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Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits significant toxicity in humans. The accumulation of MeHg through the daily consumption of large predatory fish poses potential health risks, and the central nervous system (CNS) is the primary target of toxicity. Despite well-described neurobehavioral effects (i.e., motor impairment), the mechanisms of MeHg-induced toxicity are not completely understood. However, several lines of evidence point out the oxidative stress as an important molecular mechanism in MeHg-induced intoxication. Indeed, MeHg is a soft electrophile that preferentially interacts with nucleophilic groups (mainly thiols and selenols) from proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress, which can produce damage by several interacting mechanisms, impairing the function of various molecules (i.e., proteins, lipids, and nucleic acids), potentially resulting in modulation of different cellular signal transduction pathways. This review summarizes the general aspects regarding the interaction between MeHg with regulators of the antioxidant response system that are rich in thiol and selenol groups such as glutathione (GSH), and the selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). A particular attention is directed towards the role of the PI3K/Akt signaling pathway and the nuclear transcription factor NF-E2-related factor 2 (Nrf2) in MeHg-induced redox imbalance.

Wooden utility poles are crucial in supporting overhead telecommunication lines in Portugal. Maritime pine (Pinus pinaster Aiton) is the most common wood species used for this purpose. The durability of the poles is typically determined by the deterioration observed in their ground line. Aiming to reduce the use of new sound wooden poles, reducing the economic costs involved, and the environmental impacts, the reuse of those old wooden poles by removing the degraded part is one possible solution. This study aimed to develop and validate solutions with composed poles, specifically for the connections between the wood members, so that it is possible to more efficiently incorporate used parts into the remanufactured poles. Two types of connections were used: members joined by a cylindrical steel tube, and members joined by finger joints. The static bending moduli of elastic and rupture were tested. The mechanical properties of the reused wooden utility poles showed to be in line with the values of new sound wooden poles made of different wood species. Finally, both proposed solutions proved to be practical for use in the production of reused utility poles, which are mostly made from old timber poles.

In order to thrive in constantly changing environments, animals must adaptively respond to threatening events. Noxious stimuli are not only processed according to their absolute intensity, but also to their context. Adaptation processes can cause animals to habituate at different rates and degrees in response to permanent or repeated stimuli. Here, we used a forward genetic approach in Caenorhabditis elegans to identify a neuropeptidergic pathway, essential to prevent fast habituation and maintain robust withdrawal responses to repeated noxious stimuli. This pathway involves the FRPR-19A and FRPR-19B G-protein coupled receptor isoforms produced from the frpr-19 gene by alternative splicing. Loss or overexpression of each or both isoforms can impair withdrawal responses caused by the optogenetic activation of the polymodal FLP nociceptor neuron. Furthermore, we identified FLP-8 and FLP-14 as FRPR-19 ligands in vitro . flp-14 , but not flp-8 , was essential to promote withdrawal response and is part of the same genetic pathway as frpr-19 in vivo . Expression and cell-specific rescue analyses suggest that FRPR-19 acts both in the FLP nociceptive neurons and downstream interneurons, whereas FLP-14 acts from interneurons. Importantly, genetic impairment of the FLP-14/FRPR-19 pathway accelerated the habituation to repeated FLP-specific optogenetic activation, as well as to repeated noxious heat and harsh touch stimuli. Collectively, our data suggest that well-adjusted neuromodulation via the FLP-14/FRPR-19 pathway contributes to promote nociceptive signals in C . elegans and counteracts habituation processes that otherwise tend to rapidly reduce aversive responses to repeated noxious stimuli.

This study is aimed at examining and comparing several friction force models dealing with different friction phenomena in the context of multibody system dynamics. For this purpose, a comprehensive review of present literature in this field of investigation is first presented. In this process, the main aspects related to friction are discussed, with particular emphasis on the pure dry sliding friction, stick–slip effect, viscous friction and Stribeck effect. In a simple and general way, the friction force models can be classified into two main groups, namely the static friction approaches and the dynamic friction models. The former group mainly describes the steady-state behavior of friction force, while the latter allows capturing more properties by using extra state variables. In the present study, a total of 21 different friction force models are described and their fundamental physical and computational characteristics are discussed and compared in details. The application of those friction models in multibody system dynamic modeling and simulation is then investigated. Two multibody mechanical systems are utilized as demonstrative application examples with the purpose of illustrating the influence of the various frictional approaches on the dynamic response of the systems. From the results obtained, it can be stated that both the choice of the friction force model and friction parameters involved can significantly affect the simulated/modeled dynamic response of mechanical systems with friction.

Research on naturally cemented soils (e.g. sandstones) has increased considerably in recent years, mainly due to the growing interest in finding new offshore oil wells at depths that can sometimes exceed 1000 m. Although testing using undisturbed samples is ideal, the extraction, transport and preservation of such samples is incredibly difficult and sometimes unfeasible. Therefore, in order to study the natural cementation of these materials, triaxial compression tests were performed on an artificially cemented sand cured at effective stress of 500, 2000 and 4000 kPa and then compared with samples cured under atmospheric pressure and then sheared at the same effective stresses. Samples with different dosages were studied. Results showed that the type of curing does not present statistical influence on the peak strength values. On the other hand, the type of curing, together with the effective stress at the beginning of the shearing and the sample dosage control both the maximum stiffness values at very small strains as well as the stiffness degradation with strain. Simple mathematical models have been successfully adjusted to standardized results.

