1,354,572 research outputs found

    Part 2 of Age-related proteostatic imbalance exacerbates heart failure with preserved ejection fraction pathogenesis in old mice

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    <p>Heart failure with preserved ejection fraction (HFpEF) is a leading cause of hospitalization and death in the elderly. While aging strongly increases the incidence of HFpEF, the specific influences of aging on HFpEF at molecular and pathophysiological levels remain unclear. Here, we show that aged mice, when subjected to chronic metabolic and hypertensive stress (2-hit stress), develop an aggravated cardiometabolic HFpEF phenotype compared to younger counterparts. Aged HFpEF mice also display unique pathological characteristics reminiscent of those found in HFpEF patients. We demonstrate that age-related dysfunction in protein quality control (PQC) exacerbates proteostatic stress in HFpEF. Specifically, we demonstrate that increased protein synthesis induced by 2-hit stress combines with age-related impairment in protein degradation in aged HFpEF hearts, culminating in the accumulation of protein aggregates. These findings underscore the importance of incorporating aging into preclinical HFpEF models and support the therapeutic potentials of targeting PQC mechanisms to ameliorate disease outcomes.</p> <p>The deposited data are lc-ms data acquired on the Thermo QEx-Plus system.  For any questions, please contact mike kinter  mike-kinter at omrf.org</p> <p>This upload contains the second part of the data.  The majority of the data and a complete list of authors can be found in  10.5281/zenodo.10993216</p&gt

    Age-related proteostatic imbalance exacerbates heart failure with preserved ejection fraction pathogenesis in old mice

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    <p>Heart failure with preserved ejection fraction (HFpEF) is a leading cause of hospitalization and death in the elderly. While aging strongly increases the incidence of HFpEF, the specific influences of aging on HFpEF at molecular and pathophysiological levels remain unclear. Here, we show that aged mice, when subjected to chronic metabolic and hypertensive stress (2-hit stress), develop an aggravated cardiometabolic HFpEF phenotype compared to younger counterparts. Aged HFpEF mice also display unique pathological characteristics reminiscent of those found in HFpEF patients. We demonstrate that age-related dysfunction in protein quality control (PQC) exacerbates proteostatic stress in HFpEF. Specifically, we demonstrate that increased protein synthesis induced by 2-hit stress combines with age-related impairment in protein degradation in aged HFpEF hearts, culminating in the accumulation of protein aggregates. These findings underscore the importance of incorporating aging into preclinical HFpEF models and support the therapeutic potentials of targeting PQC mechanisms to ameliorate disease outcomes.</p> <p>The deposited data are lc-ms data acquired on the Thermo QEx-Plus system.  For any questions, please contact mike kinter  mike-kinter at omrf.org</p> <p>This upload contains the bulk of the LC-MS data.  But, due to file sizes, and addition group of files can be found at doi 10.5281/zenodo.11094720</p&gt

    Current Trends in Income of Communications Enterprises

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    Communications income shows more stability than national income, but costs appear to increase more rapidly than revenue in a boom and fall less in a depression. Author of several earlier articles * on this subject, Dr. Kinter is economist with a Chicago investment firm and lecturer on economics at Northwestern. </jats:p

    The Idaho Forester - 1985 (Vol. 66)

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    Dedication 1 Needed: Wind and Sun for Fresh Ideas, an editorial, Lynn Kinter 2 Articles and Opinions 5 Why Idaho Needs a State River System, Murray D. Feldman 6 The Evolution of Point Springs Experimental Area, Lee Sharp 8 On Three Years of Teaching at the University of Idaho, Michael Frome 10 Secondary Forest Products from Dinderesso National Forest, Janet K. Miller 12 Reminiscing-Summer Camp 1984, Robin Naugler and Cathi Bailey 15 Natural Resources Week 1984, Claire Rausch 16 School Forest Update, Harold Osborne 18 Preserving Idaho's Natural Diversity in Research Natural Areas, Charles Wellner 20 Idaho's Endowments-An Investment in the Future, Stanley Hamilton 22 Faculty Changes, Pam Vaughn 24 Communicating Through a Magazine of Natural Resources, Joe Ulliman 45 Endless Pressure, Jim Tangen-Foster 48 The Next Seventy-five Years 25 State of the College at the Portal of Change, Jim Fazio 26 Funseekers Take Heart, the Future is Ours, Charlie Wells 28 Where Are We Headed in Fisheries, Christine Moffitt 30 A Look Into the Crystal Ball, Arland Hofstrand 32 Wildlifers and Landscape Architects Plan Nongame Future, Kerry P. Reese 37 The Range Revolution: A Study in High Tech, Dave Bryant 38 Forestry Revisited: Year 2017, John Dirks 39 Leaders or Followers: Our Future as Foresters, Joe Carbone 41 Clubs and Organizations 53 SAC-A Bridge for Better Communication, Robin McCoy 54 Range Club, Steve Jirik 55 American Fisheries Society, Palouse Unit, David B. Irving 56 The Wildlife Society, Brynna Evans 57 Wrec Club Capers, Lynn Kinter 58 Beyond Logging, Diana Hammer 59 Forest Products Club, Alan Prouty 60 Xi Sigma Pi, Bruce Romig 61 Alumni News 62 Index to Advertisers 6

