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https://www.readbyqxmd.com/read/28726630/dissection-of-specific-binding-of-hiv-1-gag-to-the-packaging-signal-in-viral-rna
#1
Mauricio Comas-Garcia, Siddhartha Ak Datta, Laura Baker, Rajat Varma, Prabhakar R Gudla, Alan Rein
Selective packaging of HIV-1 genomic RNA (gRNA) requires the presence of a cis-acting RNA element called the "packaging signal" (Ψ). However, the mechanism by which Ψ promotes selective packaging of the gRNA is not well understood. We used fluorescence correlation spectroscopy and quenching data to monitor the binding of recombinant HIV-1 Gag protein to Cy5-tagged 190-base RNAs. At physiological ionic strength, Gag binds with very similar, nanomolar affinities to both Ψ-containing and control RNAs. We challenged these interactions by adding excess competing tRNA; introducing mutations in Gag; or raising the ionic strength...
July 20, 2017: ELife
https://www.readbyqxmd.com/read/28718500/neurofilament-light-as-an-immune-target-for-pathogenic-antibodies
#2
Fabiola Puentes, Baukje J van der Star, Stephanie D Boomkamp, Markus Kipp, Louis Boon, Isabel Bosca, Joel Raffel, Sharmilee Gnanapavan, Paul van der Valk, Jodie Stephenson, Susan C Barnett, David Baker, Sandra Amor
Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunisation with neuronal antigens such as neurofilament light NF-L, a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, while antibodies to NF-L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to NF-L contribute to neurodegeneration and neurological disease...
July 17, 2017: Immunology
https://www.readbyqxmd.com/read/28708447/coverage-for-gender-affirming-care-making-health-insurance-work-for-transgender-americans
#3
William V Padula, Kellan Baker
Many transgender Americans continue to remain uninsured or are underinsured because of payers' refusal to cover medically necessary, gender-affirming healthcare services-such as hormone therapy, mental health counseling, and reconstructive surgeries. Coverage refusal results in higher costs and poor health outcomes among transgender people who cannot access gender-affirming care. Research into the value of health insurance coverage for gender-affirming care for transgender individuals shows that the health benefits far outweigh the costs of insuring transition procedures...
July 14, 2017: LGBT Health
https://www.readbyqxmd.com/read/28702747/management-of-supine-hypertension-complicating-neurogenic-orthostatic-hypotension
#4
Jacquie Baker, Kurt Kimpinski
Neurogenic orthostatic hypotension (NOH) can be present in a number of disorders, including synucleinopathies, autoimmune disorders, and various genetic disorders. All are characterized by defective norepinephrine release from sympathetic terminals upon standing, resulting in impaired vasoconstriction. NOH is defined as a drop in systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg, or both, within 3 minutes of standing or head up-tilt at a minimum of 60°. However, approximately 50% of patients have associated supine hypertension, which greatly complicates treatment...
July 12, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28695731/investigating-the-interaction-of-octapeptin-a3-with-model-bacterial-membranes
#5
Mei-Ling Han, Hsin-Hui Shen, Karl A Hansford, Elena K Schneider, Sivashangarie Sivanesan, Kade D Roberts, Philip E Thompson, Anton P Le Brun, Yan Zhu, Marc-Antoine Sani, Frances Separovic, Mark A T Blaskovich, Mark A Baker, Samuel M Moskowitz, Matthew A Cooper, Jian Li, Tony Velkov
Octapeptins are cyclic lipopeptides with a broader spectrum of activity against fungi and polymyxin-resistant Gram-negative and Gram-positive bacteria. In the present study, we investigated the interaction of octapeptin A3 with asymmetric outer membrane models of Gram-negative pathogen Pseudomonas aeruginosa using neutron reflectometry, together with fluorimetric and calorimetry methods. For the first time, our neutron reflectometry results reveal that the interaction of octapeptin A3 with the Gram-negative outer membrane involves an initial transient polar interaction with the phospholipid and lipid A headgroups, followed by the penetration of the entire octapeptin molecule into the fatty acyl core of the outer membrane...
