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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 Víctor 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 synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We 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 consolidation.The 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 process.In 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 competition.The 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 endings.We 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 terminals.The 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 synapses.Finally,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 reduce transmitter release and promote withdrawal o

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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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset silvera Alexander J.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi James D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neuro

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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The Administration of Ocoxin Increases the Quality of Life of Patients with Advanced Epithelial or Metastatic Ovarian Cancer Undergoing Neoadjuvant Chemotherapy

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Journal of Cancer Therapy 2022年第9期13卷 561-584页

作者： Karen López Miguel Daniel Ricardo Martínez Ávila Lliset Álvarez Pérez Gisselle Martínez Rabasa Alejandro Linchenat Lambert Roberto Esperón Noa Lisandra Heredia Manzano Margarita De Quesada Amigó Rafael I. Reyes Velázquez Danay Corrales Otero Ramon Ropero Toirac Idelmis Curbelo Heredia Mircea Betancourt Cabeza Tania A. Agrelo Ramos Rosa María Muñoz Reyes Juan Jesús Lence Anta Rosalía Fuentes Sosa karelia silvera candó Kirenia Silva Rodríguez Zaida Lastre Sosa Mayte Robaina García Eduardo Sanz David Marquez Department of Medical Oncology INOR La Habana Cuba Department of Gynaeco-Oncology INOR La Habana Cuba Department of Anatomical Pathology INOR La Habana Cuba Department of Imaging INOR La Habana Cuba Clinical Research Section INOR La Habana Cuba Department of Onco-Psychology INOR La Habana Cuba Clinical Laboratory Department INOR La Habana Cuba Clinical Trials Pharmacy Department INOR La Habana Cuba Department of Biostatistics CENCEC La Habana Cuba Scientific Department CATALYSIS Madrid Spain

Background: 70% of ovarian cancer cases are diagnosed at an advanced stage (III or IV) of the disease and, in turn, with a high prevalence of peritoneal carcinosis and ascites, which leads to progressive malnutrition in patients, with the consequent deterioration of their general condition. There is a very important relationship between nutritional status, quality of life, survival, and the ability to tolerate multidisciplinary treatment of peritoneal carcinosis. Methods: A phase II, open-label, single-center, non-randomised clinical trial was conducted that included 36 patients with advanced disease who were administered the nutritional supplement Ocoxin, 30 ml twice a day, beginning one week before chemotherapy (CT) based on carboplatin/paclitaxel, of which they receive three cycles with neoadjuvant intent. Ocoxin treatment was continued during chemotherapy and for three weeks after completion of the last cycle, as well as during any periods for which this treatment was discontinued due to toxicity. The effect of Ocoxin on the quality of life was assessed through the QLQ C30 and QLQ OV28 questionnaires from the start of treatment until the end of the follow-up period. In addition, the Karnofsky Index and nutritional parameters were assessed. Results: There were no significant differences between adverse events versus baseline values, except in leukocytes, lymphocytes, neutrophils, ALT, and AST. There was no deterioration of the QoL scales, except for those related to the effects of chemotherapy and alopecia. Conclusions: Ocoxin as an adjuvant to chemotherapy appears to improve better tolerance to chemotherapy, showed a good safety profile, and improved quality of life. For further information on Ocoxin neoadjuvant therapy benefits, a phase III clinical trial will be needed.

关键词： Chemotherapy Radiotherapy Ovarian Cancer Oncology Quality of Life Ad-juvant Therapy Supportive Care

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Improved Oil Recovery with Waterflooding,Infill Well Placement and Polymer Flooding in Oystein Reservoir

Improved Oil Recovery with Waterflooding,Infill Well Placeme...

