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The growing demand for cost-effective and wireless sensing technologies requires the development of simple, efficient and optimized sensors able to accurately detecting external agents. Magnetoelastic resonators represent an alternative to the traditional sensing systems, able to combine all the previously cited factors. Several studies have focused on increasing their sensitivity, in order to make it closer to the market. The present study explores thermal treatments as a novel approach to enhance the sensitivity of magnetoelastic resonators, focusing on the positive impact of crystallization processes induced in magnetoelastic platforms. The experimental results confirm an enhancement of resonant frequency and quality factor of the magnetoelastic platforms as treatment temperature increases. Particularly, the sensor annealed at 550 °C shows an increase of the resonant frequency value of 45 % with respect to the as-quenched platform, being that increase of around 1700 % for the quality factor. In addition, the nanocrystallization induction leads to a self-biased resonance, consequence of the intrinsic magnetization resulting from the crystallization in Fe2B and FeCo phases. Further, the study shows the importance of stability in resonant frequency, emphasizing the potential of the 550 °C-annealed platform for mass sensor applications. Gold deposition experiments reveal the enhanced sensitivity of the sensor annealed at 550 °C of 40 % compared to the as-quenched sensor, as well as an increase of 38 % on its accuracy. These findings represent a significant step forward in the development of magnetoelastic-based mass sensors, highlighting the pivotal role of thermal treatments in optimizing sensitivity for practical and efficient external agents detection systems.

This paper conducted a systematic literature review (SLR) of peer-review documents focused on residential energy consumption. The main finding of this SLR derived from its computational implementation, filling a gap in the available literature. The paper had two main objectives: (i) the SLR itself; and (ii) to systematically identify the main policy measures oriented at reducing energy consumption recommended by the available literature and its related greenhouses gas emissions. A significant lack of a connection between scientific fields was identified. The fields of energy, engineering and environmental science are those that have addressed these topics the most. The sub-field with the largest presence is energy, with 29.5%, followed by engineering (23.9%) and the environment (21.3%). It is recommended that this gap be bridged because many of the main political measures in force to reduce residential energy consumption come from economics and need to be explored from a social science perspective to choose those measures that are more cost-effective.

Abstract Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight.

The tandem-repeat Galectin-4 (Gal-4) contains two different domains covalently linked through a short flexible peptide. Both domains have been shown to bind preferentially to A and B histo blood group antigens with different affinities, although the binding details are not yet available. The biological relevance of these associations is unknown, although it could be related to its attributed role in pathogen recognition. The presentation of A and B histo blood group antigens in terms of peripheral core structures differs among tissues and from that of the antigen-mimicking structures produced by pathogens. Herein, the binding of the N-terminal domain of Gal-4 toward a group of differently presented A and B oligosaccharide antigens in solution has been studied through a combination of NMR, isothermal titration calorimetry (ITC), and molecular modeling. The data presented in this paper allow the identification of the specific effects that subtle chemical modifications within this antigenic family have in the binding to the N-terminal domain of Gal-4 in terms of affinity and intermolecular interactions, providing a structural-based rationale for the observed trend in the binding preferences.

Among glycan-binding proteins, galectins, β-galactoside-binding lectins, exhibit relevant biological roles and are implicated in many diseases, such as cancer and inflammation. Their involvement in crucial pathologies makes them interesting targets for drug discovery. In this review, we gather the last approaches toward the specific design of glycomimetics as potential drugs against galectins. Different approaches, either using specific glycomimetic molecules decorated with key functional groups or employing multivalent presentations of lactose and N-acetyl lactosamine analogs, have provided promising results for binding and modulating different galectins. The review highlights the results obtained with these approximations, from the employment of S-glycosyl compounds to peptidomimetics and multivalent glycopolymers, mostly employed to recognize and/or detect hGal-1 and hGal-3.

Background: Dimensional models of psychopathology demonstrate that two correlated factors of fear and distress account for the covariation among depressive and anxiety disorders. Nevertheless, these models tend to exclude variables relevant to psychopathology, such as temperament traits. This study examined the joint structure of DSM-IV-based major depression and anxiety disorders along with trait negative affect in a representative sample of adult individuals residing in the cities of São Paulo and Rio de Janeiro, Brazil. Methods: The sample consisted of 3,728 individuals who were administered sections D (phobic, anxiety and panic disorders) and E (depressive disorders) of the Composite International Diagnostic Interview (CIDI) 2.1 and a validated version of the Positive and Negative Affect Schedule. Data were analyzed using correlational and structural equation modeling. Results: Lifetime prevalence ranged from 2.4% for panic disorder to 23.2% for major depression. Most target variables were moderately correlated. A two-factor model specifying correlated fear and distress factors was retained and confirmed for models including only diagnostic variables and diagnostic variables along with trait negative affect. Conclusions: This study provides support for characterization of internalizing psychopathology and trait negative affect in terms of correlated dimensions of distress and fear. These results have potential implications for psychiatric taxonomy and for understanding the relationship between temperament and psychopathology.

