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Design and redesign journey of a drug for transthyretin amyloidosis

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Neural Regeneration Research 2025年第4期20卷 1096-1097页

作者： Francisca Pinheiro salvador Ventura Institut de Biotecnologia i Biomedicina Departament de Bioquímica i Biologia MolecularUniversitat Autònoma de BarcelonaBellaterraSpain

The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as ***(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic *** systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the *** hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).

关键词： amyloid aggregation senile

Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría Javier García-Pardo salvador Ventura Institut de Biotecnologia i de Biomedicina(IBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

Relation between Mass and Radius of Exoplanets Distinguished by their Density

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Research in Astronomy and Astrophysics 2023年第6期23卷 47-55页

作者： alberto S.Betzler joséG.V.Miranda Centro de Ciência e Tecnologia em Energia e Sustentabilidade Universidade Federal do Recôncavo da BahiaFeira de SantanaBahia44.085-132Brazil Instituto de Fisica Universidade Federal da BahiaSalvadorBahia40.170-115Brazil

The formation of the solar system has been studied since the 18th century and received a boost in 1995 with the discovery of the first exoplanet,51 Pegasi *** investigations increased the number of confirmed planets to about5400 to *** possible internal structure and composition of these planets can be inferred from the relationship between planet mass and radius,*** have analyzed the M-R relation of a selected sample of iron-rock and ice-gas planets using a fractal approach to their *** application of fractal theory is particularly useful to define the physical meaning of the proportionality constant and the exponent in an empirical M-R power law in exoplanets,but this does not necessarily mean that they have an internal fractal *** M-R relations based on this sample are M=(1.46±0.08)R^(2.6±0.2)for the rocky population(3.6≤ρ≤14.3 g cm^(-3)),with 1.5≤M≤39M_(⊕),and M=(0.27±0.04)R^(2.7±0.2)for ice-gas planets(0.3≤ρ≤2.1 g cm^(-3))with 5.1≤M≤639 M_(⊕)(or■2 M_(J))and orbital periods greater than 10 *** M-R relations have in their density range a great predictive power for the determination of the mass of exoplanets and even for the largest icy moons of the solar *** average fractal dimension of these planets is D=2.6±0.1,indicating that these objects likely have a similar degree of heterogeneity in their densities and a nearly similar composition in each *** M-R diagram shows a"gap"between ice-gas and iron-rock *** gap is a direct consequence of the density range of these two *** empirically propose an upper mass limit of about 100 M_(⊕),so that an M-R relation for ice-gas planets in a narrow density range is defined by M∝R^(3).

关键词： planets and satellites:formation planets and satellites:terrestrial planets planets and satellites:gaseous planets

Optimizing urban traffic control using a rational agent

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Journal of Zhejiang University-Science C(Computers and Electronics) 2014年第12期15卷 1123-1137页

作者： salvador IBARRA-MARTíNEZ josé A.CASTN-ROCHA Julio LARIA-MENCHACA Engineering School Autonomous University of Tamaulipas

This paper is devoted to developing and evaluating a set of technologies with the objective of designing a methodology for the implementation of sophisticated traffic lights by means of rational agents. These devices would be capable of optimizing the behavior of a junction with multiple traffic signals, reaching a higher level of autonomy without losing reliability, accuracy, or efficiency in the offered services. In particular, each rational agent in a traffic signal will be able to analyze the requirements and constraints of the road, in order to know its level of demand. With such information, the rational agent will adapt its light cycles with the view of accomplishing more fluid traffic patterns and minimizing the pollutant environmental emissions produced by vehicles while they are stopped at a red light, through using a case-based reasoning(CBR) adaptation. This paper also integrates a microscopic simulator developed to run a set of tests in order to compare the presented methodology with traditional traffic control methods. Two study cases are shown to demonstrate the efficiency of the introduced approach, increasing vehicular mobility and reducing harmful activity for the environment. For instance, in the first scenario, taking into account the studied traffic volumes, our approach increases mobility by 23% and reduces emissions by 35%. When the roads are managed by sophisticated traffic lights, a better level of service and considerable environmental benefits are achieved, demonstrating the utility of the presented approach.

关键词： Rational agents Traffic light control Optimization Traffic mobility

What is the prognosis of emphysematous pyelonephritis associated with extended-spectrum beta-lactamases producing microorganisms?

