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https://www.readbyqxmd.com/read/28819986/knowledge-of-palliative-care-among-community-dwelling-adults
#1
Elissa Kozlov, Meghan McDarby, M Carrington Reid, Brian D Carpenter
OBJECTIVE: To identify what laypersons know about palliative care using the Palliative Care Knowledge Scale (PaCKS). A secondary aim was to establish preliminary normative data for the PaCKS. METHODS: A sample of 301 adults were recruited via Amazon's Mechanical Turk database. Participants were administered the PaCKS along with a demographic questionnaire. RESULTS: The mean score on the 13-item PaCKS was 5.25 (standard deviation = 4.77, range: 0-13), the median was 5, and the mode was 0, with a significant proportion of participants selecting "I don't know" for every item...
January 1, 2017: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/28819312/shared-peptide-binding-of-hla-class-i-and-ii-alleles-associate-with-cutaneous-nevirapine-hypersensitivity-and-identify-novel-risk-alleles
#2
Rebecca Pavlos, Elizabeth J McKinnon, David A Ostrov, Bjoern Peters, Soren Buus, David Koelle, Abha Chopra, Ryan Schutte, Craig Rive, Alec Redwood, Susana Restrepo, Austin Bracey, Thomas Kaever, Paisley Myers, Ellen Speers, Stacy A Malaker, Jeffrey Shabanowitz, Yuan Jing, Silvana Gaudieri, Donald F Hunt, Mary Carrington, David W Haas, Simon Mallal, Elizabeth J Phillips
Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding specificities and binding pocket structure...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810786/reducing-the-cost-of-using-collocation-to-compute-vibrational-energy-levels-results-for-ch2nh
#3
Gustavo Avila, Tucker Carrington
In this paper, we improve the collocation method for computing vibrational spectra that was presented in the work of Avila and Carrington, Jr. [J. Chem. Phys. 143, 214108 (2015)]. Known quadrature and collocation methods using a Smolyak grid require storing intermediate vectors with more elements than points on the Smolyak grid. This is due to the fact that grid labels are constrained among themselves and basis labels are constrained among themselves. We show that by using the so-called hierarchical basis functions, one can significantly reduce the memory required...
August 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28794233/characterization-of-mycobacterium-tuberculosis-specific-cells-using-mhc-class-ii-tetramers-reveals-phenotypic-differences-related-to-hiv-infection-and-tuberculosis-disease
#4
Natalie Strickland, Tracey L Müller, Natacha Berkowitz, Rene Goliath, Mary N Carrington, Robert J Wilkinson, Wendy A Burgers, Catherine Riou
A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4(+) T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4(+) T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28781123/the-high-affinity-interaction-between-orc-and-dna-that-is-required-for-replication-licensing-is-inhibited-by-2-arylquinolin-4-amines
#5
Nicola J Gardner, Peter J Gillespie, Jamie T Carrington, Emma J Shanks, Stuart P McElroy, Emma J Haagensen, Julie A Frearson, Andrew Woodland, J Julian Blow
In late mitosis and G1, origins of DNA replication must be "licensed" for use in the upcoming S phase by being encircled by double hexamers of the minichromosome maintenance proteins MCM2-7. A "licensing checkpoint" delays cells in G1 until sufficient origins have been licensed, but this checkpoint is lost in cancer cells. Inhibition of licensing can therefore kill cancer cells while only delaying normal cells in G1. In a high-throughput cell-based screen for licensing inhibitors we identified a family of 2-arylquinolin-4-amines, the most potent of which we call RL5a...
August 17, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28766084/comparison-of-the-eq-5d-3l-and-the-sf-6d-sf-12-contemporaneous-utility-scores-in-patients-with-cardiovascular-disease
#6
Sanjeewa Kularatna, Joshua Byrnes, Yih Kai Chan, Chantal F Ski, Melinda Carrington, David Thompson, Simon Stewart, Paul A Scuffham
PURPOSE: Multi-attribute utility instruments (MAUIs) are widely used to measure utility weights. This study sought to compare utility weights of two popular MAUIs, the EQ-5D-3L and the SF-6D, and inform researchers in the selection of generic MAUI for use with cardiovascular (CVD) patients. METHODS: Data were collected in the Young@Heart study, a randomised controlled trial of a nurse-led multidisciplinary home-based intervention compared to standard usual care...