Objetivo: Valorar la utilidad del control ponderal como método rutinario de garantía de calidad en la preparación de las unidades nutrientes parenterales (UNP). Material y métodos: En acuerdo con su frecuencia de utilización se seleccionaron dos formulaciones de nutrición parenteral, una de preparación externa (NP-I) y otra de preparación interna (NPH-2500). Como variable respuesta se utiliza la diferencia relativa entre el peso experimental y el peso teórico. Esta diferencia, expresada en porcentaje, define el error gravimétrico de preparación (EGP). El control ponderal se realizó sobre 615 UNP, de las cuales 337 (55%) corresponden a la formulación NPH-2500 y 278 (45%) a la formulación NP-I. La calidad de la preparación de las UNP se establece mediante el cálculo de la exactitud (media del EGP) y la precisión (raíz cuadrada de la media del cuadrado de los EGP), y se definieron los límites de alerta e invalidación de estos parámetros. La utilidad del control ponderal se estableció mediante el tiempo necesario para detectar un error gravimétrico de preparación superior al 5%. Resultados: La prevalencia global de un EGP mayor del 5% es inferior al 0,6% (IC 95%: 0,0 a 0,6%). La exactitud global fue 1,01% (IC 95%: 0,96 a 1,05%). La diferencia entre la exactitud de la NPH-2500, 0,66% (IC 95%: 0,62 a 0,70%), y la NPI, 1,42% (IC 95%: 1,36 a 1,49%) fue estadísticamente significativa. El porcentaje de UNP situado fuera de los límites de invalidación de la precisión fue significativamente superior en la formulación NPH-2500, 2,67% (IC 95%: 2,36 a 3,00%), que en la formulación NP-1, 0,36% (IC 95%: 0,25 a 0,49%). En el resto de casos no se detectaron diferencias estadísticamente significativas. Conclusión: El control ponderal es una estrategia que, posiblemente, de forma conjunta a otros métodos, complemente los procesos de garantía de calidad definidos para mejorar la preparación de unidades nutrientes parenterales.Objective: To assess the usefulness of weight monitoring as a routine quality assurance method in the preparation of parenteral nutrient units (PUNs). Material and methods: In accordance with their frequency of use, two parenteral nutrition formulations were chosen, one prepared externally (NP-I) and the other internally (NPH-2500). The relative difference between the experimental weight and the theoretical weight was used as the response variable. This difference, expressed as a percentage, defines the preparation gravimetric error (EGP in its Spanish acronym) Weight monitoring was effected on 615 PUNs, of which 337 (55%) corresponded to the NPH-2500 formulation and 278 (45%) to the NP-I formulation. The quality of the preparation of the PUNs was established by means of the calculation of the exactness (mean EGP) and precision (square root of the mean of the squares of the EGP values), and the alert and invalidation limits for these parameters were defined. The usefulness of weight monitoring was established by the time needed to detect a preparation gravimetric error of more than 5%. Results: The overall prevalence of EGP in excess of 5% was less than 0.6% (95% CI: 0.0 to 0.6%). The overall exactness was 1.01% (95% CI: 0.96 to 1.05%). The difference between the exactness of NPH-2500, 0.66% (95% CI: 0.62 to 0.70%), and NP-I, 1.42% (95% CI: 1.36 to 1.49%), was statistically significant. The percentage of PUNs located outside the limits of invalidation for precision was significantly higher in the NPH-2500 formulation, 2.67% (95% CI: 2.36 to 3.00%), than in the NP-I formulation, 0.36% (95% CI: 0.25 to 0.49%). No statistically significant differences were detected in the remaining cases. Conclusion: Weight monitoring is a strategy that, possibly in combination with other methods, may complement the quality assurance processes defined to improve the preparation of parenteral nutrient units.

The tensile fracture strength of a sandwich panel, with a center-cracked core made from an elastic-brittle diamond-celled honeycomb, is explored by analytical models and finite element simulations. The crack is on the midplane of the core and loading is normal to the faces of the sandwich panel. Both the analytical models and finite element simulations indicate that linear elastic fracture mechanics applies when a K-field exists on a scale larger than the cell size. However, there is a regime of geometries for which no K-field exists; in this regime, the stress concentration at the crack tip is negligible and the net strength of the cracked specimen is comparable to the unnotched strength. A fracture map is developed for the sandwich panel with axes given by the sandwich geometry. The effect of a statistical variation in the cell-wall strength is explored using Weibull theory, and the consequences of a stochastic strength upon the fracture map are outlined. [DOI: 10.1115/1.2912995] Keywords: finite element analysis, fracture, toughness, elastic behaviour, lattice materials

