40 research outputs found
Molecular dynamics simulation of the phosphorylation-induced conformational changes of a tau peptide fragment
Aggregation of the microtubule associated protein tau (MAPT) within neurons of the brain is the leading cause of tauopathies such as Alzheimer's disease. MAPT is a phospho-protein that is selectively phosphorylated by a number of kinases in vivo to perform its biological function. However, it may become pathogenically hyperphosphorylated, causing aggregation into paired helical filaments and neurofibrillary tangles. The phosphorylation induced conformational change on a peptide of MAPT (htau225-250) was investigated by performing molecular dynamics simulations with different phosphorylation patterns of the peptide (pThr231 and/or pSer235) in different simulation conditions to determine the effect of ionic strength and phosphate charge. All phosphorylation patterns were found to disrupt a nascent terminal ß-sheet pattern (226VAVVR230 and 244QTAPVP249), replacing it with a range of structures. The double pThr231/pSer235 phosphorylation pattern at experimental ionic strength resulted in the best agreement with NMR structural characterization, with the observation of a transient α-helix (239AKSRLQT245). PPII helical conformations were only found sporadically throughout the simulations
Dics verticals dissipadors d'energia. Estudi d'una pala esmorteĂŻdora
Aquesta tesina pertany a l’à mbit de l’Enginyeria MarĂtima, i el seu objectiu principal Ă©s aportar nous coneixements sobre els dics verticals perforats, i les seves noves possibles aplicacions, com sĂłn la dissipaciĂł d’energia mareomotriu incident mitjançant la implantaciĂł d’una pala esmorteĂŻdora en el parament exterior del dic.
Aquesta estructura es basa en els clà ssics dics verticals, afegint la particularitat de que al parament exterior s’hi troba una paret mòbil que funciona com un pèndul invertit. El seu moviment s’utilitza per dissipar part de l’energia mareomotriu incident i aixà disminuir l’ona reflectida i les oscil·lacions del mar al parament exterior. Durant l’estudi es discutiran diferents formes de construir un dic d’aquestes qualitats intentant obtenir una combinació de propietats òptima dins de les múltiples opcions estudiades.
S’han realitzat uns assajos fĂsics (2009) al laboratori del LIM de la UPC, concretament al nou canal de generaciĂł d’onatge CIEMito. Aquest assajos sĂłn gran part del cos d’aquesta tesina, doncs sĂłn la base de l’estudi. A partir d’ells s’estudia la viabilitat o no d’aquest projecte d’investigaciĂł i la seva possible implantaciĂł en un futur en la façana mediterrĂ nia.
El document es divideix en tres grans parts: l’estat de l’art, els assajos fĂsics i les conclusions. A l’estat de l’art hi trobem dues parts diferenciades: la primera parla sobre els dics verticals en general de forma introductiva, per conduir al lector a la temĂ tica, i la segona tracta un estat de l’art mĂ©s especialitzat, centrat en els propis dics verticals perforats.
Els assajos fĂsics realitzats al laboratori del LIM conten amb una descripciĂł dels models utilitzats i una explicaciĂł dels assajos, aixĂ com la metodologia emprada. En aquests apartats s’explica exactament com s’ha realitzat tot el procediment d’experiments i obtenciĂł de dades.
Pel que fa a les conclusions, primerament s’analitzen les dades obtingudes durant els assajos i a partir d’aquests resultats es troba una combinació de propietats òptimes per al seu funcionament. De tot aquest raonament sorgeixen les conclusions.
Per calcular de forma quantitativa el funcionament d’aquests models s’ha emprat el concepte de Coeficient de reflexió, que relaciona l’alçada d’ona incident en una estructura de contenció amb l’alçada d’ona reflectida. D’aquesta forma es pot obtenir una quantificació tangible del bon o mal funcionament de l’estructura en termes de dissipació d’energia mareomotriu.
Als annexes de la tesina s’hi inclouen els resultats de tots els assajos realitzat per que es puguin observar els comportaments de cada tipus de dic sota la influència de les diverses condicions marĂtimes estudiades. Aquests annexes poden servir de base per a propers estudis
Projecte de l'EDAR i dels col·lectors en alta del municipi de Cabra del Camp (Alt Camp)
El present projecte es redacta amb la finalitat d’establir els criteris bà sics per a la definició de les obres de tractament més adequat de les aigües residuals de la
població de Cabra del Camp a la comarca de l’Alt Camp, que permeti abocar l’aigua
tractada complint amb els lĂmits establerts inalitat d’establir els criteris bĂ sics per a la definiciĂł de les obres de tractament mĂ©s adequat de les aigĂĽes residuals de la
població de Cabra del Camp a la comarca de l’Alt Camp, que permeti abocar l’aigua
tractada complint amb els lĂmits establerts per la Directiva 91/271 de 21 de maig
Challenges in bimetallic multilayer structure formation: Pt growth on Cu monolayers on Ru(0001)
In a joint experimental and theoretical study, we investigate the formation and morphology of PtCu/Ru(0001) bimetallic surfaces grown at room and higher temperatures under UHV conditions.</p
Heterogeneidad fenotĂpica en el Sistema de SecreciĂłn tipo III de Pseudomonas syringae durante la interacciĂłn con la planta
La heterogeneidad fenotĂpica es un fenĂłmeno que se ha descrito en poblaciones bacterianas de diversas especies. Un patrĂłn de expresiĂłn gĂ©nica heterogĂ©neo puede llegar a volverse bimodal en ambientes homogĂ©neos, proceso conocido como bistabilidad. El desarrollo de mĂ©todos de análisis de cĂ©lulas individuales, como la microscopĂa confocal, la citometrĂa o la microfluĂdica, ha llevado a la identificaciĂłn de nuevos ejemplos de variaciĂłn fenotĂpica y de biestabilidad. La relevancia de estos procesos se ha demostrado en patĂłgenos humanos y de animales. No obstante, se conoce muy poco sobre la relevancia de este tipo de procesos en el proceso de adaptaciĂłn a huĂ©spedes no animales.
