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A new method to assess the quality of additive manufacturing (AM) metal powders using the triboelectric charging concept is demonstrated using CpTi, Ti6Al4V, AlSi10Mg, IN 738, and SS 316L powders. For each powder tested, the surface chemical composition was first analyzed using X-ray photoelectron spectroscopy (XPS) to determine the composition of the passivation layer. Some modifications to the current GranuCharge™ setup, developed by GranuTools™, were then performed by incorporating a flow rate measuring tool to assess how tribocharging is affected as a function of flow rate. Variations in the tribocharging response have been found with the flow rate of CpTi, AlSi10Mg and SS 316L powders. Moreover, results suggest that the tribocharging behavior might not be the same even with powders fabricated with the same passivation process. Finally, the compressed exponential model of Trachenko and Zaccone was used to reproduce the tribocharging behavior of the powders. The models were found to work best when the stretch constant β = 1.5, which is identical to the value found in other systems such as structural glasses, colloidal gels, entangled polymers, and supercooled liquids, which experience jamming when motion of individual particles become restricted, causing their motion to slow down. [ABSTRACT FROM AUTHOR]

Metal-fused filament fabrication (MF3), which is a variation of the conventional fused filament fabrication (FFF), has recently gained interest due to its distinctive process flexibility and rapid prototyping capability to produce metallic parts. With respect to the additive manufacturing (AM) of aluminum alloys, most efforts have been centered on laser powder bed fusion technologies, with limited activities focused on binder-based processes due to challenges in the sintering of aluminum powders. With respect to MF3, one challenge for fabricating metallic components is the appropriate selection of a binder mixture, enabling the extrusion of a filament with high metallic volume content. In this paper, a mixture of biodegradable aliphatic polyester thermoplastic is used as a binder phase to act as the carrier for AlSi10Mg alloy powders. [ABSTRACT FROM AUTHOR]

Phasins are proteins located on the surface of poly-3-hydroxybutyrate (P3HB) granules that affect the metabolism of the polymer, the size and number of the granules, and some also have stress-protecting and growth-promoting effects. This study evaluated the effect of inactivating two new phasins (PhbP2 or PhbP3) on the cellular growth, production, and molecular mass of P3HB in cultures under low or high oxygen transfer rates (OTR). The results revealed that under high OTRₘₐₓ conditions (between 8.1 and 8.9 mmol L -1 h -1 ), the absence of phasins PhbP2 and PhbP3 resulted in a strong negative effect on the growth rate; in contrast, the rates of specific oxygen consumption increased in both cases. This behavior was not observed under a low oxygen transfer rate (3.9 ± 0.71 mol L -1 h -1 ), where cellular growth and oxygen consumption were the same for the different strains evaluated. It was observed that at high OTR, the absence of PhbP3 affected the production of P3HB, decreasing it by 30% at the end of cultivation. In contrast, the molecular weight remained constant over time. In summary, the absence of phasin PhbP3 significantly impacted the growth rate and polymer synthesis, particularly at high maximum oxygen transfer rates (OTRₘₐₓ).

Lactic acid has been applied as a precursor for hydrogen (H 2 ) production from substrates rich in lactic acid bacteria (LAB), focusing on microbial interactions between producing and consuming LAB tested with model substrates. Therefore, this study evaluated the effect of single and combined lactic acid-consuming bacteria on mesophilic H 2 production in batch tests from lactic acid from fermented food waste (FW). Megasphaera elsdenii, Clostridium beijerinckii, and Clostridium butyricum were inoculated at different ratios (v/v). Additionally, thermal pretreated sludge (TPS) was added to the strain mixtures. The highest production was obtained with M. elsdenii, C. beijerinckii, and C. butyricum (17:66:17 ratio), obtaining 1629.0 mL/L reactor . The optimal mixture (68:32:0 of M. elsdenii and C. beijerinckii) enriched with TPS reached 1739.3 ± 98.6 mL H 2 /L reactor , consuming 98 % of lactic acid added. M. elsdenii and Clostridium strains enhance H 2 production from lactic acid as they persist in a microbial community initially dominated by LAB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Lipoatrophia semicircularis is a benign pathology characterized by subcutaneous tissue atrophy that affects the skin and related structures. Its etiology remains unclear; however, in the recent few years, it has been proposed that electrostatic charges could be a potential factor. Based on this hypothesis, the aim of this work is to study the cause-effect relation between electrostatic energy and LS, providing insights into the molecular mechanisms. For this purpose, an experimental murine model was created using obese mice. One group served as a control and the other groups involved charging clothes with varying connections to the ground: through the skin, through the clothes or not connected to the ground). Skin biopsies showed that the most significant lesions, including lipophagic granulomas with inflammatory infiltrate, were found in the first group (connected to the ground through the skin). Lipophagic reactions without an inflammatory infiltrate were observed in the other groups subjected to electrical discharges. In the control mice, no histological changes were observed. Oxidative processes were also measured in lower limbs tissue. Malondialdehyde levels significantly increased in the lower limbs after electrostatic discharges. However, the presence of ground through a wire attached to highly conductive clothes around the thigh significantly reduced the effect of electrostatic charges on lipid peroxidation. To our knowledge, this is the first study in which an experimental model has been used to reproduce LS induced by electrostatic energy, suggesting a cause-effect relationship between electrostatic charge and discharge with fat tissue lesion.

