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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs v.ctor Cilleros-mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura Nadal marta Tomàs Carolina Silvera-Simón manel m.Santafé maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Pathological aspects of so called "hilar cholangiocarcinoma"

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World Journal of Gastrointestinal Oncology 2013年第7期5卷 159-170页

作者： v.ctor m castellano-megías Carolina Ibarrola-de Andrés Francisco Colina-Ruizdelgado Department of Pathology Hospital Universitario de Fuenlabrada28041 MadridSpain. Department of Pathology Hospital Universitario "12 de Octubre"28041 MadridSpain.

Cholangiocarcinoma(CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a ***,"hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or,more commonly,the extrahepatic hilar ***,a major distinction can be made between papillary and non-papillary ***,most hilar CCs are well to moderately differentiated conventional type(biliary) ***,CK7,CK20,CEA and mUC1 are normally expressed,being mUC2 positive in less than 50% of *** main premalignant lesions are known:biliary intraepithelial neoplasia(BilIN) and intraductal papillary neoplasm of the biliary tract(IPNB).IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma.A series of 29 resected hilar CC from our archives is ***(82.8%) were conventional type adenocarcinomas,mostly well to moderately differentiated,although with a broad morphological spectrum;three cases exhibited a poorly differentiated cell component resembling signet ring *** was observed in 5(17.2%),four of them with an associated invasive carcinoma.A clear cell type carcinoma,an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

关键词： Cholangiocarcinoma Bile duct carcinoma Hilar cholangiocarcinoma Perihilar cholangiocarcinoma Klatskin tumor Extrahepatic bile duct carcinoma Hepatic hilum

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Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas

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World Journal of Gastrointestinal Oncology 2014年第9期6卷 311-324页

作者： v.ctor m castellano-megías Carolina Ibarrola-de Andrés Guadalupe López-Alonso Francisco Colina-Ruizdelgado Department of Pathology Hospital Universitario de Fuenlabrada Department of Pathology Hospital Universitario "12 de Octubre"

Intraductal papillary mucinous neoplasm(IPmN) of the pancreas is a noninvasive epithelial neoplasm of mucinproducing cells arising in the main duct(mD) and/or branch ducts(BD) of the *** ducts are dilated and filled with neoplastic papillae and mucus in variable *** lacks ovarian-type stroma,unlike mucinous cystic neoplasm,and is defined as a grossly visible entity(≥ 5 mm),unlike pancreatic intraepithelial *** the use of high-resolution imaging techniques,very small IPmNs are increasingly being *** IPmNs are solitary and located in the pancreatic head,although 20%-40% are *** classification in mD type,BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management *** on cytoarchitectural atypia,IPmN is classified into low-grade,intermediategrade and high-grade *** on histological features and mucin(mUC) immunophenotype,IPmNs are classified into gastric,intestinal,pancreatobiliary and oncocytic *** different phenotypes can be observed together,with the IPmN classified according to the predominant *** pathways have been suggested:gastric phenotype corresponds to less aggressive uncommitted cells(mUC1-,mUC2-,mUC5 AC +,mUC6 +) with the capacity to evolve to intestinal phenotype(intestinal pathway)(mUC1-,mUC2 +,mUC5 AC +,mUC6- or weak +) or pancreatobiliary /oncocytic phenotypes(pyloropancreatic pathway)(mUC1 +,mUC 2-,mUC5 AC +,mUC 6 +) becoming more *** of IPmN is excellent but critically worsens when invasive carcinoma arises(about 40% of IPmNs),except in some cases of minimal *** clinical challenge is to establish which IPmNs should be removed because of their higher risk of developing invasive *** resected,they must be extensively sampled or,much better,submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.

