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The study of Carbamoyl Phosphate synthetase 1 Deficiency sheds Light on the Mechanism for switching On/Off the Urea Cycle

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Journal of Genetics and Genomics 2015年第5期42卷 249-260页

作者： Carmen Díez-Fernández José gallego Johannes H?berle Javier Cervera Vicente Rubio Institute for Biomedicine of Valencia of the spanish Research Council Medical school of the Catholic University of Valencia University Children's Hospital Zurich and Children's Research Center Centre for Biomedical Networking Research on Rare Diseases of the Carlos Ⅲ Health Institute

Carbamoyl phosphate synthetase i （CPs1） deficiency （CPs1D） is an inborn error of the urea cycle having autosomal （2q34） recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPs1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPs1 deficiency that map in the 20-kDa C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPs 1, N-acetyl- L-glutamate （NAG）, is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPs1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-L- glutamate （a registered drug, the analog of NAG）. Our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the 134-~4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPs1.

关键词： Urea cycle diseases Inborn errors Hyperammonemia site-directed mutagenesis Restrained molecular dynamics Allosteric regulation Carbamoyl phosphate synthetase 1 Enzyme

Indoor and outdoor BTX levels in Barcelona City metropolitan area and Catalan rural areas

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Journal of Environmental sciences 2008年第9期20卷 1063-1069页

作者： E. gallego F. X. Roca X. Guardino M. G. Rosell Environmental Centre Laboratory Polytechnic University of Catalonia (LCMA-UPC) National Centre of Work Conditions (INsHT)

Five aromatic hydrocarbons (benzene, toluene, and three isomeric xylenes) were monitored in indoor and outdoor air of 7 public buildings and 54 private homes, located in Barcelona City metropolitan area and in several rural areas of Catalonia. The sampling was carried out over four periods: spring-summer and winter of 2000, and summer and winter of 2001. Passive ORsA 5 Dra¨ger samplers were used for benzene, toluene, and xylenes (BTX) adsorption. BTX were extracted with carbon disulphide and analysed using ...

关键词： benzene toluene and xylenes (BTX) indoor air outdoor air

1D alignment of proteins and other nanoparticles by using reversible covalent bonds on cyclic peptide nanotubes

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Organic Chemistry Frontiers 2022年第5期9卷 1226-1233页

作者： Juan M.Priegue Iria Louzao Ivan gallego Javier Montenegro Juan R.Granja singular Research Centre in Chemical Biology and Molecular Materials (CIQUS)Organic Chemistry DepartmentUniversity of Santiago de Compostela(USC)15782 Santiago de CompostelaSpain

self-assembling cyclic peptide nanotubes are supramolecular structures whose diameter and external surface properties are precisely *** this communication we describe a general strategy to align different molecules on... 详细信息

关键词： nanoparticles alignment surface

An experimental study on the conversion between IFPUG and UCP functional size measurement units

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Journal of Zhejiang University-science C(Computers and Electronics) 2014年第3期15卷 161-173页

作者： Juan J.CUADRADO-gallego Alain ABRAN Pablo RODRíGUEZ-sORIA Miguel A.LARA Ecole de Technologie supérieure-ETs 1100 Notre-Dame Ouest Computer science Department University of Alcala

The use of functional size measurement(FsM) methods in software development organizations is growing during the years. Also, object oriented(OO) techniques have become quite a standard to design the software and, in particular, Use Cases is one of the most used techniques to specify functional requirements. Main FsM methods do not include specific rules to measure the software functionality from its Use Cases analysis. To deal with this issue some other methods like Kramer's functional measurement method have been developed. Therefore, one of the main issues for those organizations willing to use OO functional measurement method in order to facilitate the use cases count procedure is how to convert their portfolio functional size from the previously adopted FsM method towards the new method. The objective of this research is to find a statistical relationship for converting the software functional size units measured by the International Function Point Users Group(IFPUG) function point analysis(FPA) method into Kramer-smith's use cases points(UCP) method and vice versa. Methodologies for a correct data gathering are proposed and results obtained are analyzed to draw the linear and non-linear equations for this correlation. Finally, a conversion factor and corresponding conversion intervals are given to establish the statistical relationship.