    CRUCIAL EXPERIMENTS IN CLIMATE SCIENCE

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    numerical experiments, climateThis article discusses the interplay between computational experiments and scientific advancement in dynamical meteorology and climate dynamics. In doing so, the emphasis is on the dual role of computations in prediction and experimentation, permitting the development of physical insight and confidence in the mechanistic insight through verification. Modern climate dynamics has steadily evolved because of the ready access to computational power that has developed over the past quarter century. The landscape for state-of-the-art computational climate science is changing rapidly, however, with the drive toward greater complexity in climate models in order to more fully represent the interactions among components, the need for higher-resolution atmospheric and oceanic models to fully capture critical aspects of the variability in these components, and the advent of petascale and (eventually) exascale computing facilities. Finally, the manner in which the combination of these changes will likely alter the planning and execution of grand-challenge computational experiments and what this might mean in terms of collaborative climate science is discussed

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Metabolic and Stress Response Changes Precede Disease Onset in the Spinal Cord of Mutant SOD1 ALS Mice

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    &lt;p&gt;Many Amyotrophic Lateral Sclerosis (ALS) patients experience hypermetabolism, or an increase in measured versus calculated metabolic rate. The cause of hypermetabolism and the effects on neuronal metabolism in ALS are currently unknown, but the efficacy of dietary interventions shows promise for metabolism as an ALS therapeutic target. The goal of this study is to measure changes in metabolic pathways as a function of disease progression in spinal cords of the SOD1G93A mouse model of ALS. We conducted a comprehensive assessment of protein expression for metabolic pathways, antioxidants, chaperones, and proteases in lumbar spinal cord from male SOD1G93A mice at pre-onset, onset, and end-stages of the disease using targeted proteomic analysis. These results reveal that protein content of metabolic proteins including proteins involved in glycolysis, &beta;‐oxidation, and mitochondrial metabolism is altered in SOD1G93A mouse spinal cord well before disease onset. The changes in mitochondrial metabolism proteins are associated with decreased maximal respiration and glycolytic flux in SOD1G93A dermal fibroblasts and increased hydrogen peroxide and lipid hydroperoxide production in mitochondria from sciatic nerve and gastrocnemius muscle fibers at end stage of disease. Consistent with redox dysregulation, expression of the glutathione antioxidant system is decreased, and peroxiredoxins and catalase expression are increased. In addition, stress response proteases and chaperones, including those involved in the mitochondrial unfolded protein response, are induced before disease onset. In summary, we report that metabolic and stress response changes occur in SOD1G93A lumbar spinal cord before motor symptom onset, and are primarily caused by SOD1G93A expression and do not vary greatly as a function of disease course.&lt;/p&gt;These files can be opened using the program Skyline. The program is free to download at: https://skyline.ms/project/home/software/Skyline/begin.view The general experimental design was two genotypes (WT and G93A) with three groups of mice within each genotype (preonset, onset, and endstage). The samples were analyzed by three different targeted protein quantification panels (1antioxidant and glycolysis, 2beta oxidation, and 3krebs cycle). For each panel, the name is a general description of most, but not all, of the proteins measured in the panel

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines.

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    Promonocytic (U1) and T lymphocytic (ACH-2) cell lines chronically infected with human immunodeficiency virus type 1 (HIV-1) constitutively express low levels of virus, but expression can be induced by phorbol esters and cytokines. Whereas ACH-2 cells produce infectious virions, U1 cells produce defective, noninfectious particles. Although 3'-azido-3'-deoxythimidine (AZT) prevented acute HIV infection of susceptible cells, it did not prevent the induction of HIV expression in the infected cell lines. In contrast, interferon alpha (IFN-alpha) inhibited the release of reverse transcriptase and viral antigens into the culture supernatant after phorbol ester stimulation of both cell lines. Further, IFN-alpha suppressed the production or release (or both) of whole HIV virions, but had no effect on the amount of cell-associated viral proteins. Also, after phorbol ester stimulation of ACH-2 cells, IFN-alpha reduced the number of infectious viral particles secreted into the culture supernatant, but had no effect on the infectivity of cell-associated virus. These findings lend support to the combined use of antiviral agents that have action at both the early (AZT) and the late (IFN-alpha) stages of HIV replication
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