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作者： Jeanice silvera EYANG ONIANE 中国石油大学(北京)

学位级别：硕士

目前的估计表明,成熟油田预计产量下降,可能在世界各地造成碳氢化合物供需之间的差距。尽管非常规油气储量巨大,但它们需要高能量和高能量才能开采石油,而新油田的开发变得复杂和昂贵。因此,人们越来越有兴趣开发高效和有效的改进石油... 详细信息

目前的估计表明,成熟油田预计产量下降,可能在世界各地造成碳氢化合物供需之间的差距。尽管非常规油气储量巨大,但它们需要高能量和高能量才能开采石油,而新油田的开发变得复杂和昂贵。因此,人们越来越有兴趣开发高效和有效的改进石油采收方法,以提高老化资源的采收率。本研究采用商业日食软件对三种IOR（注水,填充井和聚合物驱）模拟对比方法进行了讨论。主要目标是比较它们在回收率和净现值方面的表现。这种方法是使用由Uni CIPR综合石油研究中心首席研究员?ystein pettersen提供的油藏模拟样本数据的案例研。由于低渗透岩石和压力下降,该案例是一个油田遇到石油生产困难。为了解决这个问题,第一种方法是修改井筒中的局部储层压力（WBHP）。尽管石油采收率有所提高,但研究目标尚未完成。水被注入水库维持压力。结果轻微增加了石油产量。由于分配压力问题,储层的某些区域仍然会出现枯竭情况。然后进行网格细化研究,并在每个区域进行深入观察。此外,还增加了三家新的石油生产商（OP2,OP3和OP4）和两台新的注水器（WI2和WI3）。随着油井生产商和井注入量的增加,压力趋于稳定,石油产量增加。最后,使用聚合物驱油来了解可以回收多少油。对注水和聚合物驱油进行灵敏度分析,以执行适当的井注入,合适的组成和注入时间。最后,进行经济评估以确定哪种方法在净现值方面最有利可图。结果表明,就聚合物而言,我们使用高浓度聚合物并考虑到聚合物的升高速率,所以我们的NPV没有增加。

关键词：压力观测注水填充井位聚合物驱储层优化

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Changes in the Composition and Abundance of Phytoplankton in a Coastal Lagoon of Baja California,Mexico,during 2011

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Open Journal of Marine Science 2015年第2期5卷 169-181页

作者： María Fernanda Gracia-Escobar Roberto Millán-Núnez Enrique Valenzuela-Espinoza Adriana González-silvera Eduardo Santamaría-del-Angel Facultad de Ciencias Marinas Universidad Autónoma de Baja CaliforniaEnsenadaMéxico Instituto de Investigaciones Oceanológicas Universidad Autónoma de Baja CaliforniaEnsenadaMéxico

A time series with weekly sampling was conducted from February 20, to December 16, 2011 at a station in the interior of the San Quintín Bay to estimate seasonal changes in the composition and abundance of phytoplankton. Water temperature was recorded and the upwelling index was calculated for the period. Phytoplankton abundance was estimated and phytoplankton were identified by using an inverted microscope and the CHEMTAX program. There were 16 positive phytoplankton anomalies during the year, but only three were considered to be blooms. The blooms were dominated by diatoms and were recorded in the winter, spring and summer. Different genera composed 80% of the total phytoplankton abundance of each of the blooms. The first bloom consisted of diatoms of the genera Pseudo-nitzschia sp. (15.7%), Skeletonema sp. (14.6%), Eucampia sp. (7%), and Navicula sp. (7%);a haptophyte of the genus Imantonia sp. (13.1%);and dinoflagellates of the genus Prorocentrum sp. (4.6%). The second bloom consisted mainly of diatoms of the genera Guinardia sp. (30.6%), Pseudo-nitzschia sp. (21.5%), Skeletonema sp. (14.5%), Chaetoceros sp. (8.4%) and Eucampia sp. (5.3%). The third bloom consisted of Chaetoceros sp. (46.3%), Pseudo-nitzschia sp. (22.6%), Skeletonema sp. (7.29%), and Imantonia sp. (6%). Dinoflagellates were observed in the winter, summer and autumn, but they contributed less biomass than diatoms. Prorocentrum sp., Gymnodinium sp., and Ceratium sp. were among the dinoflagellates that were observed. The differences in abundance and composition of phytoplankton groups in the blooms in San Quintín Bay during 2011 were due primarily to seasonal changes in the physical and chemical factors of the seawater and to upwelling events.