Mutations in two highly related chromatin-remodeling complexes, BRG1/BRM-associated factor (BAF) and Polybromo-associated BAF (PBAF), cause various neurodevelopmental conditions. Although BAF activity is required at multiple steps of nervous system development, the specific neural functions of PBAF remain largely unexplored. Through an unbiased genetic screen in C. elegans , we identify here critical roles for PBAF in postmitotic neuronal identity. In nerve cord motor neurons, PBAF represses gene expression by antagonizing the terminal selector-type transcription factor UNC-3 (EBF1-4). In contrast, PBAF activates gene expression in caudal motor neurons. This dichotomy in PBAF function generates distinct motor neuron identities. PBAF disruption leads to locomotion defects. Genetic, genomic, and biochemical data suggest that the cell type-specific functions of PBAF in different motor neuron groups arise via its recruitment to specific gene loci by conserved transcription factors, such as MAB-9/TBX20. Altogether, our findings provide a conceptual framework to understand specific neuronal defects that arise in neurological conditions caused by mutations in broadly expressed chromatin-remodeling complexes. Mutations in the PBAF chromatin-remodeling complex cause various neurodevelopmental disorders. This study shows that PBAF shapes distinct motor neuron identities, revealing how its disruption impairs movement and offering insight into neurodevelopmental disorders caused by PBAF mutations.

This study describes a dataset containing urban fire events that took place in mainland Portugal between 2013 and 2022. The Regulation n.º3317-A/2018, established by the Portuguese National Emergency and Civil Protection Authority ( Autoridade Nacional de Emergência e Proteção Civil , ANEPC), defines the Operations Management System ( Sistema de Gestão de Operações , SGO). Among other attributions, this system allows to manage the lyfe-cycle of the urban fire events, from ignition to extinction, through the Operations Decision Support System ( Sistema de Apoio à Decisão Operacional , SADO). This system supports the systematic collection of a minimum set of data on each event. All instances included in the dataset were retrieved from SADO. To make the data suitable for analytic purposes, several pre-processing actions were taken, including the steps of data transformation and cleaning. The dataset was further validated by a set of technical procedures aiming to verify both data correctness and utility. The final dataset provides the most recent multi-year record of Portuguese urban fires including 27 variables on 72641 events.

Eligibility and indication for autologous hematopoietic stem cell transplantation (HSCT) in patients with lymphoma are increasing. Acute kidney injury (AKI) is a known complication of HSCT with studies including a miscellaneous of hematological diagnoses and using different definitions of AKI. We aimed to evaluate incidence, risk factors and prognostic impact of AKI post-HSCT in patients with lymphoma submitted to autologous HSCT using the KDIGO classification with both serum creatinine and urinary output criteria. We performed a single-center retrospective cohort study including patients with lymphoma admitted for autologous HSCT. We used survival analysis with competing risks to evaluate cumulative incidence of AKI, AKI risk factors and AKI impact on disease-free survival. We used Cox regression for impact of AKI on overall survival. We used backward stepwise regression to create multivariable models. A total of 115 patients were included. Cumulative incidence of AKI: 63.7% 100 d post-HSCT. First diagnosis criteria: creatinine in 54.8%, urinary output in 41.1% and both in 4.1%. AKI highest stage: 1 in 57.5%, 2 in 17.8% and 3 in 24.7%. Variables independently associated with higher incidence of AKI were: use of nephrotoxic drugs (HR: 2.87, 95% CI: 1.07-7.65; p = 0.035), mucositis (HR: 1.95, 95% CI: 1.16-3.29; p = 0.012) and shock (HR: 2.63, 95% CI: 1.19-5.85; p = 0.017). Moderate to severe AKI was independently associated with lower overall survival (HR: 2.04, 95% CI: 1.06-3.94; p = 0.033). No association with relapse nor progression to chronic kidney disease (CKD) was found. AKI affects almost two thirds of patients with lymphomas submitted to autologous HSCT. Nephrotoxic drugs, mucositis and shock are important independent AKI risk factors. More than one third of AKI episodes are moderate to severe and these are associated with lower overall survival.

Recently, there seems to be an increasing amount of interest in the use of the tail conditional expectation (TCE) as a useful measure of risk associated with a production process, for example, in the measurement of risk associated with stock returns corresponding to the manufacturing industry, such as the production of electric bulbs, investment in housing development, and financial institutions offering loans to small-scale industries. Companies typically face three types of risk (and associated losses from each of these sources): strategic (S); operational (O); and financial (F) (insurance companies additionally face insurance risks) and they come from multiple sources. For asymmetric and bounded losses (properly adjusted as necessary) that are continuous in nature, we conjecture that risk assessment measures via univariate/bivariate Kumaraswamy distribution will be efficient in the sense that the resulting TCE based on bivariate Kumaraswamy type copulas do not depend on the marginals. In fact, almost all classical measures of tail dependence are such, but they investigate the amount of tail dependence along the main diagonal of copulas, which has often little in common with the concentration of extremes in the copula’s domain of definition. In this article, we examined the above risk measure in the case of a univariate and bivariate Kumaraswamy (KW) portfolio risk, and computed TCE based on bivariate KW type copulas. For illustrative purposes, a well-known Stock indices data set was re-analyzed by computing TCE for the bivariate KW type copulas to determine which pairs produce minimum risk in a two-component risk scenario.