Neurobiological bases of autism and cellular models for its experimental study

Autism Spectrum Disorders (ASD) are a functional alteration of the cerebral cortex, which presents structural neurodevelopmental anomalies that affect synaptic function and the pattern of connections within and between cortical columns. From its etiological aspect, ASD has an important genetic load, considering a polygenic disorder, derived from a combination of "de novo" genetic mutations, associated to a predisposition derived from common inherited variations. The main genetic anomalies associated with ASD involve genes that encode proteins of the synapse. Thus, in patients with ASD, alterations in the initial development of the synapses have been described in the connection circuits between complex processing cortical areas. The molecular complexity observed in the predisposition to develop an ASD, together with the diversity of structural phenotypes, has made animal models reproduce only partially the ASD. To advance in the experimental study it is therefore necessary to develop representative models, such as cellular models derived from human cells. In recent decades, the advances in stem cell biology give us a way to apply experimental paradigms in cells derived from individuals with ASD. Currently, induced pluripotent cells (IPs) derived from human adult cells allow deepening the study of molecular and cellular bases of the neuronal development in humans, as well as the anomalies in this development, which give rise to disorders such as ASD. However, they present inherent problems derived from the experimental manipulation that involves the reprogramming of gene expression, therefore other models are also been explored

Effects of wearing a full body compression garment during recovery from an ultra-trail race

In sport disciplines with high levels of muscle damage such as an ultra-trail competition, full body compression garments (FBCG) may have an ergogenic effect during the recovery process. The aim of the study was to assess the influence of FBCG worn for 24 h immediately after a 107-km ultra-trail on delayed onset muscle soreness (DOMS), muscle damage, inflammatory and renal response. Thirty-two athletes (19 males and 13 females; VO2peak: 54.1 ± 5.2 ml O2/kg/min) participated in the study. The following blood markers were analysed before, immediately after, at 24 and 48 h post-race: lactate dehydrogenase, creatine kinase, C-reactive protein and creatinine. The glomerular filtration rate was also calculated. Delayed onset muscle soreness was evaluated before, immediately after and at 24 h post-race. On arrival at the finishing line, athletes were randomised into one of two recovery groups (FBCG and control group). The results showed that wearing FBCG did not influence the evolution of any of the blood markers up to 48 h after the race (p > .05). However, FBCG group presented a lower increase in posterior leg DOMS (11.0 ± 46.2% vs 112.3 ± 170.4%, p = .03, d = 0.8). Therefore, although FBCG is not useful for reducing muscle damage and inflammatory response after an ultra-trail race, its use may still be recommended as a recovery method to reduce muscle soreness

Influence of atmospheric conditions on the power production of utility-scale wind turbines in yaw misalignment

The intentional yaw misalignment of leading, upwind turbines in a wind farm, termed wake steering, has demonstrated potential as a collective control approach for wind farm power maximization. The optimal control strategy, and resulting effect of wake steering on wind farm power production, are in part dictated by the power degradation of the upwind yaw misaligned wind turbines. In the atmospheric boundary layer, the wind speed and direction may vary significantly over the wind turbine rotor area, depending on atmospheric conditions and stability, resulting in freestream turbine power production which is asymmetric as a function of the direction of yaw misalignment and which varies during the diurnal cycle. In this study, we propose a model for the power production of a wind turbine in yaw misalignment based on aerodynamic blade elements which incorporates the effects of wind speed and direction changes over the turbine rotor area in yaw misalignment. A field experiment is performed using multiple utility-scale wind turbines to characterize the power production of yawed freestream operating turbines depending on the wind conditions, and the model is validated using the experimental data. The resulting power production of a yaw misaligned variable speed wind turbine depends on a nonlinear interaction between the yaw misalignment, the atmospheric conditions, and the wind turbine control system.Comment: 37 pages, 15 figure

Highly efficient full-wave electromagnetic analysis of 3D arbitrarily-shaped waveguide microwave devices using an integral equation technique

A novel technique for the full-wave analysis of 3-D complex waveguide devices is presented. This new formulation, based on the Boundary Integral-Resonant Mode Expansion (BI-RME) method, allows the rigorous full-wave electromagnetic characterization of 3-D arbitrarily shaped metallic structures making use of extremely low CPU resources (both time and memory). The unknown electric current density on the surface of the metallic elements is represented by means of Rao-Wilton-Glisson basis functions, and an algebraic procedure based on a singular value decomposition is applied to transform such functions into the classical solenoidal and nonsolenoidal basis functions needed by the original BI-RME technique. The developed tool also provides an accurate computation of the electromagnetic fields at an arbitrary observation point of the considered device, so it can be used for predicting high-power breakdown phenomena. In order to validate the accuracy and efficiency of this novel approach, several new designs of band-pass waveguides filters are presented. The obtained results (S-parameters and electromagnetic fields) are successfully compared both to experimental data and to numerical simulations provided by a commercial software based on the finite element technique. The results obtained show that the new technique is specially suitable for the efficient full-wave analysis of complex waveguide devices considering an integrated coaxial excitation, where the coaxial probes may be in contact with the metallic insets of the component.This work was supported by the Ministerio de Economia y Competitividad, Spanish Government, under the Research Projects TEC2013-47037-C5-1-R and TEC2013-47037-C5-4-R.Vidal Pantaleoni, A.; San Blas Oltra, ÁA.; Quesada Pereira, FD.; Pérez Soler, FJ.; Gil Raga, J.; Vicente Quiles, CP.; Gimeno Martinez, B.... (2015). Highly efficient full-wave electromagnetic analysis of 3D arbitrarily-shaped waveguide microwave devices using an integral equation technique. Radio Science. 50(7):642-655. https://doi.org/10.1002/2015RS005685S64265550

