Ancient origin of the CAG expansion causing Huntington disease in a Spanish population

25 p. Figuras, tablas, bibliografíaHuntington disease (HD, MIM# 143100) is an autosomal dominant neurodegenerative disorder characterized clinically by progressive motor impairment, cognitive decline, and emotional deterioration. The disease is caused by the abnormal expansion of a CAG trinucleotide repeat in the first exon of the huntingtin gene in chromosome 4p16.3. HD is spread worldwide and it is generally accepted that few mutational events account for the origin of the pathogenic CAG expansion in most populations. We have investigated the genetic history of HD mutation in 83 family probands from the Land of Valencia, Eastern Spain. An analysis of the HD/CCG repeat in informative families suggested that at least two main chromosomes were associated in the Valencian population, one associated with allele 7 (77 mutant chromosomes) and one associated with allele 10 (2 mutant chromosomes). Haplotype A-7-A (H1) was observed in 47 out of 48 phase-known mutant chromosomes, obtained by segregation analysis, through the haplotype analysis of rs1313770-HD/CCGrs82334, as it also was in 120 out of 166 chromosomes constructed by means of the PHASE program. The genetic history and geographical distribution of the main haplotype H1 were both studied by constructing extended haplotypes with flanking STRs D4S106 and D4S3034. We found that we were able to determine the age of the CAG expansion associated with the haplotype H1 as being between 4,700 and 10,000 years ago. Furthermore, we observed a nonhomogenous distribution in the different regions associated with the different extended haplotypes of the ancestral haplotype H1, suggesting that local founder effects have occurred.This work was supported by the Fondo de investigación Sanitaria (FIS grant 01/1159), the Instituto de Salud Carlos III (grant G03/56) for the Spanish Network on Cerebellar Ataxias, and the Generalitat Valenciana (grant GRUPOS03/015).Peer reviewe

Association of Polymorphisms in the Interleukin 6 Receptor Complex with Obesity and Hyperandrogenism

10 pages, 5 tables.Objective: Interleukin-6 (IL-6), is an inflammatory cytokine that may influence the pathogenesis of obesity and hyperandrogenism. IL-6 exerts its actions through a heterodimeric receptor consisting of two membrane-bound glycoproteins: an 80-kDa IL-6 binding unit (IL6R-alpha) and a 130-kDa IL-6 signal transducer (gp130). Genetic variability at these loci might contribute to explain the development of obesity and hyperandrogenism. Research Methods and Procedures: We have evaluated the possible association of several polymorphisms in the IL6R-alpha and gp130 genes with obesity and/or hyperandrogenism in a case-control study involving 143 hyperandrogenic patients and 45 healthy women from Spain. Results: A microsatellite CA-repeat polymorphism in the IL6R-alpha locus was associated with obesity. The frequency of the common 149-bp allele was markedly increased in obese women compared with controls when considering patients and controls as a whole (0.41 vs. 0.29, chi2 = 17.085, p < 0.050). On the other hand, the uncommon Arg148 allele of the Gly148Arg polymorphism in the gp130 gene was more frequent in controls compared with hyperandrogenic patients (0.17 vs. 0.08, chi2 = 5.605, p = 0.026). Controls carrying Arg148 alleles had lower 11-deoxycortisol and 17-hydroxyprogesterone concentrations, a lower response of androstenedione to 1–24 adrenocorticotropin, and an almost significant decrease in free testosterone levels, suggesting that Arg148 alleles in the gp130 gene have a protective effect against androgen excess and adrenal hyperactivity. Discussion: Polymorphisms in the gp130 and IL6R-alpha loci influence hyperandrogenism and obesity, respectively. Our present results further suggest that proinflammatory genotypes are involved in the pathogenesis of these common metabolic disorders.This work was supported by grants from the Consejería de Educación, Comunidad de Madrid, Spain (Proyectos 08.6/0022/1998, 08.6/0024.2/2000, and 08.6/0010/2001), and from the Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo, Spain (Proyectos FIS 00/0414 and 02/0741 to H.F.E.-M.Peer reviewe

On the bulk modulus and natural frequency of fullerene and nanotube carbon structures obtained with a beam based method