July 11, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28689374/identification-of-oat1-oat3-as-contributors-to-cisplatin-toxicity
#6
S Hu, A F Leblanc, A A Gibson, K W Hong, J Y Kim, L J Janke, L Li, A Vasilyeva, D B Finkelstein, J A Sprowl, D H Sweet, E Schlatter, G Ciarimboli, Jhm Schellens, S D Baker, N Pabla, A Sparreboom
Cisplatin is among the most widely used anticancer drugs and known to cause a dose-limiting nephrotoxicity, which is partially dependent on the renal uptake carrier OCT2. We here report a previously unrecognized, OCT2-independent pathway of cisplatin-induced renal injury that is mediated by the organic anion transporters OAT1 and OAT3. Using transporter-deficient mouse models, we found that this mechanism regulates renal uptake of a mercapturic acid metabolite of cisplatin that acts as a precursor of a potent nephrotoxin...
July 8, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28677901/big-conductance-calcium-activated-potassium-channel-openers-control-spasticity-without-sedation
#7
David Baker, Gareth Pryce, Cristina Visintin, Sofia Sisay, Alexander I Bondarenko, W S Vanessa Ho, Samuel J Jackson, Thomas E Williams, Sarah Al-Izki, Ioanna Sevastou, Masahiro Okuyama, Wolfgang F Graier, Lesley A Stevenson, Carolyn Tanner, Ruth Ross, Roger G Pertwee, Christopher M Henstridge, Andrew J Irving, Jesse Schulman, Keith Powell, Mark D Baker, Gavin Giovannoni, David L Selwood
BACKGROUND & PURPOSE: The initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis, whilst avoiding the sedative, side-effect-potential associated with cannabis. (R,Z)-3-(6-(dimethylamino)-6-oxohex-1-enyl)-N-(1-hydroxypropan-2-yl)benzamide (VSN16R) was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drug-like agents to target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate: activity, efficacy, pharmacokinetics and mechanism of action of the molecule...
July 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28662114/novel-glycopolymer-sensitizes-burkholderia-cepacia-complex-isolates-from-cystic-fibrosis-patients-to-tobramycin-and-meropenem
#8
Vidya P Narayanaswamy, Scott Giatpaiboon, Shenda M Baker, William P Wiesmann, John J LiPuma, Stacy M Townsend
Burkholderia cepacia complex (Bcc) infection, associated with cystic fibrosis (CF) is intrinsically multidrug resistant to antibiotic treatment making eradication from the CF lung virtually impossible. Infection with Bcc leads to a rapid decline in lung function and is often a contraindication for lung transplant, significantly influencing morbidity and mortality associated with CF disease. Standard treatment frequently involves antibiotic combination therapy. However, no formal strategy has been adopted in clinical practice to guide successful eradication...
2017: PloS One
https://www.readbyqxmd.com/read/28634816/critical-biological-parameters-modulate-affinity-as-a-determinant-of-function-in-t-cell-receptor-gene-modified-t-cells
#9
Timothy T Spear, Yuan Wang, Kendra C Foley, David C Murray, Gina M Scurti, Patricia E Simms, Elizabeth Garrett-Mayer, Lance M Hellman, Brian M Baker, Michael I Nishimura
T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28598353/cellular-consequences-of-diminished-protein-o-mannosyltransferase-activity-in-baker-s-yeast
#10
Ewa Zatorska, Lihi Gal, Jaro Schmitt, Daniela Bausewein, Maya Schuldiner, Sabine Strahl
O-Mannosylation is a type of protein glycosylation initiated in the endoplasmic reticulum (ER) by the protein O-mannosyltransferase (PMT) family. Despite the vital role of O-mannosylation, its molecular functions and regulation are not fully characterized. To further explore the cellular impact of protein O-mannosylation, we performed a genome-wide screen to identify Saccharomyces cerevisiae mutants with increased sensitivity towards the PMT-specific inhibitor compound R3A-5a. We identified the cell wall and the ER as the cell compartments affected most upon PMT inhibition...
