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Not all arrestins are created equal: Therapeutic implications of the functional diversity of the β-arrestins in the heart

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World Journal of Cardiology 2019年第2期11卷 47-56页

作者： Anastasios lymperopoulos Shelby l Wertz Celina M Pollard victoria l desimine Jennifer Maning Katie A McCrink laboratory for the Study of Neurohormonal Control of the Circulation Department of Pharmaceutical Sciences (Pharmacology) College of PharmacyNova Southeastern University Jackson Memorial Hospital Massachusetts General Hospital

The two ubiquitous, outside the retina, G protein-coupled receptor(GPCR)adapter proteins, β-arrestin-1 and-2(also known as arrestin-2 and-3,respectively), have three major functions in cells: GPCR desensitization, i.e.,receptor decoupling from G-proteins; GPCR internalization via clathrin-coated pits; and signal transduction independently of or in parallel to G-proteins. Bothβ-arrestins are expressed in the heart and regulate a large number of cardiac GPCRs. The latter constitute the single most commonly targeted receptor class by Food and Drug Administration-approved cardiovascular drugs, with about onethird of all currently used in the clinic medications affecting GPCR *** β-arrestin-1 and-2 play important roles in signaling and function of several GPCRs, in particular of adrenergic receptors and angiotensin II type 1 receptors,in cardiac myocytes, they have been a major focus of cardiac biology research in recent years. Perhaps the most significant realization coming out of their studies is that these two GPCR adapter proteins, initially thought of as functionally interchangeable, actually exert diametrically opposite effects in the mammalian myocardium. Specifically, the most abundant of the two β-arrestin-1 exerts overall detrimental effects on the heart, such as negative inotropy and promotion of adverse remodeling post-myocardial infarction(MI). In contrast, β-arrestin-2 is overall beneficial for the myocardium, as it has anti-apoptotic and antiinflammatory effects that result in attenuation of post-MI adverse remodeling,while promoting cardiac contractile function. Thus, design of novel cardiac GPCRligands that preferentially activate β-arrestin-2 over β-arrestin-1 has the potential of generating novel cardiovascular therapeutics for heart failure and other heart diseases.

关键词： Adverse remodeling β-arrestin Biased signaling Cardiac myocyte Cardiac fibroblast contractility Functional divergence G protein-coupled receptor Heart failure Hormone Myocardial infarction Signal transducer

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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2l,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2l RHBDF2

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A Tutorial on Federated learning from Theory to Practice:Foundations,Software Frameworks,Exemplary Use Cases,and Selected Trends

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 824-850页

作者： M.victoria luzón Nuria Rodríguez-Barroso Alberto Argente-Garrido Daniel Jiménez-lópez Jose M.Moyano Javier Del Ser Weiping Ding Francisco Herrera Department of Software Engineering Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Computer Science and Artificial Intelligence Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Communications Engineering University of the Basque Country(UPV/EHU)and also with TECNALIABasque Research&Technology Alliance(BRTA)Spain School of Information Science and Technology Nantong UniversityNantong 226019China

When data privacy is imposed as a necessity,Federated learning(Fl)emerges as a relevant artificial intelligence field for developing machine learning(Ml)models in a distributed and decentralized *** allows Ml models to be trained on local devices without any need for centralized data transfer,thereby reducing both the exposure of sensitive data and the possibility of data interception by malicious third *** paradigm has gained momentum in the last few years,spurred by the plethora of real-world applications that have leveraged its ability to improve the efficiency of distributed learning and to accommodate numerous participants with their data *** virtue of Fl,models can be learned from all such distributed data sources while preserving data *** aim of this paper is to provide a practical tutorial on Fl,including a short methodology and a systematic analysis of existing software ***,our tutorial provides exemplary cases of study from three complementary perspectives:i)Foundations of Fl,describing the main components of Fl,from key elements to Fl categories;ii)Implementation guidelines and exemplary cases of study,by systematically examining the functionalities provided by existing software frameworks for Fl deployment,devising a methodology to design a Fl scenario,and providing exemplary cases of study with source code for different Ml approaches;and iii)Trends,shortly reviewing a non-exhaustive list of research directions that are under active investigation in the current Fl *** ultimate purpose of this work is to establish itself as a referential work for researchers,developers,and data scientists willing to explore the capabilities of Fl in practical applications.