In this work, the natural frequency of vibration and Bulk modulus under hydrostatic pressure conditions of carbon nanotubes and fullerenes are investigated. For this purpose, three-dimensional finite element modelling is used in order to evaluate the vibration characteristics and radial stiffness for different nanotube and fullerene sizes. The atomistic method implemented in this work is based on the notion that nanotubes, or fullerenes, are geometrical frame-like structures where the primary bonds between two neighbouring atoms act like load-bearing beam members, whereas an individual atom acts as the joint of the related load-bearing system. The current numerical simulations results are compared with data reported by other authors, highlighting the greater simplicity and the lower computational cost of the model implemented in this work compared to other molecular dynamics models, maintaining accuracy in the results provided.The authors are indebted to the Ministerio de Economía y Competitividad de España (Projects DPI2011-24068 and DPI2011-23191) for the financial support.Publicad

Evaluating the computational performance of the Xilinx Ultrascale+ EG Heterogeneous MPSoC

The emergent technology of Multi-Processor System-on-Chip (MPSoC), which combines heterogeneous computing with the high performance of Field Programmable Gate Arrays (FPGAs) is a very interesting platform for a huge number of applications ranging from medical imaging and augmented reality to high-performance computing in space. In this paper, we focus on the Xilinx Zynq UltraScale EG Heterogeneous MPSoC, which is composed of four different processing elements (PE): a dual-core Cortex-R5, a quad-core ARM Cortex-A53, a graphics processing unit (GPU) and a high end FPGA. Proper use of the heterogeneity and the different levels of parallelism of this platform becomes a challenging task. This paper evaluates this platform and each of its PEs to carry out fundamental operations in terms of computational performance. To this end, we evaluate image-based applications and a matrix multiplication kernel. On former, the image-based applications leverage the heterogeneity of the MPSoc and strategically distributes its tasks among both kinds of CPU cores and the FPGA. On the latter, we analyze separately each PE using different matrix multiplication benchmarks in order to assess and compare their performance in terms of MFlops. This kind of operations are being carried out for example in a large number of space-related applications where the MPSoCs are currently gaining momentum. Results stand out the fact that different PEs can collaborate efficiently with the aim of accelerating the computational-demanding tasks of an application. Another important aspect to highlight is that leveraging the parallel OpenBLAS library we achieve up to 12 GFlops with the four Cortex-A53 cores of the platform, which is a considerable performance for this kind of devices.This work has been supported by the Spanish Government through TIN2017-82972-R, ESP2015-68245-C4-1-P, the Valencian Regional Government through PROMETEO/2029/109 and the Universitat Jaume I through UJI-B2019-36. We thank Prof. L. Kosmidis and M. M. Trompouki for providing us the OpenGL ES 2.0 code implementation of the matrix multiplication

Helping the family carers of Alzheimer's patients: from theory... to practice: a preliminary study

[Abstract] Alzheimer's disease (AD) represents one of the most important health issues in the western world. The ongoing care that the AD patient requires typically causes high stress levels, fatigue, irritation and depression in the caregiver, as well as socio-economical problems. The current study aimed to introduce a support program for carers of AD patients, in order to improve their quality of life. A Questionnaire for Carers and an Anxiety State Feature Questionnaire (STAI) was used to assess the carers. Results showed an overall improvement in the carers' health. Their subjective wellbeing increased, and though their situation had not changed, they nevertheless described feeling les s trapped. It can be concluded that possibly the mere fact that the carers feel that they have help available is enough to endorse the value of the program

Hematotoxicity of magnetite nanoparticles coated with polyethylene glycol: in vitro and in vivo studies

