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Abstract Over the last decades, air pollution emissions have decreased substantially; however, inequities in air pollution persist. We evaluate county-level racial/ethnic and socioeconomic disparities in emissions changes from six air pollution source sectors (industry [SO2], energy [SO2, NOx], agriculture [NH3], commercial [NOx], residential [particulate organic carbon], and on-road transportation [NOx]) in the contiguous United States during the 40 years following the Clean Air Act (CAA) enactment (1970-2010). We calculate relative emission changes and examine the differential changes given county demographics using hierarchical nested models. The results show racial/ethnic disparities, particularly in the industry and energy generation source sectors. We also find that median family income is a driver of variation in relative emissions changes in all sectors—counties with median family income >$75 K vs. less generally experience larger relative declines in industry, energy, transportation, residential, and commercial-related emissions. Emissions from most air pollution source sectors have, on a national level, decreased following the United States CAA. In this work, we show that the relative reductions in emissions varied across racial/ethnic and socioeconomic groups.

Summary: Seven healthy, physically active men (n = 3) and women (n = 4) (30.7 ± 7.5 years, 172.7 ± 8.7 cm, 70.4 ± 11.6 kg, 23.6 ± 4.1 kg/m2, 49.2 ± 8.4 mL/kg/min) supplemented for 14 days with a placebo (PLA) or 1 × 1010 CFU doses of the probiotic Veillonella atypica FB0054 (FitBiomics, New York, NY). Participants had safety panels, hemodynamics, lactate, and anaerobic capacity assessed. Stool samples were collected to evaluate for metagenomic and metabolomic changes. Exhaustion times were not different between groups, whereas anaerobic capacity tended to shorten with PLA (61.14 ± 72.04 s; 95% CI: −5.49, 127.77 s, p = 0.066) with no change with VA (13.29 ± 100.13 s, 95% CI: −79.32, 105.89 s, p = 0.738). No changes in lactate, hemodynamics, or bacterial community changes were observed, whereas 14 metabolites exhibited differential expression patterns with VA supplementation. In conclusion, VA maintained exercise performance that tended to decline in PLA. Supplementation was well tolerated with no changes in safety markers or reported adverse events.

Conformational heterogeneity is key to understand how macromolecular function and structure converge. Here, the authors propose an algorithm designed to estimate structural landscapes directly from Cryo-EM particle images.

ObjectiveTo examine the efficacy of supplementing with a multi-strain probiotic (MSP) on changes associated with mood, anxiety, and neurotransmitter levels.MethodIn a randomized, double-blind, placebo-controlled fashion, 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented with a single capsule of MSP (a total daily dose of 4 × 109 live cells comprised of a 1 × 109 live cells dose from each of the following strains: Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04, Probiotical S.p.A., Novara, Italy) or a maltodextrin placebo (PLA). After 0, 2, 4, and 6 weeks of supplementation and 3 weeks after ceasing supplementation, study participants completed the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), and Leiden Index of Depression Sensitivity (LEIDS-R) questionnaires and had plasma concentrations of cortisol, dopamine, serotonin, and C-reactive protein determined.ResultsBDI, STAI, and total LEIDS-R scores were reduced from baseline (p 0.05) were reported in PLA. When compared to PLA, MSP scores for state anxiety, trait anxiety, and LEIDS-R (hopeless, aggression, rumination, and total score) were significantly lower (p 0.05) in plasma dopamine, C-reactive protein, or cortisol concentrations were observed between groups.ConclusionMSP supplementation resulted in widespread improvements in several questionnaires evaluating mood, anxiety, and depression in young, healthy men and women. MSP supplementation increased serotonin increased after 6 weeks of MSP supplementation with no change in dopamine, C-reactive protein, or cortisol.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05343533, NCT05343533.

AMPA glutamate receptors, mediate the majority of excitatory signaling in the brain. Here the authors show how the auxiliary subunit TARP-γ8 shapes gating kinetics, ion conductance and rectification properties of the heteromeric GluA1/2 AMPA receptor.

