Successful object encoding induces increased directed connectivity in presymptomatic early-onset Alzheimer's disease

Background: Recent studies report increases in neural activity in brain regions critical to episodic memory at preclinical stages of Alzheimer’s disease (AD). Although electroencephalography (EEG) is widely used in AD studies, given its non-invasiveness and low cost, there is a need to translate the findings in other neuroimaging methods to EEG. Objective: To examine how the previous findings using functional magnetic resonance imaging (fMRI) at preclinical stage in presenilin-1 E280A mutation carriers could be assessed and extended, using EEG and a connectivity approach. Methods: EEG signals were acquired during resting and encoding in 30 normal cognitive young subjects, from an autosomal dominant early-onset AD kindred from Antioquia, Colombia. Regions of the brain previously reported as hyperactive were used for connectivity analysis. Results: Mutation carriers exhibited increasing connectivity at analyzed regions. Among them, the right precuneus exhibited the highest changes in connectivity. Conclusion: Increased connectivity in hyperactive cerebral regions is seen in individuals, genetically-determined to develop AD, at preclinical stage. The use of a connectivity approach and a widely available neuroimaging technique opens the possibility to increase the use of EEG in early detection of preclinical AD.Postprint (author's final draft

Interactions of P1B, the silencing suppressor protein from Cucumber Vein Yellowing Virus, with plant factors that contribute to its biological functions.

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 11-01-2016Esta tesis tiene embargado el acceso al texto completo hasta el 11-07-201

Quantum hobbit routing: Annealer implementation of generalized Travelling Salesperson Problem

In this paper, we present an implementation of a Job Selection Problem (JSP) -- a generalization of the well-known Travelling Salesperson Problem (TSP) -- of $N=9$ jobs on its Quadratic Unconstrained Binary Optimization (QUBO) form, using $\mathcal{O}(N)$ qubits on DWave's Advantage$\_$system4.1 quantum annealing device. The best known quantum algorithm for TSP to date uses $\mathcal{O}(N^2)$ qubits. A solution is found using the quantum method. However, since hardware is not yet able to compensate the increase in search-space size, no present overall advantage is achieved when comparing the quantum results with either exhaustive or equiprobably sampled classical solutions of the problem

Degradación enzimática de TRH y análogos en semen humano. Posible función en la fertilidad

Recientemente se ha descrito la presencia en semen humano de un péptido similar a la hormona liberadora de tirotropina (TRH) directamente implicado en la fertilidad, habiéndose denominado FPP (péptido promotor de la fertilidad). Se han determinado las actividades de las peptidasas más importantes en la degradación de estos péptidos en semen en distintos diagnósticos. Aunque se registran diferencias significativas en la actividad enzimática entre los distintos diagnósticos, dichas variaciones no son lo suficientemente claras como para aceptar estas peptidasas como marcadores válidos.Ugalkortasun arloan egindako azken aurkikuntzen artean tirotropinaren hormona askatzailearen (TRH) antzeko peptido baten aurkikuntza azpimarratzekoa da. Peptido honek ugalkortasunaren prozesuan eragin zuzena duela aurkitu da, izan ere ugalkortasuna errazten duen peptidoa izendatu diote (FPP). Haziko zatikietan ematen den peptido hauen apurketan peptidasa garrantzitsuenen funtzioa ezartzeko asmoz eta ugalkortasunarekin erlazionatutako diagnostiko adierazle bezala balio dezaketen frogatzeko asmoz, bere aktibitate entzimatikoak neurtu dira. Diagnostiko desberdinen artean aldaketa adierazgarriak badira ere, diferentziak ez dira nahiko argiak peptidasa hauek adierazle baliogarri bezala onartzeko.Parmi les derniers découvertes réalisées dans le champ de la fertilité il faut détacher la présence dans le liqueur seminale humain d'un peptide similaire à l'hormone libératrice de tirotropina (TRH) directèment impliqué dans ce procés qui a été nommé FPP (fertilization promoting peptide). A fin d'etablir le rol des peptidases les plus importants dans la dégradation de ses peptides dans les fractions seminales et de vérifier s'ils peuvent servir comme marqueurs des divers diagnostiques seminalesm rélationés avec la fertilité, les activités enzimatiques ant été déterminés. Malgré les differences significatives parmi les deux diagnostiques, ces variations ne sont pas suffisamment clairs pour accepterces peptidases comme des marqueurs valids.Recently it has been described the presence in human semen of a thyrotropin-releasing hormone (TRH) like peptide, directly implicated in the fertility and therefore it has been called fertilization promoting peptide (FPP). We have measured the activities of the most important peptidases in the degradation of these peptides in semen in different diagnostics. Although there are significative differences among the diagnostics, these variations are not clear enough to accept these peptidases like valid markers