June 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28544780/spinal-metastatic-disease-a-review-of-the-role-of-the-multidisciplinary-team
#11
REVIEW
Mark Curtin, Robert P Piggott, Evelyn P Murphy, Sudarshan Munigangaiah, Joseph F Baker, John P McCabe, Aiden Devitt
Historically, a simple approach centered on palliation was applicable to the majority of patients with metastatic spinal disease. With advances in diagnosis and treatment, a more complicated algorithm has devolved requiring a multidisciplinary approach with institutional commitment and support. We performed a database review including pertinent articles exploring the multidisciplinary management of spinal metastatic disease. The wide variation in clinical presentation and tumor response to treatment necessitates a multidisciplinary approach that integrates the diagnosis and treatment of the cancer, symptom management, and rehabilitation for optimal care of patients with spinal metastases...
May 24, 2017: Orthopaedic Surgery
https://www.readbyqxmd.com/read/28453523/the-mismatch-repair-and-meiotic-recombination-endonuclease-mlh1-mlh3-is-activated-by-polymer-formation-and-can-cleave-dna-substrates-in-trans
#12
Carol M Manhart, Xiaodan Ni, Martin A White, Joaquin Ortega, Jennifer A Surtees, Eric Alani
Crossing over between homologs is initiated in meiotic prophase by the formation of DNA double-strand breaks that occur throughout the genome. In the major interference-responsive crossover pathway in baker's yeast, these breaks are resected to form 3' single-strand tails that participate in a homology search, ultimately forming double Holliday junctions (dHJs) that primarily include both homologs. These dHJs are resolved by endonuclease activity to form exclusively crossovers, which are critical for proper homolog segregation in Meiosis I...
April 2017: PLoS Biology
https://www.readbyqxmd.com/read/28409469/experimental-systems-to-study-yeast-pexophagy
#13
Shun-Ichi Yamashita, Masahide Oku, Yasuyoshi Sakai, Yukio Fujiki
Peroxisome abundance is tightly regulated according to the physiological contexts, through regulations of both proliferation and degradation of the organelles. Here, we describe detailed methods to analyze processes for autophagic degradation of peroxisomes, termed pexophagy, in yeast organisms. The assay systems include a method for biochemical detection of pexophagy completion, and one for microscopic visualization of specialized membrane structures acting in pexophagy. As a model yeast organism utilized in studies of pexophagy, the methylotrophic yeast Komagataella phaffii (Pichia pastoris) is referred to in this chapter and related information on the studies with baker's yeast (Saccharomyces cerevisiae) is also included...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28402750/an-efficient-nurse-practitioner-led-community-based-service-model-for-delivering-coordinated-care-to-persons-with-serious-mental-illness-at-risk-for-homelessness
#14
Jeannemarie Baker, Jasmine L Travers, Penelope Buschman, Jacqueline A Merrill
BACKGROUND: Access to mental health care is a struggle for those with serious mental illness (SMI). About 25% of homeless suffer from SMI, compared with 4.2% of the general population. OBJECTIVE: From 2003 to 2012, St. Paul's Center (SPC) operated a unique model to provide quality care to the homeless and those at risk for homelessness, incarceration, and unnecessary hospitalization because of SMI. Data were available for analysis for the years 2008 to 2010. DESIGN: The SPC was developed, managed, and staffed by board-certified psychiatric/mental health nurse practitioners, offering comprehensive mental health services and coordinated interventions...
April 1, 2017: Journal of the American Psychiatric Nurses Association
https://www.readbyqxmd.com/read/28399855/characterisation-of-a-murine-model-of-the-late-asthmatic-response
#15
Katie Baker, Kristof Raemdonck, Robert J Snelgrove, Maria G Belvisi, Mark A Birrell
BACKGROUND: The incidence of asthma is increasing at an alarming rate. While the current available therapies are effective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In the search to understand disease pathogenesis and find effective therapies hypotheses are often tested in animal models before progressing into clinical studies. However, current dogma is that animal model data is often not predictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challenge induced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal model systems...