ABSTRACT: Herd-level diagnosis of paratuberculosis using a pool-milk ELISA (pool size: n ≤ 50) is a novel, economical, and convenient method to identify blood serological Mycobacterium avium ssp. paratuberculosis (MAP) antibody–positive herds. To date, the diagnostic performance of the pool-milk ELISA has been described only under laboratory conditions where herd prevalence was simulated by the preparation of milk pools consisting of milk samples of cows with a known MAP status determined by fecal culture. In our observational study, test performance under field conditions was studied using pooled milk and individual blood samples. A total of 486 herds within the MAP prevalence reduction program of Lower Saxony, from which pooled milk and individual blood ELISA results were available, were assigned to this study. Data were analyzed for the period between January 1 and December 31, 2018, the first year after herd testing became obligatory in this federal state of Germany. To evaluate whether pooled milk samples reliably distinguish between herds with a MAP-apparent blood serological within-herd prevalence (MAP-Ab-WHPapp) ≥5% and herds with a MAP-Ab-WHPapp

Yoon, Munoz, et al. investigate the rate of de novo coding and non-coding variants in families with high- and low-risk for autism using whole-genome sequence data from collections of families with autism. They demonstrate that de novo intronic variants increase the risk of autism, that the contribution of de novo variants is significantly larger in low-risk families, and that de novo variants contribute to 30-39% of cases of all autism.

Summary: The emergence of SARS-CoV-2 variants necessitates rational assessment of their impact on the recognition and neutralization of the virus by the host cell. We present a comparative analysis of the interactions of Alpha, Beta, Gamma, and Delta variants with cognate molecules (ACE2 and/or furin), neutralizing nanobodies (Nbs), and monoclonal antibodies (mAbs) using in silico methods, in addition to Nb-binding assays. Our study elucidates the molecular origin of the ability of Beta and Delta variants to evade selected antibodies, such as REGN10933, LY-CoV555, B38, C105, or H11-H4, while being insensitive to others including REGN10987. Experiments confirm that nanobody Nb20 retains neutralizing activity against the Delta variant. The substitutions T478K and L452R in the Delta variant enhance associations with ACE2, whereas P681R promotes recognition by proteases, thus facilitating viral entry. The Ab-specific responses of variants highlight how full-atomic structure and dynamics analyses are required for assessing the response to newly emerging variants.

Recent years have seen several hybrid simulation methods for exploring the conformational space of proteins and their complexes or assemblies. These methods often combine fast analytical approaches with computationally expensive full atomic molecular dynamics (MD) simulations with the goal of rapidly sampling large and cooperative conformational changes at full atomic resolution. We present here a systematic comparison of the utility and limits of four such hybrid methods that have been introduced in recent years: MD with excited normal modes (MDeNM), collective modes-driven MD (CoMD), and elastic network model (ENM)-based generation, clustering, and relaxation of conformations (ClustENM) as well as its updated version integrated with MD simulations (ClustENMD). We analyzed the predicted conformational spaces using each of these four hybrid methods, applied to four well-studied proteins, triosephosphate isomerase (TIM), 3-phosphoglycerate kinase (PGK), HIV-1 protease (PR) and HIV-1 reverse transcriptase (RT), which provide extensive ensembles of experimental structures for benchmarking and comparing the methods. We show that a rigorous multi-faceted comparison and multiple metrics are necessary to properly assess the differences between conformational ensembles and provide an optimal protocol for achieving good agreement with experimental data. While all four hybrid methods perform well in general, being especially useful as computationally efficient methods that retain atomic resolution, the systematic analysis of the same systems by these four hybrid methods highlights the strengths and limitations of the methods and provides guidance for parameters and protocols to be adopted in future studies.