Plant growth-promoting rhizobacteria, such as Bacillus spp., establish beneficial associations with plants and may inhibit the growth of phytopathogenic fungi. However, these bacteria are subject to multiple biotic stimuli from their competitors, causing stress and modifying their development. This work is a study of an in vitro interaction between two model microorganisms of socioeconomic relevance, using population dynamics and transcriptomic approaches. Co-cultures of Bacillus velezensis 83 with the phytopathogenic fungus Colletotrichum gloeosporioides 09 were performed to evaluate the metabolic response of the bacteria under conditions of non-nutritional limitation. The bacterial response was associated with the induction of a stress-resistant phenotype, characterized by a lower specific growth rate, but with antimicrobial production capacity. About 12% of co-cultured B. velezensis 83 coding sequences were differentially expressed, including the up-regulation of the general stress response (sigB regulon), and the down-regulation of alternative carbon sources catabolism (glucose preference). Defense strategies in B. velezensis are a determining factor in order to preserve the long-term viability of its population. Mostly, the presence of the fungus does not affect the expression of antibiosis genes, except for those corresponding to surfactin/bacillomycin D production. Indeed, the up-regulation of antibiosis genes expression is associated with bacterial growth, regardless of the presence of the fungus. This behavior in B. velezensis 83 resembles the strategy used by the classical Greek phalanx formation: by sacrificing growth rate and metabolic versatility, resources can be redistributed to defense (stress resistant phenotype) while maintaining the attack (antibiosis capacity). The presented results are the first characterization of the molecular phenotype at the transcriptome level of a biological control agent under biotic stress caused by a phytopathogen without nutrient limitation., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

RBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the contribution of rbfox1 to behaviour, we used rbfox1 sa15940 , a zebrafish mutant line with TL background. We found that rbfox1 sa15940 mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a second rbfox1 mutant line with a different genetic background (TU), rbfox1 del19 , and found that rbfox1 deficiency affects behaviour similarly in this line, although there were some differences. rbfox1 del19 mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity than rbfox1 sa15940 fish. Taken together, these results suggest that mutations in rbfox1 lead to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present in Rbfox1-deficient mice and in patients with different psychiatric conditions. Our study, thus, highlights the evolutionary conservation of rbfox1 function in behaviour and paves the way to further investigate the mechanisms underlying rbfox1 pleiotropy on the onset of neurodevelopmental and psychiatric disorders., (© 2024. The Author(s).)

RBFOX1 functions as a master regulator of thousands of genes, exerting a pleiotropic effect on numerous neurodevelopmental and psychiatric disorders. A potential mechanism by which RBFOX1 may impact these disorders is through its modulation of serotonergic neurotransmission, a common target for pharmacological intervention in psychiatric conditions linked to RBFOX1 . However, the precise effects of RBFOX1 on the serotonergic system remain largely unexplored. Here we show that homozygous rbfox1 sa15940 zebrafish, which express a shorter, aberrant rbfox1 mRNA, have significantly reduced serotonin levels in telencephalon and diencephalon. We observed that the acute administration of fluoxetine partially reverses the associated behavioural alterations. The hyperactive phenotype and altered shoaling behaviour of the rbfox1 sa15940/sa15940 zebrafish could be reversed with acute fluoxetine exposure in the Open Field and the Shoaling test, respectively. However, in the other paradigms, hyperactivity was not diminished, suggesting a distinct intrinsic motivation for locomotion in the different paradigms. Acute fluoxetine exposure did not reverse the alterations observed in the aggression and social novelty tests, suggesting the involvement of other neurological mechanisms in these behaviours. These findings underscore the importance of investigating the intricate working mechanisms of RBFOX1 in neurodevelopmental and psychiatric disorders to gain a better understanding of the associated disorders along with their pharmacological treatment.

