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Do age-associated changes of voltage-gated sodium channel isoforms expressed in the mammalian heart predispose the elderly to atrial fibrillation?

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World Journal of Cardiology 2020年第4期12卷 123-135页

作者： Emmanuel Isaac stephanie m cooper Sandra A Jones mahmoud Loubani Department of Cardiothoracic Surgery Hull University Teaching HospitalsCottingham HU165JQUnited Kingdom Department of Biomedical Sciences University of HullHull HU67RXUnited Kingdom

Atrial fibrillation(AF)is the most common cardiac arrhythmia *** prevalence of the disease increases with age,strongly implying an age-related process underlying the *** a time when people are living longer than ever before,an exponential increase in disease prevalence is predicted *** unraveling the underlying mechanics of the disease is paramount for the development of innovative treatment and prevention *** role of voltage-gated sodium channels is fundamental in cardiac electrophysiology and may provide novel insights into the arrhythmogenesis of ***_v1.5 is the predominant cardiac isoform,responsible for the action potential *** studies have demonstrated that Na_v1.8(an isoform predominantly expressed within the peripheral nervous system)is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic *** studies have shown a decline in Na_v1.5 leading to a diminished action potential upstroke during phase ***,the study of human tissue demonstrates an inverse expression of sodium channel isoforms;reduction of Na_v1.5 and increase of Na_v1.8 in both heart failure and ventricular *** strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the diseased *** aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging *** review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through the examination of laboratory and clinical based evidence.

关键词： Voltage-gated Sodium channels Ageing Atrial fibrillation Nav1.5 Nav1.8 Late sodium current Cardiac electrophysiology

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Androgens and prostate disease

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Asian Journal of Andrology 2014年第2期16卷 248-255,I0009页

作者： Lori A cooper stephanie T Page Departments of medicine Division of Endocrinology and Metabolism University of Washington Seattle University of Washington and Harborview medical Center Seattle Washington USA.

A growing body of literature has established the anabolic benefits of testosterone （T） therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease.

关键词： androgens male hypogonadism prostate testosterone

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Engineering personalized neural tissue using functionalized transcription factors

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Neural Regeneration Research 2016年第10期11卷 1570-1571页

作者： stephanie m.willerth department of mechanical engineering and division of medical sciences university of victoria centre for biomedical research university of victoria international collaboration on repair discoveries university of british columbia

Diseases and disorders of the central nervous system often require significant interventions to restore lost function due to their com- plexity. Examples of such disorders include Parkinson＇s disease, Alzheimer＇s disease, multiple sclerosis, traumatic brain injury, and spinal cord in）ury. These diseases and disorders result trom healthy cells being destroyed, which in turn causes dysfunction in the cen- tral nervous system, The death of these cells can trigger a cascade of events that affect the rest of the body, causing symptoms that become progressively worse over time. Developing strategies for repairing the damage to the central nervous system remains chal- lenging, in part due to its inability to regenerate.

关键词： cell Engineering personalized neural tissue using functionalized transcription factors

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The influence of fire frequency on the abundance of maerua subcordata in the Serengeti National Park, Tanzania

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Journal of Plant Ecology 2012年第4期5卷 400-406页

作者： Ayron m.Strauch stephanie Eby Department of Biology Tufts University163 Packard AvenueMedfordMA 02155USA Department of Ecology and Evolutionary Biology 106A Guyot HallPrinceton UniversityPrincetonNJ 08544USA Present address:Department of Ecology and Evolutionary Biology Yale UniversityPO Box 208106165 Prospect StreetNew HavenCT 06520-8106USA

Aims Invasive species alter the composition and function of communities,threatening the conservation of important ecosystems *** savanna ecosystems,fire plays a key role by modifying biogeochemical cycles and shaping the composition and structure of vegetation *** many studies have examined the long-term effects of fire frequency on grassland communities,few studies have examined the relationship between fire regime and woody species *** The Serengeti ecosystem is an ecologically and economically valuable natural resource in East Africa whose conservation is currently threatened by a variety of factors,including invasive *** determined the abundance of maerua subcordata,a noxious woody shrub,in three different regions of the Serengeti National Park,*** then examined the influence of fire frequency,developed through the use of 7 years of moderate Resolution Imaging Spectroradiometer(mODIS)imagery,on *** *** Findings In all regions,burned transects had significantly greater abundances of *** compared to unburned ***,the number of times each transect burned from 2000 to 2006 had a significant positive effect on the abundance of *** and the number of years since a transect last burned had a significant negative relationship with *** results are particularly important as this species provides little forage value and is potentially toxic to wildlife and *** studies are needed to determine the ecological consequences of increasing *** abundance,as the potential expansion of noxious shrubs into protected areas of important conservation status is of serious concern.

