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Manipulation of bicarbonate concentration in sperm capacitation media improves in vitro fertilisation output in porcine species

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Journal of Animal Science and Biotechnology 2019年第2期10卷 375-389页

作者： Cristina Soriano-úbeda Jon Romero-Aguirregomezcorta Carmen Matás pablo e.visconti Francisco A.García-Vázquez Department of Physiology Faculty of Veterinary ScienceInternational Excellence Campus for Higher Education and Research“Campus Mare Nostrum”University of Murcia30100 MurciaSpain Institute for Biomedical Research of Murcia(IMIB-Arrixaca) MurciaSpain Department of Physiology Faculty of Medicine and NursingUniversity of the Basque Country UPV/EHULeioaBizkaiaSpain.4Department of Veterinary and Animal SciencesUniversity of MassachusettsAmherstMAUSA.

Background: The in vivo concentration of bicarbonate(HCO3-), one of the essential sperm capacitating effectors,varies greatly in the different environments sperm go through from cauda epididymis to the fertilisation site. On the contrary, porcine in vitro sperm capacitation and fertilisation media usually contains a standard concentration of25 mmol/L, and one of the main problems presented is the unacceptable high incidence of polyspermy. This work hypothesised that by modifying the HCO3-concentration of the medium, the output of in vitro sperm capacitation and fertilisation could be increased.Results: Once exposed to the capacitation medium, the intracellular pH(pHi) of spermatozoa increased immediately even at low concentrations of HCO3-, but only extracellular concentrations of and above 15 mmol/L increased the substrates protein kinase A phosphorylation(pPKAs). Although with a significant delay, 15 mmol/L of HCO3-stimulated sperm linear motility and increased other late events in capacitation such as tyrosine phosphorylation(Tyr-P) to levels similar to those obtained with 25 mmol/L. This information allowed the establishment of a new in vitro fertilisation(IVF)system based on the optimization of HCO3-concentration to 15 mmol/L, which led to a 25.3% increment of the viable zygotes(8.6% in the standard system vs. 33.9%).Conclusions: Optimising HCO3-concentrations allows for establishing an IVF method that significantly reduced porcine polyspermy and increased the production of viable zygotes. A concentration of 15 mmol/L of HCO3-in the medium is sufficient to trigger the in vitro sperm capacitation and increase the fertilisation efficiency in porcine.

关键词： Adcy10 Boar Monospermy PKA

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Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

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Neural Regeneration Research 2024年第8期19卷 1835-1841页

作者： Irene Navarro-Lobato Mariam Masmudi-Martín Manuel F.López-Aranda Juan F.López-Téllez Gloria Delgado pablo Granados-Durán Celia Gaona-Romero Marta Carretero-Rey Sinforiano Posadas María e.Quiros-Ortega Zafar U.Khan Laboratory of Neurobiology Centro de Investigaciones Médico Sanitarias(CIMES)University of MalagaMalagaSpain Department of Medicine Faculty of MedicineUniversity of MalagaMalagaSpain Centro de Investigación Biomédica en Red de enfermedades Neurodegenerativas(CIBeRNeD) Institute of Health Carlos IIIMadridSpain the Donders Institute for Brain Cognition and Behaviour Radboud UniversityNijmegenThe Netherlands the Brain Metastasis Group National Cancer Research Centre(CNIO)MadridSpain the Department of Neurobiology University of California-Los AngelesLos AngelesCAUSA

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

关键词： behavioral performance brain-derived neurotrophic factor cognitive dysfunction episodic memory memory circuit activation memory deficits memory enhancement object recognition memory prevention of memory loss regulator of G protein signaling

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effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

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World Journal of Gastroenterology 2024年第11期30卷 1545-1555页

