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Abstract Background Children with genetic conditions are at increased risk for mental health and neurodevelopmental problems, often accompanied by significant parental distress. Genetic and family factors can impact children and parents’ mental health. Early parenting interventions, like the Incredible Years® programs, have demonstrated to improve parental distress and children’s mental health. The recent version for young children with language delays or autism spectrum disorder (IY-ASLD®) has shown to be feasible and effective to support parents in their children’s developmental trajectories. The effectiveness of treatments for children with genetic conditions and neurodevelopmental problems is largely unexplored, leaving significant gaps in evidence-based options. Clinicians lack guidance, especially when patients exhibit language or social communication impairments but do not meet diagnostic criteria for a full-blown autism spectrum disorder (ASD). We aim to fill this gap, providing evidence on the feasibility and effectiveness of the IY-ASLD® intervention for such patients. Methods We designed a prospective multicenter pragmatic randomized controlled trial including approximately 68 children aged 3 to 7 years, recruited from three tertiary care reference hospitals. Inclusion criteria will necessitate genetic confirmation of a neurodevelopmental disorder along with language, communication, or socialization difficulties. Individuals with an ASD diagnosis will be excluded. All subjects are included in a territorial register for rare conditions (ReMin, Registre de Malalties Minoritàries de Catalunya). Families will randomly be assigned to the intervention or the control group. The intervention will be held online by clinical psychologists and child and adolescent psychiatrists. Discussion Our group has recently piloted the online implementation of the IY-ASLD® intervention for the first time in Spain, for parents of children with language delays, socialization difficulties, or ASD, but not genetically determined. Our multicenter research consortium is well-positioned to recruit patients with rare conditions and implement efficient treatment pathways within the National Health System. Given the geographical dispersion of families affected by rare conditions, the online format offers logistical advantages and improved therapy access, enhancing homogeneity across all patients. The results of this study will inform clinicians and policymakers about evidence-based treatment options for this vulnerable and overlooked group of young children. Trial registration ClinicalTrials.gov NCT06125093 . Date of registration: first submitted 2023–10-23; first posted 2023–11-09. URL of trial registry record.

Summary: Cohesin mediates the 3-D structure of chromatin and is involved in maintaining genome stability and function. The cohesin core comprises Smc1 and Smc3, elongated-shaped proteins that dimerize through globular domains at their edges, called head and hinge. ATP binding to the Smc heads induces their dimerization and the formation of two active sites, while ATP hydrolysis results in head disengagement. This ATPase cycle is essential for driving cohesin activity. We report on the development of the first cohesin-inhibiting peptide (CIP). The CIP binds Smc3 in vitro and inhibits the ATPase activity of the holocomplex. Treating yeast cells with the CIP prevents cohesin’s tethering activity and, interestingly, leads to the accumulation of cohesin on chromatin. CIP3 also affects cohesin activity in human cells. Altogether, we demonstrate the power of peptides to inhibit cohesin in cells and discuss the potential application of CIPs as a therapeutic approach.

A internacionalização do ensino superior ganhou grande repercussão nas universidades brasileiras, que passam a ter cada vez mais inserção no cenário científico e acadêmico internacional, evidenciada pelos rankings elaborados por organismos internacionais. Dado que a internacionalização vem sendo gradativamente institucionalizada nas universidades, no âmbito do planejamento e da estrutura organizacional, o presente estudo busca compreender as razões que as motivam a participar do processo. Entender as razões contribui no estabelecimento de políticas específicas para o tema, visto que é etapa inicial para o planejamento. Classificado como uma pesquisa descritiva, com abordagem qualitativa, o estudo delimitou três instituições federais de ensino superior (IFES) no Ceará com ações reconhecidas de internacionalização. Na pesquisa de campo, realizaram-se entrevistas com gestores das IFES envolvidos no fenômeno, e na pesquisa documental coletaram-se dados sobre o histórico de atuação das IFES na internacionalização. Os resultados evidenciam que as principais razões consistem em: capacitação docente, capacitação discente nas dimensões profissional e cultural, busca por reputação e reconhecimento e pressões ambientais. As diferenças entre as IFES podem ser explicadas pela sua história e missão institucional. Os resultados são convergentes com a literatura e contribuem como diretrizes na elaboração do planejamento de políticas institucionais para internacionalização.