August 1, 2017: Quality of Life Research
https://www.readbyqxmd.com/read/28758781/development-of-restricted-and-repetitive-behaviors-from-15-to-77-months-stability-of-two-distinct-subtypes
#7
Mirko Uljarević, Bronia Arnott, Sarah J Carrington, Elizabeth Meins, Charles Fernyhough, Helen McConachie, Ann Le Couteur, Susan R Leekam
A community sample of 192 parents reported on their children's restricted and repetitive behaviors (RRBs) at mean ages 15 months (N = 138), 26 months (N = 191), and 77 months (N = 125) using the Repetitive Behavior Questionnaire-2 (RBQ-2). Consistent with previous factor analytic research, 2 factors were found at each age: 1 comprising repetitive sensory and motor behaviors (RSM), and the other comprising insistence on sameness behaviors including rigidity, routines, and restricted interests (IS). Regression analyses indicated that RSM and IS subtypes develop independently...
July 31, 2017: Developmental Psychology
https://www.readbyqxmd.com/read/28746848/natural-conformational-sampling-of-human-tnf%C3%AE-visualized-by-double-electron-electron-resonance
#8
Bruce Carrington, William K Myers, Peter Horanyi, Mark Calmiano, Alastair D G Lawson
Double electron-electron resonance in conjunction with site-directed spin labeling has been used to probe natural conformational sampling of the human tumor necrosis factor α trimer. We suggest a previously unreported, predeoligomerization conformation of the trimer that has been shown to be sampled at low frequency. A model of this trimeric state has been constructed based on crystal structures using the double-electron-electron-resonance distances. The model shows one of the protomers to be rotated and tilted outward at the tip end, leading to a breaking of the trimerous symmetry and distortion at a receptor-binding interface...
July 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28709253/publisher-s-note-general-scaling-relations-for-locomotion-in-granular-media-phys-rev-e-95-052901-2017
#9
James Slonaker, D Carrington Motley, Qiong Zhang, Stephen Townsend, Carmine Senatore, Karl Iagnemma, Ken Kamrin
This corrects the article DOI: 10.1103/PhysRevE.95.052901.
June 2017: Physical Review. E
https://www.readbyqxmd.com/read/28704647/hiv-1-mediated-downmodulation-of-hla-c-impacts-target-cell-recognition-and-antiviral-activity-of-nk-cells
#10
Christian Körner, Camille R Simoneau, Philipp Schommers, Mitchell Granoff, Maja Ziegler, Angelique Hölzemer, Sebastian Lunemann, Janet Chukwukelu, Björn Corleis, Vivek Naranbhai, Douglas S Kwon, Eileen P Scully, Stephanie Jost, Frank Kirchhoff, Mary Carrington, Marcus Altfeld
It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition while leaving HLA-C unaltered in order to prevent NK cell activation by engaging inhibitory NK cell receptors, but it was recently observed that most primary isolates of HIV-1 can mediate HLA-C downmodulation. Now we report that HIV-1-mediated downmodulation of HLA-C was associated with reduced binding to its respective inhibitory receptors. Despite this, HLA-C-licensed NK cells displayed reduced antiviral activity compared to their unlicensed counterparts, potentially due to residual binding to the respective inhibitory receptors...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28695282/host-genetic-variation-and-hiv-disease-from-mapping-to-mechanism
#11
REVIEW
Vivek Naranbhai, Mary Carrington
This review aims to provide a summary of current knowledge of host genetic effects on human immunodeficiency virus (HIV) disease. Mapping of simple single nucleotide polymorphisms (SNP) has been largely successful in HIV, but more complex genetic associations involving haplotypic or epigenetic variation, for example, remain elusive. Mechanistic insights explaining SNP associations are incomplete, but continue to be forthcoming. The number of robust immunogenetic correlates of HIV is modest and their discovery mostly predates the genome-wide era...
