Progressive alterations in polysomal architecture and activation of ribosome stalling relief factors in a mouse model of Huntington's disease.

Given their highly polarized morphology and functional singularity, neurons require precise spatial and temporal control of protein synthesis. Alterations in protein translation have been implicated in the development and progression of a wide range of neurological and neurodegenerative disorders, including Huntington's disease (HD). In this study we examined the architecture of polysomes in their native brain context in striatal tissue from the zQ175 knock-in mouse model of HD. We performed 3D electron tomography of high-pressure frozen and freeze-substituted striatal tissue from HD models and corresponding controls at different ages. Electron tomography results revealed progressive remodelling towards a more compacted polysomal architecture in the mouse model, an effect that coincided with the emergence and progression of HD related symptoms. The aberrant polysomal architecture is compatible with ribosome stalling phenomena. In fact, we also detected in the zQ175 model an increase in the striatal expression of the stalling relief factor EIF5A2 and an increase in the accumulation of eIF5A1, eIF5A2 and hypusinated eIF5A1, the active form of eIF5A1. Polysomal sedimentation gradients showed differences in the relative accumulation of 40S ribosomal subunits and in polysomal distribution in striatal samples of the zQ175 model. These findings indicate that changes in the architecture of the protein synthesis machinery may underlie translational alterations associated with HD, opening new avenues for understanding the progression of the disease.

Comparative study of postpartum sexual function: Second-degree tears versus episiotomy outcomes.

PURPOSE: The effects of episiotomy and second-degree tears on postpartum sexual function are key areas of enquiry in women's health research. Episiotomy and second-degree tears are common procedures and injuries that occur during childbirth. Understanding their impact on post-childbirth sexuality is crucial to women's overall well-being. This study aimed to examine the relationship between episiotomy, second-degree tears, and post childbirth sexuality. METHODS: A cross-sectional design was employed, including 83 women who gave birth to Cáceres in 2017. Participants were evaluated based on sociodemographic and sexual health factors. RESULTS: No significant differences were found in dyspareunia or sexual function between women who underwent episiotomies and those with second-degree tears. However, women who underwent episiotomies waited longer before resuming sexual activity after childbirth. Factors such as age, number of previous births, employment status, educational level, and breastfeeding status affected the timing and frequency of postpartum sexual activity. CONCLUSION: Dyspareunia negatively affects various aspects of sexual function. When comparing episiotomy and second-degree tears, their impacts on postpartum sexual function were similar. However, episiotomy delays the resumption of sexual activity. Sociodemographic factors significantly influence postpartum sexual health. These findings highlight the importance of individualised interventions and support for new mothers during the postpartum period to address potential sexual health concerns.

Ductular reaction-associated neutrophils promote biliary epithelium proliferation in chronic liver disease.

BACKGROUND & AIMS: Ductular reaction expansion is associated with poor prognosis in patients with advanced liver disease. However, the mechanisms promoting biliary cell proliferation are largely unknown. Here, we identify neutrophils as drivers of biliary cell proliferation and the defective wound-healing response. METHODS: The intrahepatic localization of neutrophils was evaluated in patients with chronic liver disease. Neutrophil dynamics were analyzed by intravital microscopy and neutrophil-labeling assays in DDC-treated mice. Neutrophil depletion or inhibition of recruitment was achieved using a Ly6g antibody or a CXCR1/2 inhibitor, respectively. Mice deficient in PAD4 (peptidyl arginine deiminase 4) and ELANE/NE (neutrophil elastase) were used to investigate the mechanisms underlying ductular reaction expansion. RESULTS: In this study we describe a population of ductular reaction-associated neutrophils (DRANs), which are in direct contact with biliary epithelial cells in chronic liver diseases and whose numbers increased in parallel with disease progression. We show that DRANs are immobilized at the site of ductular reaction for a prolonged period of time. In addition, liver neutrophils display a unique phenotypic and transcriptomic profile, showing a decreased phagocytic capacity and increased oxidative burst. Depletion of neutrophils or inhibition of their recruitment reduces DRANs and the expansion of ductular reaction, while mitigating liver fibrosis and angiogenesis. Mechanistically, neutrophils deficient in PAD4 and ELANE abrogate neutrophil-induced biliary cell proliferation, thus indicating the role of neutrophil extracellular traps and elastase release in ductular reaction expansion. CONCLUSIONS: Overall, our study reveals the accumulation of DRANs as a hallmark of advanced liver disease and a potential therapeutic target to mitigate ductular reaction and the maladaptive wound-healing response. IMPACT AND IMPLICATIONS: Our results indicate that neutrophils are highly plastic and can have an extended lifespan. Moreover, we identify a new role of neutrophils as triggers of expansion of the biliary epithelium. Overall, the results of this study indicate that ductular reaction-associated neutrophils (or DRANs) are new players in the maladaptive tissue-healing response in chronic liver injury and may be a potential target for therapeutic interventions to reduce ductular reaction expansion and promote tissue repair in advanced liver disease.

Factors Associated with Quality of Life in Relatives of Adults with Serious Mental Illness: A Systematic Review.