In this article, characterization of fully patterned zinc-tin oxide (ZTO)-based memristive devices with feature sizes as small as 25 µm2 is presented. The devices are patterned via lift-off with a platinum bottom contact and a gold-titanium top contact. An on/off ratio of more than two orders of magnitude is obtained without the need for electroforming processes. Set operation is a current controlled process, whereas the reset is voltage dependent. The temperature dependency of the electrical characteristics reveals a bulk-dominated conduction mechanism for high resistance states. However, the charge transport at low resistance state is consistent with Schottky emission. Synaptic properties such as potentiation and depression cycles, with progressive increases and decreases in the conductance value under 50 successive pulses, are shown. This validates the potential use of ZTO memristive devices for a sustainable and energy-efficient brain-inspired deep neural network computation.

Neuromorphic computation based on resistive switching devices represents a relevant hardware alternative for artificial deep neural networks. For the highest accuracies on pattern recognition tasks, an analog, linear, and symmetric synaptic weight is essential. Moreover, the resistive switching devices should be integrated with the supporting electronics, such as thin-film transistors (TFTs), to solve crosstalk issues on the crossbar arrays. Here, an a-Indium-gallium-zinc-oxide (IGZO) memristor is proposed, with Mo and Ti/Mo as bottom and top contacts, with forming-free analog switching ability for an upcoming integration on crossbar arrays with a-IGZO TFTs for neuromorphic hardware systems. The development of a TFT compatible fabrication process is accomplished, which results in an a-IGZO memristor with a high stability and low cycle-to-cycle variability. The synaptic behavior through potentiation and depression tests using an identical spiking scheme is presented, and the modulation of the plasticity characteristics by applying non-identical spiking schemes is also demonstrated. The pattern recognition accuracy, using MNIST handwritten digits dataset, reveals a maximum of 91.82% accuracy, which is a promising result for crossbar implementation. The results displayed here reveal the potential of Mo/a-IGZO/Ti/Mo memristors for neuromorphic hardware.

Neuromorphic computing has been gaining momentum for the past decades and has been appointed as the replacer of the outworn technology in conventional computing systems. Artificial neural networks (ANNs) can be composed by memristor crossbars in hardware and perform in-memory computing and storage, in a power, cost and area efficient way. In optoelectronic memristors (OEMs), resistive switching (RS) can be controlled by both optical and electronic signals. Using light as synaptic weigh modulator provides a high-speed non-destructive method, not dependent on electrical wires, that solves crosstalk issues. In particular, in artificial visual systems, OEMs can act as the artificial retina and combine optical sensing and high-level image processing. Therefore, several efforts have been made by the scientific community into developing OEMs that can meet the demands of each specific application. In this review, the recent advances in inorganic OEMs are summarized and discussed. The engineering of the device structure provides the means to manipulate RS performance and, thus, a comprehensive analysis is performed regarding the already proposed memristor materials structure and their specific characteristics. Moreover, their potential applications in logic gates, ANNs and, in more detail, on artificial visual systems are also assessed, taking into account the figures of merit described so far.

DNA-damaging chemotherapy agents such as cisplatin have been the first line of treatment for cancer for decades. While chemotherapy can be very effective, its long-term success is often reduced by intrinsic and acquired drug resistance, accompanied by chemotherapy-resistant secondary malignancies. Although the mechanisms causing drug resistance are quite distinct, they are directly connected to mutagenic translesion synthesis (TLS). The TLS pathway promotes DNA damage tolerance by supporting both replication opposite to a lesion and inaccurate single-strand gap filling. Interestingly, inhibiting TLS reduces both cisplatin resistance and secondary tumor formation. Therefore, TLS targeting is a promising strategy for improving chemotherapy. MAD2L2 (i.e., Rev7) is a central protein in TLS. It is an essential component of the TLS polymerase zeta (ζ), and it forms a regulatory complex with Rev1 polymerase. Here we present the discovery of two small molecules, c#2 and c#3, that directly bind both in vitro and in vivo to MAD2L2 and influence its activity. Both molecules sensitize lung cancer cell lines to cisplatin, disrupt the formation of the MAD2L2-Rev1 complex and increase DNA damage, hence underlining their potential as lead compounds for developing novel TLS inhibitors for improving chemotherapy treatments.