Aim: To study whether additional measurements of motility characteristics of spermatozoa by computer assisted semen analysis (CASA) were more sensitive indicators of reduced semen quality than estimates of percentages of motile, rapid or progressive cells. Methods: Intermittent scrotal insulation was applied to 6 rams for 16 h per day for 21 days or to 2 of these for 12 h per day for 28 days in the following year. Semen was collected and evaluated by CASA immediately and either frozen or stored at 30°C or 5°C before re-evaluation. Results: Intermittent scrotal insulation caused falls in the percentage of motile, progressive and rapid sperm, as did freezing-thawing and storage at 30°C or 5°C. Motility characteristics (amplitude of lateral head displacement, mean path velocity, mean progressive velocity and curvilinear velocity), as determined by CASA fell only when the percentage of motile sperm was already reduced. Freezing and thawing or liquid storage of the semen from insulated rams caused a greater fall in the percentage of motile and rapid sperm than control semen, but only affected the motility characteristics when the percentage of motile sperm was already reduced. Conclusion: Intermittent scrotal insulation affected not only the motility of the freshly collected sperm, but also their ability to withstand the additional stress of storage. The additional data on motility characteristics obtained by CASA appeared to be no more a sensitive indicator than the percentage of motile cells of reductions in semen quality. [ABSTRACT FROM AUTHOR]

Background: Sports supplements (SSs) are widely used among team sport athletes; however, evidence supporting the use of SSs among football referees at the elite level is scarce. The aim of the present study was to analyze the consumption of SSs among referees with respect to their level of competition and referee type (main referees (MRs) vs. assistant referees (ARs))., Methods: A total of 106 football referees participated in this study, with 46.2% from the First Spanish Division and 53.8% from the Second Spanish Division, representing 84.13% of the total number of referees. Each participant completed a validated questionnaire about SS consumption, with the SSs classified according to the Australian Institute of Sport (AIS) ABCD system: Group A has strong evidence for enhancing athlete health and performance, Group B shows potential benefits but needs more evidence, Group C has inconclusive evidence against use, and Group D includes prohibited substances., Results: A total of 84.0% of the MRs and ARs reported the consumption of at least one SS. Differences were found only in the consumption of medical supplements between division ( p = 0.016) and type of referee ( p = 0.041), though no significant differences were found among the remaining AIS SS categories ( p > 0.05). Sport performance (49.6%), Internet (41.0%), and dietitian-nutritionists (31.7%) were the primary reason for SS consumption, purchase location, and source of information, respectively. The most frequently consumed SS were whey protein (45.3%), followed by creatine (33.0%), sport bars and sports drinks (28.3%), and caffeine (19.8%)., Conclusions: MRs and ARs reported a high prevalence of dietary supplement (SS) consumption, with significant differences between division and referee type observed only in medical supplement consumption.