August 2017: Immunogenetics
https://www.readbyqxmd.com/read/28691082/fully-gapped-superconductivity-with-no-sign-change-in-the-prototypical-heavy-fermion-cecu2si2
#12
Takuya Yamashita, Takaaki Takenaka, Yoshifumi Tokiwa, Joseph A Wilcox, Yuta Mizukami, Daiki Terazawa, Yuichi Kasahara, Shunichiro Kittaka, Toshiro Sakakibara, Marcin Konczykowski, Silvia Seiro, Hirale S Jeevan, Christoph Geibel, Carsten Putzke, Takafumi Onishi, Hiroaki Ikeda, Antony Carrington, Takasada Shibauchi, Yuji Matsuda
In exotic superconductors, including high-Tc copper oxides, the interactions mediating electron Cooper pairing are widely considered to have a magnetic rather than a conventional electron-phonon origin. Interest in this exotic pairing was initiated by the 1979 discovery of heavy-fermion superconductivity in CeCu2Si2, which exhibits strong antiferromagnetic fluctuations. A hallmark of unconventional pairing by anisotropic repulsive interactions is that the superconducting energy gap changes sign as a function of the electron momentum, often leading to nodes where the gap goes to zero...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28686870/intestinal-enteroendocrine-lineage-cells-possess-homeostatic-and-injury-inducible-stem-cell-activity
#13
Kelley S Yan, Olivier Gevaert, Grace X Y Zheng, Benedict Anchang, Christopher S Probert, Kathryn A Larkin, Paige S Davies, Zhuan-Fen Cheng, John S Kaddis, Arnold Han, Kelly Roelf, Ruben I Calderon, Esther Cynn, Xiaoyi Hu, Komal Mandleywala, Julie Wilhelmy, Sue M Grimes, David C Corney, Stéphane C Boutet, Jessica M Terry, Phillip Belgrader, Solongo B Ziraldo, Tarjei S Mikkelsen, Fengchao Wang, Richard J von Furstenberg, Nicholas R Smith, Parthasarathy Chandrakesan, Randal May, Mary Ann S Chrissy, Rajan Jain, Christine A Cartwright, Joyce C Niland, Young-Kwon Hong, Jill Carrington, David T Breault, Jonathan Epstein, Courtney W Houchen, John P Lynch, Martin G Martin, Sylvia K Plevritis, Christina Curtis, Hanlee P Ji, Linheng Li, Susan J Henning, Melissa H Wong, Calvin J Kuo
Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5(+) ISCs, the most well-defined ISC pool, but Bmi1-GFP(+) cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP(+) cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1(+) cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28673295/the-impact-of-racial-discrimination-on-the-health-of-australian-indigenous-children-aged-5-10%C3%A2-years-analysis-of-national-longitudinal-data
#14
Carrington C J Shepherd, Jianghong Li, Matthew N Cooper, Katrina D Hopkins, Brad M Farrant
BACKGROUND: A growing body of literature highlights that racial discrimination has negative impacts on child health, although most studies have been limited to an examination of direct forms of racism using cross-sectional data. We aim to provide further insights on the impact of early exposure to racism on child health using longitudinal data among Indigenous children in Australia and multiple indicators of racial discrimination. METHODS: We used data on 1239 Indigenous children aged 5-10 years from Waves 1-6 (2008-2013) of Footprints in Time, a longitudinal study of Indigenous children across Australia...
July 3, 2017: International Journal for Equity in Health
https://www.readbyqxmd.com/read/28667019/retrotransposons-are-the-major-contributors-to-the-expansion-of-the-drosophila-ananassae-muller-f-element
#15
Wilson Leung, Christopher D Shaffer, Elizabeth J Chen, Thomas J Quisenberry, Kevin Ko, John M Braverman, Thomas C Giarla, Nathan T Mortimer, Laura K Reed, Sheryl T Smith, Srebrenka Robic, Shannon R McCartha, Danielle R Perry, Lindsay M Prescod, Zenyth A Sheppard, Ken J Saville, Allison McClish, Emily A Morlock, Victoria R Sochor, Brittney Stanton, Isaac C Veysey-White, Dennis Revie, Luis A Jimenez, Jennifer J Palomino, Melissa D Patao, Shane M Patao, Edward T Himelblau, Jaclyn D Campbell, Alexandra L Hertz, Maddison F McEvilly, Allison R Wagner, James Youngblom, Baljit Bedi, Jeffery Bettincourt, Erin Duso, Maiye Her, William Hilton, Samantha House, Masud Karimi, Kevin Kumimoto, Rebekah