The protein kinase D (PKD) family members regulate the fission of cargo vesicles at the Golgi complex and play a pro-oncogenic role in triple-negative breast cancer (TNBC). Whether PKD facilitates the secretion of tumor-promoting factors in TNBC, however, is still unknown. Using the pharmacological inhibition of PKD activity and siRNA-mediated depletion of PKD2 and PKD3, we identified the PKD-dependent secretome of the TNBC cell lines MDA-MB-231 and MDA-MB-468. Mass spectrometry-based proteomics and antibody-based assays revealed a significant downregulation of extracellular matrix related proteins and pro-invasive factors such as LIF, MMP-1, MMP-13, IL-11, M-CSF and GM-CSF in PKD-perturbed cells. Notably, secretion of these proteins in MDA-MB-231 cells was predominantly controlled by PKD2 and enhanced spheroid invasion. Consistently, PKD-dependent secretion of pro-invasive factors was more pronounced in metastatic TNBC cell lines. Our study thus uncovers a novel role of PKD2 in releasing a pro-invasive secretome., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Introduction: Co-occurrence of substance use disorders (SUD) and other behavioral conditions, such as stress-related, aggressive or risk-taking behaviors, in the same individual has been frequently described. As dopamine (DA) and serotonin (5-HT) have been previously identified as key neurotransmitters for some of these phenotypes, we explored the genetic contribution of these pathways to SUD and these comorbid phenotypes in order to better understand the genetic relationship between them., Methods: We tested the association of 275 dopaminergic genes and 176 serotonergic genes with these phenotypes by performing gene-based, gene-set and transcriptome-wide association studies in 11 genome-wide association studies (GWAS) datasets on SUD and related behaviors., Results: At the gene-wide level, 68 DA and 27 5-HT genes were found to be associated with at least one GWAS on SUD or related behavior. Among them, six genes had a pleiotropic effect, being associated with at least three phenotypes: ADH1C , ARNTL , CHRNA3, HPRT1 , HTR1B and DRD2 . Additionally, we found nominal associations between the DA gene sets and SUD, opioid use disorder, antisocial behavior, irritability and neuroticism, and between the 5-HT-core gene set and neuroticism. Predicted gene expression correlates in brain were also found for 19 DA or 5-HT genes., Discussion: Our study shows a pleiotropic contribution of dopaminergic and serotonergic genes to addiction and related behaviors such as anxiety, irritability, neuroticism and risk-taking behavior, highlighting a role for DA genes, which could explain, in part, the co-occurrence of these phenotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Antón-Galindo, Cabana-Domínguez, Torrico, Corominas, Cormand and Fernàndez-Castillo.)

Clinical manifestations related to hypomagnesemia and/or deficiency of vitamin D are frequent in patients with an extended course of coronavirus disease-2019 (long COVID). To evaluate hypomagnesemia and hydroxyvitamin D deficiency in patients with long COVID. A total of 125 adults with a diagnosis of long COVID were enrolled in a cross-sectional study. Participants were allocated into a risk (hypomagnesemia and hydroxyvitamin D deficiency) or control (serum magnesium and hydroxyvitamin D within normal ranges) group. Hypomagnesemia and 25-hydroxyvitamin D deficiency were defined based on serum level ≤1.8 mg/dL and <30 ng/mL, respectively. The number of clinical manifestations of long COVID were significantly higher in the risk compared to the control group. Fatigue, memory loss, attention disorders, joint pain, anxiety, sleep disorders, myalgia, and depression, all of which are related to hypomagnesemia and/or 25-hydroxyvitamin D deficiency, were among the 10 most frequent manifestations in the risk group. The adjusted odds ratio for the association between hypomagnesemia and hydroxyvitamin D deficiency during long COVID was 3.1; 95% CI 2.3-12.4, p=0.005. Our results show that patients suffering with long COVID had a deficiency in magnesium and 25-hydroxyvitamin D which correlated with the number of associated clinical manifestations.