Premise: The GlobalTree Portal, hosted by Botanic Gardens Conservation International, provides access to information on the approximately 58,000 tree species worldwide. Included in the GlobalTree Portal is the Conservation Action Tracker, a dynamic and collaborative database to identify and monitor conservation actions for tree species globally., Methods: The Conservation Action Tracker collates conservation action information at the species level, including species recovery/action plans, ex situ collections, propagation protocols, in situ management, species protection policy, and education/awareness campaigns., Results: To date, the Conservation Action Tracker contains conservation action information for 4126 tree species, including 2161 threatened species, of which 659 are classified as Vulnerable, 783 as Endangered, and 719 as Critically Endangered. It covers conservation action information for at least one tree species in every country; however, more information is needed for 89% of Vulnerable, 87% of Endangered, and 77% of Critically Endangered tree species., Discussion: Monitoring species conservation actions can support the prioritization and scaling up of conservation practices by sharing knowledge, increasing collaboration, enabling the identification of conservation gaps, and making the information available to be used by decision-makers. Tracking conservation actions at the species level is, therefore, essential to guide future conservation efforts. Increasing the amount of data in the Conservation Action Tracker will improve the tool's ability to guide future conservation efforts and avoid the extinction of tree species., (© 2024 The Authors. Applications in Plant Sciences published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Cystathionine γ-lyase (CGL) is a PLP-dependent enzyme that catalyzes the last step of the reverse transsulfuration route for endogenous cysteine biosynthesis. The canonical CGL-catalyzed process consists of an α,γ-elimination reaction that breaks down cystathionine into cysteine, α-ketobutyrate, and ammonia. In some species, the enzyme can alternatively use cysteine as a substrate, resulting in the production of hydrogen sulfide (H 2 S). Importantly, inhibition of the enzyme and consequently of its H 2 S production activity, makes multiresistant bacteria considerably more susceptible to antibiotics. Other organisms, such as Toxoplasma gondii, the causative agent of toxoplasmosis, encode a CGL enzyme (TgCGL) that almost exclusively catalyzes the canonical process, with only minor reactivity to cysteine. Interestingly, the substitution of N360 by a serine (the equivalent amino acid residue in the human enzyme) at the active site changes the specificity of TgCGL for the catalysis of cystathionine, resulting in an enzyme that can cleave both the CγS and the CβS bond of cystathionine. Based on these findings and to deepen the molecular basis underlying the enzyme-substrate specificity, we have elucidated the crystal structures of native TgCGL and the variant TgCGL-N360S from crystals grown in the presence of cystathionine, cysteine, and the inhibitor d,l-propargylglycine (PPG). Our structures reveal the binding mode of each molecule within the catalytic cavity and help explain the inhibitory behavior of cysteine and PPG. A specific inhibitory mechanism of TgCGL by PPG is proposed., (© 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Background: Autism spectrum condition or 'autism' is associated with numerous genetic risk factors including the polygenic 16p11.2 microdeletion. The balance between excitatory and inhibitory neurons in the cerebral cortex is hypothesised to be critical for the aetiology of autism making improved understanding of how risk factors impact on the development of these cells an important area of research. In the current study we aim to combine bioinformatics analysis of human foetal cerebral cortex gene expression data with anatomical and electrophysiological analysis of a 16p11.2 +/- rat model to investigate how genetic risk factors impact on inhibitory neuron development., Methods: We performed bioinformatics analysis of single cell transcriptomes from gestational week (GW) 8-26 human foetal prefrontal cortex and anatomical and electrophysiological analysis of 16p11.2 +/- rat cerebral cortex and hippocampus at post-natal day (P) 21., Results: We identified a subset of human interneurons (INs) first appearing at GW23 with enriched expression of a large fraction of risk factor transcripts including those expressed from the 16p11.2 locus. This suggests the hypothesis that these foetal INs are vulnerable to mutations causing autism. We investigated this in a rat model of the 16p11.2 microdeletion. We found no change in the numbers or position of either excitatory or inhibitory neurons in the somatosensory cortex or CA1 of 16p11.2 +/- rats but found that CA1 Sst INs were hyperexcitable with an enlarged axon initial segment, which was not the case for CA1 pyramidal cells., Limitations: The human foetal gene expression data was acquired from cerebral cortex between gestational week (GW) 8 to 26. We cannot draw inferences about potential vulnerabilities to genetic autism risk factors for cells not present in the developing cerebral cortex at these stages. The analysis 16p11.2 +/- rat phenotypes reported in the current study was restricted to 3-week old (P21) animals around the time of weaning and to a single interneuron cell-type while in human 16p11.2 microdeletion carriers symptoms likely involve multiple cell types and manifest in the first few years of life and on into adulthood., Conclusions: We have identified developing interneurons in human foetal cerebral cortex as potentially vulnerable to monogenic autism risk factors and the 16p11.2 microdeletion and report interneuron phenotypes in post-natal 16p11.2 +/- rats., (© 2022. The Author(s).)

Sustainable wildlife management is necessary to guarantee the viability of source populations; but it is rarely practiced in the tropics. The yellow anaconda (Eunectes notaeus) has long been harvested for its leather. Since 2002 its harvest has operated under a management program in northeastern Argentina, which relies on adaptive management practices, that limit the minimum body length permitted for harvesting, the number of active hunters and the length of hunting seasons. Here we investigated the effects of yellow anaconda harvest on its demography based on 2002-2019 data and show that exploitation levels are sustainable. The gradual reduction in annual hunting effort, due to a decrease in the number of hunters and hunting season duration, reduced the total number of anacondas harvested. Conversely, captures per unit effort increased across the study period. The body size of anacondas was not influenced by the harvesting, and more females than males were caught. We also found that a decrease in mean temperature positively influenced anaconda harvest and the capture of giant individuals. Because sustainable use is a powerful tool for conservation, and anacondas are widespread in South America, these discoveries are highly applicable to other species and regions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Camera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: An important aspect of achievement goals is the persistence and determination that the person possesses in order to achieve it. Spain does not have an adequate instrument for its measurement. First, this article had the aim of adapt and validate the Motivational Persistence Scale of Constantin et al. in a Spanish population and athletes. Second, it had the aim of prove the relationship with deliberate practice and performance., Methods: In this study, 384 university students participated, where the factor structure was analyzed by means of a Confirmatory Factor Analysis (CFA). In study 2 of 169 athletes was used to confirm its validity in a homogeneous population and its predictive capacity on the hours of deliberate practice (DP) and performance., Results: The AFC showed a two-factor structure, reducing the original three-factor structure, presenting a good fit in both Spanish and homogeneous population of athletes and achieving a significant predictive capacity on deliberate practice. The new dimensions were Purpose Pursuing (PP) and Recurrence of Unattained Purposes (RUP)., Conclusions: Overall, our results provide evidence that this scale could be a useful tool for the assessment of Persistence in the Spanish adult and athlete population.

