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Adenosine A1 receptor ligands bind toα-synuclein:implications forα-synuclein misfolding andα-synucleinopathy in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 809-834页

作者： Elisabet Jakova Mohamed Taha Moutaoufik Jeremy S.Lee Mohan Babu francisco S.Cayabyab Department of Surgery College of MedicineUniversity of SaskatchewanSaskatoonSKCanada Department of Chemistry and Biochemistry Faculty of ScienceUniversity of ReginaReginaSKCanada Department of Biochemistry Microbiology and ImmunologyCollege of MedicineUniversity of SaskatchewanSaskatoonSKCanada.

Background:Accumulatingα-synuclein(α-syn)aggregates in neurons and glial cells are the staples of many synucleinopathy disorders,such as Parkinson’s disease(PD).Since brain adenosine becomes greatly elevated in ageing brains and chronic adenosine A1 receptor(A1R)stimulation leads to neurodegeneration,we determined whether adenosine or A1R receptor ligands mimic the action of known compounds that promoteα-syn aggregation(e.g.,the amphetamine analogue 2-aminoindan)or inhibitα-syn aggregation(e.g.,Rasagiline metabolite 1-aminoindan).In the present study,we determined whether adenosine,A1R receptor agonist N^(6)-Cyclopentyladenosine(CPA)and antago-nist 8-cyclopentyl-1,3-dipropylxanthine(DPCPX)could directly interact withα-syn to modulateα-syn aggregation and neurodegeneration of dopaminergic neurons in the substantia nigra(SN).Methods:Nanopore analysis and molecular docking were used to test the binding properties of CPA and DPCPX withα-syn in ***-Dawley rats were administered with 7-day intraperitoneal injections of the A1R ligands and 1-and 2-aminoindan,and levels ofα-syn aggregation and neurodegeneration were examined in the SN pars compacta and hippocampal regions using confocal imaging and Western ***:Using nanopore analysis,we showed that the A1R agonists(CPA and adenosine)interacted with the N-terminus ofα-syn,similar to 2-aminoindan,which is expected to promote a“knot”conformation andα-syn *** contrast,the A1R antagonist DPCPX interacted with the N-and C-termini ofα-syn,similar to 1-aminoindan,which is expected to promote a“loop”conformation that preventsα-syn *** docking studies revealed that adenosine,CPA and 2-aminoindan interacted with the hydrophobic core ofα-syn N-terminus,whereas DPCPX and 1-aminoindan showed direct binding to the N-and C-terminal hydrophobic *** imaging and Western blot analyses revealed that chronic treatments with CPA alone or in combination with 2-aminoindan increasedα-syn

关键词： Alpha-synucleinopathy Adenosine A1 receptor N6-cyclopentyladenosine 8-cyclopentyl-1 3-dipropylxanthine 1-aminoindan 2-aminoindan Neuroprotection Neurodegeneration Protein misfolding

Interspecific plant interaction via root exudates structures the disease suppressiveness of rhizosphere microbiomes

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Molecular Plant 2023年第5期16卷 849-864页

作者： Xingang Zhou Jingyu Zhang Muhammad Khashi u Rahman Danmei Gao Zhong Wei Fengzhi Wu francisco Dini-Andreote Key Laboratory of Biology and Genetic Improvement of Horticultural Crops(Northeast Region) Ministry of Agriculture and Rural AffairsDepartment of HorticultureNortheast Agricultural UniversityChangjiang 600Harbin 150030P.R.China Jiangsu Provincial Key Lab for Organic Solid Waste Utilization National Engineering Research Center for Organic-based FertilizersJiangsu Collaborative Innovation Center for Solid Organic Waste Resource UtilizationNanjing Agricultural UniversityWeigang No.1Nanjing 210095P.R.China Department of Plant Science&Huck Institutes of the Life Sciences The Pennsylvania State UniversityUniversity ParkPAUSA

Terrestrial plants can affect the growth and health of adjacent plants via interspecific ***,we studied the mechanism by which plant root exudates affect the recruitment of the rhizosphere microbiome in adjacent plants—with implications for plant protection—using a tomato(Solanum lycopersicum)–potatoonion(Allium cepa ***)intercropping ***,we showed that the intercropping system results in a disease-suppressive rhizosphere microbiome that protects tomato plants against Verticillium wilt disease caused by the soilborne pathogen Verticillium ***,16S rRNA gene sequencing revealed that intercropping with potatoonion altered the composition of the tomato rhizosphere microbiome by promoting the colonization of specific Bacillus *** taxon was isolated and shown to inhibit *** growth and induce systemic resistance in tomato ***,a belowground segregation experiment found that root exudates mediated the interspecific interaction between potatoonion and ***,experiments using split-root tomato plants found that root exudates from potatoonion,especially taxifolin—a flavonoid compound—stimulate tomato plants to recruit plant-beneficial bacteria,such as Bacillus ***,ultra-high-pressure liquid chromatography–mass spectrometry analysis found that taxifolin alters tomato root exudate chemistry;thus,this compound acts indirectly in modulating root colonization by Bacillus *** results revealed that this intercropping system can improve tomato plant fitness by changing rhizosphere microbiome recruitment via the use of signaling chemicals released by root exudates of *** study revealed a novel mechanism by which interspecific plant interaction modulates the establishment of a disease-suppressive microbiome,thus opening up new avenues of research for precision plant microbiome manipulations.