Symptoms in the acute phase of Chagas disease are usually mild and nonspecific. However, after several years, severe complications like dilated heart failure and even death may arise in the chronic phase. Due to the lack of specific symptoms in the acute phase, the aim of this work was to describe and analyze the cardiac histopathology during this phase in a CD1 mouse model by assessing parasitism, fibrotic damage, and the presence and composition of a cellular infiltrate, to determine its involvement in the pathogenesis of lesions in the cardiac tissue. Our results indicate that the acute phase lasts about 62 days post-infection (dpi). A significant increase in parasitemia was observed since 15 dpi, reaching a maximum at 33 dpi (4.1 × 10 6 ). The presence of amastigote nests was observed at 15-62 dpi, with a maximum count of 27 nests at 35 dpi. An infiltrate consisting primarily of macrophages and neutrophils was found in the cardiac tissue within the first 30 days, but the abundance of lymphocytes showed an 8 ≥ fold increase at 40-62 dpi. Unifocal interstitial fibrosis was identified after 9 dpi, which subsequently showed a 16 ≥ fold increase at 40-60 dpi, along with a 50% mortality rate in the model under study. The increased area of fibrotic lesions revealed progression in the extent of fibrosis, mainly at 50-62 dpi. The presence of perivasculitis and thrombus circulation disorders was seen in the last days (62 dpi); finally, cases of myocytolysis were observed at 50 and 62 dpi. These histopathological alterations, combined with collagen deposition, seem to lead to the development of interstitial fibrosis and damage to the cardiac tissue during the acute phase of infection. This study provides a more complete understanding of the patterns of histopathological abnormalities involved in the acute phase, which could help the development of new therapies to aid the preclinical tests of drugs for their application in Chagas disease.

Ultrasound-assisted extraction (UAE) is an efficient and sustainable method for extracting bioactive compounds from agro-industrial by-products. Moreover, it has been reported that ultraviolet A (UVA) radiation can induce the biosynthesis and accumulation of bioactive phenolic compounds. This study optimized the efficiency of ultrasound-assisted extraction (UAE) for recovering ultraviolet A (UVA)-induced phenolic compounds in strawberry by-products (RF-N). The impact of three factors (solid-liquid ratio, ethanol concentration, and ultrasound power) on total phenolic compound (TPC) kinetics using Peleg's model was investigated. The developed model showed a suitable fit for both RF-N and strawberry by-products treated with UVA (RF-E). The optimal UAE conditions obtained were of a 1:30 ratio, 46% ethanol, and 100% ultrasound power, resulting in an average yield of 13 g total phenolics kg -1 . The bioaccessibility of phenolic compounds during in-vitro digestion was 36.5%, with agrimoniin being the predominant compound. UAE combined with UVA treatment increased the bioactivity of RF extracts, displaying significant anti-proliferative effects on HT29 and Caco-2 cancer cell lines, as well as anti-inflammatory potential and cellular antioxidant activity. The ultrasound proved to be a sustainable and effective technique for extracting phenolic compounds from RF, contributing to the valorization of strawberry agro-industrial by-products, and maximizing their nutraceutical potential.

Introduction: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors., Methods: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR)., Results: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not., Conclusion: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Protein kinase D (PKD) is a serine/threonine kinase family that controls important cellular functions, most notably playing a key role in the secretory pathway at the trans-Golgi network. Aberrant expression of PKD isoforms has been found mainly in breast cancer, where it promotes various cellular processes such as growth, invasion, survival and stem cell maintenance. In this review, we discuss the isoform-specific functions of PKD in breast cancer progression, with a particular focus on how the PKD controlled cellular processes might be linked to deregulated membrane trafficking and secretion. We further highlight the challenges of a therapeutic approach targeting PKD to prevent breast cancer progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gutiérrez-Galindo, Yilmaz and Hausser.)