关键词： Data privacy distributed machine learning federated learning software frameworks

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An electropenetrography waveform library for the probing and ingestion behaviors of Culex tarsalis on human hands

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Insect Science 2024年第4期31卷 1165-1186页

作者： Anastasia M.W.Cooper Samuel B.Jameson victoria Pickens Cameron Osborne Elaine A.Backus Kristopher Silver Dana N.Mitzel Department of Entomology Kansas State UniversityManhattanKansasUSA Department of Tropical Medicine Tulane University School of Public Health and Tropical MedicineNew OrleansLos AngelesUSA USDA Agricultural Research Service San Joaquin Valley Agricultural Sciences CenterParlierCaliforniaUSA National Bio and Agro-Defense Facility USDA Agricultural Research ServiceManhattanKansasUSA

Culex tarsalis Coquillett(Diptera:Culicidae)mosquitoes are capable of vectoring numerous pathogens affecting public and animal ***,the probing behaviors of mosquitoes are poorly understood because they occur in opaque ***(EPG)has the potential to elucidate these behaviors by recording the electrical signals generated during *** used an AC–DC EPG with variable input resistors(Ri levels)to construct a waveform library for *** feeding on human *** events associated with mosquito probing were used to characterize waveforms at four Ri levels and with two electrical current *** optimal settings for EPG recordings of *** probing on human hands was an Ri level of 10^(7)Ohms using an applied signal of 150 millivolts alternating *** for *** included those previously observed and associated with probing behaviors in Aedes aegypti l.(Diptera:Culicidae):waveform families J(surface salivation),K(stylet penetration through the skin),l(types 1 and 2,search for a blood vessel/ingestion site),M(types 1 and 2,ingestion),N(type 1,an unknown behavior which may be a resting and digestion phase),and W(withdrawal).However,we also observed variations in the waveforms not described in ***,which we named types l3,M3,M4,and *** investigation enhances our understanding of mosquito probing *** also provides a new tool for the automated calculation of peak *** work will facilitate future pathogen acquisition and transmission studies and help identify new pest and disease management targets.

关键词： AC-DC blood feeders electrical penetration graph EPG human hands mosquitoes waveform library

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Cancer immunotherapy with envelopedself-amplifying mRNA CARG-2020 thatmodulates Il-12,Il-17 and PD-l1 pathways toprevent tumor recurrence

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Acta Pharmaceutica Sinica B 2024年第1期14卷 335-349页

作者： Ju Chen Bhaskara Reddy Madina Elham Ahmadi Timur Olegovich Yarovinsky Marie Marthe Krady Eileen victoria Meehan Isabella China Wang Xiaoyang Ye Elise Pitmon Xian-Yong Ma Bijan Almassian Valerian Nakaar Kepeng Wang Department of Immunology School of MedicineUniversity of Connecticut Health CenterFarmingtonCT 06030USA CaroGen Corporation FarmingtonCT 06030USA The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine Foshan Hospital of Traditional Chinese MedicineFoshan 528000China The loomis Chaffee School WindsorCT 06095USA

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for ***,we describe the application of virus-like vesicles(VlV)for delivery of three immunomodulators alone and in combination,as a promising approach for cancer *** vectors were designed to deliver single chain interleukin(Il)-12,shorthairpin RNA(shRNA)targeting programmed death ligand 1(PD-l1),and a dominant-negative form of Il-17 receptor A(dn-Il17RA)as a single payload or as a combination *** delivery of the VlV vector expressing Il-12 alone,as well as the trivalent vector(designated CARG-2020)eradicated large established ***,only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice,indicating a benefit of the combined *** abscopal effects of CARG-2020 on the non-injected contralateral tumors,as well as protection from the tumor cell re-challenge,suggest immune-mediated mechanism of protection and establishment of immunological ***,CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting *** ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

关键词： Virus-like vesicles Oncolytic virus Il-12 Il-17 PD-l1 T cell exhaustion Combination therapy Cancer immunotherapy

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Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction

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World Journal of Cardiology 2020年第5期12卷 192-202页

作者： Natalie Cora Jennifer Ghandour Celina Marie Pollard victoria lynn desimine Krysten Elaine Ferraino Janelle Marie Pereyra Rachel Valiente Anastasios lymperopoulos laboratory for the Study of Neurohormonal Control of the Circulation Department of Pharmaceutical Sciences(Pharmacology)College of PharmacyNova Southeastern UniversityFort LauderdaleFL 33328-2018United States