关键词： intercropping microbiome rhizosphere root exudates soilborne disease

Twenty-four-hour movement guidelines during middle adolescence and their association with glucose outcomes and type 2 diabetes mellitus in adulthood

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Journal of Sport and Health Science 2023年第2期12卷 167-174页

作者： Antonio García-Hermoso Joséfrancisco López-Gil Yasmin Ezzatvar Robinson Ramírez-Vélez Mikel Izquierdo Navarrabiomed Hospital Universitario de Navarra(HUN)Universidad Publica de Navarra(UPNA)IdiSNAPamplona 31008Spain Health and Social Research Center Universidad de Castilla-La ManchaCuenca 16007Spain Department of Nursing Universitat de ValenciaValencia 46010Spain

Purpose:The aim of the present study was to determine the association between adherence to the 24-h movement guidelines during middle adolescence and glucose outcomes(glycated hemoglobin and fasting glucose)and type 2 diabetes mellitus(T2DM)in adulthood,14 and 22 years ***:We analyzed data from apparently healthy adolescents aged 12-18 years who participated in WavesⅠandⅡ(1994-1996,n=14,738),WaveⅣ(2008-2009,n=8913),and Wave V(2016-2018,n=3457)of the National Longitudinal Study of Adolescent to Adult Health(Add Health)in the United *** activity,screen time,and sleep duration were measured using questionnaires,and the 24-h guidelines were defined as:5 or more times moderate-to-vigorous physical activity per week,≤2 h per day of screen time,and 9-11 h of sleep for 12-13 years and 8-10 h for 14-17 *** and venous whole blood was collected and analyzed to determine glycated hemoglobin and fasting glucose for WavesⅣandⅤ,***:Only 2.1%of the adolescents met all the 3 guidelines,and 37.8%met none of *** both wavesⅣandⅤ,adolescents who met physical activity and screen time guidelines had lower odds of T2DM in adulthood than those who did not meet any of these guidelines(WaveⅣ;prevalence ratio(PR)=0.57,95%confidence interval(95%CI):0.21-0.89;Wave V:PR=0.43,95%CI:0.32-0.74).Only for Wave V did adolescents who met all 3 guidelines have lower odds of T2DM at follow-up compared with those who did not meet any of these guidelines(PR=0.47,95%CI:0.24-0.91).Also,for each increase in meeting one of the 24-h recommendations,the odds of T2DM decreased by 18%(PR=0.82,95%CI:0.61-0.99)and 15%(PR=0.85,95%CI:0.65-0.98)in adulthood for WavesⅣandⅤ,***:Promoting all 24-h movement guidelines in adolescence,especially physical activity and screen time,is important for lowering the potential risk of T2DM in adulthood.

关键词： Glucose metabolism Glycated hemoglobin Physical activity Screen time Sleep duration

Different strategies of treatment for uterine cervical carcinoma stage ⅠB2-ⅡB

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World Journal of Clinical Oncology 2014年第2期5卷 86-92页

作者： Lucas Minig María Guadalupe Patrono Nuria romero Juan francisco Rodríguez Moreno Jesús Garcia-Donas Gynecologic Oncology Program Clara Campal Comprehensive Cancer CenterHM Hospitales28050 Madrid Spain Gynecologic Oncology Program Medical Oncology Department Clara Campal Comprehensive Cancer Center HM Hospitales28050 Madrid Spain

Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage ⅠB2-ⅡB.

关键词： Locally advanced cervical cancer Federation of Gynecology and Obstetrics stage ⅠB2-ⅡB Radiotherapy Neoajuvant chemotherapy Radical hysterectomy

Cardiogenic shock due to left main related myocardial infarction:is revascularization enough?

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Journal of Geriatric Cardiology 2022年第2期19卷 152-157页

作者： francisco Galván-Román Elena Puerto Roberto Martín-Asenjo Albert Ariza-Solé Department of Cardiology Bellvitge University Hospital.Grup de Malalties Cardiovasculars.Institut d´InvestigacióBiomèdica de Bellvitge(IDIBELL).L’Hospitalet de LlobregatBarcelonaSpain Department of Cardiology Doce de Octubre University Hospital.Instituto de Investigación Sanitaria Hospital 12 de Octubre(imas12).MadridSpain*The authors contributed equally to this manuscript

The incidence of cardiogenic shock(CS)complicating acute myocardial infarction(AMI-CS)remains between 3%and 10%and in-hospital mortality is hardly less than 30%.[1-3]In addition,the economic cost of caring for these patients is high.[4]Revascularization in the acute phase is the only measure that has demonstrated to modify the prognosis of AMI-CS.