Background: In research and production, reproducibility is a key factor, to meet high quality and safety standards and maintain productivity. For microbial fermentations, complex substrates and media components are often used. The complex media components can vary in composition, depending on the lot and manufacturing process. These variations can have an immense impact on the results of biological cultivations. The aim of this work was to investigate and characterize the influence of the complex media component yeast extract on cultivations of Azotobacter vinelandii under microaerobic conditions. Under these conditions, the organism produces the biopolymer alginate. The focus of the investigation was on the respiration activity, cell growth and alginate production., Results: Yeast extracts from 6 different manufacturers and 2 different lots from one manufacturer were evaluated. Significant differences on respiratory activity, growth and production were observed. Concentration variations of three different yeast extracts showed that the performance of poorly performing yeast extracts can be improved by simply increasing their concentration. On the other hand, the results with well-performing yeast extracts seem to reach a saturation, when their concentration is increased. Cultivations with poorly performing yeast extract were supplemented with grouped amino acids, single amino acids and micro elements. Beneficial results were obtained with the supplementation of copper sulphate, cysteine or a combination of both. Furthermore, a correlation between the accumulated oxygen transfer and the final viscosity (as a key performance indicator), was established., Conclusion: The choice of yeast extract is crucial for A. vinelandii cultivations, to maintain reproducibility and comparability between cultivations. The proper use of specific yeast extracts allows the cultivation results to be specifically optimised. In addition, supplements can be applied to modify and improve the properties of the alginate. The results only scratch the surface of the underlying mechanisms, as they are not providing explanations on a molecular level. However, the findings show the potential of optimising media containing yeast extract for alginate production with A. vinelandii, as well as the potential of targeted supplementation of the media., (© 2023. The Author(s).)

In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The factors underlying the evolution of lesions following infection by Trypanosoma cruzi and, in some cases, the persistence of its antigens and the host response, with the ensuing development of clinically observable cardiac damage, are analyzed in this review.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder resulting from the interaction between genetic and environmental risk factors. It is well known that ADHD co-occurs frequently with other psychiatric disorders due, in part, to shared genetics factors. Although many studies have contributed to delineate the genetic landscape of psychiatric disorders, their specific molecular underpinnings are still not fully understood. The use of animal models can help us to understand the role of specific genes and environmental stimuli-induced epigenetic modifications in the pathogenesis of ADHD and its comorbidities. The aim of this review is to provide an overview on the functional work performed in rodents, zebrafish and fruit fly and highlight the generated insights into the biology of ADHD, with a special focus on genetics and epigenetics. We also describe the behavioral tests that are available to study ADHD-relevant phenotypes and comorbid traits in these models. Furthermore, we have searched for new models to study ADHD and its comorbidities, which can be useful to test potential pharmacological treatments., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The revalorization of agro-industrial by-products by applying ultraviolet A (UVA) radiation to biofortify with phenolic compounds has been studied in recent times, showing improvements in the individual and total phenolic content and their bioactivity. Therefore, the main aim of this work was to optimize the biofortification process of phenolic compounds by UVA radiation to strawberry agro-industrial by-products (RF). Moreover, the effect of UVA radiation on the potential biological activity of the phenolics accumulated in RF due to the treatment was also determined., Methods: The assays followed a factorial design with three variables at three levels: UVA dose (LOW, MEDIUM, and HIGH), storage temperature (5, 10, and 15°C), and storage time (0, 24, 48, and 72 h). At each experimental condition, phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO) enzymatic activities, total phenolic compound content (TPC), phenolics profile (TPC HPLC ), and agrimoniin content (AGN) were evaluated; and the optimal UVA dose, storage time, and temperature were determined. In vitro bioaccessibility of the accumulated phenolic compound was studied on RF tissue treated with UVA at optimal process conditions. The digested extracts were tested for antiproliferative activity in colorectal cancer cells, cellular antioxidant capacity, and anti-inflammatory activity., Results: The results showed that applying UVA-HIGH (86.4 KJ/m 2 ) treatment and storing the tissue for 46 h at 15°C increased PAL activity (260%), phenolic content (240%), and AGN (300%). The biofortification process improves the bioaccessibility of the main phenolic compound of RF by 9.8 to 25%. The digested optimum extract showed an IC50 for HT29 and Caco-2 cells of 2.73 and 5.43 μg/mL, respectively, and presented 60% cellular antioxidant capacity and 30% inhibition of NOX production., Conclusion: The RF treated with UVA is an excellent source of phenolic compounds; specifically, ellagitannins and the UVA radiation proved to be efficient in biofortify RF, significantly improving the phenolic compounds content and their bioactive properties with adequate bioaccessibility, adding value to the strawberry agro-industrial by-products., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Villamil-Galindo, Antunes-Ricardo, Piagentini and Jacobo-Velázquez.)

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability., (© 2022. The Author(s).)