Pax6 is a well-known regulator of early neuroepithelial progenitor development. Its constitutive loss has a particularly strong effect on the developing prethalamus, causing it to become extremely hypoplastic. To overcome this difficulty in studying the long-term consequences of Pax6 loss for prethalamic development, we used conditional mutagenesis to delete Pax6 at the onset of neurogenesis and studied the developmental potential of the mutant prethalamic neurons in vitro. We found that Pax6 loss affected their rates of neurite elongation, the location and length of their axon initial segments, and their electrophysiological properties. Our results broaden our understanding of the long-term consequences of Pax6 deletion in the developing mouse forebrain, suggesting that it can have cell-autonomous effects on the structural and functional development of some neurons., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

The global expansion of road networks threatens apex predator conservation and ecosystem functioning. This occurs through wildlife-vehicle collisions, habitat loss and fragmentation, reduced genetic connectivity and increased poaching. We reviewed road impacts on 36 apex predator species and assessed their risk from current roads based on road exposure and species vulnerability. Our findings reveal all apex predators are exposed to road impacts. Eight of the ten species with the highest risk occur in Asia, although other high-risk species are present in the Americas, Africa and Europe. The sloth bear suffers the highest risk of all apex predators, followed by the tiger and dhole. Based on species risk from roads, we propose a widely applicable method to assess the potential impact of future roads on apex predators. We applied this method to proposed road developments in three areas: the Brazilian Amazon, Africa, and Nepal, to locate high-impact road segments. Roughly 500 protected areas will be intersected by these roads, threatening core apex predator habitats. We advocate the need for rigorous road development planning to apply effective mitigation measures as an urgent priority and to avoid construction in wilderness areas and predator strongholds., (© 2022. The Author(s).)

The ALFRED (Allelic Loss Featuring Rare Damaging) in silico method was developed to identify cancer predisposition genes through the identification of somatic second hits. By applying ALFRED to ~10,000 tumor exomes, 49 candidate genes were identified. We aimed to assess the causal association of the identified genes with colorectal cancer (CRC) predisposition. Of the 49 genes, NSD1 , HDAC10 , KRT24 , ACACA and TP63 were selected based on specific criteria relevant for hereditary CRC genes. Gene sequencing was performed in 736 patients with familial/early onset CRC or polyposis without germline pathogenic variants in known genes. Twelve (predicted) damaging variants in 18 patients were identified. A gene-based burden test in 1596 familial/early-onset CRC patients, 271 polyposis patients, 543 TCGA CRC patients and >134,000 controls (gnomAD, non-cancer), revealed no clear association with CRC for any of the studied genes. Nevertheless, (non-significant) over-representation of disruptive variants in NSD1 , KRT24 and ACACA in CRC patients compared to controls was observed. A somatic second hit was identified in one of 20 tumors tested, corresponding to an NSD1 carrier. In conclusion, most genes identified through the ALFRED in silico method were not relevant for CRC predisposition, although a possible association was detected for NSD1 , KRT24 and ACACA .

To identify the putative amygdalar complex in cartilaginous fishes, our first step was to obtain evidence that supports the existence of a pallial amygdala in the catshark Scyliorhinus canicula, at present the prevailing chondrichthyan model in comparative neurobiology and developmental biology. To this end, we analyzed the organization of the lateral walls of the telencephalic hemispheres of adults, juveniles, and early prehatching embryos by immunohistochemistry against tyrosine hydroxylase (TH), somatostatin (SOM), Pax6, serotonin (5HT), substance P (SP), and Met-enkephalin (MetEnk), calbindin-28k (CB), and calretinin (CR), and by in situ hybridization against regulatory genes such as Tbr1, Lhx9, Emx1, and Dlx2. Our data were integrated with those available from the literature related to the secondary olfactory projections in this shark species. We have characterized two possible amygdalar territories. One, which may represent a ventropallial component, was identified by its chemical signature (moderate density of Pax6-ir cells, scarce TH-ir and SOM-ir cells, and absence of CR-ir and CB-ir cells) and gene expressions (Tbr1 and Lhx9 expressions in an Emx1 negative domain, as the ventral pallium of amniotes). It is perhaps comparable to the lateral amygdala of amphibians and the pallial amygdala of teleosts. The second was a territory related to the pallial-subpallial boundary with abundant Pax6-ir and CR-ir cells, and 5HT-ir, SP-ir, and MetEnk-ir fibers capping dorsally the area superficialis basalis. This olfactory-related region at the neighborhood of the pallial-subpallial boundary may represent a subpallial amygdala subdivision that possibly contains migrated cells of ventropallial origin., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Cysteine plays a major role in the redox homeostasis and antioxidative defense mechanisms of many parasites of the phylum Apicomplexa. Of relevance to human health is Toxoplasma gondii , the causative agent of toxoplasmosis. A major route of cysteine biosynthesis in this parasite is the reverse transsulfuration pathway involving two key enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL). CBS from T. gondii ( Tg CBS) catalyzes the pyridoxal-5́-phosphate-dependent condensation of homocysteine with either serine or O -acetylserine to produce cystathionine. The enzyme can perform alternative reactions that use homocysteine and cysteine as substrates leading to the endogenous biosynthesis of hydrogen sulfide, another key element in maintaining the intracellular redox equilibrium. In contrast with human CBS, Tg CBS lacks the N-terminal heme binding domain and is not responsive to S-adenosylmethionine. Herein, we describe the structure of a Tg CBS construct that lacks amino acid residues 466-491 and shows the same activity of the native protein. Tg CBS Δ466-491 was determined alone and in complex with reaction intermediates. A complementary molecular dynamics analysis revealed a unique domain organization, similar to the pathogenic mutant D444N of human CBS. Our data provides one missing piece in the structural diversity of CBSs by revealing the so far unknown three-dimensional arrangement of the CBS-type of Apicomplexa. This domain distribution is also detected in yeast and bacteria like Pseudomonas aeruginosa . These results pave the way for understanding the mechanisms by which Tg CBS regulates the intracellular redox of the parasite, and have far-reaching consequences for the functional understanding of CBSs with similar domain distribution., (© 2021 The Authors.)

