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https://www.readbyqxmd.com/read/28634816/critical-biological-parameters-modulate-affinity-as-a-determinant-of-function-in-t-cell-receptor-gene-modified-t-cells
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28353685/strong-population-structure-in-a-species-manipulated-by-humans-since-the-neolithic-the-european-fallow-deer-dama-dama-dama
#13
K H Baker, H W I Gray, V Ramovs, D Mertzanidou, Ç Akın Pekşen, C C Bilgin, N Sykes, A R Hoelzel
Species that have been translocated and otherwise manipulated by humans may show patterns of population structure that reflect those interactions. At the same time, natural processes shape populations, including behavioural characteristics like dispersal potential and breeding system. In Europe, a key factor is the geography and history of climate change through the Pleistocene. During glacial maxima throughout that period, species in Europe with temperate distributions were forced south, becoming distributed among the isolated peninsulas represented by Anatolia, Italy and Iberia...
July 2017: Heredity
https://www.readbyqxmd.com/read/28335351/modified-nanoemulsions-with-iron-oxide-for-magnetic-resonance-imaging
#14
Yongyi Fan, Rui Guo, Xiangyang Shi, Steven Allen, Zhengyi Cao, James R Baker, Su He Wang
A nanoemulsion (NE) is a surfactant-based, oil-in-water, nanoscale, high-energy emulsion with a mean droplet diameter of 400-600 nm. When mixed with antigen and applied nasally, a NE acts as a mucosal adjuvant and induces mucosal immune responses. One possible mechanism for the adjuvant effect of this material is that it augments antigen uptake and distribution to lymphoid tissues, where the immune response is generated. Biocompatible iron oxide nanoparticles have been used as a unique imaging approach to study the dynamics of cells or molecular migration...
November 25, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28258775/a-markov-model-for-planning-and-permitting-offshore-wind-energy-a-case-study-of-radio-tracked-terns-in-the-gulf-of-maine-usa
#15
Alexana Cranmer, Jennifer R Smetzer, Linda Welch, Erin Baker
Quantifying and managing the potential adverse wildlife impacts of offshore wind energy is critical for developing offshore wind energy in a sustainable and timely manner, but poses a significant challenge, particularly for small marine birds that are difficult to monitor. We developed a discrete-time Markov model of seabird movement around a colony site parameterized by automated radio telemetry data from common terns (Sterna hirundo) and Arctic terns (S. paradisaea), and derived impact functions that estimate the probability of collision fatality as a function of the distance and bearing of wind turbines from a colony...
May 15, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28255438/lactate-in-the-brain-an-update-on-its-relevance-to-brain-energy-neurons-glia-and-panic-disorder
#16
REVIEW
Laurel Riske, Rejish K Thomas, Glen B Baker, Serdar M Dursun
Lactate is considered an important metabolite in the human body, but there has been considerable debate about its roles in brain function. Research in recent years has suggested that lactate from astrocytes may be crucial for supporting axonal function, especially during times of high metabolic demands or hypoglycemia. The astrocyte-neuron lactate transfer shuttle system serves a protective function to ensure a supply of substrates for brain metabolism, and oligodendrocytes appear to also influence availability of lactate...
February 2017: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/28244001/relating-clinical-and-electrophysiological-parameters-in-death-determination-in-a-laboratory-model-of-progressive-hypoxemia
#17
Eugene Park, Elaine Liu, Sam D Shemie, Andrew J Baker
BACKGROUND: Death after withdrawal of mechanical ventilation frequently follows the sequence of progressive hypoxemia and hypotension leading to cardiac arrest. Accurate timing of the determination of death is fundamental to trust in controlled donation after circulatory death (cDCD) programs and is generally based on cessation of circulation (pulselessness), brain function (apnea), and the passage of time. If death is understood to be the unresuscitatable loss of brain function, the clinical determination that death following apnea and pulselessness has occurred is largely inferential...
February 27, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28242621/a-farnesylated-coxiella-burnetii-effector-forms-a-multimeric-complex-at-the-mitochondrial-outer-membrane-during-infection
#18
Laura F Fielden, Jennifer H Moffatt, Yilin Kang, Michael J Baker, Chen Ai Khoo, Craig R Roy, Diana Stojanovski, Hayley J Newton
Coxiella burnetii, the causative agent of Q fever, establishes a unique lysosome-derived intracellular niche termed the Coxiella-containing vacuole (CCV). The Dot/Icm-type IVB secretion system is essential for the biogenesis of the CCV and the intracellular replication of Coxiella Effector proteins, translocated into the host cell through this apparatus, act to modulate host trafficking and signaling processes to facilitate CCV development. Here we investigated the role of CBU0077, a conserved Coxiella effector that had previously been observed to localize to lysosomal membranes...
May 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28217743/regulation-of-nitrogen-metabolism-by-gata-zinc-finger-transcription-factors-in-yarrowia-lipolytica
#19
Kyle R Pomraning, Erin L Bredeweg, Scott E Baker
Fungi accumulate lipids in a manner dependent on the quantity and quality of the nitrogen source on which they are growing. In the oleaginous yeast Yarrowia lipolytica, growth on a complex source of nitrogen enables rapid growth and limited accumulation of neutral lipids, while growth on a simple nitrogen source promotes lipid accumulation in large lipid droplets. Here we examined the roles of nitrogen catabolite repression and its regulation by GATA zinc finger transcription factors on lipid metabolism in Y...
January 2017: MSphere
https://www.readbyqxmd.com/read/28161400/memory-b-cells-are-major-targets-for-effective-immunotherapy-in-relapsing-multiple-sclerosis
#20
REVIEW
David Baker, Monica Marta, Gareth Pryce, Gavin Giovannoni, Klaus Schmierer
Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells...
February 2017: EBioMedicine
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