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

Classification of red grapes according to their state of ripeness using a low-cost multispectral device

[ES] El objetivo del presente trabajo fue evaluar la idoneidad de un sensor multiespectral de bajo costo para la determinación del estado de maduración de uvas tintas. El dispositivo propuesto se basa en un sensor multiespectral, con 18 bandas de detección en el rango entre los 410 y los 940 nm. La recogida de muestras se llevó a cabo en un viñedo comercial situado en Rociana del Condado, Huelva. El dispositivo propuesto se utilizó para adquirir la respuesta espectral de 80 racimos de uva en condiciones de laboratorio. Tras esto, cada una de las muestras fue analizada mediante métodos estándar de laboratorio para obtener indicadores objetivos de su estado de maduración (sólidos solubles totales y acidez). Los 18 valores de reflectancia ofrecidos por el sensor fueron usados como datos de entrada para entrenar redes neuronales artificiales para la clasificación de las muestras de uva en función de los parámetros objetivo. Los resultados obtenidos fueron prometedores, lo cual allana el camino hacia la implementación de un sistema para la monitorización del estado de maduración de uvas asequible para los vinicultores.[EN] The present work aims to evaluate a low-cost multispectral device for non-destructive grape ripening status assessment. The proposed device is based on a multispectral sensor, with a spectral response of 18 channels in a range from 410 to 940 nm. The experimental validation was carried out in a commercial vineyard in Rociana del Condado, Huelva. The proposed device was used to analyze 80 grape samples under laboratory conditions. After being processed with the proposed device the grape samples were analyzed with standard chemical methods to generate ground truth values of ripening status indicators (solid soluble content, and acidity). The 18-reflectance data corresponding to the spectral channels of the employed sensor, were used as input variables for developing artificial neural network models to classify the berries samples based on the mentioned ripeness indicators. The obtained results were promising, which paves the way for the implementation of a portable grape ripening appraisal system affordable for grape growers

Etapas del ciclo de vida en el desarrollo del turismo religioso: una comparación de estudios de caso

The religious tourism is a strategic development option for many destinations. It requires a tourism orientation, significant private and public capital investment, and a willingness on the part of religious authorities to adapt to visitor needs. The aim of this article is to examine the development of Catholic tourism in different Mexican and European regions and assess related life-cycle implications. Recommendations are made for developing the potential of the Mexican religious regions, and for advancement of the religious tourism destination life-cycle concept.El turismo religioso es una opción estratégica de desarrollo para muchos destinos. Requiere orientación al turismo, importante inversión de capital privado y público, y predisposición de las autoridades eclesiásticas para adaptarse a las necesidades del visitante. Este artículo examina el turismo religioso de carácter católico en distintos lugares de México y Europa y valora implicaciones relacionadas con el ciclo de vida. Finalmente, se hacen recomendaciones para desarrollar el potencial de los lugares analizados, y para el avance del concepto de ciclo de vida de destinos turísticos religiosos

Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study

<p>Abstract</p> <p>Background</p> <p>The phytocannabinoid cannabidiol (CBD) exhibits antioxidant and antiinflammatory properties. The present study was designed to explore its effects in a mouse model of sepsis-related encephalitis by intravenous administration of lipopolysaccharide (LPS).</p> <p>Methods</p> <p>Vascular responses of pial vessels were analyzed by intravital microscopy and inflammatory parameters measured by qRT-PCR.</p> <p>Results</p> <p>CBD prevented LPS-induced arteriolar and venular vasodilation as well as leukocyte margination. In addition, CBD abolished LPS-induced increases in tumor necrosis factor-alpha and cyclooxygenase-2 expression as measured by quantitative real time PCR. The expression of the inducible-nitric oxide synthase was also reduced by CBD. Finally, preservation of Blood Brain Barrier integrity was also associated to the treatment with CBD.</p> <p>Conclusions</p> <p>These data highlight the antiinflammatory and vascular-stabilizing effects of CBD in endotoxic shock and suggest a possible beneficial effect of this natural cannabinoid.</p

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

Materialities, Space, Mind: Archaeology of Visual Cognition

A perceptual study of different styles of prehistoric Galician ceramics (from 6000 to 2000 BP) conducted by eye-tracking, underpins the material engagement of mind by showing that the visual world fosters the entanglement between doing, seeing, and designing through history. This text examines how materializations of human practices relate to cognition and to socio-cultural contexts. By combining evidence on the relationship between material culture and perceptual reactions, our text aims to understand the entanglement between the mind, objects and the world. We apply measurable and numeric techniques, providing an archaeometric approach to cognitive topics by combining neurosciences with interpretive and reflective research. This research provides new insights into the material culture, contributes to the understanding of the relationship between mind and the material world, and accounts for the transitive engagement between the way of thinking, seeing and making things. Thus, the text contributes to an understanding of the material forces driving perception and thought