关键词： Phytoplankton Bloom Pigments CHEMTAX Coastal Lagoon

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单原子氢——一种新的稳态气体

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真空与低温 1982年第1期 33-36页

作者： D.I.silvera 陈隆智

氢是最简单的化学元素,由一个质子和一个电子组成。原子氢是宇宙空间中最多的元素,不过,那里漫无边际,平均密度为1个原子/米~3。地球上的氢也很多,但是,只在诸如水或双原子分子氢中以分子形式存在。普通教科书的观点是:原子氢不能作为... 详细信息

氢是最简单的化学元素,由一个质子和一个电子组成。原子氢是宇宙空间中最多的元素,不过,那里漫无边际,平均密度为1个原子/米~3。地球上的氢也很多,但是,只在诸如水或双原子分子氢中以分子形式存在。普通教科书的观点是:原子氢不能作为中等密度的相对稳定(亚稳态)的气体而存在。我们阿姆斯特丹大学的研究小组不久前研制了一种获得稳态原子氢气体的工艺。已在几次实验中获得成功,为物理世界提供了一种陌生的新物质。早在上个世纪就知道的获得原子氢的一个方法是对氢气通电。电流使分子分解成中性原子并产生紫红色辉光放电。让光按波长而展开的分光光谱仪显示它由许多被叫做谱线的离散的颜色组成。解释单个氢原子光发射谱线遇到的困难曾导致1920年量子力学的发展,第二

关键词：原子氢合成分子超流性稳态

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分形分析改善胰腺导管腺癌CT肿瘤大小测量:与大体病理和多参数MRI的比较

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国际医学放射学杂志 2022年第5期 616-616页

作者： F.Michallek M.A.Haouari O.Dana A.Perrot S.silvera A.Dallongeville 徐璐

摘要目的肿瘤大小的测量对于胰腺导管腺癌（PDA）的肿瘤分期和病人划分至关重要。然而，由于不能准确显示肿瘤边缘，CT经常低估肿瘤大小。基于CT的分形维数（FD）

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Changes in the Abundance and Composition of Phytoplankton in a Coastal Lagoon during Neap-Spring Tide Conditions

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Open Journal of Marine Science 2014年第2期4卷 80-100页

作者： María Fernanda Gracia-Escobar Roberto Millán-Núnez Adriana González-silvera Eduardo Santamaría-del-Angel Víctor F.Camacho-Ibar Charles C.Trees Facultad de Ciencias Marinas Universidad Autónoma de Baja CaliforniaEnsenadaMéxico Instituto de Investigaciones Oceanológicas Universidad Autónoma de Baja CaliforniaEnsenadaMéxico NATO Undersea Research Centre La SpeziaItaly

The objective of this work was to estimate the changes in abundance and composition of phytoplankton in a coastal lagoon in Baja California, México during neap-spring tide conditions. Sampling was conducted from the 7th to the 16th of October 2004. Surface water was collected at 18 stations distributed across the bay during day time at high tide. Also, a time series was collected at a fixed station;surface water was collected every two hours from 8:00 to 18:00. High temperatures, low salinities and low nutrient concentrations at the oceanic end indicated weak or non upwelling conditions during this period. The phytoplankton community was characterized using an inverted microscope and the chemical taxonomy program CHEMTAX, based on pigment concentration estimated by high performance liquid chromatography (HPLC). The phytoplankton concentration was two times lower during this period than during periods of upwelling in the same year. Cryptophytes and diatoms were the most abundant groups estimated by CHEMTAX. Statistical analyses of the effect of tidal conditions on phytoplankton composition indicate that Zone A is strongly affected by tides, and that tidal effects are lessened at the inner zones. Differences in phytoplankton abundance between zones and between tidal conditions indicate that phytoplankton distribution is patchy in the lagoon.