关键词： infarction acute mortality

Antibiotics,gut microbiota,and irritable bowel syndrome:What are the relations?

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World Journal of Gastroenterology 2022年第12期28卷 1204-1219页

作者： Zarina Mamieva Elena Poluektova Valery Svistushkin Vasily Sobolev Oleg Shifrin francisco Guarner Vladimir Ivashkin Department of Internal Disease Propaedeutics N.V.Sklifosovsky Institute of Clinical MedicineI.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia Department of Ear Throat and Nose DiseasesN.V.Sklifosovsky Institute of Clinical MedicineI.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia Digestive System Research Unit Vall d’Hebron Research InstituteBarcelona 08035Spain

Irritable bowel syndrome(IBS)is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits(constipation,diarrhea,or both),and it is often accompanied by symptoms of abdominal bloating and *** is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care *** extensive research,the etiology and underlying pathophysiology of IBS remain incompletely *** mechanisms involved in its pathogenesis include increased intestinal permeability,changes in the immune system,visceral hypersensitivity,impaired gut motility,and emotional ***,accumulating evidence has highlighted the important role of the gut microbiota in the development of *** dysbiosis within the gut is thought to contribute to all aspects of its multifactorial *** last few decades have also seen an increasing interest in the impact of antibiotics on the gut ***,antibiotics have been suggested to play a role in the development of *** research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in *** suggestion is further supported by data from cohort and case-control studies,indicating that antibiotic treatment is associated with an increased risk of *** paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.

关键词： Gut microbiota Irritable bowel syndrome Antibiotics Intestinal barrier Gut motility Gut sensitivity

Local Fourier Analysis for Edge-Based Discretizations on Triangular Grids

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Numerical Mathematics(Theory,Methods and Applications) 2015年第1期8卷 78-96页

作者： Carmen Rodrigo francisco Sanz francisco J.Gaspar francisco J.Lisbona Department of Applied Mathematics University of ZaragozaC/Maria de Luna 350018ZaragozaSpain BIFI University of Zaragoza C/Pedro Cerbuna 1250009ZaragozaSpain Department of Applied Mathematics University of ZaragozaC/Pedro Cerbuna 1250009ZaragozaSpain

In this paper,we present a local Fourier analysis framework for analyzing the different components within multigrid solvers for edge-based discretizations on triangular *** different stencils associated with edges of different orientation in a triangular mesh make this analysis *** resulting tool is demonstrated for the vector Laplace problem discretized by mimetic finite difference *** from the local Fourier analysis,as well as experimentally obtained results,are presented to validate the proposed analysis.

关键词： Multigrid local Fourier analysis edge-based discretizations mimetic finite differences

A multidimensional review of the cash management problem

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Financial Innovation 2023年第1期9卷 1840-1874页

作者： francisco Salas‑Molina Juan A.Rodríguez‑Aguilar Montserrat Guillen Universitat Politècnica de València Ferrándiz y Carbonell03801 AlcoySpain IIIA‑CSIC Campus UAB08913 CerdanyolaSpain Universitat de Barcelona Av.Diagonal69008034 BarcelonaSpain

In this paper,we summarize and analyze the relevant research on the cash manage-ment problem appearing in the ***,we identify the main dimensions of the cash management ***,we review the most relevant contributions in this field and present a multidimensional analysis of these contributions,according to the dimensions of the *** this analysis,several open research questions are highlighted.

关键词： Cash management Models Dimensions Review

Virtual Conductance Based Cascade Voltage Controller for VSCs in Islanded Operation Mode

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Journal of Modern Power Systems and Clean Energy 2022年第6期10卷 1704-1713页

作者： francisco Jesús Matas-Díaz Manuel Barragán-Villarejo Juan Carlos Olives-Camps Juan Manuel Mauricio JoséMaría Maza-Ortega Department of Elec‐trical Engineering Universidad de SevillaSeville 41092Spain

Voltage source converters have become the main enabler for the integration of distributed energy resources in *** the case of islanded operation,these devices normally set the amplitude and frequency of the network voltage by means of a cascade controller composed of an outer voltage control loop and an inner current control *** strategies to compute the gains of both control loops have been proposed in the literature in order to obtain a fast and decoupled response of the voltages at the point of common *** paper proposes an alternative and simple methodology based on the introduction of a virtual conductance in the classic cascade *** strategy allows to design each control loop independently,obtaining a closed-loop response of a first-order *** this way,the gains of each control loop are easily derived from the parameters of the LC coupling filter and the desired closed-loop time ***,a state observer is included in the controller to estimate the inductor current of the LC filter in order to reduce the number of required measurements.A laboratory testbed is used to validate and compare the proposed *** experimental results demonstrate the effectiveness of the proposal both in steady-state and transient regimes.

关键词： Voltage source converter microgrid cascade controller virtual conductance