The animal health and welfare status in European organic dairy production does not in all aspects meet the organic principles and consumers’ expectations and needs to be improved. To achieve this, tailored herd health planning, targeted to the specific situation of individual farms could be of use. The aim of this study was to apply herd health planning in a structured participatory approach, with impact matrix analysis, not previously used in this context, in European organic dairy farms and to assess changes in animal health and welfare. Herd health planning farm visits were conducted on 122 organic dairy farms in France, Germany and Sweden. The farmer, the herd veterinarian and/or an advisor took part in the farm discussions. The researcher served as facilitator. Baseline data on the animal health status of the individual farm, collected from national milk recording schemes, were presented as an input for the discussion. Thereafter a systematic impact matrix analysis was performed. This was to capture the complexity of individual farms with the aim to identify the farm-specific factors that could have a strong impact on animal health. The participants (i.e. farmer, veterinarian and advisor) jointly identified areas in need of improvement, taking the health status and the interconnected farm system components into account, and appropriate actions were jointly identified. The researcher took minutes during the discussions, and these were shared with the participants. No intervention was made by the researcher, and further actions were left with the participants. The number of actions per farm ranged from 0 to 22. The change in mortality, metabolic diseases, reproductive performance and udder health was assessed at two time points, and potential determinators of the change were evaluated with linear regression models. A significant association was seen between change in udder health, as measured by the somatic cell count, and country. At the first follow-up, a significant association was also found between change in the proportion of prolonged calving interval and the farmers’ desire to improve reproductive health as well as with an increase in herd size, but this was not seen at the second follow-up. The degree of implementation of the actions was good (median 67%, lower quartile 40%, upper quartile 83%). To conclude, the degree of implementation was quite high, improvement of animal health could not be linked to the herd health planning approach. However, the approach was highly appreciated by the participants and deserves further study.

The simulation of terrestrial ecosystem processes, using numerical biosphere-atmosphere models that can be coupled to the Atmospheric Models, assist in a better diagnosis and forecast of climate and weather. To be able to represent a particular region, biome or ecosystem, the model parameters need to be adjusted for local conditions. This work aims to assess the Luus-Jaakola (LJ) method in the optimization of the parameters in a two-stream radiative transfer model applied to a vegetation canopy. Solar radiation components (incident, S↓, and reflected, S↑) were measured above a sugarcane crop in a Tropical region from February 17 to 24, 2006. Among the combinations of internal and external iterations evaluated for Luss-Jaakola method, 60/30 (external/internal) iterations presented more precise albedo (∝ = S↑/S↓) simulated (r^2 = 0.7386) and, for the accuracy of the simulated ∝, even though the 60/40 combination had the smallest percentual error (6.40%), the 60/30 combination was 0.03% higher. The precision and accuracy of S↑ was greater with the parameters obtained by the inverse problem with the combination of 60/30 (external/internal) iterations respectively. In general, the behavior of simulated S↑ at the top of the canopy was underestimated compared to the observed S↑, especially in the early morning. For the simulated ∝ at the top of the canopy, the model's overestimation was observed at the lowest values of albedo. When the largest albedos are observed, only at the beginning of the day the model underestimated the values. As shown by the tests result, the parameters optimized by Luus-Jaakola method have an adequate representation of the observed data.

In this study, we report the impact of structural 4H-SiC epitaxial defects on the electrical characteristics and blocking capabilities of SiC power devices. The detection and classification of the various crystal defects existing in 4H-SiC epitaxial layers and substrates was carried out with a commercial inspection tool using an optical microscope with a photoluminescence channel (PL). After the fabrication of dedicated test structures, devices that contain a single crystal defect were selected and electrically tested in reverse bias mode. Photon emission microscopy was performed to enable the localization of the leakage current spots within the devices. Thus, a direct correlation of the various crystal defects with the reduced blocking capability mechanism was made. This evaluation helps to set directions and build a strategy towards the reduction of critical defects in order to improve the performance of SiC devices for high power applications.