Identificación de biomarcadores en la enfermedad de Alzheimer usando análisis de conectividad efectiva a partir de registros de electroencefalografía

RESUMEN: La enfermedad de Alzheimer (EA) es la causa más común de demencia, la cual afecta generalmente a personas después de los 65 años de edad. Algunas mutaciones genéticas inducen la aparición temprana de EA ayudando a monitorear la evolución de los síntomas y los cambios fisiológicos en diferentes etapas de la enfermedad. En Colombia existe un gran grupo familiar con la mutación PSEN1 E280A, con una edad media de aparición de los síntomas de 46,8 años. La EA ha sido definida como un síndrome de desconexión; en consecuencia, enfoques de redes podrían ayudar a capturar diferentes características de la enfermedad. El objetivo del presente trabajo es identificar un biomarcador en la EA que permita realizar el seguimiento del proceso neurodegenerativo. Se registró una electroencefalografía (EEG) durante la codificación de información visual en cuatro grupos de sujetos: portadores de la mutación PSEN1 E280A asintomáticos y con deterioro cognitivo leve y dos grupos control de no portadores. Para cada sujeto se estimó la conectividad efectiva utilizando la Función de Transferencia Directa dirigida y se extrajeron tres medidas de grafos: fuerza de entrada, fuerza de salida y fuerza total. Se calculó una relación entre el estado cognitivo y la edad de los participantes con las características de conectividad. Para aquellas medidas de conectividad que tuvieran una relación con la edad o la escala clínica, se evaluó su desempeño como variable de diagnóstico. Se encontró que la fuerza de conectividad saliente en la región parieto-occipital derecha está relacionada con la edad del grupo de los portadores (r = −0,54, p = 0,0036), y que tiene alta sensibilidad y especificidad para distinguir entre portadores y no portadores (67 % de sensibilidad y 80 % de especificidad en casos asintomáticos, y 83 % de sensibilidad y 67 % de especificidad en casos sintomáticos). Esta relación indica que la fuerza de conectividad saliente podría estar relacionada con el proceso neurodegenerativo de la enfermedad y podría ayudar a realizar un seguimiento de la conversión desde la etapa asintomática hacia la demencia.ABSTRACT: Alzheimer’s disease (AD) is the most common cause of dementia, which generally affects people over 65 years old. Some genetic mutations induce early onset of AD and help to track the evolution of the symptoms and the physiological changes at different stages of the disease. In Colombia there is a large family group with the PSEN1 E280A mutation with a median age of 46,8 years old for onset of symptoms. AD has been defined as a disconnection syndrome; consequently, network approaches could help to capture different features of the disease. The aim of the current work is to identify a biomarker in AD that helps in the tracking of the neurodegenerative process. Electroencephalography (EEG) was recorded during the encoding of visual information for four groups of individuals: asymptomatic and mild cognitive impairment carriers of the PSEN1 E280A mutation, and two non-carrier control groups. For each individual, the effective connectivity was estimated using the direct Directed Transfer Function and three measurements from graph theory were extracted: input strength, output strength and total strength. A relation between the cognitive status and age of the participants with the connectivity features was calculated. For those connectivity measures in which there is a relation with the age or the clinical scale, the performance as a diagnostic feature was evaluated. We found that output strength connectivity in the right occipito-parietal region is related to age of the carrier groups (r = −0,54, p = 0,0036) and has a high sensitivity and high specificity to distinguish between carriers and non-carriers (67 % sensitivity and 80 % specificity in asymptomatic cases, and 83 % sensitivity and 67 % specificity in symptomatic cases). This relationship indicates that output strength connectivity could be related to the neurodegenerative process of the disease and could help to track the conversion from the asymptomatic stage to dementia

