Wnt/β-catenin signaling stimulates the expression and synaptic clustering of the autism-associated Neuroligin 3 gene

Indexación: Scopus.Synaptic abnormalities have been described in individuals with autism spectrum disorders (ASD). The cell-adhesion molecule Neuroligin-3 (Nlgn3) has an essential role in the function and maturation of synapses and NLGN3 ASD-associated mutations disrupt hippocampal and cortical function. Here we show that Wnt/β-catenin signaling increases Nlgn3 mRNA and protein levels in HT22 mouse hippocampal cells and primary cultures of rat hippocampal neurons. We characterized the activity of mouse and rat Nlgn3 promoter constructs containing conserved putative T-cell factor/lymphoid enhancing factor (TCF/LEF)-binding elements (TBE) and found that their activity is significantly augmented in Wnt/β-catenin cell reporter assays. Chromatin immunoprecipitation (ChIP) assays and site-directed mutagenesis experiments revealed that endogenous β-catenin binds to novel TBE consensus sequences in the Nlgn3 promoter. Moreover, activation of the signaling cascade increased Nlgn3 clustering and co-localization with the scaffold PSD-95 protein in dendritic processes of primary neurons. Our results directly link Wnt/β-catenin signaling to the transcription of the Nlgn3 gene and support a functional role for the signaling pathway in the dysregulation of excitatory/inhibitory neuronal activity, as is observed in animal models of ASD.https://www.nature.com/articles/s41398-018-0093-y.pd

Acumulação diferencial de nutrientes por cinco cultivares de milho (zea mays L): II - acumulação de micronutrientes

The objective of the present work was to examine the differences in growth, yield, accumulation and transport of nutrients between the cultivars Agroceres 256, Agroceres 504, Centralmex, H-7974 and Piranão. The experiment was carried out in the municipality of Piracicaba, State of São Paulo, Brazil. The soil type was a sandy oxisol of medium fertility, except for K which was low. The experimental set-up was a randon block design with four replications. Common cultivation practices were followed, and the fertilizer used consisted of 83 g of a formula: 30-120-70, per meter lenght at planting, and 33 g of the formula: 50-0-45 per meter lenght as dressing 22 days after germination. The plant population density was 50,000 per hectare. Plants were collected for analysis at 20 days after germination, and there after at intervals of 20 days up to 120 days. The plants were divided into "stems + leaves", tassels, and ears for chemical analysis of Cu, Fe, Mn and Zn. Conclusions: Accumulation of nutrients - Differences in the accumulation of micronutrients appeared before the period of rapid growth (20 days) although afterwards no differences were detectable. - The maximum level of nutrients are attained in the following period (in days): Cu (101 -104); Fe (106-120); Mn (82-94); Zn (87-108). - The maximum quantities taken-up (in mg/plant) are: Cu (2.06-3.49); Fe (26.66- -36.29); Mn (9.92-14.39); Zn (5.88-6.69). Transport of nutrients - The transport of nutrients into the ears of the different cultivars are (per ha harvested): Cu (26-35 g); Fe (200-220 g); Mn (90-140 g); Zn (160-250 g).No presente trabalho, os autores apresentam os resultados de um ensaio de campo empregando os cultivares Agroceres 256, Agroceres 504, Centralmex, H-7974 e Piranao no sentido de aquilatar diferenças na acumulação e exportação de micronutrientes. O ensaio foi conduzido num regossol de fertilidade mediana, exceto em relação ao K que é baixo, situado no município de Piracicaba, SP. O delineamento experimental utilizado foi de blocos ao acaso com 4 repetições. Foram seguidas as práticas culturais comuns e a adubação constituiu de 83 g da fórmula 30--120-70 por metro linear por ocasião do plantio e 33 g por metro linear da fórmula 50-0-4, em cobertura 22 dias após a germinação. Plantas foram coletadas a partir dos 20 dias após a germinação, em intervalos de 20 dias até os 120 dias. As plantas foram divididas em "colmo + folhas", pendão e espiga e analisadas para B, Cu, Fe, Mn e Zn. Concluíram os autores que diferenças na acumulação de micronutrientes manifestam-se antes da fase de crescimento intenso. Os cultivares atingem o máximo da quantidade dos nutrientes nas seguintes épocas, em dias:Cu (61-85); Fe (71-76); Mn (82-94); Zn (87-108). Verificaram, ainda, que as quantidades máximas extraídas em mg/planta são:Cu (2,06--3,49); Fe (26,66-36,28); Mn (9,92-14,39); Zn (5,88-6,69). Finalmente a exportação de nutrientes nas espigas por hectare (50.000 plantas) colhidas é: Cu (26-35 g); Fe (200-220 g); Mn (90-140 g) e Zn (160-250 g)