Production diseases in dairy cows are multifactorial, which means they emerge from complex interactions between many different farm variables. Variables with a large impact on production diseases can be identified for groups of farms using statistical models, but these methods cannot be used to identify highly influential variables in individual farms. This, however, is necessary for herd health planning, because farm conditions and associated health problems vary largely between farms. The aim of this study was to rank variables according to their anticipated effect on production diseases on the farm level by applying a graph-based impact analysis on 192 European organic dairy farms. Direct impacts between 13 pre-defined variables were estimated for each farm during a round-table discussion attended by practitioners, that is farmer, veterinarian and herd advisor. Indirect impacts were elaborated through graph analysis taking into account impact strengths. Across farms, factors supposedly exerting the most influence on production diseases were ‘feeding’, ‘hygiene’ and ‘treatment’ (direct impacts), as well as ‘knowledge and skills’ and ‘herd health monitoring’ (indirect impacts). Factors strongly influenced by production diseases were ‘milk performance’, ‘financial resources’ and ‘labour capacity’ (directly and indirectly). Ranking of variables on the farm level revealed considerable differences between farms in terms of their most influential and most influenced farm factors. Consequently, very different strategies may be required to reduce production diseases in these farms. The method is based on perceptions and estimations and thus prone to errors. From our point of view, however, this weakness is clearly outweighed by the ability to assess and to analyse farm-specific relationships and thus to complement general knowledge with contextual knowledge. Therefore, we conclude that graph-based impact analysis represents a promising decision support tool for herd health planning. The next steps include testing the method using more specific and problem-oriented variables as well as evaluating its effectiveness.

In 4H silicon carbide, aluminum implantation causes unusual high compensation ratios as obtained from Hall effect investigations by fitting the neutrality equation with a single acceptor. We show that this approach cannot fully describe the experimental data, in particular in case of moderate doping and at high measurement temperatures above 450 K. We develop two extended models by adding an additional acceptor- or donor-like defect to the equation. Both approaches describe the data well. However, it turns out that an additional aluminum-correlated acceptor is the more reasonable choice. In this case, the compensation ratio stays almost independent of the implantation dose between 30 % and 40 %. The deep acceptor is located at EV + (280–400) meV.

ABSTRACT Objectives A few Brazilian researches correlate personality disorders (PD) and substance related disorders (SRD). The aim of the present study is to investigate the association between them, to evaluate the PD frequency among chemical dependents inpatients, this comorbidity association with social and demographic characteristics, used drug of choice, its impact on clinical evolution until the moment of their committal, the frequency of relapse, self-help group – and psychotherapic adherence among SRD patients six months following committal. Methods A 101 inpatients sample of chemical dependents was enrolled in 2 hospitals. The following instruments were applied: a questionnaire for social and demographic characteristics identification and drug use pattern, some questions from the sixth version of the Addiction Severity Index (ASI-6), the SCID-II questionnaire and specific questions concerning psychotherapic and self-help groups participation, and medication use. Results From these 101 patients, 55.4% were diagnosed with PD, being avoidant (14.9%), borderline (11.9%) and antisocial (8.9%) the more frequent ones found. PD patients had an earlier crack use in life (p = 0.038) and had also more previous treatments than the ones without PD (p = 0.005). Borderline PD patients were less worried to substance use problem (p = 0.003). After 6-months follow-up, no statistical significance was found between patients with and without PD regarding drug use or treatment adherence. Conclusion A high PD diagnosis was found in drug use inpatients. Patients diagnosed with SRD and PD need the identification of this comorbidity and of their personality characteristics in order to plan a more comprehensive and effective treatment.

In this study, we analyse the climatic impacts on the grape harvest date (GHD) in Burgundy (France) on interannual and decadal time scales. We affirm that the GHD is mainly influenced by the local April-to-August temperature (AAT) and provide the spatial expansion of this relationship. The spatial correlation pattern yields similar results for the instrumental and pre-instrumental period, indicating the consistency of the pre-instrumental field data with the instrumental GHD-spring/summer relationship. We find a previously undocumented second climate impact on the GHD. The winter temperature is significantly correlated with the GHD on decadal-to-multidecadal time scales and affects the GHD independently of the AAT. A multiple linear regression model, with AAT and decadal winter temperature as predictors, was found to be the best model to describe the GHD time series for the instrumental period. Stability tests of the correlations over time yield that both impacts on the GHD, AAT and decadal winter temperature, strengthen during the instrumental period. Using partial correlation analysis, we demonstrate that this is partly caused by a change in the winter–spring/summer temperature relationship. Summarising, the GHD is well suited to reconstruct interannual variations of the spring/summer temperature over large parts of Europe, even if the changing winter–spring/summer relation might affect the reconstruction in a second order. For decadal time scales, the December-to-August temperature shows the strongest relationship to the GHD and, therefore, proposes that the GHD can be used for European temperature reconstructions beyond the spring/summer season. Finally, we argue that our findings regarding the changed winter–spring/summer relation are relevant for physical and biological systems in several ways and should be analysed by other long-term proxy data and available model simulations.