Accepted Manuscript.-- et al.Hematotoxicity of magnetite nanoparticles coated with dimercaptosuccinic acid (DMSA) and polyethylene glycol (PEG) has been evaluated by determining their safety in vitro and in vivo in a rat model up to 30 days after administration of a single dose. The in vitro analysis consists of global plasma coagulation (PT, aPTT, and fibrinogen) and platelet aggregation tests while the hematotoxicity studies in vivo include a complete blood count and the possible genotoxic effect analysis in the bone marrow hematopoietic function. Prolonged aPTT values indicate a higher anticoagulant effect for NP-DMSA compared with PEG-coated nanoparticles as a consequence of the higher surface charge of the former. The in vivo tests showed that these bioferrofluids do not cause genotoxic effects, affect erythropoiesis or increase the number of immature erythrocytes in the bone marrow at the analyzed dose. However, nanoparticle administration showed a significant effect on the leukocyte counts in animals treated with DMSA coated nanoparticles 24 h after injection. This response is not observed in animals treated with PEG modified nanoparticles which justifies the use of this polymer in biomasking strategies.L.M.A.A. acknowledges financial support from the Spanish Ministry of Science and Innovation FPI research grants. Technical support from the University Hospital Lozano Blesa, Zaragoza, Spain and from María Angeles Gracia, Ana Isabel Martínez de Ternero, Maria Rosa Borrell Sanz. AR holds a predoctoral fellowship from a CSIC-CITMA collaborative project (B01CU2009; ICMM, 2011–2014) and a short-term fellowship from CNPq (DTI-2; 383934/2013-3). This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (MAT2011-23641 and MAT2011-25991).Peer Reviewe

Human papillomavirus-like particles vaccine efficiently produced in a non-fermentative system based on insect larva

8 p., 3 figures, 1 table of contents and bibliographySexually transmitt ed human papillomavirus (HPV) infections cause most cervical cancers. The inability to propagate HPV in vitro has led to the development of alternative approaches to antigen production for vaccine development. In the present work we describe a l ow - cost eff icient production of HPV virus - like particles (VLPs) in a non - fermentative system based on baculovirus and Trichoplusia ni ( T. ni ) insects. The L1 protein from HPV 16 was expressed by a recombinant baculovirus in larva at levels that reached 18 to 21 mg pe r g of fresh insect biomass. It represents about 2.5 times the L1 production yields obtained per g of insect cells using the same recombinant baculovirus. Under electron microscopy, purified VLPs produced in larvae were indistinguishable from those produce d in Sf - 21 insect cell cultures, presenting identical shape and size . Immunization of mice with the insect - derived VLPs induced a potent immune response similar to that obtained with insect cells - derived VLPs. The use of live insect larvae as “mini bioreac tors” opens up the possibility of cost - effective production of a vaccine against cervical cancer produced by papillomavirus, with special application in human populations where production costs restrain their use.This work was partially supported by Grants BIO2005-00155 and CPE03-022-C5-2 from the Ministerio de Educación y Ciencia and INIA, respectively, and by funds from the company Alternative Gene Expression S.L. (ALGENEX).Peer reviewe

Evaluación y resultados de la instauración de un programa de terapia de grupo dirigido a un colectivo de cuidadores familiares de enfermos de Alzheimer

[Resumen] La terapia de grupo es una de las actividades que se han mostrado más positivas como apoyo a los cuidadores familiares de enfermos de Alzheimer; por ello, en este trabajo pre - sentamos un programa de ayuda a cuidadores de enfermos de Alzheimer, en donde la terapia de grupo es una de las actividades establecidas con dos funciones; por un lado contrarrestar el aislamiento de los cuidadores; mientras que por el otro será ayudarlos a superar los sentimientos negativos que suscitan su situación. Los resultados que presentamos, corresponden a un periodo de intervención de seis meses, valorados mediante el STAI; en ellos se muestra como muy afectiva tanto para la reducción de la ansiedad como para el establecimiento de un sistema de comunicación acerca de la problemática común y de la búsqueda de soluciones percibiendo los cuidado - res estas actuaciones como excelentes para su bienestar.[Abstract] The group therapy is one of the activities that have been shown more positive as sup - port to the family caregivers of AD; for it, in this work we introduce a program of help to caregivers; where the group therapyl is one of the established activities with two functions: counteracting the isolation of the caregivers and helping them to overcome the negative fee - lings that raise their situation. The results that we present, correspond to a period of intervention of six months, valued by the STAI. Results point out to be very effective for the reduction of the anxiety like for the establishment of a communication system about the common problem and the search of solutions, perceiving the caregivers these performances as excellent for their wellfare