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171.
Fang Liu Kratika Singhal Rowan Matney Swati Acharya Cezmi A. Akdis Kari C. Nadeau Allis S. Chien Ryan D. Leib 《Proteomics》2020,20(11)
The analytical scale of most mass‐spectrometry‐based targeted proteomics assays is usually limited by assay performance and instrument utilization. A recently introduced method, called triggered by offset, multiplexed, accurate mass, high resolution, and absolute quantitation (TOMAHAQ), combines both peptide and sample multiplexing to simultaneously improve analytical scale and quantitative performance. In the present work, critical technical requirements and data analysis considerations for successful implementation of the TOMAHAQ technique based on the study of a total of 185 target peptides across over 200 clinical plasma samples are discussed. Importantly, it is observed that significant interference originate from the TMTzero reporter ion used for the synthetic trigger peptides. This interference is not expected because only TMT10plex reporter ions from the target peptides should be observed under typical TOMAHAQ conditions. In order to unlock the great promise of the technique for high throughput quantification, here a post‐acquisition data correction strategy to deconvolute the reporter ion superposition and recover reliable data is proposed. 相似文献
172.
Maryam Ghodrati Siahmazgi Mohammad Ali Nasiri Khalili Mehdi Zeinoddini Fathollah Ahmadpour Sirus Khodadadi 《International journal of peptide research and therapeutics》2020,26(2):767-774
Immunotoxin is a recombinant fusion toxin which has been developed to kill cancer cells selectively. DT389GCSF as a new immunotoxin consists of a truncated 相似文献
173.
Neekun Sharma Anthony M. Belenchia Ryan Toedebusch Lakshmi Pulakat Chetan P. Hans 《Journal of cellular and molecular medicine》2020,24(13):7393-7404
Clinical and experimental studies show that angiotensin II (AngII) promotes vascular pathology via activation of AngII type 1 receptors (AT1Rs). We recently reported that NP‐6A4, a selective peptide agonist for AngII type 2 receptor (AT2R), exerts protective effects on human vascular cells subjected to serum starvation or doxorubicin exposure. In this study, we investigated whether NP‐6A4–induced AT2R activation could mitigate AngII‐induced abdominal aortic aneurism (AAA) using AngII‐treated Apoe?/? mice. Male Apoe?/? mice were infused with AngII (1 µg/kg/min) by implanting osmotic pumps subcutaneously for 28 days. A subset of mice was pre‐treated subcutaneously with NP‐6A4 (2.5 mg/kg/day) or vehicle for 14 days prior to AngII, and treatments were continued for 28 days. NP‐6A4 significantly reduced aortic stiffness of the abdominal aorta induced by AngII as determined by ultrasound functional analyses and histochemical analyses. NP‐6A4 also increased nitric oxide bioavailability in aortic tissues and suppressed AngII‐induced increases in monocyte chemotactic protein‐1, osteopontin and proteolytic activity of the aorta. However, NP‐6A4 did not affect maximal intraluminal aortic diameter or AAA incidences significantly. These data suggest that the effects of AT2R agonist on vascular pathologies are selective, affecting the aortic stiffness and proteolytic activity without affecting the size of AAA. 相似文献
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176.
Ouimette Andrew P. Ollinger Scott V. Lepine Lucie C. Stephens Ryan B. Rowe Rebecca J. Vadeboncoeur Matthew A. Tumber-Davila Shersingh J. Hobbie Erik A. 《Ecosystems》2020,23(4):715-729
Ecosystems - Carbon (C) fluxes among different components of plant growth are important to forest ecosystem C cycling and are strongly influenced by species composition and resource availability.... 相似文献
177.
Shai Meiri Luciano Avila Aaron M. Bauer David G. Chapple Indraneil Das Tiffany M. Doan Paul Doughty Ryan Ellis Lee Grismer Fred Kraus Mariana Morando Paul Oliver Daniel Pincheira‐Donoso Marco Antonio Ribeiro‐Junior Glenn Shea Omar Torres‐Carvajal Alex Slavenko Uri Roll 《Global Ecology and Biogeography》2020,29(9):1515-1530
178.
Jason D. Roh Nicholas Houstis Andy Yu Bliss Chang Ashish Yeri Haobo Li Ryan Hobson Carolin Lerchenmüller Ana Vujic Vinita Chaudhari Federico Damilano Colin Platt Daniel Zlotoff Richard T. Lee Ravi Shah Michael Jerosch‐Herold Anthony Rosenzweig 《Aging cell》2020,19(6)
Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age‐related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24–30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age‐related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF. 相似文献
179.
Jessica F. Needham Jeffrey Chambers Rosie Fisher Ryan Knox Charles D. Koven 《Global Change Biology》2020,26(10):5734-5753
Elevated atmospheric carbon dioxide (eCO2) is predicted to increase growth rates of forest trees. The extent to which increased growth translates to changes in biomass is dependent on the turnover time of the carbon, and thus tree mortality rates. Size‐ or age‐dependent mortality combined with increased growth rates could result in either decreased carbon turnover from a speeding up of tree life cycles, or increased biomass from trees reaching larger sizes, respectively. However, most vegetation models currently lack any representation of size‐ or age‐dependent mortality and the effect of eCO2 on changes in biomass and carbon turnover times is thus a major source of uncertainty in predictions of future vegetation dynamics. Using a reduced‐complexity form of the vegetation demographic model the Functionally Assembled Terrestrial Ecosystem Simulator to simulate an idealised tropical forest, we find increases in biomass despite reductions in carbon turnover time in both size‐ and age‐dependent mortality scenarios in response to a hypothetical eCO2‐driven 25% increase in woody net primary productivity (wNPP). Carbon turnover times decreased by 9.6% in size‐dependent mortality scenarios due to a speeding up of tree life cycles, but also by 2.0% when mortality was age‐dependent, as larger crowns led to increased light competition. Increases in aboveground biomass (AGB) were much larger when mortality was age‐dependent (24.3%) compared with size‐dependent (13.4%) as trees reached larger sizes before death. In simulations with a constant background mortality rate, carbon turnover time decreased by 2.1% and AGB increased by 24.0%, however, absolute values of AGB and carbon turnover were higher than in either size‐ or age‐dependent mortality scenario. The extent to which AGB increases and carbon turnover decreases will thus depend on the mechanisms of large tree mortality: if increased size itself results in elevated mortality rates, then this could reduce by about half the increase in AGB relative to the increase in wNPP. 相似文献
180.
Alessio Collalti Mark G. Tjoelker Günter Hoch Annikki Mkel Gabriele Guidolotti Mary Heskel Giai Petit Michael G. Ryan Giovanna Battipaglia Giorgio Matteucci Iain Colin Prentice 《Global Change Biology》2020,26(3):1739-1753
Two simplifying hypotheses have been proposed for whole‐plant respiration. One links respiration to photosynthesis; the other to biomass. Using a first‐principles carbon balance model with a prescribed live woody biomass turnover, applied at a forest research site where multidecadal measurements are available for comparison, we show that if turnover is fast the accumulation of respiring biomass is low and respiration depends primarily on photosynthesis; while if turnover is slow the accumulation of respiring biomass is high and respiration depends primarily on biomass. But the first scenario is inconsistent with evidence for substantial carry‐over of fixed carbon between years, while the second implies far too great an increase in respiration during stand development—leading to depleted carbohydrate reserves and an unrealistically high mortality risk. These two mutually incompatible hypotheses are thus both incorrect. Respiration is not linearly related either to photosynthesis or to biomass, but it is more strongly controlled by recent photosynthates (and reserve availability) than by total biomass. 相似文献