关键词： mucinous pancreatic cysts Intraductal papillary mucinous neoplasm main duct intraductal papillary mucinous neoplasm Branch duct intraductal papillary mucinous neoplasm mucins

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Bedrock outcropping in the accumulation zone of the largest glacier in mexico(Glaciar Norte of Citlaltépetl),as evidence of a possible accelerated extinction

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Journal of mountain Science 2023年第2期20卷 338-354页

作者： SOTO v.ctor Colegio de Geografía Facultad de EconomíaUniversidad VeracruzanaAv.Xalapa s/nObrero Campesina91020XalapaVer.México

The highest volcano in mexico,at the same time the third largest mountain in North America(Citlaltépetl,5610 m a.s.l.),is home to the largest glacier in the *** of the extinction of the Popocatépetl glacier(5500 m a.s.l.)caused by eruptive activity,and the almost disappearance of the Iztaccíhuatl glaciers(5220 m a.s.l.)due to the lower elevation of the mountain,the Glaciar Norte of Citlatépetl has been the only glacier that has shown a certain degree of stability as a response to the altitude in which it is ***,as occurs in almost all glaciers on the planet,the retreat of its glacier terminus has been ***,during the last years the thickness of its upper part began to decrease rapidly until its bedrock was exposed for the first time in *** to its ecosystem importance and because it is the main glacier in mexico,as well as the only one in the world located at latitude 19°N,in this work its current dimensions are updated,as well as the local climatology that governs the current state of the glacier is pointed *** study was based on the analysis of high-resolution Sentinel-2 optical images,as well as through Sentinel-1 SAR images,with the support of climatological information from the study ***,the outcropping of the bedrock in the accumulation zone and the consequent horizontal retreat of the upper part of the glacier are documented;at the same time,the decrease in the thickness of the ice along it is *** rocky outcrop in the accumulation zone suggests that the flow dynamics of the ice towards the ablation zone will be considerably less,accelerating the retreat of the glacier ***,the ascent of the glacial front to 5102 m *** the modelled altitude of the equilibrium line to 5276 m *** reported as a warning signal in terms of snow catchment and mass balance;likewise,the decrease of 23%of its surface is also indicated regarding the surface reduction monitoring that has been done

关键词： Bedrock outcrop Citlaltépetl glacier Glacial accumulation zone Glacier retreat Glacial thickness

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Risk of cancer,with special reference to extra-intestinal malignancies,in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2013年第48期19卷 9359-9365页

作者： Alicia Algaba Iván Guerra ngel Castao Gema de la Poza v.ctor m castellano montserrat López Fernando Bermejo Department of Gastroenterology Hospital Universitario de Fuenlabrada 28942 Madrid Spain Department of Pathology Hospital Universitario de Fuenlabrada28942 Madrid Spain

AIm:To determine the incidence and characteristics of intestinal and extra-intestinal cancers among patients with inflammatory bowel disease in a Spanish hospital and to compare them with those of the local ***:This was a prospective,observational,7-year follow-up,cohort *** incidence,incidence rates based on person-years of follow-up and relative risk were calculated for patients with inflammatory bowel disease and compared with the background *** incidence of cancer was determined using a hospital-based data registry from Hospital Universitario de *** data and details about time from diagnosis of inflammatory bowel disease to occurrence of cancer,disease extent,inflammatory bowel disease treatment,cancer therapy and cancer evolution were also collected in the inflammatory bowel disease ***:Eighteen of 590 patients with inflammatory bowel disease developed cancer[cumulative incidence=3%(95%CI:1.58-4.52)vs 2%(95%CI:1.99-2.11)in the background population;RR=1.5;95%CI:0.97-2.29].The cancer incidence among inflammatory bowel disease patients was 0.53%(95%CI:0.32-0.84)per patient-year of *** with inflammatory bowel disease had a significantly increased relative risk of urothelial carcinoma(RR=5.23,95%CI:1.95-13.87),appendiceal mucinous cystadenoma(RR=36.6,95%CI:7.92-138.4),neuroendocrine carcinoma(RR=13.1,95%CI:1.82-29.7)and rectal carcinoid(RR=8.94,95%CI:1.18-59.7).Colorectal cancer cases were not ***:The overall risk of cancer did not significantly increase in our inflammatory bowel disease ***,there was an increased risk of urinary bladder cancer and,with less statistical power,an increased risk of appendiceal mucinous cystadenoma and of neuroendocrine *** cancer risk was low in our series.