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Asian Journal of Urology 2022年第2期9卷 146-151页

作者： joséIván Robles-Torres Marco alberto Ocaña-Munguía joséGustavo Arrambide-Herrera Adrián Mauricio Martínez-Fernández Rodrigo Romero-Mata Lauro salvador Gómez-Guerra Urology Department Hospital Universitario"Dr.Jose´Eleuterio Gonza´lez"Universidad Auto´noma de Nuevo LeonMonterreyNuevo LeonMexico

Objective:To describe the microbiological characteristics in emphysematous pyelonephritis(EPN),demonstrate the frequency of extended-spectrum beta-lactamase(ESBL)microorganisms,and determine if these microorganisms are associated with the prognosis of patients with ***:We conducted a retrospective study in patients with a diagnosis of EPN in a tertiary care hospital of the northeast region of Mexico during the period from January 2011 to January *** variables were analyzed to determine association with the presence of ESBL-producing *** significance was set with p<***:A total of 63 patients were included;55(87.3%)of them were females,with a median age of 55(interquartile range:45-65)*** management was indicated in 38.1%;42.9%were treated with ureteral stent;12.7%with open or percutaneous drainage;15.8%with early nephrectomy;and 9.5%with delayed *** mortality was 13(20.6%)cases;23(36.5%)cases required admission to the intensive care *** most frequent microorganism isolated was Escherichia coli(n=34,53.9%).ESBL microorganisms were found in 31.7%of the *** significant association of ESBL was found with admission to the intensive care unit,or with increased ***:To our knowledge,this is the first study that evaluates ESBL microorganisms as a prognostic factor in *** factors associated with a poor prognosis in patients with EPN have been *** microbiological factors,specifically ESBL-producing bacteria,do not seem to influence in the prognosis of these patients.

关键词： Emphysematous pyelonephritis Extended spectrum betalactamase Mortality Intensive care unit admission

Denervated muscle extract promotes recovery of muscle atrophy through activation of satellite cells. An experimental study

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Journal of Sport and Health Science 2019年第1期8卷 23-31页

作者： Eduardo Aguera salvador Castilla Evelio Luque Ignacio Jimena Ignacio Ruz-Caracuel Fernando Leiva-Cepas jos Pea Department of Neurology Maimonides Institute for Biomedical Research IMIBIC Reina Sofia University Hospital University of Cordoba Department of Critical Care and Emergency Reina Sofia University Hospital University of Cordoba Department of Morphological Sciences Section of Histology Faculty of Medicine and Nursing Maimonides Institute for Biomedical Research IMIBICReina Sofia University Hospital University of Cordoba

Purpose: The objective of the present study was to determine whether a denervated muscle extract(DmEx) could stimulate satellite cell response in denervated ***: Wistar rats were divided into 4 groups: normal rats, normal rats treated with DmEx, denervated rats, and denervated rats treated with DmEx. The soleus muscles were examined using immunohistochemical techniques for proliferating cell nuclear antigen, desmin, and myogenic differentiation antigen(MyoD), and electron microscopy was used for analysis of the satellite ***: The results indicate that while denervation causes activation of satellite cells, DmEx also induces myogenic differentiation of cells localized in the interstitial space and the formation of new muscle fibers. Although DmEx had a similar effect in nature on innervated and denervated muscles, this response was of greater magnitude in denervated vs. intact ***: Our study shows that treatment of denervated rats with DmEx potentiates the myogenic response in atrophic denervated muscles.

关键词： Muscle atrophy Muscle denervation Muscle extract Myogenic response Satellite cell Skeletal muscle

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

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World Journal of Gastroenterology 2006年第9期12卷 1367-1372页

作者： Francisco Eizayaga Camila Scorticati Juan P Prestifilippo salvador Romay Maria A Fernandez josé L Castro Abraham Lemberg Juan C Perazzo Laboratory of Portal Hypertension Department of Pathophysiology School of Pharmacy and BiochemistryUniversity of Buenos AiresBuenos AiresArgentina Catedra de Farmacología School of Pharmacy and Biochemistry University of Buenos Aires Buenos Aires Argentina Laboratory of Portal Hypertension Department of Pathophysiology School of Pharmacy and Biochemistry University of Buenos Aires Buenos AiresArgentina

AIM： To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 dafer ligation when portal pressure is spontaneously normalized. METHODS： Adult male Wistar rats were divided into four groups： Group Ⅰ： Sham14d, sham operated; Group Ⅱ： PHil, portal vein stenosis, （both groups were used 14 days after surgery）; Group Ⅲ： Sham4od, Sham operated and Group Ⅳ： PH4od Portal vein stenosis （Groups Ⅱ and Ⅳ used 40 d afer surgery）. Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS： Forty days afer stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION： The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.