关键词： software engineering Requirements analysis Functional size measurement Use cases analysis Object oriented Function point analysis Use cases points

study on Blood Cell Immune Response in Water Buffaloes Infected Acutely with F. hepatica

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Agricultural sciences in China 2002年第2期1卷 221-226页

作者： Award Daugschies J.Gonzalez-gallego Institute of Parasitology Hannover School of Veterinary Medicine Bunteweg 17 D-30559 Hannover GermanyDepartment of Physiology Pharmacology and Toxicology University of Leon Leon 24071 Spain

Action mechanism of blood cell immune response in water buffaloes against acute infection with F. Hepatica was studied. The results showed that after water buffaloes were infected, the total levels of WBC surpassed control group during whole infection period; Eosinophiles (%) of DC were higher than control group at the 2nd week until 19th week, and then dropped and was close to control group; Neutrophiles(%) was low or significantly lower than control group within the 5 - 16th weeks; The total levels of lymphocytes (%) was lower than control group during the whole infection period; T-lymphocytes (%) dropped significantly, but B-lymphocytes(%) had opposite changes from the first week of infection, and they were close to the control group after 11 weeks; RBC-CR] and RBC-IC rosette rates dropped and rose during 2 - 16 and 2-18 weeks, respectively, and then approached the same between both groups. It was suggested that the violent changes of specific and nonspecific immune responses in water buffaloes with acute F. hepatica infection are related with the mechanism against infection with F. hepatica together.

关键词： Water buffalo Fasciola hepatica Infection Blood cell Immune response

The first meteorological observations at a tropical high elevation site:Antisana,1846

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Journal of Mountain science 2016年第6期13卷 1047-1055页

作者： Aria Ma M.FARRONA Fernando DOMINGUEZ-CAsTRO Ma Cruz gallego Jose M.VAQUERO Departamento de Fisica Facultad de CienciasUniversidad de ExtremaduraBadajoz 06071Spain Instituto de Fisica de Cantabria(UC-CsIC) Santander 39005Spain Departamento de Ingenieria Civily Ambiental Escuela Politecnica NacionalQuito 170112Ecuador Instituto Nacional de Meteorologiae Hidrologia Quito 170135Ecuador instituto universitario de investigación del agua cambio climático y sostenibilidad (iacys) universidad de extremaduraBadajoz 06071，Spain departamento de física centro universitario de mérida universidad de extremaduraMerida 06800Spain

Antisana is a stratovolcano with an associated glacier located in the Ecuadorian Andes. Dr Aguirre made meteorological readings every day, at every hour from sunrise to sunset, from December 1845 to December 1846, at Antisana using a meteorological station at 4060 mamsl （meters above mean sea level）. Unfortunately, only the monthly average data have been preserved. These meteorological data are here studied and compared with the closest modern stations for monthly values of temperature, rainfall, and pressure. According to these comparisons, the year 1846 was rainy and cold in comparison with the current climate. Moreover, these observations have been useful to help resolve a debate about a possible E1Nifio event in 1846 with the high precipitation in Antisana and Quito in 1846 discarding the occurrence of an E1 Nifio event. The probable occurrence of a La Nifia event is discussed. These data are the earliest known systematic instrumental meteorological observations taken at above 4000 mamsl.

关键词： Early instrumental records Glacier Pastclimate conditions

Red cell distribution width in patients with HIV infection

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Open Journal of Internal Medicine 2012年第1期2卷 7-10页

作者： María L.gallego Isabel A.Pérez-Hernández Rosario Palacios Josefa Ruiz-Morales Enrique Nuno Manuel Márquez jesús santos Unidad de Gestión Clínica de Enfermedades Infecciosas Hospital Universitario Virgen de la VictoriaMálagaSpain

Objective: To examine the association between elevated levels of red cell distribution width (RDW) and cardiovascular risk factors (CVRF) and metabolic syndrome (Ms) in HIV-patients. Methods: Cross-sectional study including all asymptomatic HIV-outpatients under follow-up during 2007. Patients completed a questionnaire about CVRF, underwent a physical examination, and an 8-hour fasting blood analysis. Elevated RDW was defined as ≥75th percentile. Patients with and without an elevated RDW were compared. Results: 666 patients (79.3% men) were included: mean age 44.7 years, mean CD4 506/mm3 and 87.5% on antiretroviral therapy (85.3% with undetectable viral load). Mean RDW was 13.7% (range: 7.7% - 33.6%;75th percentile, 14.1%). The prevalence per quartile of Ms was 15.7%, 9.3%, 18.8% and 16.6% and of patients with CVRF > 20% was 8.4%, 4.0%, 4.4%, and 6.4%, respectively (p > 0.05);23.4% of the patients had an elevated RDW (>14.1%). The top percentile of RDW was associated with AIDs (OR 1.6;95% CI, 1.0 - 2.4;p = 0.02), detectable viral load (OR 1.5;95% CI, 1.01 - 2.4;p = 0.04) and hypertension (OR 2.3;95% CI, 1.4 - 4.0;p = 0.001). Conclusions: In HIV-outpatients, higher RDW is related with detectable viral load and with AIDs. Although it was associated with hypertension, we found no relation with Ms nor with higher cardiovascular risk.