Acumulação diferencial de nutrientes por cinco cultivares de milho (Zea mays L.): I - acumulação de macronutrientes

The objective of the present work was to examine the differences in growth, yield, accumulation and transport of nutrients between the cultivars Agroceres 256, Agroceres 504, Centralmex, H-7974 and Piranão. The experiment was carried out in the municipality of Piracicaba, State of São Paulo, Brazil. The soil type was a sandy oxisol of medium fertility, expect for K which was low. The experimental set-up was a randon block design with four replications. Common cultivation practices were followed, and the fertilizer used consisted of 83 g of a formula: 30-120-70, per meter length at planting, and 33 g of the formula: 50-0-45 per meter length as dressing 22 days after germination. The plant population density was 50,000 per hectare. Plants were collected for analysis at 20 days after germination, and there after at intervals of 20 days up to 120 days. The plants were divided into "stems + leaves", tassels, and ears for chemical analysis of N, P, K, Ca, Mg and S. Conclusions: Growth - The cultivars produce maximum quantities of dry matter of 327 to 381 g per plant at the age of 100 to 106 days. - Differences between cultivars in terms of dry matter accumulation in the vegetative parts of the plant is not necessarily relate to the dry weight of the ear. Accumulation of nutrients - There are no differences in the quantity of N, P and K taken-up by the cultivars, although during the period of rapid growth some differences may appear. - Differences in the accumulation of Ca, Mg and S are detected when the quantities of these nutrients approach the maximum. The cultivar H-7974 presented the highest quantities of Ca and Mg where as Agroceres 504 was richest in S. - The maximum level of nutrients are attained in the following period in days: N (89-100); P (101 -120); K (58-66); Ca (75-94); Mg (100-120) and S (93-95). - The maximum quantities taken-up in mg/plant are:N (3,169-3,878);P (541-642); K (3,850-4,693); Ca (582-782); Mg (654-943); S (444-799). Yield - No differences were found between cultivars for grain production. Transport of nutrients - The re were no differences in the amounts of nutrients in the grain between cultivars. - The transport of nutrients into the ears of the different cultivars are the following order (per hectare harvested, 50,000 plants): N (111-143 kg); P (22-30 kg); K (30-45 kg); Ca (0.7-1.1 kg); Mg (10-12 kg) and S (9-13 kg).No presente trabalho, os autores apresentam os resultados de um ensaio de campo empregando os cultivares Agroceres 256, Agroceres 504, Centralmex, H-7974 e Piranão no sentido de aquilatar diferenças no crescimento, produção e acumulação e exportação de nutrientes. O ensaio foi conduzido num regossol de fertilidade mediana, exceto em relação ao K que é baixo, situado no Município de Piracicaba, SP. O delineamento experimental utilizado foi de blocos ao acaso com 4 repetições. Foram seguidas as práticas culturais comuns, e a adubação constituiu de 83 g da fórmula 30-120-70 por metro linear por ocasião do plantio e 33 g por metro linear da fórmula 50-0-4, em cobertura 22 dias após a germinação. Plantas foram coletadas a partir dos 20 dias após a germinação, em intervalos de 20 dias até os 120 dias. As plantas foram divididas em "colmo + folhas", pendão e espiga e analisadas para N, P, K, Ca, Mg e S. Concluíram os autores que diferenças entre cultivares na acumulação de matéria seca na parte vegetativa não se traduzem, necessariamente, por um aumento de peso da matéria seca na espiga. Os cultivares atingem o máximo da quantidade de nutrientes nas seguintes épocas, em dias: N (89-100); P (101-120); K (58-66); Ca (74-94); Mg (100-120); S (93-95). Verificaram, ainda, que as quantidades máximas extraídas em mg/planta são: N (3169-3878); P (541-642); K (3850-4693); Ca (582-782); Mg (654-943); S (444-799). Finalmente, a exportação de nutrientes nas espigas por hectare (50.000 plantas) colhidas é: N (111-143 kg); P (22-30 kg); Ca (0,7-1,1 kg); Mg (10-12kg); S(9-13kg)

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

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