Lee, Darryl Lopez, George Odisho, Ricky Prasad, Holly Lyn Robbins, Tanveer Sandhu, Tracy Selfridge, Kara Tsukashima, Hani Yosif, Nighat P Kokan, Latia Britt, Alycia Zoellner, Eric P Spana, Ben T Chlebina, Insun Chong, Harrison Friedman, Danny A Mammo, Chun L Ng, Vinayak S Nikam, Nicholas U Schwartz, Thomas Q Xu, Martin G Burg, Spencer M Batten, Lindsay M Corbeill, Erica Enoch, Jesse J Ensign, Mary E Franks, Breanna Haiker, Judith A Ingles, Lyndsay D Kirkland, Joshua M Lorenz-Guertin, Jordan Matthews, Cody M Mittig, Nicholaus Monsma, Katherine J Olson, Guillermo Perez-Aragon, Alen Ramic, Jordan R Ramirez, Christopher Scheiber, Patrick A Schneider, Devon E Schultz, Matthew Simon, Eric Spencer, Adam C Wernette, Maxine E Wykle, Elizabeth Zavala-Arellano, Mitchell J McDonald, Kristine Ostby, Peter Wendland, Justin R DiAngelo, Alexis M Ceasrine, Amanda H Cox, James E B Docherty, Robert M Gingras, Stephanie M Grieb, Michael J Pavia, Casey L Personius, Grzegorz L Polak, Dale L Beach, Heaven L Cerritos, Edward A Horansky, Karim A Sharif, Ryan Moran, Susan Parrish, Kirsten Bickford, Jennifer Bland, Juliana Broussard, Kerry Campbell, Katelynn E Deibel, Richard Forka, Monika C Lemke, Marlee B Nelson, Catherine O'Keeffe, S Mariel Ramey, Luke Schmidt, Paola Villegas, Christopher J Jones, Stephanie L Christ, Sami Mamari, Adam S Rinaldi, Ghazal Stity, Amy T Hark, Mark Scheuerman, S Catherine Silver Key, Briana D McRae, Adam S Haberman, Sam Asinof, Harriette Carrington, Kelly Drumm, Terrance Embry, Richard McGuire, Drew Miller-Foreman, Stella Rosen, Nadia Safa, Darrin Schultz, Matt Segal, Yakov Shevin, Petros Svoronos, Tam Vuong, Gary Skuse, Don W Paetkau, Rachael K Bridgman, Charlotte M Brown, Alicia R Carroll, Francesca M Gifford, Julie Beth Gillespie, Susan E Herman, Krystal L Holtcamp, Misha A Host, Gabrielle Hussey, Danielle M Kramer, Joan Q Lawrence, Madeline M Martin, Ellen N Niemiec, Ashleigh P O'Reilly, Olivia A Pahl, Guadalupe Quintana, Elizabeth A S Rettie, Torie L Richardson, Arianne E Rodriguez, Mona O Rodriguez, Laura Schiraldi, Joanna J Smith, Kelsey F Sugrue, Lindsey J Suriano, Kaitlyn E Takach, Arielle M Vasquez, Ximena Velez, Elizabeth J Villafuerte, Laura T Vives, Victoria R Zellmer, Jeanette Hauke, Charles R Hauser, Karolyn Barker, Laurie Cannon, Perouza Parsamian, Samantha Parsons, Zachariah Wichman, Christopher W Bazinet, Diana E Johnson, Abubakarr Bangura, Jordan A Black, Victoria Chevee, Sarah A Einsteen, Sarah K Hilton, Max Kollmer, Rahul Nadendla, Joyce Stamm, Antoinette E Fafara-Thompson, Amber M Gygi, Emmy E Ogawa, Matt Van Camp, Zuzana Kocsisova, Judith L Leatherman, Cassie M Modahl, Michael R Rubin, Susana S Apiz-Saab, Suzette M Arias-Mejias, Carlos F Carrion-Ortiz, Patricia N Claudio-Vazquez, Debbie M Espada-Green, Marium Feliciano-Camacho, Karina M Gonzalez-Bonilla, Mariela Taboas-Arroyo, Dorianmarie Vargas-Franco, Raquel Montañez-Gonzalez, Joseph Perez-Otero, Myrielis Rivera-Burgos, Francisco J Rivera-Rosario, Heather L Eisler, Jackie Alexander, Samatha K Begley, Deana Gabbard, Robert J Allen, Wint Yan Aung, William D Barshop, Amanda Boozalis, Vanessa P Chu, Jeremy S Davis, Ryan N Duggal, Robert Franklin, Katherine Gavinski, Heran Gebreyesus, Henry Z Gong, Rachel A Greenstein, Averill D Guo, Casey Hanson, Kaitlin E Homa, Simon C Hsu, Yi Huang, Lucy Huo, Sarah Jacobs, Sasha Jia, Kyle L Jung, Sarah Wai-Chee Kong, Matthew R Kroll, Brandon M Lee, Paul F Lee, Kevin M Levine, Amy S Li, Chengyu Liu, Max Mian Liu, Adam P Lousararian, Peter B Lowery, Allyson P Mallya, Joseph E Marcus, Patrick C Ng, Hien P Nguyen, Ruchik Patel, Hashini Precht, Suchita Rastogi, Jonathan M Sarezky, Adam Schefkind, Michael B Schultz, Delia Shen, Tara Skorupa, Nicholas C Spies, Gabriel Stancu, Hiu Man Vivian Tsang, Alice L Turski, Rohit Venkat, Leah E Waldman, Kaidi Wang, Tracy Wang, Jeffrey W Wei, Dennis Y Wu, David D Xiong, Jack Yu, Karen Zhou, Gerard P McNeil, Robert W Fernandez, Patrick Gomez Menzies, Tingting Gu, Jeremy Buhler, Elaine R Mardis, Sarah C R Elgin
The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison...