Traditional agave spirits such as mezcal or tequila are produced all over Mexico using different species of Agave . Amongst them, A. angustifolia is the most popular given its agricultural extension. A. angustifolia is a wild species extensively distributed from North to Central America, and previous studies show that it is highly related to the tequila agave A. tequilana . In different regions of Mexico, A. angustifolia is cultivated under different types and levels of management, and although traditional producers identify several landraces, for the non-trained eye there are no perceivable differences. After interviews with producers from different localities in Jalisco, Mexico, we sampled A. angustifolia plants classified as different landraces, measured several morphological traits, and characterized their genetic differentiation and diversity at the genome-wide level. We included additional samples identified as A. tequilana and A. rhodacantha to evaluate their relationship with A. angustifolia . In contrast with previous studies, our pool of ca 20K high quality unlinked SNPs provided more information and helped us to distinguish different genetic groups that are congruent with the ethnobotanical landraces. We found no evidence to genetically delimitate A. tequilana , A. rhodacantha and A. angustifolia . Our large genome level dataset allows a better understanding of the genetic identity of important A. angustifolia traditional and autochthonous landraces.

Primary cilia are hair-like protrusions of the plasma membrane that function as cellular antennae and are present on most cells in the human body. Primary cilia dysfunction leads to severe diseases, commonly termed 'ciliopathies'. A significant symptom of certain ciliopathies is obesity, and current research aims to identify contributing mechanisms of obesity development in these patients. Western lifestyle-associated factors can trigger chronic inflammation, or metaflammation, which can also attribute to obesity-associated metabolic disorders. However, obese individuals can also be 'metabolically healthy', as discussed for a subset of patients with obesity and ciliopathy. Here, we propose that primary cilia signaling might modulate specific immune cell phenotypes, behaviors, and functions, which might impact inflammatory responses in the context of ciliopathies and beyond., Competing Interests: Declaration of interest The authors declare no conflicting interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: According to the International League Against Epilepsy (ILAE) criteria, epilepsy can be diagnosed after one unprovoked (or reflex) seizure when there is a ≥60% of seizure recurrence in the next decade. The application of this diagnostic criterion, however, is challenging because the risk of recurrence based on different etiologies is not easily retrievable from the literature., Objective: To assess etiologies that permit a diagnosis of epilepsy after a single unprovoked seizure., Methods: We conducted a systematic review of the literature search using PubMed, Scopus, and Cochrane library from January 1950 to December 2020 with the keywords: recurrence, risk of recurrence, absolute risk, risk ratio, risk, seizures, epilepsy, structural, infectious, metabolic, immune, and genetic. We included articles that reported estimates of risks of a subsequent unprovoked seizure. Etiologies were categorized according to the ILAE epilepsy classification. The quality of the evidence was evaluated with PRISMA. Descriptive statistics were used., Results: A total of 25,044 articles resulted from searching three databases. After authors removed duplicates, 18,911 articles remained. We screened by title and abstract, 40 articles were reviewed and finally, two articles were included. The mean follow-up was 8 years and the mean for a risk to present a subsequent unprovoked seizure was 66.6% and included structural etiologies as stroke, traumatic brain injury, cavernous malformation, arteriovenous malformation, and neuroinfections (unspecified agents). Study quality characteristics are classified with low strength of evidence and moderate-quality cohort., Conclusions: We found that stroke, traumatic brain injury, cavernous or arteriovenous malformations, and unspecified CNS infections can meet the epilepsy diagnosis after one unprovoked seizure based on low strength of evidence and moderate quality of cohorts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Global pandemics like Zika (ZIKV) factor into pregnancy planning and avoidance, yet little is known about how primary care providers (PCPs) incorporate public health guidance into contraceptive counseling. Study objectives include: 1) determining the impact of the ZIKV pandemic on contraceptive counseling changes; and 2) assessing PCP knowledge and practice regarding contraception, ZIKV, and CDC ZIKV guidelines., Methods: Study components included: (1) a retrospective review of electronic health records of non-pregnant, reproductive age women presenting for preventive health visits between 2014 and 2017 assessed using interrupted time series analyses (ITSA) to identify changes in documentation of ZIKV risk assessment and contraceptive counseling; and (2) a sequential, cross-sectional study with quantitative surveys and qualitative, semi-structured interviews of PCPs providing preventive care to non-pregnant patients at eight federally qualified health centers in Utah. We performed descriptive analyses on survey data and analyzed qualitative data for dominant themes using a modified Health Belief Model., Results: We conducted 6634 chart reviews yielding 9840 visits. The ITSA did not reveal changes in ZIKV risk assessment or contraceptive counseling. Twenty-two out of 40 (55%) eligible providers participated in the provider component. Participants averaged 69 and 81% correct on contraceptive and ZIKV knowledge questions, respectively. Sixty-five percent reported counseling consistent with CDC ZIKV guidelines. Qualitative analysis found providers unlikely to prioritize ZIKV risk assessment in contraceptive counseling for non-pregnant patients., Conclusions: PCPs who care for non-pregnant women are knowledgeable about contraception and ZIKV; however, there was no change in ZIKV risk assessment or contraceptive counseling. This stresses the importance of developing strategies to improve guideline uptake., (© 2021. The Author(s).)