BACKGROUND Tobacco-related products,containing the highly addictive nicotine together with numerous other harmful toxicants and carcinogens,have been clearly associated with coronary artery disease,heart failure,stroke,and other heart *** the mechanisms by which nicotine contributes to heart disease is elevation of the renin-angiotensin-aldosterone system(RAAS)***,and its major metabolite in humans cotinine,have been reported to induce RAAS activation,resulting in aldosterone elevation in *** has various direct and indirect adverse cardiac *** is produced by the adrenal cortex in response to angiotensin II(AngII)activating AngII type 1 *** activity increases in chronic smokers,causing raised aldosterone levels(nicotine exposure causes the same in rats).AngII receptors exert their cellular effects via either G proteins or the twoβarrestins(βarrestin1 and-2).AIM Since adrenal?arrestin1 is essential for adrenal aldosterone production and nicotine/cotinine elevate circulating aldosterone levels in humans,we hypothesized that nicotine activates adrenal?arrestin1,which contributes to RAAS activation and heart disease *** We studied human adrenocortical zona glomerulosa H295R cells and found that nicotine and cotinine upregulateβarrestin1 mRNA and protein levels,thereby enhancing AngII-dependent aldosterone synthesis and *** In contrast,siRNA-mediatedβarrestin1 knockdown reversed the effects of nicotine on AngII-induced aldosterone production in H295 R ***,nicotine promotes hyperaldosteronism via adrenalβarrestin1,thereby precipitating cardiac dysfunction,also in vivo,since nicotine-exposed experimental rats with adrenal-specificβarrestin1 knockdown display lower circulating aldosterone levels and better cardiac function than nicotine-exposed control animals with normal adrenalβarrestin1 *** Adrenalβarrestin1 upregulation is one of the mechanisms by whic

关键词： Adrenocortical zona glomerulosa cell Aldosterone βarrestin Nicotine Signal transduction Tobacco-related heart disease

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The Making of a Health Profession:How Chinese Medicine Became a Nationally Registered Allied Health Profession in Australia

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Chinese Medicine and Culture 2024年第1期7卷 51-62页

作者： John l McDonald Judy B James School of Chinese Medicine Endeavour College of Natural HealthSouthport 4215Australia Acupuncture Now Australia Brisbane 4120Australia

In 2012, traditional Chinese medicine(TCM) practitioners in Australia became nationally-registered allied health professionals in three categories: acupuncturist, Chinese herbal medicine practitioner, and Chinese herbal medicine dispenser. Australia was the first Western country to introduce national registration for Chinese medicine, followed by Portugal and, recently, New Zealand. The practice of TCM in Australia can be traced back to the beginning of Chinese immigration to Australia during the victorian Gold Rush which began in the 1850s. The process which led to national registration commenced in the early 1970s with the establishment of the first acupuncture courses. Decades of gradual development of courses from unaccredited part-time diplomas to accredited bachelor degrees, and the development, by the profession, of national consensus on educational standards were essential elements in the process which led to registration. Professional associations, such as the Australian Acupuncture and Chinese Medicine Association ltd.(AACMA), also developed a framework of professional selfregulation, including Codes of Ethics, Codes of Conduct, ongoing professional development requirements and Infection Control Guidelines, and provided leadership in the development of the profession. After decades of tribalism and division within the TCM profession, the National Academic Standards Committee brought almost all stakeholders together to reach a consensus on the Australian Guidelines for Traditional Chinese Medicine Education which were published by AACMA in 2001. Professional associations also collaborated on joint submissions to the government in support of registration, which was introduced first in the state of victoria in 2000, and subsequently became national in 2012. Despite national registration, some barriers still remain, and professional associations continue to lobby the federal government for inclusion in Medicare, chronic disease management scheme, and Veterans

关键词： Acupuncture Chinese medicine Registration Regulation Education Standards Australia TCM

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Determination of Soil Aggregate Porosity Using the Modified Water Saturation Method

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Pedosphere 2019年第6期29卷 794-800页

作者： David MORET-FERNáNDEZ María victoria lóPEZ Departamento de Suelo y Agua Estación Experimental de Aula Dei Consejo Superior de Investigaciones Científicas (EEAD-CSIC)