关键词： Serengeti fire savanna maerua subcordata mODIS

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Immunological roulette: Luck or something more? Considering the connections between host and environment in TB

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Cellular & molecular Immunology 2018年第3期15卷 226-232页

作者： John E Pearl mrinal Das Andrea m cooper Department of Infection Immunity and Inflammation Leicester Tuberculosis Research Group(LTBRG)University of LeicesterUniversity RoadLeicesterLE17RHUK

Accurate prediction of which patient will progress from a sub-clinical mycobacterium tuberculosis infection to active tuberculosis represents an elusive,yet critical,clinical research *** the individual perspective,progression can be considered to be the product of a series of unfortunate events or even a run of bad ***,we identify the subtle physiological relationships that can influence the odds of progression to active TB and how this progression may reflect directed dysbiosis in a number of interrelated *** infected individuals who progress to disease have apparently good immune responses,but these responses are,at times,compromised by either local or systemic environmental *** disease promoting processes,such as tissue-damaging granulomata,usually manifest in the lung,but illness is *** apparent dichotomy between local and systemic reflects a clear need to define the factors that promote progression to active disease within the context of the body as a physiological *** discuss aspects of the host environment that can impact expression of immunity,including the microbiome,glucocorticoid-mediated regulation,catecholamines and interaction between the gut,liver and *** suggest the importance of integrating precision medicine into our analyses of experimental outcomes such that apparently conflicting results are not contentious,but rather reflect the impact of these subtle relationships with our environment and microbiota.

关键词： gut-liver-lung axis microbiome tuberculosis

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The impact of hypoxic-ischemic brain injury on stem cell mobilization,migration,adhesion,and proliferation

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Neural Regeneration Research 2018年第7期13卷 1125-1135页

作者： stephanie m.Parry Eric S.Peeples Department of Pediatrics University of Nebraska Medical Center

Neonatal hypoxic-ischemic encephalopathy continues to be a significant cause of death or neurodevelopmental delays despite standard use of therapeutic *** use of stem cell transplantation has recently emerged as a promising supplemental therapy to further improve the outcomes of infants with hypoxic-ischemic *** the injury,the brain releases several chemical mediators,many of which communicate directly with stem cells to encourage mobilization,migration,cell adhesion and *** manuscript reviews the biomarkers that are released from the injured brain and their interactions with stem cells,providing insight regarding how their upregulation could improve stem cell therapy by maximizing cell delivery to the injured tissue.

关键词： brain-derived neurotrophic hypoxia inducible erythropoietin factor matrix metalloproteinase neonatal stromal cell-derived vascular endothelial growth

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Determining the mechanism behind yoga’s effects on preventing the symptoms of Alzheimer’s disease

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Neural Regeneration Research 2020年第2期15卷 261-262页

作者： Adithy Hassan meghan Robinson stephanie m. Willerth Division of medical Sciences 3800 Finnerty RoadUniversity of VictoriaVictoriaBritish ColumbiaCanada The Vancouver Prostate Centre VancouverBritish ColumbiaCanada Department of mechanical Engineering University of VictoriaVictoriaBritish ColumbiaCanadaCentre for Biomedical ResearchUniversity of VictoriaVictoriaBritish ColumbiaCanadaInternational Collaboration on Repair DiscoveriesUniversity of British ColumbiaVancouverBritish ColumbiaCanada

Background on the relationship between meditation/yoga practice and its effect on Alzheimer's disease (AD): Dementia refers to a variety of conditions that affect the normal function of the brain, leading to symptoms like memory loss, issues with problem solving, difficulty in processing thoughts and disordered language (mcKhann et al., 2011).