P. syringae es una bacteria patĂłgena de plantas con un amplio rango de hospedador, existiendo más de 50 patovares. La virulencia de Pseudomonas syringae dependiende del Sistema de SecreciĂłn Tipo III (T3SS) y de los efectores tipo III (T3E). Mediante fusiones transcripcionales a proteĂnas fluorescentes generadas en el genoma de P. syringae pv. phaseolicola, y el uso de microscopĂa de fluorescencia y citometrĂa de flujo, nuestro laboratorio ha demostrado que la expresiĂłn del T3SS y de T3E es heterogĂ©nea en el interior de la planta y biestable en medio mĂnimo. En este trabajo presentamos los resultados obtenidos en nuestro análisis del impacto de la expresiĂłn heterogĂ©nea del T3SS para la adaptaciĂłn a la planta, que incluyen la evaluaciĂłn de la viabilidad de las variantes (T3SSON/T3SSOFF) en el apoplasto de la hoja, y de la dinámica de expresiĂłn en la poblaciĂłn en diferentes escenarios de activaciĂłn de defensa en la planta.Universidad de Málaga. Campus de Excelencia Internacional AndalucĂa Tech
Metilasas y metilación en la regulación génica de Pseudomonas syringae
La metilaciĂłn del ADN llevada a cabo por metilasas no asociadas a enzimas de restricciĂłn, conocidas como metilasas huĂ©rfanas, es un mecanismo epigenĂ©tico ampliamente extendido en bacterias y archeas. La especificidad de motivos y los patrones de metilaciĂłn de las metilasas huĂ©rfanas sugieren su participaciĂłn en la regulaciĂłn gĂ©nica y en la replicaciĂłn del ADN [1]. En E. coli y en Salmonella, este mecanismo se ha asociado a la regulaciĂłn del inicio de la replicaciĂłn, la reparaciĂłn de errores del ADN y la transcripciĂłn. En poblaciones clonales de dichas especies, la metilaciĂłn del ADN tambiĂ©n está implicada en la apariciĂłn de heterogeneidad fenotĂpica, con una fuerte implicaciĂłn en virulencia [2]. Sin embargo, poco se sabe del papel de la metilaciĂłn en Pseudomonas syringae. P. syringae es una importante bacteria fitopatĂłgena, responsable de una gran variedad de enfermedades de plantas y con un alto impacto en la producciĂłn agrĂcola a nivel mundial. Esta bacteria tambiĂ©n se usa frecuentemente como modelo para el estudio de las interacciones planta-patĂłgeno [3]. Con el objetivo de descifrar la importancia de la metilaciĂłn en P. syringae, nuestro grupo decidiĂł abordar la caracterizaciĂłn de este mecanismo epigenĂ©tico en dicho patĂłgeno. Para ello, se han estudiado las metilasas identificadas en P. syringae y se ha establecido su metiloma. Con respecto al metiloma, hemos identificado diversos motivos de metilaciĂłn.Universidad de Málaga. Campus de Excelencia Internacional AndalucĂa Tech
Phenotypically heterogeneous loci in the plant pathogen Pseudomonas syringae.
Phenotypic heterogeneity usually refers to the co-existance of different phenotypes within a population. Phenotypic differences may arise through genetic variation (genomic rearrangements or mutations) or through the response to differences in the stimuli as encountered within the microenvironment. But also, sometimes, the sources of variation may not be deterministic, i.e. directly related to stimuli, but a consequence of molecular noise in gene expression and/or a programmed event under genetic or epigenetic control. A particular example of phenotypic heterogeneity is bistability. Bistability occurs when a bacterial clonal population splits into two subpopulations showing distinct phenotypes. Phenotypic heterogeneity can be beneficial in fluctuating environments by allowing some individuals within the clonal population to survive sudden changes (risk-spreading). It can also benefit the entire population through cooperation between individuals displaying phenotypic differences (division of labour). These processes and their biological relevance have been described in some animal pathogens, but little is known about them in plant-pathosystems.
Pseudomonas syringae is a plant-pathogenic bacterium whose virulence depends on the expression of a type III secretion system (T3SS). Our team has previously reported that T3SS expression is bistable under inducing conditions, generating two subpopulations (T3SSON/T3SSOFF) that show differences in virulence. We have identified other loci including genes related to motility, biofilm formation and DNA methylation that also display phenotypic heterogeneity to very different degrees and with different dynamics and are at different stages on their molecular and biological characterization. Our latest advances on this front will be presented and discussed.Universidad de Málaga. Campus de Excelencia Internacional AndalucĂa Tech
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030