FUNDAMENTO: A doença renal crônica (DRC) caracteriza-se pela alta prevalência de aterosclerose. Uma vez que o estresse oxidativo e a disfunção endotelial são promotores da aterosclerose, é interessante verificar se as duas condições estão associadas em pacientes com DRC, ainda sem doença cardiovascular (DCV) clínica. OBJETIVO: Avaliar as relações entre o estresse oxidativo e a função endotelial em pacientes com DRC estágio 5, sem DCV. MÉTODOS: Foram estudados 22 pacientes com DRC, não-diabéticos, não-fumantes, sem DCV e tratados por hemodiálise; além de 22 indivíduos normais. Em todos os indivíduos foram avaliados a reatividade vascular, dependente e independente de endotélio (ultra-som de alta resolução da artéria braquial), e o estresse oxidativo (níveis plasmáticos de substâncias reativas ao ácido tiobarbitúrico - TBARS). RESULTADOS: A reatividade vascular dependente de endotélio (6,0 ± 4,25% vs. 11,3 ± 4,46%, p FUNDAMENTO: La enfermedad renal crónica (ERC) se caracteriza por la alta prevalencia de aterosclerosis Siendo el estrés oxidativo y la disfunción endotelial promotores de la aterosclerosis, es interesante verificar si las dos condiciones están asociadas en pacientes con ERC, aun sin enfermedad cardiovascular (ECV) clínica. OBJETIVO: Evaluar las relaciones entre el estrés oxidativo y la función endotelial en pacientes con ERC estado 5, sin ECV. MÉTODOS: Se estudiaron 22 pacientes con ERC, no diabéticos, no fumadores, sin ECV y tratados por hemodiálisis; además de 22 individuos normales. En todos los individuos se evaluaron la reactividad vascular, dependiente e independiente de endotelio (ecografía de alta resolución de la arteria braquial), y el estrés oxidativo (niveles plasmáticos de sustancias reactivas al ácido tiobarbitúrico - TBARS). RESULTADOS: La reactividad vascular dependiente de endotelio (6,0 ± 4,25% vs. 11,3 ± 4,46%, p BACKGROUND: Chronic kidney disease (CKD) is characterized by the high prevalence of atherosclerosis. Considering that endothelial dysfunction and oxidative stress are promoters of atherosclerosis, it is of interest to verify whether the two conditions are associated in CKD patients still free of clinical cardiovascular disease (CVD). OBJECTIVE: To evaluate the association between oxidative stress and endothelial function in end-stage CKD patients without clinically evident CVD. METHODS: We studied 22 nondiabetic, nonsmoker CKD patients without clinical CVD treated by maintenance hemodialysis and 22 healthy controls. Endothelium- dependent and independent vascular reactivity and oxidative stress, as determined by the plasma levels of thiobarbituric acid-reactive substances - TBARS, were evaluated in all subjects. RESULTS: Endothelium-dependent (6.0 ± 4.25 vs. 11.3 ± 4.46 %, p< 0.001) and endothelium-independent (11.9 ± 7.68 vs. 19.1 % ± 6.43 %, p< 0.001) vascular reactivity were reduced, while TBARS (2.63 ± 0.51 vs. 1.49 ± 0.42 nmols/mL) was increased in CKD patients when compared to controls. TBARS levels were significantly related to endothelium-dependent vascular reactivity (r= - 0.56, p< 0.001) and to systolic blood pressure (r= - 0.48, p= 0.002). CONCLUSION: Oxidative stress is increased in CKD patients free of CVD and is associated with endothelial dysfunction in patients and controls. The results suggest that oxidative stress and endothelial dysfunction may be involved in the increased susceptibility of CKD patients to CVD and cardiovascular complications.