetation
#19
Agustina Barros, Catherine Marina Pickering
When visitors are not constrained to remain on formal trails, informal trail networks can develop and damage plant communities in protected areas. These networks can form in areas with low growing vegetation, where formal trails are limited, where there is limited regulation and where vegetation is slow to recover once disturbed. To demonstrate the extent of impacts from unregulated recreational use, we assessed damage to alpine vegetation by hikers and pack animals in the highest protected area in the southern Hemisphere: Aconcagua Park, in the Andes...
April 15, 2017: Environmental Management
https://www.readbyqxmd.com/read/28408462/intent-to-treat-leukemia-remission-by-cd19car-t-cells-of-defined-formulation-and-dose-in-children-and-young-adults
#20
Rebecca A Gardner, Olivia Finney, Colleen Annesley, Hannah Brakke, Corinne Summers, Kasey Leger, Marie Bleakley, Christopher Brown, Stephanie Mgebroff, Karen Spratt, Virginia Hoglund, Catherine Lindgren, Assaf P Oron, Daniel Li, Stanley R Riddell, Julie R Park, Michael C Jensen
Transitioning CD19-directed CAR-T cells from early phase trials in relapsed patients to a viable therapeutic approach with predictable efficacy and low toxicity for broad application in patients with high unmet need is currently complicated by product heterogeneity resulting from transduction of undefined T cell mixtures, variability of transgene expression, and terminal differentiation of cells at the end of culture. A phase 1 trial of 45 children and young adults with relapsed or refractory B-lineage ALL was conducted using a CD19 CAR product of defined CD4/CD8 composition, uniform CAR expression, and limited effector differentiation...
April 13, 2017: Blood
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