关键词： Blood-brain barrier Rats Prehepatic portal hypertension

ddRAD sequencing-based genotyping for population structure analysis in cultivated tomato provides new insights into the genomic diversity of Mediterranean‘da serbo’type long shelf-life germplasm

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Horticulture Research 2020年第1期7卷 1047-1060页

作者： Salvatore Esposito Teodoro Cardi Gabriele Campanelli Sara Sestili María joséDíez salvador Soler Jaime Prohens Pasquale Tripodi CREA Research Centre for Vegetable and Ornamental Crops Pontecagnano(SA)Italy CREA Research Centre for Vegetable and Ornamental Crops Monsampolo del Tronto(AP)TrontoItaly Instituto de Conservación y Mejora de la Agrodiversidad Valenciana Universitat Politècnica de València46022 ValenciaSpain

Double digest restriction-site associated sequencing(ddRAD-seq)is a flexible and cost-effective strategy for providing in-depth insights into the genetic architecture of germplasm *** this methodology,we investigated the genomic diversity of a panel of 288 diverse tomato(Solanum lycopersicum L.)accessions enriched in‘da serbo’(called‘de penjar’in Spain)long shelf life(LSL)materials(152 accessions)mostly originating from Italy and *** rest of the materials originate from different countries and include landraces for fresh consumption,elite cultivars,heirlooms,and breeding *** from their LSL trait,‘da serbo’landraces are of remarkable interest for their *** identified 32,799 high-quality SNPs,which were used for model ancestry population structure and non-parametric hierarchical *** genetic subgroups were revealed,clearly separating most‘da serbo’landraces,but also the Spanish germplasm,suggesting a subdivision of the population based on type and geographical *** disequilibrium(LD)in the collection decayed very rapidly within<5 *** then investigated SNPs showing contrasted minor frequency allele(MAF)in‘da serbo’materials,resulting in the identification of high frequencies in this germplasm of several mutations in genes related to stress tolerance and fruit maturation such as CTR1 and ***,a mini-core collection of 58 accessions encompassing most of the diversity was selected for further exploitation of key *** findings suggest the presence of a genetic footprint of the‘da serbo’germplasm selected in the Mediterranean ***,we provide novel insights on LSL‘da serbo’germplasm as a promising source of alleles for tolerance to stresses.

关键词： germplasm breeding shelf

Chaotic Lid-Driven Square Cavity Flows at Extreme Reynolds Numbers

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Communications in Computational Physics 2014年第3期15卷 596-617页

作者： salvador Garcia Instituto de Ciencias Fisicas y Matematicas Universidad Austral de ChileCasilla 567ValdiviaChile

This paper investigates the chaotic lid-driven square cavity flows at extreme Reynolds *** observations have been made from this ***,at extreme Reynolds numbers two principles add at the genesis of tiny,loose counterclockwise-or clockwise-rotating *** concerns the arousing of them owing to the influence of the clockwise-or counterclockwise currents nearby;the other,the arousing of counterclockwise-rotating eddies near attached to the moving(lid)top wall which moves from left to ***,unexpectedly,the kinetic energy soon reaches the qualitative temporal limit’s pace,fluctuating briskly,randomly inside the total kinetic energy range,fluctuations which concentrate on two distinct fragments:one on its upper side,the upper fragment,the other on its lower side,the lower fragment,switching briskly,randomly from each other;and further on many small fragments arousing randomly within both,switching briskly,randomly from one *** the Reynolds number Re→∞,both distance and then close,and the kinetic energy fluctuates shorter and shorter at the upper fragment and longer and longer at the lower fragment,displaying tall high spikes which enlarge and then *** the time t→∞(at the Reynolds number Re fixed)they recur from time to time with roughly the same *** the most part,at the upper fragment the leading eddy rotates clockwise,and at the lower fragment,in stark contrast,it rotates *** Re=109 the leading eddy-at its qualitative temporal limit’s pace—appears to rotate solely counterclockwise.

关键词： Navier-Stokes equations lid-driven square cavity flows chaos