Introduction: Few studies assess postoperative outcomes after discharge in the ambulatory setting. The aim of this study was to investigate postoperative pain and adverse effects at 24 h and at 7 days after day surgery using an e-health follow-up smartphone-based application named SATELIA®., Materials and Methods: This retrospective, observational and monocentric cohort study was conducted at the University Hospital of Bordeaux. All eligible patients for SATELIA® follow-up between May 2018 and June 2019 were screened for the analysis. Data were extracted from two databases. Those with a missing primary outcome were excluded from the analysis. The main outcome was the worst pain score on POD 1, self-reported via SATELIA®. The secondary outcomes were the incidence of adverse effects on POD1, as well as the worst pain score and adverse effects on POD7. Quantitative data were reported by the median (IQR) and categorical data were presented as absolute numbers (%)., Results: A total of 2283 patients were screened for analysis, from which 592 were excluded due to missing data for the main outcome; 1691 patients were thus finally included. The median worst pain score at POD 1 was 3.0 (1.0-5.0); 35.5% (n = 601/1691) and 29.1% (n = 492/1691) of the patients reported moderate-to-severe pain at POD1 and POD7, respectively., Conclusion: This retrospective study shows that 35.5% of patients experience moderate-to-severe pain after day surgery. Even if SATELIA® should be further developed and evaluated, it also demonstrates the interest of using phone based software to follow patients after discharge and ensure a better personalised management., (Copyright © 2021 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Objective: Germline TP53 pathogenic (P) variants cause Li-Fraumeni syndrome (LFS), an aggressive multitumor-predisposing condition. Due to the implementation of multigene panel testing, TP53 variants have been detected in individuals without LFS suspicion, for example, patients with colorectal cancer (CRC). We aimed to decipher whether these findings are the result of detecting the background population prevalence or the aetiological basis of CRC., Design: We analysed TP53 in 473 familial/early-onset CRC cases and evaluated the results together with five additional studies performed in patients with CRC (total n=6200). Control population and LFS data were obtained from Genome Aggregation Database (gnomAD V.2.1.1) and the International Agency for Research on Cancer (IARC) TP53 database, respectively. All variants were reclassified according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), following the ClinGen TP53 Expert Panel specifications., Results: P or likely pathogenic (LP) variants were identified in 0.05% of controls (n=27/59 095) and 0.26% of patients with CRC (n=16/6200) (p<0.0001) (OR=5.7, 95% CI 2.8 to 10.9), none of whom fulfilled the clinical criteria established for TP53 testing. This association was still detected when patients with CRC diagnosed at more advanced ages (>50 and>60 years) were excluded from the analysis to minimise the inclusion of variants caused by clonal haematopoiesis. Loss-of-function and missense variants were strongly associated with CRC as compared with controls (OR=25.44, 95% CI 6.10 to 149.03, for loss of function and splice-site alleles, and OR=3.58, 95% CI 1.46 to 7.98, for missense P or LP variants)., Conclusion: TP53 P variants should not be unequivocally associated with LFS. Prospective follow-up of carriers of germline TP53 P variants in the absence of LFS phenotypes will define how surveillance and clinical management of these individuals should be performed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight.

Early-onset colorectal cancer (EOCRC), defined as that diagnosed before the age of 50, accounts for 10-12% of all new colorectal cancer (CRC) diagnoses. Epidemiological data indicate that EOCRC incidence is increasing, despite the observed heterogeneity among countries. Although the cause for such increase remains obscure, ≈13% (range: 9-26%) of EOCRC patients carry pathogenic germline variants in known cancer predisposition genes, including 2.5% of patients with germline pathogenic variants in hereditary cancer genes traditionally not associated with CRC predisposition. Approximately 28% of EOCRC patients have family history of the disease. This article recapitulates current evidence on the inherited syndromes that predispose to EOCRC and its familial component. The evidence gathered support that all patients diagnosed with an EOCRC should be referred to a specialized genetic counseling service and offered somatic and germline pancancer multigene panel testing. The identification of a germline pathogenic variant in a known hereditary cancer gene has relevant implications for the clinical management of the patient and his/her relatives, and it may guide surgical and therapeutic decisions. The relative high prevalence of hereditary cancer syndromes and familial component among EOCRC patients supports further research that helps understand the genetic background, either monogenic or polygenic, behind this increasingly common disease.

