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Yao Hu Adrienne M. Stilp Caitlin P. McHugh Shuquan Rao Deepti Jain Xiuwen Zheng John Lane Sébastian Méric de Bellefon Laura M. Raffield Ming-Huei Chen Lisa R. Yanek Marsha Wheeler Yao Yao Chunyan Ren Jai Broome Jee-Young Moon Paul S. de Vries Brian D. Hobbs Alexander P. Reiner 《American journal of human genetics》2021,108(5):874-893
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Mario Rincón-Barrado Sanna Olsson Tamara Villaverde Belén Moncalvillo Lisa Pokorny Alan Forrest Ricarda Riina Isabel Sanmartín 《植物分类学报:英文版》2021,59(5):915-934
Wide-range geographically discontinuous distributions have long intrigued scientists. We explore the role of ecology, geology, and dispersal in the formation of these large-scale disjunctions, using the angiosperm tribe Putorieae (Rubiaceae) as a case study. From DNA sequences of nuclear ITS and six plastid markers, we inferred a phylogeny with 65% of all known Putorieae species. Divergence times, ancestral ranges, and diversification rate shifts were then estimated using Bayesian inference. We further explored species climatic tolerances and performed ancestral niche reconstruction to discriminate among alternative speciation modes, including geographical and ecological vicariance, and ecogeographical, ecological, and dispersal-mediated speciation. As a result, we identified seven major clades in Putorieae, some of which exhibit striking geographical disjunctions, matching the Rand Flora pattern, with sister species in the Canary Islands andeastern and southern Africa. Initial diversification within the tribe occurred in the early Miocene, coincident with a period of climate warming; however, most clades diverged within the last 10 Myr. Aridification and high extinction rates, coupled with ecological vicariance, explain the oldest disjunctions. Adaptation to new environmental conditions, after allopatry, is observed in several clades. Dispersal, either long-distance or via corridors made available by mountain uplift, is behind the most recent disjunctions. Some of these events were followed by ecological speciation and rapid diversification, with species becoming adapted to xeric or increasingly colder continental climates. We show that an integrative approach may help discriminate among speciation modes invoked to explain disjunctions at macroevolutionary time scales, even when extinction has erased the signature of past events. 相似文献
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Stephen Baine Ingrid Bonilla Andriy Belevych Andrei Stepanov Lisa E. Dorn Radmila Terentyeva Dmitry Terentyev Federica Accornero Cynthia A. Carnes Sandor Gyorke 《Journal of cellular and molecular medicine》2021,25(10):4637-4648
Heart failure (HF) is characterized by asymmetrical autonomic balance. Treatments to restore parasympathetic activity in human heart failure trials have shown beneficial effects. However, mechanisms of parasympathetic-mediated improvement in cardiac function remain unclear. The present study examined the effects and underpinning mechanisms of chronic treatment with the cholinesterase inhibitor, pyridostigmine (PYR), in pressure overload HF induced by transverse aortic constriction (TAC) in mice. TAC mice exhibited characteristic adverse structural (left ventricular hypertrophy) and functional remodelling (reduced ejection fraction, altered myocyte calcium (Ca) handling, increased arrhythmogenesis) with enhanced predisposition to arrhythmogenic aberrant sarcoplasmic reticulum (SR) Ca release, cardiac ryanodine receptor (RyR2) hyper-phosphorylation and up-regulated store-operated Ca entry (SOCE). PYR treatment resulted in improved cardiac contractile performance and rhythmic activity relative to untreated TAC mice. Chronic PYR treatment inhibited altered intracellular Ca handling by alleviating aberrant Ca release and diminishing pathologically enhanced SOCE in TAC myocytes. At the molecular level, these PYR-induced changes in Ca handling were associated with reductions of pathologically enhanced phosphorylation of RyR2 serine-2814 and STIM1 expression in HF myocytes. These results suggest that chronic cholinergic augmentation alleviates HF via normalization of both canonical RyR2-mediated SR Ca release and non-canonical hypertrophic Ca signaling via STIM1-dependent SOCE. 相似文献
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Angus R. Hibbins Yahya E. Choonara Pradeep Kumar Lisa C. du Toit Viness Pillay 《AAPS PharmSciTech》2013,14(3):935-949
The purpose of this study was to develop a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity which could be utilized within a binary drug delivery system. Avicel® RC/CL type R-591 was included within the in situ hot melt dispersion mini-pellet formulations to determine the physicomechanical effect this compound would have on the mini-pellet formulations. The physicomechanical properties of the hot melt in situ mini-pellet formulations were mathematically fitting to regression curves. Physicomechanical adjustment of the in situ hot melt dispersion mini-pellet formulations could be mathematically predicted with the derived regression curve equations. The addition of Avicel® RC/CL type R-591 increased the physicomechanical properties such as matrix hardness and increased total disintegration of the in situ hot melt dispersion mini-pellet formulations. The utilization of a physicomechanically customizable oral metal chelatory in situ hot melt dispersion mini-pellet entity within a binary drug delivery system would to achieve a synergistically enhance the activity of a drug-carrying entity or a permeation enhancing entity within a single drug delivery unit. The experimental results indicated that weights of the pellets that achieved optimal hardness ranged between 35 and 45 mg. The melt–dispersion formulations disintegrated within shorter time periods and maintained higher ethylenediaminetetraacetic acid (EDTA) concentrations whereas melt–dispersion formulations which included Avicel® had superior physicomechanical properties. Disintegration times ranged between 1,000 s for melt–dispersions containing EDTA and methyloxy polyethylene glycol 2000 (mPEG) only, to >6,000 s for melt–dispersions comprising EDTA, mPEG, and Avicel®. 相似文献
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