August 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28662919/risk-factor-management-and-atrial-fibrillation-clinics-saving-the-best-for-last
#16
REVIEW
Rajiv Mahajan, Rajeev K Pathak, Anand Thiyagarajah, Dennis H Lau, Francis E Marchlinski, Sanjay Dixit, John D Day, Jeroen M L Hendriks, Melinda Carrington, Jonathan M Kalman, Prashanthan Sanders
Atrial fibrillation (AF) is a leading cause of cardiovascular morbidity and mortality worldwide. Management of AF is a complex process involving: 1) the prevention of thromboembolic complications with anticoagulation; 2) rhythm control; and 3) the detection and treatment of underlying heart disease. However, cardiometabolic risk factors, such as obesity, hypertension, diabetes mellitus, and obstructive sleep apnoea, have been proposed as contributors to the expanding epidemic of atrial fibrillation (AF). Thus, a fourth pillar of AF care would include aggressive targeting of interdependent, modifiable cardiovascular risk factors as part of an integrated care model...
September 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28655350/serum-biochemical-parameters-and-cytokine-profiles-associated-with-natural-african-trypanosome-infections-in-cattle
#17
Soale Majeed Bakari, Jennifer Afua Ofori, Kwadwo Asamoah Kusi, George Kwame Aning, Gordon Akanzuwine Awandare, Mark Carrington, Theresa Manful Gwira
BACKGROUND: Animal African trypanosomiasis (AAT) greatly affects livestock production in sub-Saharan Africa. In Ghana prevalence of AAT is estimated to range between 5 and 50%. Studies have reported serum biochemical aberrations and variability in cytokine profiles in animals during infection. However, information regarding the biochemical parameters and cytokine profiles associated with natural infections are limited. This study was therefore aimed at investigating changes in the levels of serum biochemical parameters and inflammatory cytokines during a natural infection...
June 27, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28654566/prospective-state-and-trait-predictors-of-daily-medication-adherence-behavior-in-hiv
#18
Paul F Cook, Sarah J Schmiege, Whitney Starr, Jane M Carrington, Lucy Bradley-Springer
BACKGROUND: Many persons living with HIV (PLWH) are nonadherent to medication. Trait level measures that ask about predictors of adherence in the abstract may not adequately capture state level daily variability that more directly impacts adherence. OBJECTIVES: This preliminary study was designed to test six predictors of electronically monitored adherence at both the state and trait levels and to compare their relative effects. METHODS: Using a smartphone, 87 PLWH completed randomly cued daily surveys on thoughts, mood, stress, coping, social support, and treatment motivation...
July 2017: Nursing Research
https://www.readbyqxmd.com/read/28650381/potential-for-immune-driven-viral-polymorphisms-to-compromise-antiretroviral-based-pre-exposure-prophylaxis-for-prevention-of-hiv-1-infection
#19
Hiroyuki Gatanaga, Zabrina L Brumme, Emily Adland, Gustavo Reyes-Terán, Santiago Avila-Rios, Carlos R Mejía-Villatoro, Tsunefusa Hayashida, Takayuki Chikata, Giang Van Tran, Kinh Van Nguyen, Rita I Meza, Elsa Y Palou, Humberto Valenzuela-Ponce, Juan M Pascale, Guillermo Porras-Cortés, Marvin Manzanero, Guinevere Q Lee, Jeffrey N Martin, Mary N Carrington, Mina John, Simon Mallal, Art F Y Poon, Philip Goulder, Masafumi Takiguchi, Shinichi Oka
OBJECTIVE: Long-acting rilpivirine is a candidate for pre-exposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (RT-E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing Human Leukocyte Antigen (HLA)-B*18 where RT-E138X arises as an immune escape mutation. We investigate the global prevalence, B*18-linkage and replicative cost of RT-E138X and its regional implications for rilpivirine PrEP...
June 23, 2017: AIDS
https://www.readbyqxmd.com/read/28649982/structural-and-regulatory-diversity-shape-hla-c-protein-expression-levels
#20
Gurman Kaur, Stephanie Gras, Jesse I Mobbs, Julian P Vivian, Adrian Cortes, Thomas Barber, Subita Balaram Kuttikkatte, Lise Torp Jensen, Kathrine E Attfield, Calliope A Dendrou, Mary Carrington, Gil McVean, Anthony W Purcell, Jamie Rossjohn, Lars Fugger
Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules...
June 26, 2017: Nature Communications
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