关键词： HIV Red Cell Distribution Width Cardiovascular Risk Metabolic syndrome

Local renin angiotensin system and sperm DNA fragmentation

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Asian Journal of Andrology 2022年第2期24卷 139-146页

作者： María Victoria Aparicio Prieto María Victoria Rodríguez gallego Asier Valdivia Palacín Yosu Franco Iriarte Gotzone Hervás Barbara Enrique Echevarría Orella Luis Casis saenz Human Reproduction Unit Cruces University HospitalBarakaldo 48903Spain Human Reproduction Unit San Pedro HospitalLogroño 26006Spain Department of Physiology Faculty of Medicine and NursingUniversity of the Basque Country(UPV/EHU)Leioa 48940Spain Human Reproduction Unit Ruber International HospitalMadrid 28034Spain

The renin angiotensin system(RAs)appears to influence male fertility at multiple *** this work,we analyzed the relationship between the RAs and DNA *** male volunteers were divided into two groups(25 each):control(DNA fragmentation≤20%)and pathological(DNA fragmentation>20%)*** of five peptidases controlling RAs were measured fluorometrically:prolyl endopeptidase(which converts angiotensin[A]I and A II to A 1–7),neutral endopeptidase(NEP/CD10:A I to A 1–7),aminopeptidase N(APN/CD13:A III to A IV),aminopeptidase A(A II to A III)and aminopeptidase B(A III to A IV).Angiotensin-converting enzyme(A I to A II),APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays,as were the receptors of all RAs components:A II receptor type 1(AT1R),A II receptor type 2(AT2R),A IV receptor(AT4R or insulin-regulated aminopeptidase[IRAP]),(pro)renin receptor(PRR)and A 1–7 receptor or Mas receptor(MasR)None of the enzymes that regulate levels of RAs components,except for APN/CD13(decrease in fragmented cells),showed significant differences between both *** of RAs receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented *** of AT1R(94.3%normozoospermic vs 84.1%fragmented),AT4R(96.2%vs 95.3%)and MasR(97.4%vs 87.2%)was similar between the ***2R(87.4%normozoospermic vs 63.1%fragmented)and PRR(96.4%vs 48.2%)were higher in non-fragmented *** findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAs peptides.

关键词： DNA fragmentation local renin angiotensin system sperm fertility

Advancing 5G Network Applications Lifecycle security:An ML-Driven Approach

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Computer Modeling in Engineering & sciences 2024年第11期141卷 1447-1471页

作者： Ana Hermosilla Jorge gallego-Madrid Pedro Martinez-Julia Jordi Ortiz Ved P.Kafle Antonio skarmeta Information and Communications Engineering Department University of MurciaMurcia30100Spain Research&Development Department Odin Solutions S.L.Murcia30007Spain Network Architecture Laboratory Network Research InstituteNational Institute of Information and CommunicationsTokyo184-8795Japan Engineering and Applied Techniques Department University Center of Defense at the Spanish Air Force AcademyMurcia30729Spain

As 5th Generation(5G)and Beyond 5G(B5G)networks become increasingly prevalent,ensuring not only networksecurity but also the security and reliability of the applications,the so-called network applications,becomesof paramount *** paper introduces a novel integrated model architecture,combining a networkapplication validation framework with an AI-driven reactive system to enhance security in *** proposedmodel leverages machine learning(ML)and artificial intelligence(AI)to dynamically monitor and respond tosecurity threats,effectively mitigating potential risks before they impact the network *** dualapproach not only validates the functionality and performance of network applications before their real deploymentbut also enhances the network’s ability to adapt and respond to threats as they *** implementation ofthis model,in the shape of an architecture deployed in two distinct sites,demonstrates its practical viability *** application validation with proactive threat detection and response,the proposed modeladdresses critical security challenges unique to 5G *** paper details the model,architecture’sdesign,implementation,and evaluation of this solution,illustrating its potential to improve network securitymanagement in 5G environments *** findings highlight the architecture’s capability to ensure boththe operational integrity of network applications and the security of the underlying infrastructure,presenting asignificant advancement in network security.

关键词： Network application network function virtualization machine learning security 5G