Bacillus spp. are well known plant growth promoting bacteria (PGPB) and biological control agents (BCA) due to their capacity to synthesize a wide variety of phytostimulant and antimicrobial compounds. B. velezensis 83 is a strain marketed in Mexico as a foliar biofungicide (Fungifree AB™) which has been used for biological control of five different genera of phytopathogenic fungi ( Colletotrichum, Erysiphe, Botrytis, Sphaerotheca, Leveillula ) in crops of agricultural importance such as mango, avocado, papaya, citrus, tomato, strawberry, blueberry, blackberry and cucurbits, among others. In this work, the potential of plant growth promotion of B. velezensis 83 was evaluated on different phenological stages of tomato plants as well as the biocontrol efficacy of B. velezensis 83 formulations (cells and/or metabolites) against B. cinerea infection on leaves and postharvest fruits. Greenhouse grown tomato plants inoculated with a high concentration (1 × 10 8 CFU/plant) of B. velezensis 83 yielded 254 tons/Ha•year of which the 64% was first quality tomato (≥100 g/fruit), while the control plants produced less than 184 tons/Ha•year with only 55% of first quality tomato. Additionally, in vitro assays carried out with leaves and fruits, shown that the B. velezensis 83 cells formulation had an efficacy of control of B. cinerea infection of ∼31% on leaves and ∼89% on fruits, while the metabolites formulation had an efficacy of control of less than 10%. Therefore, it was concluded that spores (not the metabolites) are the main antagonism factor of Fungifree AB™. The high effectivity of B. cinerea control on fruits by B. velezensis 83, opens the possibility for a postharvest use of this biofungicide., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V.)

Introduction: The pandemics crisis had consequences in psychological adjustment of persons all over the world. The current study analyzes comparatively the topics of quality of life, and well-being, considering as predictors trait anxiety, feeling of threat, difficulty to relax, empathy and pro-social attitude, health care, sleep quality and optimism, in a population of German and Portuguese adults during the pandemics, in order to obtain a deeper understanding of the psychological reactions to crisis across countries and cultures. Methods: A sample of 470 adults divided in three age groups - -young adults (18-34 years), middle-age adults (34-54 years) and old adults (55 years and older)- completed a self-report questionnaire assessing socio-demographic data, quality of life, well-being, quality of sleep, trait anxiety, Coronavirus threat, optimism regarding the pandemics, difficulty to relax, empathy, and pro-social attitude during the pandemics period. Results: Portuguese participants expresses higher empathy and pro-social attitude and health care but in Germany people have higher quality of sleep. Young adults (a) rated their quality of life lower than middle-age adults and old adults, (b) showed also lower optimism than middle-age and old adults, and (c) showed lower well-being than middle-age,. Conclusions: Young adults rated their quality of life, optimism and well-being during pandemics lower than middle-age and old adults, and experienced higher levels of trait anxiety and difficulty to relax. It seems that young adults show a lower psychological adjustment than other age groups during COVID-19 crisis. It is concluded that quality of life, optimism, and well-being during the pandemics are affected differently according to country and group of age, suggesting individual differences across cultures and ages, and consequently the need of specific interventions to cope with the psychological reactions to pandemics crisis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Candeias, Galindo, Stueck, Portelada and Knietzsch.)

In an environment characterized by high unemployment rates among people with disabilities, the objective of the present work is to analyze entrepreneurship as a labor option which fully inserts people with intellectual disabilities (PwID) into their societies. In order to carry out this research, a case study methodology based on social network analysis has been adopted, given the nature of the variables analyzed. The results indicate that the fact of having managed to start up the company has been an important source of self-confidence and inspiration, as well as increasing and intensifying the social networks of PwID involved in the entrepreneurial project., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barba-Sánchez, Salinero, Jiménez-Estevez and Galindo.)