关键词： Extra-intestinal cancer Inflammatory bowel disease Cancer risk Background population Urothelial carcinoma Appendiceal mucinous cystadenoma Neuroendocrine carcinoma Rectal carcinoid

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Current status of the genetic susceptibility in attenuated adenomatous polyposis

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World Journal of Gastrointestinal Oncology 2019年第12期11卷 1101-1114页

作者： v.ctor Lorca Pilar Garre Laboratorio de Oncología molecular Grupo de Investigación Clínica y Traslacional en OncologíaHospital Clínico San CarlosMadrid 28040Spain Laboratorio de Oncología molecular Servicio de OncologíaHospital Clínico San CarlosMadrid 28040Spain

Adenomatous polyposis(AP)is classified according to cumulative adenoma number in classical AP(CAP)and attenuated AP(AAP).Genetic susceptibility is the major risk factor in CAP due to mutations in the known high predisposition genes APC and ***,the contribution of genetic susceptibility to AAP is lower and less *** predisposition genes have been recently proposed,and some of them have been validated,but their scarcity hinders accurate risk estimations and prevalence *** is a heterogeneous condition in terms of severity,clinical features and ***,clinicians do not have strong discriminating criteria for the recommendation of the genetic study of known predisposition genes,and the detection rate is *** and knowledge of new AAP high predisposition genes are of great importance to offer accurate genetic counseling to the patient and family *** review aims to update the genetic knowledge of AAP,and to expound the difficulties involved in the genetic analysis of a highly heterogeneous condition such as AAP.

关键词： Attenuated adenomatous polyposis Genetic susceptibility High predisposition gene Genetic heterogeneity Colorectal cancer

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Freeze-thaw cycles and associated geomorphology in a post-glacial environment:current glacial,paraglacial,periglacial and proglacial scenarios at Pico de Orizaba volcano,mexico

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Journal of mountain Science 2024年第6期21卷 1954-1977页

作者： v.ctor SOTO Carlos m.WELSH R. Kenji YOSHIKAWA Hugo DELGADO GRANADOS Centro de Ciencias de la Tierra Universidad VeracruzanaCircuito Gonzalo Aguirre BeltránS/NZona Universitaria91090XalapaMéxico Water and Environmental Research Center University of Alaska FairbanksFairbanksAlaska 99775USA Instituto de Geofísica Universidad Nacional Autónoma de MéxicoCiudad de México 04150México Department of Earth and Environmental Sciences Ludwig Maximilians UniversitätMunich 80333Germany

The glacial history of Pico de Orizaba indicates that during the Last Glacial maximum,its icecap covered up to~3000 m asl;due to the air temperature increasing,its main glacier has retreated to 5050 m *** retraction of the glacier has left behind an intense climatic instability that causes a high frequency of freeze-thaw cycles of great intensity;the resulting geomorphological processes are represented by the fragmentation of the bedrock that occupies the upper parts of the *** is a notable lack of studies regarding the fragmentation and erosion occurring in tropical high mountains,and the associated geomorphological risks;for this reason,as a first stage of future continuous research,this study analyzes the freezing and thawing cycles that occur above 4000 m asl,through continuous monitoring of surface ground *** results allow us to identify and characterize four zones:glacial,paraglacial,periglacial and *** was found that the paraglacial zone presents an intense drop of temperature,of up to~9℃ in only sixty *** rock fatigue and intense freeze-thaw cycles that occur in this area are responsible for the high rate of rock disintegration and represent the main factor of the constant slope dynamics that occur at the *** activity decreases,both in frequency and intensity,according to the distance to the glacier,which is where the temperature presents a certain degree of stability,until reaching the proglacial zone,where cycles are almost non-existent,and therefore there is no gelifraction *** geomorphological processes have resulted in significant alterations to the mountain slopes,which can have severe consequences in terms of risk and water.

