VDR gene polymorphisms on risk of osteoporotic hip fracture in an adult population spanish

La osteoporosis es una enfermedad esquelética compleja multifactorial con un fuerte componente genético, caracterizada por un deterioro en la microestructura ósea que causa fragilidad ósea y un incremento en el riesgo de fracturas osteoporóticas. El gen VDR podría estar fuertemente involucrado en el riesgo de fractura. El objetivo de este trabajo fue investigar la asociación entre polimorfismos del gen VDR y la susceptibilidad a fractura de cadera (FC). Se reclutaron 147 pacientes andaluces (102 con factores de riesgos de fracturas osteoporóticas y 45 con metabolismo óseo normal). El aislamiento de ADN se realizó a partir de 300 mL de sangre, genotipando 2 SNPs: BsmI y FokI mediante PCRRFLP (PCR-Restriction Fragment Length Polymorphism). Todas las fracturas fueron confirmadas por rayos-X mientras que el riesgo de fracturas a través de la escala FRAX y DMO. Los resultados se evaluaron estadísticamente, considerando significativo valores de p<0,05. La edad media de los pacientes fracturados fue de 68,5 años, cuyas frecuencias alélicas fueron 64.7% G y 68.6% C para BsmI y FokI, respectivamente. La prevalencia de estos SNPs en la población caso fueron: 43,3% GA, 43.3% GG y 13,7% AA para BsmI y 49,0% CC, 39,20% CT, 11,8% TT para FokI. Las frecuencias de los alelos y genotipos no mostraron diferencias entre pacientes con riesgo de fracturas y pacientes control. Las frecuencias están acorde con las demostradas en HapMap para población europeacaucásica. No se encontró ninguna asociación significativa entre estos SNPs y la susceptibilidad a las FC en la población adulta andaluza.Osteoporosis is a multifactorial complex skeletal disease with strong genetic component, characterized by a deterioration of bone microstructure that causes bone fragility and an increased risk of osteoporotic fractures. VDR gene could be strongly involved in the risk of fracture. The aim of this study was to investigate the association between VDR gene polymorphisms and susceptibility to hip fracture (HF). 147 Andalusian patients were recruited (102 with risk factors for osteoporotic fractures and 47 with normal bone metabolism). DNA isolation was performed from 300 mL of blood, genotyping 2 SNPs: BsmI and FokI by PCR-RFLP (PCR-Restriction Fragment Length Polymorphism). All fractures were confirmed by X-rays while the risk of fractures through FRAX level and BMD. The results were statistically evaluated, considering significant p-values <0.05. The average age of fractured patients was 68.5 years, whose allele frequencies were 64.7% G and 68.6% C for BsmI and FokI, respectively. Prevalence of these SNPs in the case population were: 43.3% GA, 43.3% GG and 13.7% AA BsmI and 49.0 % CC, 39.2% CT, 11.8% TT for FokI. The frequencies of alleles and genotypes showed no differences between patients with and without risk of hip fracture. The frequencies are agree to HapMap for European-Caucasian population. It was found no significant association between these SNPs and susceptibility to HF in the adult population of Andalusia

Range extensions along western Atlantic for Epialtidae crabs (Brachyura, Majoidea) genera Acanthonyx Latreille, 1828 and Epialtus H. Milne Edwards, 1834

The present study provided information extending the known geographical distribution of three species of majoid crabs, the epialtids Acanthonyx dissimulatus Coelho, 1993, Epialtus bituberculatus H. Milne Edwards, 1834, and E. brasiliensis Dana, 1852. Specimens of both genera from different carcinological collections were studied by comparing morphological characters. We provide new data that extends the geographical distributions of E. bituberculatus to the coast of the states of Paraná and Santa Catarina (Brazil), and offer new records from Belize and Costa Rica. Epialtus brasiliensis is recorded for the first time in the state of Rio Grande do Sul (Brazil), and A. dissimulatus is reported from Quintana Roo, Mexico. The distribution of A. dissimulatus, previously known as endemic to Brazil, has a gap between the states of Espírito Santo and Rio de Janeiro. However, this restricted southern distribution is herein amplified by the Mexican specimens

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presented. ISSN:0029-5515 ISSN:1741-432

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease

3D effects on transport and plasma control in the TJ-II stellarator

The effects of 3D geometry are explored in TJ-II from two relevant points of view: neoclassical transport and modification of stability and dispersion relation of waves. Particle fuelling and impurity transport are studied considering the 3D transport properties, paying attention to both neoclassical transport and other possible mechanisms. The effects of the 3D magnetic topology on stability, confinement and Alfvén Eigenmodes properties are also explored, showing the possibility of controlling Alfvén modes by modifying the configuration; the onset of modes similar to geodesic acoustic modes are driven by fast electrons or fast ions; and the weak effect of magnetic well on confinement. Finally, we show innovative power exhaust scenarios using liquid metals