The use of the CNIC-Polypill in real-life clinical practice: opportunities and challenges in patients at very high risk of atherosclerotic cardiovascular disease – expert panel meeting report

Although the cardiovascular (CV) polypill concept is not new and several guidelines state that a CV polypill should be considered an integral part of a comprehensive CV disease (CVD) prevention strategy, there are still some barriers to its implementation in the real-world setting, mainly in secondary CV prevention. As the CNIC-polypill is the only one approved for secondary CV prevention in patients with atherosclerotic CVD in 27 countries worldwide, a panel of four discussants and 30 participants from 18 countries conveyed in a virtual meeting on April 21, 2022, to discuss key clinical questions regarding the practical use of the CNIC-Polypill and barriers to its implementation. Data presented showed that, although the use of the CV polypill is not explicitly mentioned in the current 2021 European Society of Cardiology guidelines on CVD prevention, it may be used in any patient for secondary CVD prevention tolerating all their components to improve outcomes through different aspects. The favourable results of the Secondary Prevention of Cardiovascular Disease in the Elderly (SECURE) trial now reinforce this recommendation. The panellists presented algorithms on how to switch from any baseline regimen when starting treatment with the CNIC-polypill in different situations, including patients with hypertension, dyslipidaemia, and a previous CV event; at discharge after a cardiovascular event; in chronic ischemic conditions; and in cases of polypharmacy. The panellists and expert discussants did agree that available studies conducted so far with the CNIC-polypill demonstrate that it is as efficacious as the monocomponents, equipotent drugs, or other therapies; reduces the risk of experiencing recurrent major CV events; improves medication adherence; reduces health care costs and resources compared to patients treated with loose drugs; and the patients prefer it over the multipill strategy. In conclusion, the data presented by the participants provided the evidence behind the use of the CNIC-polypill to help fulfil the goal of encouraging its adoption by physicians.info:eu-repo/semantics/publishedVersio

Application of Photon Strength Functions to (n,g ) Measurements with the n_TOF TAC

The neutron capture cross section measurements at the CERN n_TOF facility are performed using a new detection system, the segmented Total Absorption Calorimeter (TAC). All measurements are performed in reference to the well known 197Au s (n,g ). The accuracy of the measurements depends on the accuracy of the TAC detection efficiency, which is calculated by means of Monte Carlo simulations. In this MC simulation photon strength functions and level densities play a major role as ingredients used for the generation of primary events, that is the electromagnetic cascades following the (n,g ) process. We have calculated the TAC detection efficiency for the case of 197Au(n,g ) by adjusting the photon strength functions of 198Au so that the simulation reproduces the experimental data. Both the MC method and the uncertainty of the results are discussed.JRC.D.5-Neutron physic

The global abundance of tree palms

Aim Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change. Location Tropical and subtropical moist forests. Time period Current. Major taxa studied Palms (Arecaceae). Methods We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure. Results On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work. Conclusions Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests

Berry Flesh and Skin Ripening Features in Vitis vinifera as Assessed by Transcriptional Profiling

Background Ripening of fleshy fruit is a complex developmental process involving the differentiation of tissues with separate functions. During grapevine berry ripening important processes contributing to table and wine grape quality take place, some of them flesh- or skin-specific. In this study, transcriptional profiles throughout flesh and skin ripening were followed during two different seasons in a table grape cultivar ‘Muscat Hamburg’ to determine tissue-specific as well as common developmental programs. Methodology/Principal Findings Using an updated GrapeGen Affymetrix GeneChip® annotation based on grapevine 12×v1 gene predictions, 2188 differentially accumulated transcripts between flesh and skin and 2839 transcripts differentially accumulated throughout ripening in the same manner in both tissues were identified. Transcriptional profiles were dominated by changes at the beginning of veraison which affect both pericarp tissues, although frequently delayed or with lower intensity in the skin than in the flesh. Functional enrichment analysis identified the decay on biosynthetic processes, photosynthesis and transport as a major part of the program delayed in the skin. In addition, a higher number of functional categories, including several related to macromolecule transport and phenylpropanoid and lipid biosynthesis, were over-represented in transcripts accumulated to higher levels in the skin. Functional enrichment also indicated auxin, gibberellins and bHLH transcription factors to take part in the regulation of pre-veraison processes in the pericarp, whereas WRKY and C2H2 family transcription factors seems to more specifically participate in the regulation of skin and flesh ripening, respectively. Conclusions/Significance A transcriptomic analysis indicates that a large part of the ripening program is shared by both pericarp tissues despite some components are delayed in the skin. In addition, important tissue differences are present from early stages prior to the ripening onset including tissue-specific regulators. Altogether, these findings provide key elements to understand berry ripening and its differential regulation in flesh and skin.This study was financially supported by GrapeGen Project funded by Genoma España within a collaborative agreement with Genome Canada. The authors also thank The Ministerio de Ciencia e Innovacion for project BIO2008-03892 and a bilateral collaborative grant with Argentina (AR2009-0021). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years