作者： Juan pablo Stefanolo Verónica Segura Martina Grizzuti Abel Heredia Isabel Comino Ana Florencia Costa Roberto Puebla María Paz Temprano Sonia Isabel Niveloni Gabriel de Diego María e Oregui edgardo Gustavo Smecuol Mauricio C de Marzi elena F Verdú Carolina Sousa Julio César Bai Small Bowel Section Department of MedicineGastroenterology Hospital of Buenos Aires“Dr.C.Bonorino Udaondo”Buenos Aires 1264Argentina Department of Microbiology and Parasitology Faculty of PharmacyUniversity of SevilleSeville 41080Spain Department of Medicine Dr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Basic and Applied Research Group in Immunology and Bioactives(GIBAIB) Institute of Ecology and Sustainable Development(INEDES)National University of LujanLuján 6700Buenos AiresArgentina Department of Medicine Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamilton L8S 4L8OntarioCanada Facultad de Medicina Universidad del SalvadorBuenos Aires C1051ABBArgentina

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PeP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.MeTHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PeP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PeP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by eLISA every Tuesday and Friday during run-ins and treatments.ReSULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(es,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PeP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PeP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PeP arm was significantly lower(PeP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PeP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-P

关键词： Celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

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离子通道、磷酸化和哺乳动物精子获能

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Asian Journal of Andrology 2011年第3期13卷 395-405,511页

作者： pablo e.visconti Dario Krapf Jose Luis de la Vega-Beltran Juan Jose Acevedo Alberto Darszon Department of Veterinary and Animal Science Paige Labs University of Massachusets Amherst MA 01003 USA Institute of Molecular and Cell Biology of Rosario （CONICeTUNR） and Area Biologia Facultad de Ciencias Biologicas y Farmaceuticas UNR Rosario 2000 Argentina Departamento de Genetica del Desarrollo y Fisiologia Molecular Institute de Biotecnologia Universidad Nacional Autonoma de Mexico （UNAM） Cuemavaca Merelos C.P. 62510 Mexico Departamento de Fisiologia y Farmacologia Facultad de Medicina Universidad Autenoma del Estado de Morelas Cuernavaca C.P. 62510 Mexico

有性生殖动物需要精子和卵子之间进行精心协调的交流才能产生新的个体。精子获能是发生在女性生殖系统中的生殖细胞成熟的一个复杂现象，让精子能够和卵子联结并融合，是哺乳动物生育的必要条件。精子获能过程包括了质膜重组、离子渗透... 详细信息

有性生殖动物需要精子和卵子之间进行精心协调的交流才能产生新的个体。精子获能是发生在女性生殖系统中的生殖细胞成熟的一个复杂现象，让精子能够和卵子联结并融合，是哺乳动物生育的必要条件。精子获能过程包括了质膜重组、离子渗透调节、胆固醇减少和许多蛋白质磷酸化状态的变化。研究精子离子通道的新工具能用更好的时空解析度将细胞内的离子变化和蛋白图像化，这些工具正在一步步阐明离子运输和磷酸化状态中的一系列调节是如何引起获能的。最近的证据表明有两条平行的通路调节引起获能的磷酸化发生。其中一条通路要求蛋白激酶A活化，另一条通路需要丝氨酸／苏氨酸磷酸酶失活。本文综述了精子获能所要求的离子运输参与和磷酸化信号处理。理解导致生育的分子机制，对于人们应对男性不育率升高、开发安全的以雄性配子为基础的避孕药、通过辅助生殖策略保持生物多样性都至关重要。

关键词：获能离子通道脂类磷酸化精子

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Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation

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World Journal of Transplantation 2024年第2期14卷 126-134页

作者： Gabriel Lazzarotto-da-Silva Leandro A Scaffaro Mauricio Farenzena Lucas Prediger Rafaela K Silva Flávia Heinz Feier Tomaz J M Grezzana-Filho pablo D Rodrigues Alexandre de Araujo Mario Reis Alvares-da-Silva Roberta C Marchiori Cleber Rosito Pinto Kruel Marcio Fernandes Chedid Department of Liver Transplant and Hepatobiliary Surgery Unit Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Department of Interventional Radiology Unit Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil Department of Gastroenterology and Hepatology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-007Brazil

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAe)has been replaced by transarterial chemoembolization(TACe).However,the superiority of TACe over TAe has not been consistently shown in the literature.AIM To compare the outcomes of TACe and TAe in patients with HCC awaiting LT.MeTHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACe or TAe.Some patients also underwent percutaneous ethanol injection(PeI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.ReSULTS Twelve(18.5%)patients in the TACe group(only TACe and TACe+PeI;n=65)and 3(7.9%)patients in the TAe group(only TAe and TAe+PeI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACe and TAe groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACe group and 29(76.3%)of the 38 patients in the TAe group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACe and TAe groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACe and TAe groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCL

关键词： Hepatocellular carcinoma Transarterial embolization Transarterial chemoembolization Liver transplantation Locoregional therapy Bridging

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Control-based Fault Current Limiter for Minimizing Impact of Distributed Generation Units on Protection Systems

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Journal of Modern Power Systems and Clean energy 2023年第2期11卷 643-650页

作者： pablo e.Muñoz Ricardo J.Mantz Sergio A.González Instituto LeICI UNLPCONICETLa Plata 1900La PlataArgentina Commission of Scientific Researches of the Buenos Aires Province(CICpBA) La PlataArgentina

Distributed generation units(DGUs)bring some problems to the existing protection system,such as those associated with protection blinding and sympathetic tripping.It is known that fault current limiters(FCLs)help minimize the negative impact of DGUs on the protection system.In this paper,a control-based FCL is proposed,i.e.,the FCL is integrated into the DGU control law.To this end,a predictive control strategy with fault current limitation is suggested.In this way,a DGU is controlled,not only for power exchange with the power grid but also to limit its fault current contribution.The proposal is posed as a constrained optimization problem allowing taking into account the current limit explicitly in the design process as a closed-loop solution.A linear approximation is proposed to cope with the inherent nonlinear constraints.The proposal does not require incorporating extra equipment or mechanisms in the control loop,making the design process simple.To evaluate the proposed control-based FCL,both protection blinding and sympathetic tripping scenarios are considered.The control confines the DGU currents within the constraints quickly,avoiding large transient peaks.Therefore,the impact on the protection system is reduced without the necessity that the DGU goes out of service.

关键词： Distributed generation distribution network protection power electronic converter fault current limiter model-based predictive controller

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Linking plant metabolism and immunity through methionine biosynthesis

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Molecular Plant 2022年第1期15卷 6-8页

作者： Francisco escaray Amelia Felipo-Benavent pablo Vera Instituto de Biología Molecular y Celular de Plantas Universidad Politécnica de Valencia-C.S.I.CCiudad Politécnica de la InnovaciónEdificio 8EIngeniero Fausto Elios/n46022 ValenciaSpain

Plants respond to pathogenic cues with a transcriptional reprog-ramming that leads to de novo production of defense-related pro-teins and a huge variety of secondary metabolites(e.g.,phyto-alexins,phenolics,etc.).Activation of these host defenses,which contribute to halt the intruder as part of the resistance,im-plies an increased demand for metabolic energy and carbon skel-etons derived from primary metabolism(Bolton,2009).

关键词： metabolism immunity Bolton

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Impact of pre- and peri-operative risk factors on length of stay and hospital readmission following minimally-invasive partial nephrectomy

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Asian Journal of Urology 2024年第1期11卷 72-79页

作者： Vanessa A.Lukas Rahul Dutta Ashok K.Hemal Matvey Tsivian Timothy e.Craven Nicholas A.Deebel David D.Thiel Ram Anil Pathak Brigham and Women's Hospital Division of UrologyDepartment of Surgery75 Francis StreetBostonMAUSA Atrium Health Wake Forest Baptist Medical Center Department of Urology1 Medical Center BlvdWinston-SalemNCUSA Mayo Clinic Florida Department of Urology4500 San Pablo RoadJacksonvilleFLUSA