Severe peripheral nerve injuries represent a large clinical problem with relevant challenges such as the development of successful synthetic scaffolds as substitutes to autologous nerve grafting. Numerous studies have reported the use of polyesters and type I collagen-based nerve guidance conduits (NGCs) to promote nerve regeneration through critical nerve defects while providing protection from external factors. However, none of the commercially available hollow bioresorbable NGCs have demonstrated superior clinical outcomes to an autologous nerve graft. Hence, new materials and NGC geometries have been explored in the literature to mimic the native nerve properties and architecture. Here, we report a novel blend of a natural medium chain length polyhydroxyalkanoate (MCL-PHA) with a synthetic aliphatic polyester, poly(ε-caprolactone) (PCL), suitable for extrusion-based high-throughput manufacturing. The blend was designed to combine the excellent ability of PHAs to support the growth and proliferation of mammalian cells with the good processability of PCL. The material exhibited excellent neuroregenerative properties and a good bioresorption rate, while the extruded porous tubes exhibited similar mechanical properties to the rat sciatic nerve. The NGCs were implanted to treat a 10 mm long sciatic nerve defect in rats, where significant differences were found between thin and thick wall thickness implants, and both electrophysiological and histological data, as well as the number of recovered animals, provided superior outcomes than the well-referenced synthetic Neurolac NGC.

Thalamocortical axons (TCAs) cross several tissues on their journey to the cortex. Mechanisms must be in place along the route to ensure they connect with their targets in an orderly fashion. The ventral telencephalon acts as an instructive tissue, but the importance of the diencephalon in TCA mapping is unknown. We report that disruption of diencephalic development by Pax6 deletion results in a thalamocortical projection containing mapping errors. We used conditional mutagenesis to test whether these errors are due to the disruption of pioneer projections from prethalamus to thalamus and found that, although this correlates with abnormal TCA fasciculation, it does not induce topographical errors. To test whether the thalamus contains navigational cues for TCAs, we used slice culture transplants and gene expression studies. We found the thalamic environment is instructive for TCA navigation and that the molecular cues netrin 1 and semaphorin 3a are likely to be involved. Our findings indicate that the correct topographic mapping of TCAs onto the cortex requires the order to be established from the earliest stages of their growth by molecular cues in the thalamus itself., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Substrate type determines nesting success and fitness in turtles and is a critical consideration for nesting area protection and restoration. Here, we evaluated the effect of substrate on nest removal by humans in the eastern Brazilian Amazon. We analyzed substrate composition and fate of 216 P. unifilis nests along 88 km of rivers. River segment and substrate type were the most important predictors of nest removal by humans. We found up to 36% lower removal of nests in fine sand and experimental results support the hypothesis that wind more often obscures tracks of nesting females in substrates with more (>66%) fine sand. Our findings are useful for informing the restoration of artificial nesting areas across the Amazon, as nesting area substrates should be selected not only to maintain hatchling sex ratios, but also to minimize nest removal by humans.

Peripheral nerves are basic communication structures guiding motor and sensory information from the central nervous system to receptor units. Severed peripheral nerve injuries represent a large clinical problem with relevant challenges to successful synthetic nerve repair scaffolds as substitutes to autologous nerve grafting. Numerous studies reported the use of hollow tubes made of synthetic polymers sutured between severed nerve stumps to promote nerve regeneration while providing protection for external factors, such as scar tissue formation and inflammation. Few approaches have described the potential use of a lumen structure comprised of microchannels or microfibers to provide axon growth avoiding misdirection and fostering proper healing. Here, we report the use of a 3D porous microchannel-based structure made of a photocurable methacrylated polycaprolactone, whose mechanical properties are comparable to native nerves. The neuro-regenerative properties of the polymer were assessed in vitro, prior to the implantation of the 3D porous structure, in a 6-mm rat sciatic nerve gap injury. The manufactured implants were biocompatible and able to be resorbed by the host's body at a suitable rate, allowing the complete healing of the nerve. The innovative design of the highly porous structure with the axon guiding microchannels, along with the observation of myelinated axons and Schwann cells in the in vivo tests, led to a significant progress towards the standardized use of synthetic 3D multichannel-based structures in peripheral nerve surgery.