April 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28399806/current-challenges-and-possible-solutions-to-improve-access-to-care-and-treatment-for-hepatitis-c-infection-in-vietnam-a-systematic-review
#16
REVIEW
Alessandra Berto, Jeremy Day, Nguyen Van Vinh Chau, Guy E Thwaites, Ngoc Nghiem My, Stephen Baker, Thomas C Darton
BACKGROUND: Hepatitis C infection is a major public health concern in low- and middle-income countries where an estimated 71.1 million individuals are living with chronic infection. The World Health Organization (WHO) has recently released new guidance for hepatitis C virus (HCV) treatment programs, which include improving the access to new direct-acting antiviral agents. In Vietnam, a highly populated middle-income country, the seroprevalence of HCV infection is approximately 4% and multiple genotypes co-circulate in the general population...
April 11, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28383362/aripiprazole-once-monthly-in-the-treatment-of-acute-psychotic-episodes-in-schizophrenia-post-hoc-analysis-of-positive-and-negative-syndrome-scale-marder-factor-scores
#17
Zahinoor Ismail, Timothy Peters-Strickland, Maia Miguelez, Ross A Baker, Peter Hertel, Anna Eramo, Na Jin, Pamela Perry, Raymond Sanchez, Robert D McQuade, John M Kane
BACKGROUND: Long-acting injectable antipsychotics are treatment options for acute and long-term treatment of patients with schizophrenia. In a previously published 12-week randomized, double-blind, placebo-controlled clinical trial of patients with schizophrenia experiencing an acute psychotic episode, aripiprazole once-monthly 400 mg (AOM 400) produced significantly greater improvement than placebo on the primary endpoint, Positive and Negative Syndrome Scale (PANSS) total score at week 10...
June 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28372335/effects-of-regular-and-long-acting-insulin-on-cognition-and-alzheimer-s-disease-biomarkers-a-pilot-clinical-trial
#18
Suzanne Craft, Amy Claxton, Laura D Baker, Angela J Hanson, Brenna Cholerton, Emily H Trittschuh, Deborah Dahl, Erin Caulder, Bryan Neth, Thomas J Montine, Youngkyoo Jung, Joseph Maldjian, Christopher Whitlow, Seth Friedman
BACKGROUND: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. OBJECTIVE: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28367140/transcriptomics-indicates-active-and-passive-metronidazole-resistance-mechanisms-in-three-seminal-giardia-lines
#19
Brendan R E Ansell, Louise Baker, Samantha J Emery, Malcolm J McConville, Staffan G Svärd, Robin B Gasser, Aaron R Jex
Giardia duodenalis is an intestinal parasite that causes 200-300 million episodes of diarrhoea annually. Metronidazole (Mtz) is a front-line anti-giardial, but treatment failure is common and clinical resistance has been demonstrated. Mtz is thought to be activated within the parasite by oxidoreductase enzymes, and to kill by causing oxidative damage. In G. duodenalis, Mtz resistance involves active and passive mechanisms. Relatively low activity of iron-sulfur binding proteins, namely pyruvate:ferredoxin oxidoreductase (PFOR), ferredoxins, and nitroreductase-1, enable resistant cells to passively avoid Mtz activation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28366115/risk-of-hospitalization-due-to-medication-nonadherence-identified-through-emrs-of-patients-with-psychosis
#20
Carrie E Andrews, Krista Baker, Carolyn J Howell, Arlene Cuerdo, Jamie A Roberts, Abdullah Chaudhary, Stephanie Lechich, Leslie G Nucifora, Dhananjay Vaidya, Ramin Mojtabai, Russell L Margolis, Akira Sawa, Frederick C Nucifora
OBJECTIVE: This study examined whether outpatients with a psychotic disorder who are at risk of hospitalization can be identified by using data from electronic medical records (EMRs). METHODS: Data from EMRs of outpatients enrolled in two clinics for treatment of psychotic disorders were abstracted. Monthly data were collected for 75 patients over two years. The study examined the association of medication nonadherence, substance use, participation in psychiatric rehabilitation, and long-acting injectable antipsychotic use in any given month with the risk of hospitalization in the subsequent month by using generalized estimating equations...
April 3, 2017: Psychiatric Services: a Journal of the American Psychiatric Association
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