Objective:We conducted an analysis of the American College of Surgeons National Surgical Quality Improvement Program database for minimally-invasive partial nephrectomy cases reported with the goal to identify pre-and peri-operative variables associated with length of stay(LOS)greater than 3 days and readmission within 30 days.Methods:Records from 2008 to 2018 for“laparoscopy,surgical;partial nephrectomy”for prolonged LOS and readmission cohorts were compiled.Univariate analysis with Chi-square,t-tests,and multivariable logistic regression analysis with odds ratios(ORs),p-values,and 95%confidence intervals assessed statistical associations.Results:Totally,20306 records for LOS greater than 3 days and 15854 for readmission within 30 days were available.Univariate and multivariable analysis exhibited similar results.For LOS greater than 3 days,undergoing non-elective surgery(OR=5.247),transfusion of greater than four units within 72 h prior to surgery(OR=5.072),pre-operative renal failure or dialysis(OR=2.941),and poor pre-operative functional status(OR=2.540)exhibited the strongest statistically significant associations.For hospital readmission within 30 days,loss in body weight greater than 10%in 6 months prior to surgery(OR=2.227)and bleeding disorders(OR=2.081)exhibited strongest statistically significant associations.Conclusion:Multiple pre-and peri-operative risk factors are independently associated with prolonged LOS and hospital readmission within 30 days of surgery using the American College of Surgeons National Surgical Quality Improvement Program data.Recognizing the risks factors that can potentially be improved prior to minimally-invasive partial nephrectomy is crucial to informing patient selection,optimization strategies,and patient education.

关键词： Minimally-invasive partial nephrectomy The American College of Surgeons National Surgical Quality Improvement Program Lengthof stay Hospital readmission

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Phase separating Rho:a widespread regulatory function of disordered regions in proteins revealed in bacteria

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3203-3205页

作者： eric Schumbera pablo Mier Miguel A.Andrade-Navarro Institute of Organismic and Molecular evolution Faculty of BiologyJohannes Gutenberg University of Mainz55128 MainzGermany

A recent study published in Science by Krypotou et al.reported the role of an intrinsically disordered region(IDR)in the transcription termination Rho protein from Bacteroides thetaiotaomicron:in response to starvation Rho phase separated,which triggered an increase in Rho activity and expression changes.1 These results demonstrate that a highly conserved protein can acquire new regulatory properties in evolution by gaining an IDR that leads to protein phase separation.

关键词： al. disordered separating

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Insects as alternative feed for ruminants:comparison of protein evaluation methods

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Journal of Animal Science and Biotechnology 2022年第4期13卷 1143-1150页

作者： pablo G.Toral Gonzalo Hervás Mariana Gabriela González-Rosales Alejandro G.Mendoza Lizbeth e.Robles-Jiménez Pilar Frutos Instituto de Ganadería de Montaña(CSIC-University of León) Finca Marzanas s/n24346 GrullerosLeónSpain Facultad de Medicina Veterinaria y Zootecnia Universidad Autónoma del Estado de MéxicoNo.100 Instituto Literario 100Col.Centro50000 TolucaEstado de MéxicoMexico.

Background:The high dependence of intensive ruminant production on soybean meal and the environmental impact of this crop encourage the search for alternative protein-rich feeds.The use of insects seems promising,but the extent of their ruminal protein degradation is largely unknown.This parameter has major influence not only on N utilization efficiency but also on the environmental burden of ruminant farming.In addition,although assessing ruminal N degradation represents a key first step to examine the potential of new feeds,it is a challenging task due to the lack of a reference method.This study was conducted to investigate the potential of 4 insects(Tenebrio molitor,Zophobas morio,Alphitobius diaperinus and Acheta domesticus)as alternative protein sources for ruminants,using 3 methodologies:1)a regression technique based on the in vitro relationship between gas production and ammonia-N concentration;2)a conventional in vitro technique of batch cultures of ruminal microorganisms,based on filtering the incubation residue through sintered glass crucibles;and 3)the in situ nylon bag technique.The in vitro intestinal digestibility of the non-degraded protein in the rumen was also determined.Soybean meal was used as a reference feedstuff.Results:Comparison of evaluation methods(regression,in vitro and in situ)did not allow to reliably select a single value of ruminal N degradation for the studied substrates,but all techniques seem to establish a similar ranking,with good correlations between methods,particularly between regression and in situ results.Regardless of the methodology,nitrogen from the 4 insects(with contents ranging from 81 to 112 g/kg of dry matter)did not show high ruminal degradation(41–76%),this value being always lower than that of soybean meal.Furthermore,the in vitro intestinal digestibility of non-degraded N was relatively high in all feeds(≥64%).Conclusion:Overall,these results support the potential of the 4 studied insects as alternative feedstuffs for ruminants.Among them,T.molitor showed th

关键词： In situ In vitro Livestock Nitrogen degradation Sheep

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