Beetroot juice (BJ) contains high levels of inorganic nitrate (NO 3 - ) and its intake has good evidence in increasing blood nitrate/nitrite concentrations. The ingestion of BJ has been associated with improvements in physical performance of endurance sports, however the literature in intermittent sports is scarce. The aim of this study was to investigate whether BJ could improve physical performance in tennis players. Thirteen well-trained tennis players (25.4 ± 5.1 years) participated in the study during their preparatory period for the tennis season. Subjects were randomly divided into two groups and performed a neuromuscular test battery after either BJ or placebo (PLA) consumption. Both trials were executed on two separate days, in randomized order, with one week of wash out period. The test battery consisted of serve velocity test (SVT), countermovement jump (CMJ), isometric handgrip strength (IHS), 5-0-5 agility test (5-0-5), and 10 m sprint (10-m). No significant differences were found in SVT (1.19%; p = 0.536), CMJ (0.96%; p = 0.327), IHS (4.06%; p = 0.069), 5-0-5 dominant and nondominant side (1.11-2.02%; p = 0.071-0.191) and 10-m (1.05%; p = 0.277) when comparing BJ and PLA ingestion. Thus, our data suggest that low doses of BJ (70 mL) consumption do not enhance tennis physical performance., Competing Interests: No potential conflict of interest was reported by the authors.

Polyhydroxyalkanoates (PHAs) have emerged as a promising biodegradable and biocompatible material for scaffold manufacturing in the tissue engineering field and food packaging. Surface modification is usually required to improve cell biocompatibility and/or reduce bacteria proliferation. Picosecond laser ablation was applied for surface micro structuring of short- and medium-chain length-PHAs and its blend. The response of each material as a function of laser energy and wavelength was analyzed. Picosecond pulsed laser modified the surface topography without affecting the material properties. UV wavelength irradiation showed halved ablation thresholds compared to VIS wavelength, revealing a greater photochemical nature of the ablation process at UV wavelength. Nevertheless, the ablation rate and, therefore, ablation efficiency did not show a clear dependence on beam wavelength. The different mechanical behavior of the considered PHAs did not lead to different ablation thresholds on each polymer at a constant wavelength, suggesting the interplay of the material mechanical parameters to equalize ablation thresholds. Blended-PHA showed a significant reduction in the ablation threshold under VIS irradiation respect to the neat PHAs. Picosecond ablation was proved to be a convenient technique for micro structuring of PHAs to generate surface microfeatures appropriate to influence cell behavior and improve the biocompatibility of scaffolds in tissue engineering., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Porous scaffolds made of elastomeric materials are of great interest for soft tissue engineering. Poly(L-lactide-co- ε -caprolactone) (PLCL) is a bio-resorbable elastomeric copolymer with tailorable properties, which make this material an appropriate candidate to be used as scaffold for vascular, tendon, and nerve healing applications. Here, extrusion was applied to produce porous scaffolds of PLCL, using NaCl particles as a leachable agent. The effects of the particle proportion and size on leaching performance, dimensional stability, mechanical properties, and ageing of the scaffolds were analyzed. The efficiency of the particle leaching and scaffold swelling when wet were observed to be dependent on the porogenerator proportion, while the secant moduli and ultimate tensile strengths were dependent on the pore size. Porosity, swelling, and mechanical properties of the extruded scaffolds were tailorable, varying with the proportion and size of porogenerator particles and showed similar values to human soft tissues like nerves and veins (E = 7-15 MPa, σ u = 7 MPa). Up to 300-mm length micro-porous PLCL tube with 400-µm thickness wall was extruded, proving extrusion as a high-throughput manufacturing process to produce tubular elastomeric bio-resorbable porous scaffolds of unrestricted length with tunable mechanical properties., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Implantable tubular devices known as nerve guidance conduits (NGCs) have drawn considerable interest as an alternative to autografting in the repair of peripheral nerve injuries. At present, there exists a lack of biodegradable, biocompatible materials for the fabrication of NGCs with physical properties which suitably match the native nerve tissue. Most of the existing reports have been confined to the traditional synthetic aliphatic polyesters due to their naturally-occurring degradation by-products, suitably slow in vivo resorption timeframes and relatively diverse and tailorable range of material properties. Moreover, these thermoplastic polymers can be processed into NGCs from various methods and further tweaking of physical properties can be achieved during fabrication. Although there have been many successful reports of nerve gap repair using NGCs made from these materials, the majority have been confined to basic tubular designs across short to medium nerve gaps with at best equivalent outcomes to autografts. This article reviews the performance of poly-α-hydroxyester tubes to date (including modifications to basic hollow conduits) and is intended to aid researchers as they aim to create biomimetic NGCs capable of bridging larger nerve gaps with superior results to autografting. Based on the existing reports, a next-generation bioresorbable NGC should involve a highly flexible poly-α-hydroxyester outer tube, most suitably from a lactide-caprolactone co-polymer, with some combination of internal lumen contact guidance and bioactive neurotrophic factors. However, detailed further experimentation and an interdisciplinary approach will be required to arrive at an ideal final configuration.