CAM development for additive manufacturing in turbo-machinery components

Additive Manufacturing (AM) has become a constantly growing up technology due to the suitability and flexibility in terms of geometry and material diversity. It is applied in high value damaged part repairs from aeronautical, medical and molds and die sectors. This paper proposes an Application Programing interface(API) to be implemented in a commercial software (NX-Siemens) with the main objective of covering a full solution to AM simulation challenges. Experimental tests were carried out in a case of study in order to verify the suitability and reliability of the developed API. The selected material (Hastelloy X) is an additional challenge to be faced; some trials were performed to obtain optimal parameters for this material. [All rights reserved Elsevier]

How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.This work was supported by the Basque Country Government (Department of Education, University and Research, Consolidated Groups IT907-16) and by the Spanish Ministry of Science and Innovation (Grant PID2019-106199RB-C21). I.V.B. and M.S.R. thank the University of the Basque Country (UPV/EHU) for the granted postdoctoral fellowship (ESPDOC19/47) and the granted pre-doctoral fellowship (PIF17/79), respectively. Additional funding was provided by the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), an initiative of the Carlos III Health Institute (ISCIII)

A Preliminary Habitat Suitability Model for Devil Rays in the Western Indian Ocean

The European tropical tuna purse seine fishery incidentally captures three highly migratory and endangered species of devil rays, spinetail devil ray Mobula mobular, sicklefin devil ray M. tarapacana, and bentfin devil ray M. thurstoni in the Indian Ocean. Due to their global decreasing populations, understanding the factors of their spatial and temporal distributions and the associated environmental conditions are fundamental for their management and conservation. Yet, the spatial and temporal distribution of devil rays in the Indian Ocean is poorly understood. Here we developed a habitat suitability model for devil rays in the Western Indian Ocean depicting the seasonal and interannual changes in their spatial distributions and underlying environmental conditions. We used bycatch data collected between the period 2010-2020 by the EU tropical tuna purse seine observer programs to determine which environmental variables influence the occurrence of devil rays using generalized additive models. A separate modelling was done for the spinetail devil ray, and for the three species of devil rays combined, since many individuals are only recorded at the genus level. The environmental variables associated with the presence of devil rays were chlorophyll, sea surface height and sea surface temperature fronts. When modelling the habitat suitability for spinetail devil ray, the most influential environmental variables were net primary production of phytoplankton and sea surface temperature fronts. Both the interannual and seasonal variability in habitat suitability of devil rays were explained by these environmental variables. We also showed that devil rays are associated to permanent hotspots in the Mascarene Plateau and Central Indian Ridge, and to seasonal hotspots in the Western Arabian Sea and Equatorial regions where there is a high occurrence of devil rays during winter monsoon. We found that setting on large tuna schools decreases the chances of devil ray bycatch. Both models predicted a higher probability of incidental catch of devil rays in fishing sets on free swimming schools of tunas than in sets on fish aggregating devices. The identified hotspots and associated environmental characteristics provide information about the habitat use and ecology of the devil rays in the Western Indian Ocean. Furthermore, the habitat suitability models, and biological hotspots identified in this study could also to be used to inform the development of future spatial management measures, including time-area closures, to minimize the interaction of pelagic fisheries with these vulnerable species

A preliminary habitat suitability model for oceanic whitetip shark in the western Indian Ocean

Understanding the temporal, spatial and environmental factors influencing species distributions is essential to minimize the interactions of vulnerable species with fisheries and can be used to identify areas of high bycatch rates and their environmental conditions. Classified as critically endangered by the International Union for the Conservation of Nature, the oceanic whitetip shark (Carcharhinus longimanus) is the second main shark species incidentally caught by the tropical tuna purse seine fishery in the western Indian Ocean. In this study, we used the European Union purse seine fishery observer data (2010-2020) and generalized additive models to develop a habitat suitability model for juvenile oceanic whitetip shark in the western Indian Ocean. Sea surface temperature was the main environmental driver suggesting a higher probability of occurrence of this shark with decreasing temperatures. The type of fishing operation also was an important predictor explaining its occurrence, suggesting a higher probability of incidentally catching this species when using fish aggregating devices as set type. Moreover, predictive maps of habitat suitability suggested the area offshore of Kenya and Somalia are an important hotspot with higher probabilities of incidentally catching this species during the summer monsoon (June to September) when upwelling takes place. The habitat suitability models developed here could be used to inform the design and testing of potential time-area closures in the Kenya-Somalia basin with the objective of minimizing the bycatch of this critically endangered species with the least possible impact on fishing operations and fishery yields of target tuna