Extending Graph (Discrete) Derivative Descriptors to N-Tuple Atom-Relations

In the present manuscript, an extension of the previously defined Graph Derivative Indices (GDIs) is discussed. To achieve this objective, the concept of a hypermatrix, conceived from the calculation of the frequencies of triple and quadruple atom relations in a set of connected sub-graphs, is introduced. This set of subgraphs is generated following a predefined criterion, known as the event (S), being in this particular case the connectivity among atoms. The triple and quadruple relations frequency matrices serve as a basis for the computation of triple and quadruple discrete derivative indices, respectively. The GDIs are implemented in a computational program denominated DIVATI (acronym for DIscrete DeriVAtive Type Indices), a module of TOMOCOMD-CARDD program. Shannon‟s entropy-based variability analysis demonstrates that the GDIs show major variability than others indices used in QSAR/QSPR researches. In addition, it can be appreciated when the indices are extended over n-elements from the graph, its quality increases, principally when they are used in a combined way. QSPR modeling of the physicochemical properties Log P and Log K of the 2-furylethylenes derivatives reveals that the GDIs obtained using the tripleand quadruple matrix approaches yield superior performance to the duplex matrix approach. Moreover, the statistical parameters for models obtained with the GDI method are superior to those reported in the literature by using other methods. It can therefore be suggested that the GDI method, seem to be a promissory tool to reckon on in QSAR/QSPR studies, virtual screening of compound datasets and similarity/dissimilarity evaluations

Chaperone-like properties of tobacco plastid thioredoxins f and m

Thioredoxins (Trxs) are ubiquitous disulphide reductases that play important roles in the redox regulation of many cellular processes. However, some redox-independent functions, such as chaperone activity, have also been attributed to Trxs in recent years. The focus of our study is on the putative chaperone function of the well-described plastid Trxs f and m. To that end, the cDNA of both Trxs, designated as NtTrxf and NtTrxm, was isolated from Nicotiana tabacum plants. It was found that bacterially expressed tobacco Trx f and Trx m, in addition to their disulphide reductase activity, possessed chaperone-like properties. In vitro, Trx f and Trx m could both facilitate the reactivation of the cysteine-free form of chemically denatured glucose-6 phosphate dehydrogenase (foldase chaperone activity) and prevent heat-induced malate dehydrogenase aggregation (holdase chaperone activity). Our results led us to infer that the disulphide reductase and foldase chaperone functions prevail when the proteins occur as monomers and the well-conserved non-active cysteine present in Trx f is critical for both functions. By contrast, the holdase chaperone activity of both Trxs depended on their oligomeric status: the proteins were functional only when they were associated with high molecular mass protein complexes. Because the oligomeric status of both Trxs was induced by salt and temperature, our data suggest that plastid Trxs could operate as molecular holdase chaperones upon oxidative stress, acting as a type of small stress protein

Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype

Introduction:TULP1 exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previously unreported and a rarely encountered TULP1 variant.Methods: Whole-exome sequencing was performed to identify potential causative variants. The pathogenicity of the identified TULP1 variants was evaluated through in silico predictors and a minigene splice assay, specifically designed to assess the effect of the unreported TULP1 variant.Results: We identified two TULP1 gene variants in a patient exhibiting unusual and symmetrical alterations in both retinas, characterized by an increase in autofluorescence along the distribution of retinal vessels. These variants included a known rare missense variant, c.1376T&gt;C, and a novel splice site variant, c.822G&gt;T. For the latter variant (c.822G&gt;T), we conducted a minigene splice assay that demonstrated the incorporation of a premature stop codon. This finding suggests a likely activation of the nonsense-mediated mRNA decay mechanism, ultimately resulting in the absence of protein production from this allele. Segregation analysis confirmed that these variants were in trans.Discussion: Our data support that individuals with biallelic TULP1 variants may present with a unique pattern of macular degeneration and periarteriolar vascular pigmentation. This study highlights the importance of further clinical and molecular characterization of TULP1 variants to elucidate genotype–phenotype correlations in the context of inherited retinal dystrophies

Reliability of 4-m and 6-m walking speed tests in elderly people with cognitive impairment

[Abstract] The purpose of this study was to evaluate the interrater and test–retest reliability of 4-m and 6-m walking speed tests in elderly people with cognitive impairment. 50 subjects aged 65 and over with cognitive impairment were selected from an adult day-care centre and a nursing home. To examine interrater reliability, 21 people were evaluated independently by two researchers who administered the 4-m and 6-m walking tests in each evaluation. For test–retest reliability, two observers administered the tests to the same 29 subjects, with a time interval of one week. Intraclass correlation coefficients (ICCs) were calculated to examine interrater and test–retest reliability. The ICCs for interrater reliability reached values of 0.96 and 0.88 for the 4-m and 6-m walking tests, respectively. In the test–retest study, the time interval was 7.4 1.17 days. The ICCs were 0.91 for the 4-m test and 0.86 for the 6-m test. The results support the use of walking tests in elderly people with cognitive impairment