关键词： effects yoga Alzheimer's disease

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A new look at auranofin,dextromethorphan and rosiglitazone for reduction of glia-mediated inflammation in neurodegenerative diseases

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Neural Regeneration Research 2015年第3期10卷 391-393页

作者： Jocelyn m.madeira stephanie m.Schindler Andis Klegeris Department of Biology University of British Columbia Okanagan Campus

Neurodegenerative disorders including Alzheimer＇s disease are characterized by chronic in- flammation in the central nervous system. The two main glial types involved in inflammatory reactions are microglia and astrocytes. While these cells normally protect neurons by providing nutrients and growth factors, disease specific stimuli can induce glial secretion of neurotoxins. It has been hypothesized that reducing glia-mediated inflammation could diminish neuronal loss. This hypothesis is supported by observations that chronic use of non-steroidal anti-inflamma- tory drugs （NSAIDs） is linked with lower incidences of neurodegenerative disease. It is possible that the NSAIDs are not potent enough to appreciably reduce chronic neuroinflammation after disease processes are fully established. Gold thiol compounds, including auranofin, comprise an- other class of medications effective at reducing peripheral inflammation. We have demonstrated that auranofin inhibits human microglia- and astrocyte-mediated neurotoxicity. Other drugs which are currently used to treat peripheral inflammatory conditions could be helpful in neu- rodegenerative disease. Three different classes of anti-inflammatory compounds, which have a potential to inhibit neuroinflammation are highlighted below.

关键词： auranofin dextromethorphan rosiglitazone Alzheimer's disease neuroinflammation neurodegeneration rnicroglia astrocytes

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Potential effects of climate change on a marine invasion： The importance of current context

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Current Zoology 2012年第1期58卷 1-8页

作者： Côté, Isabelle m. Green, stephanie J. Department of Biological Sciences Simon Fraser University 8888 University Drive Burnaby BC Canada V5A 1S6

Species invasions threaten marine biodiversity globally. There is a concern that climate change is exacerbating this problem. Here, we examined some of the potential effects of warming water temperatures on the invasion of Western Atlantic habitats by a marine predator, the Indo-Pacific lionfish （Pterois volitans and P. miles）. We focussed on two temperature-dependent aspects of lionfish life-history and behaviour： pelagic larval duration, because of its link to dispersal potential, and prey consump- tion rate, because it is an important determinant of the impacts of lionfish on native prey. Using models derived from fundamental metabolic theory, we predict that the length of time spent by lionfish in the plankton in early life should decrease with warming temperatures, with a concomitant reduction in potential dispersal distance. Although the uncertainty around change in dispersal distances is large, predicted reductions are, on average, more than an order of magnitude smaller than the current rate of range expansion of lionfisli in the Caribbean. Nevertheless, because shorter pelagic larval duration has the potential to increase local re- tention of larvae, local lionfish management will become increasingly important under projected climate change. Increasing tem- perature is also expected to worsen the current imbalance between rates of prey consumption by lionfish and biomass production by their prey, leading to a heightened decline in native reef fish biomass. However, the magnitude of climate-induced decline is predicted to be minor compared to the effect of current rates of lionfish population increases （and hence overall prey consumption rates） on invaded reefs. Placing the predicted effects of climate change in the current context thus reveals that, at least for the lionfish invasion, the threat is clear and present, rather than future [Current Zoology 58 （1）： 1-8, 2012].

关键词： Non-indigenous species Coral reefs Dispersal Ecological impacts of invasion

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The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration

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Science China(Life Sciences) 2014年第4期57卷 366-371页

作者： CLARK Charlotte EJ LIU Yaobo cooper Helen m Queensland Brain Institute The University of QueenslandBrisbane Institute of Neuroscience Soochow University

In the developing embryo,nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous *** navigational systems comprising repulsive and attractive guidance cues form chemotactic gradients along the pathway of the exploring growth ***-bound receptors detect these gradients and determine the trajectory of the migrating growth *** contrast to their benevolent role in the developing nervous system,repulsive guidance receptors are detrimental to the axon’s ability to regenerate after injury in the *** this review we explore the essential and beneficial role played by the chemorepulsive Wnt receptor,Ryk/Derailed in axon navigation in the embryonic nervous system(the Yin function).Specifically,we focus on the role of Wnt5a/Rykmediated guidance in the establishment of two major axon tracts in the mammalian central nervous system,the corticospinal tract and the corpus *** studies have also identified Ryk as a major suppressor of axonal regeneration after spinal cord ***,we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a major impediment to axon regrowth(the Yang function).

关键词： Ryk Derailed Wnt Wnt signalling axon guidance axonal regeneration spinal cord injury

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