The study aims to show the contributions of the master degree to the academic career of the egress, as tools for expanding opportunities and qualification of the server, specifically for the alumni of the Master Degree in Public Policies from Higher Education (POLEDUC) at the Federal University of Ceará. The study was developed in a documentary, census, exploratory and descriptive research, whose the unit of analysis is the graduated students from the POLEDUC, which were into groups from 2007 to 2014. The survey of the professional and academic data of the graduates was carried out in June 2016, totaling 146 graduates, where it was excluded cancellating and withdrawal enrollments. The survey indicated the prevalence of women and employees in the administrative area from the higher education institutions. It was also found that only half of the students have published some article during the course, and only a third ones have published after the master degree. Regarding of the career continuity, few graduates have entered doctoral programs; and, among the technicians, about 14% had some teaching activity after the master degree. The outcomes indicate the most of graduates of POLEDUC do not present career continuity from an academic perspective.

Trypanosoma cruzi is a protozoan parasite belonging to the Trypanosomatidae family. Although the trypanosomatids multiply predominantly by clonal generation, the presence of DNA exchange in some of them has been puzzling researchers over the years, mainly because it may represent a novel form that these organisms use to gain variability. Analysis of DNA Exchange using Thymidine Analogs (ADExTA) is a method that allows the in vitro detection and measurement of rates of DNA exchange, particularly in trypanosomatid cells, in a rapid and simple manner by indirect immunofluorescence assay (IFA). The method can be used to detect DNA exchange within one trypanosomatid lineage or among different lineages by paired analysis. The principle of this assay is based on the incorporation of two distinguishable halogenated thymidine analogs called 5′-chloro-2′-deoxyuridine (CldU) and 5′-iodo-2′-deoxyuridine (IdU) during DNA replication. After mixing the two cell cultures that had been previously incorporated with CldU and IdU separately, the presence of these unusual deoxynucleosides in the genome can be detected by specific antibodies. For this, a DNA denaturation step is required to expose the sites of thymidine analogs incorporated. Subsequently, a secondary reaction using fluorochrome-labeled antibodies will generate distinct signals under fluorescence analysis. By using this method, DNA exchange verification (i.e., the presence of both CldU and IdU in the same cell) is possible using a standard fluorescence microscope. It typically takes 2-3 days from the thymidine analogs incorporation to results. Of note, ADExTA is relatively cheap and does not require transfections or harsh genetic manipulation. These features represent an advantage when compared to other time-consuming protocols that demand DNA manipulation to introduce distinct drug-resistance markers in different cells for posterior selection.

Prader–Willi syndrome (PWS) is a rare genetic disorder characterized by a wide range of clinical manifestations, including obesity, hyperphagia, and behavioral problems. Bifidobacterium animalis subsp. lactis strain BPL1 has been shown to improve central adiposity in adults with simple obesity. To evaluate BPL1′s effects in children with PWS, we performed a randomized crossover trial among 39 patients (mean age 10.4 years). Participants were randomized to placebo–BPL1 (n = 19) or BPL1–placebo (n = 20) sequences and underwent a 12-week period with placebo/BPL1 treatments, a 12-week washout period, and a 12-week period with the crossover treatment. Thirty-five subjects completed the study. The main outcome was changes in adiposity, measured by dual-energy X-ray absorptiometry. Secondary outcomes included lipid and glucose metabolism, hyperphagia, and mental health symptoms. Generalized linear modeling was applied to assess differences between treatments. While BPL1 did not modify total fat mass compared to placebo, BPL1 decreased abdominal adiposity in a subgroup of patients older than 4.5 years (n = 28). BPL1 improved fasting insulin concentration and insulin sensitivity. Furthermore, we observed modest improvements in some mental health symptoms. A follow-up trial with a longer treatment period is warranted to determine whether BPL1 supplementation can provide a long-term therapeutic approach for children with PWS (ClinicalTrials.gov NCT03548480).

In this work, syntactic and semantic parallelisms are used to investigate relations of hyponym and hypernym between antecedent and coreferential anaphoric expression in Brazilian Portuguese. We report two studies using data from eyetracking experiments. Precisely, eye movements of 21 participants are analysed while reading a set composed of 40 sentences. Our results suggest that the coreferential processing cost for hypernym condition is lower than for hyponym condition. Although our findings corroborate previous studies on total reading times, different processing costs among constituents of the sentence could not be identified.

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