The need to find a simple method for measuring soil aggregate porosity (φ) is justified by the growing interest of researchers in this important parameter of soil physical status. The aim of this study was to present a simple method (AM) for estimating the total 0 of a single soil aggregate. In this case, soil aggregate 0 was calculated as the quotient between the pore volume, estimated from the weight of the aggregate saturated with ethanol, and the total volume (V T ) of aggregate, calculated from the particle density and dry aggregate weight. The V T estimated with AM was compared with the corresponding volume measured with the photogrammetry (PHM) technique using soil aggregates of 8–16 mm in diameter and collected from three different tillage systems: conventional tillage (CT), reduced tillage (RT), and no tillage (NT). Next, the AM was used to study the effects of the tillage system on soil aggregate φ. Although a strong relationship ( R 2 = 0.99, P l evaporation during the first 10 s before the ethanol-saturated aggregate was weighed. The use of AM to determine the effects of different tillage systems on aggregate φ showed that this method was sensitive to detect significant differences among the tillage treatments. The results showed that AM could be an accurate, simple, and inexpensive alternative to estimate φ of a single soil aggregate.

关键词： Aggregate stability Bulk density Particle density Photogrammetry technique Tillage system

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Recent progress on bimetallic NiCo and CoFe based electrocatalysts for alkaline oxygen evolution reaction: A review

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Journal of Energy Chemistry 2022年第4期31卷 101-137页

作者： Gebrehiwet Abrham Gebreslase Maria victoria Martínez-Huerta Maria Jesus lázaro Instituto de Carboquímica CSIC.Miguel LuesmaCastán 450018ZaragozaSpain Instituto de Catálisis y Petroleoquímica CSIC.Marie Curie 228049MadridSpain

The deployment of hydrogen as an energy carrier is found to be a vital alternative fuel for the future. It is expected that water electrolysis, powered by renewable energy sources, be able to scale-up hydrogen production. However, the reaction kinetic of oxygen evolution reaction(OER) is a sluggish process, which predominantly limits the efficiency of water electrolysis. This review recapitulates the recent progress and efforts made in the design and development of two selected earth-abundant bimetallic electrocatalysts(Ni Co and Co Fe) for alkaline OER. Each bimetal electrocatalyst is thoroughly outlined and discussed in five sub-sections, including bimetal(oxy) hydroxides, layered double hydroxides(lDHs) structures,oxides, composites, alloy and nanostructured electrocatalysts, and assembled with ***, a brief introduction to an in situ/operando characterization techniques and advantages for monitoring the structure of the electrocatalysts is provided. Finally, a summary outlining the challenges and conceivable approaches to advance OER performance is highlighted and discussed.

关键词： Water electrolysis Oxygen evolution reaction Bimetallic electrocatalyst Nickel Cobalt and iron

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Physiological effects of climate warming on flowering plants and insect pollinators and potential consequences for their interactions

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Current Zoology 2013年第3期59卷 418-426页

作者： victoria l. SCAVEN Nicole E. RAFFERTY Department of Soil Water and Environmental Science University of Arizona Tucson AZ 85721 USA Department of Ecology and Evolutionary Biology University of Arizona Tucson AZ 85721 USA Center for Insect Science University of Arizona Tucson AZ 85721 USA

Growing concern about the influence of climate change on flowering plants, pollinators, and the mutualistic interac- tions between them has led to a recent surge in research. Much of this research has addressed the consequences of warming for phenological and distributional shifts. In contrast, relatively little is known about the physiological responses of plants and insect pollinators to climate warming and, in particular, how these responses might affect plant-pollinator interactions. Here, we summa- rize the direct physiological effects of temperature on flowering plants and pollinating insects to highlight ways in which plant and pollinator responses could affect floral resources for pollinators, and pollination success for plants, respectively. We also con- sider the overall effects of these responses on plant-pollinator interaction networks. Plant responses to wanning, which include altered flower, nectar, and pollen production, could modify floral resource availability and reproductive output of pollinating in- sects. Similarly, pollinator responses, such as altered foraging activity, body size, and life span, could affect patterns of pollen flow and pollination success of flowering plants. As a result, network structure could be altered as interactions are gained and lost, weakened and strengthened, even without the gain or loss of species or temporal overlap. Future research that addresses not only how plant and pollinator physiology are affected by warming but also how responses scale up to affect interactions and networks should allow us to better understand and predict the effects of climate change on this important ecosystem service .

关键词： Mutualism Networks Plant-pollinator interactions Pollination Temperature Thermoregulation

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