关键词： Phytoplankton HPLC Pigments CHEMTAX Tides Coastal Lagoon

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The Italian ZECOMIX Platform: CO<sub>2</sub>Capture on Calcined Dolomite in Fluidized Bed Carbonator Unit

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Natural Resources 2014年第9期5卷 433-441页

作者： silvera Scaccia Stefano Stendardo Giuseppina Vanga Leandro Pagliari Stefano Cassani Mirko Nobili Giuseppe Messina Andrea Assettati Giuliano Guidarelli Salvatore Attanasi Caterino Stringola Andrea Grasso Ivano Cassani Antonio Calabró Pier Ugo Foscolo Department of Chemistry Chemical Engineering and Materials University of L’Aquila L’Aquila Italy Energy Efficiency UTEE-GRT ENEA-CCEI UMBRIA Perugia Italy Sustainable Combustion Laboratory (UTTEI-COMSO) C.R. ENEA Rome Italy

The Italian Zecomix platform is a gasification pilot-scale plant integrated CCS technology, whose flexibility allows operating each unit alone. For quantitative analysis of the gaseous species an analytical system based on commercially available instruments and sampling lines at various points of plant was properly designed. A Fourier Transform Infrared Spectrometric (FTIR) with portable low resolution and gas chromatographic tools were used. The fluidized bed calciner/ carbonator unit was fed with naturally occurring dolomite (about 300 kg) from quarry of Biella (Italy) and tested for CO2 capture. Carbonation reaction was conducted at around 700°C under simulated reformed synthesis gas containing 30% of CO2. Based on GC and FTIR results a CO2 retention better than 70% was achieved. The application of grain model establishing the carbonation reaction was kinetically controlled within 50 seconds and the reaction rate constant was comparable to that obtained at laboratory-scale level by thermogravimetric analyzer.

关键词： ZECOMIX Experimental Platform Dolomite CO2 Capture Fluidized Bed GC and FTIR Kinetics

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Variability in the Light Absorption Coefficient by Phytoplankton,Non-Algal Particles and Colored Dissolved Organic Matter in the Northern Gulf of California

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Open Journal of Marine Science 2018年第1期8卷 20-37页

作者： Stella P.Betancur-Turizo Adriana G.González-silvera Eduardo Santamaría-Del-Angel Roberto Millán-Núnez Eduardo Millán-Núnez Héctor García-Nava Víctor M.Godínez Laura Sánchez-Velasco Facultad de Ciencias Marinas Universidad Autonoma de Baja CaliforniaEnsenadaMéxico Grupo de Investigacion en Oceanología Facultad de Oceanografía FísicaEscuela Naval de Cadetes“Almirante Padilla”Barrio BosqueSector ManzanilloCartagena de IndiasColombia Departamento de Ecología Marina CICESEEnsenadaMéxico Instituto de Investigaciones Oceanológicas Universidad Autónoma de Baja CaliforniaEnsenadaMéxico Departamento de Oceanografía Física CICESEEnsenadaMéxico Departamento de Plancton y Ecología Marina CICIMAR-IPN.Av.Instituto Politécnico Nacional s/nLa PazMéxico

Variability of the optical properties of the northern Gulf of California (México) were analyzed for the first time based on six cruises performed from spring to summer (March to September) between 2008 and 2013. The changes observed in the absorption by three seawater components (phytoplankton, detritus and chromophoric dissolved organic matter or CDOM) were analyzed in relation to changes in bio-optical regions and composition of the phytoplankton community (determined based on phytoplankton pigments). Two regions with unique bio-optical characteristics were identified separated by a narrow transition zone: the Upper Gulf of California (UGC) and Northern Gulf of California (NGC). Despite the temporal changes in their spatial distribution they maintained particular characteristic. UGC is characterized by an average Chla of 1.78 mg/m3, the dominance of microphytoplankton (diatoms and dinoflagellates) and a stronger contribution of detritus to total light absorption. NGC is characterized by an average Chla of 0.7 mg/m3 and the predominance of picophytoplankton, characterized by the dominance of zeaxanthin (marker pigment for cyanobacteria) and/or chlorophyll b (marker pigment for green algae), along with a co-dominium by CDOM and phytoplankton to light absorption. Results indicate that Case II waters can be very different when evaluating the individual contribution by phytoplankton, detritus and CDOM to total light absorption what has to be considered for the selection of bio-optical models for each specific region what can also help to a better definition of the related uncertainties.

关键词： Light Absorption Phytoplankton CDOM Detritus Ocean Color Gulf of California

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