关键词： Freeze-Thaw Gelifraction mountain mechanical erosion Periglacial geomorphology Postglacial scenarios

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Complete fuzzy scheduling and fuzzy earned value management in construction projects

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2012年第1期13卷 56-68页

作者： José Luís PONZ-TIENDA Eugenio PELLICER v.ctor YEPES School of Building Engineering Universitat Politècnica de València School of Civil Engineering Universitat Politècnica de València Department of Construction Engineering ICITECHUniversitat Politècnica de València

This paper aims to present a comprehensive proposal for project scheduling and control by applying fuzzy earned *** goes a step further than the existing literature:in the formulation of the fuzzy earned value we consider not only its duration,but also cost and production,and alternatives in the scheduling between the earliest and latest *** mathematical model is implemented in a prototypical construction project with all the estimated values taken as fuzzy *** findings suggest that different possible schedules and the fuzzy arithmetic provide more objective results in uncertain environments than the traditional *** proposed model allows for controlling the vagueness of the environment through the adjustment of the α-cut,adapting it to the specific circumstances of the project.

关键词： Construction Earned value method(Evm) Fuzzy logic Fuzzy set Project management Scheduling

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Proteomic dynamics revealed sex-biased responses to combined heat-drought stress in marchantia

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Journal of Integrative Plant Biology 2024年第10期66卷 2226-2241页

作者： Sara Guerrero v.ctor Roces Lara García-Campa Luis valledor mónica meijón Department of Organisms and Systems BiologyFaculty of Biology/BiotechnologyInstitute of AsturiasUniversity of OviedoOviedoAsturias 33071Spain

Recent studies have documented plant responses to climate change extensively, particularly to single-stress exposures. However, critical factors for stress survival, such as sexual differentiation,are not often considered. The dioicous marchantia polymorpha stands as an evolutionary milestone,potentially preserving ancestral traits from the early colonizers. In this study, we employed proteomic analyses complemented with physiological monitoring to investigate combined heat and drought responses in Tak-1(male) and Tak-2(female)accessions of this liverwort. Additionally, targeted transcriptomics was conducted using different natural populations from contrasting *** findings revealed sex-biased dynamics among natural accessions, particularly evident under control conditions and during early stress responses. Although Tak-2 exhibited greater diversity than Tak-1 under control conditions, male accession demonstrated distinct and more rapid stress sensing and signaling. These differences in stress response appeared to be strongly related to sex-specific plasticity influenced by geoclimatic origin. Furthermore, we established distinct protein gene ages and genomic distribution trends, underscoring the importance of protein diversification over time. This study provides an evolutionary perspective on sexual divergence and stress emergence employing a systems biology approach, which allowed for the establishment of global and sex-specific interaction networks in the stress response.

关键词： abiotic stress land adaptation liverwort sex-biased response systems biology

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Discretized miller approach to assess effects on boundary layer ingestion induced distortion

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Chinese Journal of Aeronautics 2017年第1期30卷 235-248页

作者： Esteban valencia v.ctor Hidalgo Devaiah Nalianda Laskaridis Panagiotis Riti Singh Departamento de Ingeniería mecánica Facultad de Ingeniería Mecánica Escuela Politécnica Nacional Ladron de Guevara E11-253 Quito 17-01-2759 Ecuador School of Engineering Cranfield University Bedford MK430AL United Kingdom

The performance of propulsion configurations with boundary layer ingestion（BLI） is affected to a large extent by the level of distortion in the inlet flow field. Through flow methods and parallel compressor have been used in the past to calculate the effects of this aerodynamic integration issue on the fan performance; however high-fidelity through flow methods are computationally expensive, which limits their use at preliminary design stage. On the other hand, parallel compressor has been developed to assess only circumferential distortion. This paper introduces a discretized semi-empirical performance method, which uses empirical correlations for blade and performance calculations. This tool discretizes the inlet region in radial and circumferential directions enabling the assessment of deterioration in fan performance caused by the combined effect of both distortion patterns. This paper initially studies the accuracy and suitability of the semiempirical discretized method by comparing its predictions with CFD and experimental data for a baseline case working under distorted and undistorted conditions. Then a test case is examined,which corresponds to the propulsor fan of a distributed propulsion system with BLI. The results obtained from the validation study show a good agreement with the experimental and CFD results under design point conditions.

关键词： BLI Correlations Distortion Embedded propulsors Empirical mean-line analysis Turbomachinery

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