Caring for a family member with a serious mental illness often has an impact on the quality of life (QoL) of caregivers. This could have negative repercussions on their caring skills and thus affect the care provided to that individual. The aim of this paper is to identify current evidence on QoL factors affecting relatives of individuals suffering from serious mental illness. A systematic review related to the research question was conducted in six databases by two independent reviewers. The QoL factors of relatives include sociodemographic, contextual, psychological, physical, and patient factors. The findings are consistent with the results of previous research. Mental health professionals may support a family with a member diagnosed with a serious mental illness by enhancing their education about QoL factors, which would trigger and promote protective factors so that family members could assess and act on them on an ongoing basis.

The multifaceted role of cathepsins in liver disease.

Proteases are the most abundant enzyme gene family in vertebrates and they execute essential functions in all living organisms. Their main role is to hydrolase the peptide bond within proteins, a process also called proteolysis. Contrary to the conventional paradigm, proteases are not only random catalytic devices, but can perform highly selective and targeted cleavage of specific substrates, finely modulating multiple essential cellular processes. Lysosomal protease cathepsins comprise 3 families of proteases that preferentially act within acidic cellular compartments, but they can also be found in other cellular locations. They can operate alone or as part of signalling cascades and regulatory circuits, playing important roles in apoptosis, extracellular matrix remodelling, hepatic stellate cell activation, autophagy and metastasis, contributing to the initiation, development and progression of liver disease. In this review, we comprehensively summarise current knowledge on the role of lysosomal cathepsins in liver disease, with a particular emphasis on liver fibrosis, non-alcoholic fatty liver disease and hepatocellular carcinoma.

PolishEM: image enhancement in FIB-SEM.

SUMMARY: We have developed a software tool to improve the image quality in focused ion beam-scanning electron microscopy (FIB-SEM) stacks: PolishEM. Based on a Gaussian blur model, it automatically estimates and compensates for the blur affecting each individual image. It also includes correction for artifacts commonly arising in FIB-SEM (e.g. curtaining). PolishEM has been optimized for an efficient processing of huge FIB-SEM stacks on standard computers. AVAILABILITY AND IMPLEMENTATION: PolishEM has been developed in C. GPL source code and binaries for Linux, OSX and Windows are available at http://www.cnb.csic.es/%7ejjfernandez/polishem. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effects of two emergency stabilization treatments on main soil properties four years after application in a severely burnt area.

In NW of the Iberian Peninsula, the incidence of anthropogenic fires is very high and, due to the climatologic and topographical conditions, burnt soils are prone to high erosion risks. In recent years several environmental management techniques (BAER: burnt area emergency response) have been applied after some wildfires, but there are still few field studies about their effects on soils (the foundations of terrestrial ecosystems) and most of them are short-term. Aiming to fill this gap of knowledge, sixteen properties useful as soil quality indices (pH, WHC, total N, δ15N, NH4+-N, NO3--N, and NH4Ac-DTPA extractable Na, K, Ca, Mg, P, Al, Fe, Mn, Cu and Zn) were studied four years after BAER application in a severely burnt area in the 0-2 and 2-5 cm depth layers of unburnt soil (US), burnt soil untreated (BS), and burnt soil treated with two BAERs techniques: rye seeding (BSS) and straw mulching (BSM). The effects of fire on soil WHC, total N, Mg, Na, P, Zn, NO3--N, Cu and K were mitigated in both BSS and BSM, but especially in the latter. The highest values for Ca and Mn were recorded in BSM. The BAER treatments affect NO3--N, Cu and K only in the top layer, but no clear effects were found for soil pH, δ15N, NH4+-N, Al and Fe. Soil samples were quite similarly grouped by the hierarchical cluster and the principal component analyses (PCA): a) 0-2 cm layers of US plots; b) 0-2 cm layers of BSM plots; c) 2-5 cm layers of US plots; d) most of top layers of BS and BSS plots; and e) most of the 2-5 cm layers of BS, BSM and BSS plots. The distribution of soil samples in the PCA showed that straw mulching and, to a lesser extent, rye seeding reduced the distance between burnt and unburnt topsoil along Factor 1, but not along Factor 2 (explaining 56% and 29% of the variance, respectively). Consequently, these BAER treatments mitigated, but not wiped out, the effects of fire on soil quality after four years.

3D electron tomography of brain tissue unveils distinct Golgi structures that sequester cytoplasmic contents in neurons.

Macroautophagy is morphologically characterized by autophagosome formation. Autophagosomes are double-membraned vesicles that sequester cytoplasmic components for further degradation in the lysosome. Basal autophagy is paramount for intracellular quality control in post-mitotic cells but, surprisingly, the number of autophagosomes in post-mitotic neurons is very low, suggesting that alternative degradative structures could exist in neurons. To explore this possibility, we have examined neuronal subcellular architecture by performing three-dimensional (3D) electron tomography analysis of mouse brain tissue that had been preserved through high-pressure freezing. Here, we report that sequestration of neuronal cytoplasmic contents occurs at the Golgi complex in distinct and dynamic structures that coexist with autophagosomes in the brain. These structures are composed of several concentric double-membraned layers that appear to be formed simultaneously by the direct bending and sealing of discrete Golgi stacks. These structures are labelled for proteolytic enzymes, and lysosomes and late endosomes are found in contact with them, leading to the possibility that the sequestered material could be degraded inside them. Our findings highlight the key role that 3D electron tomography, together with tissue rapid-freezing techniques, will have in gaining new knowledge about subcellular architecture.

Melatonin reduces endoplasmic reticulum stress and autophagy in liver of leptin-deficient mice.

The sedentary lifestyle of modern society along with the high intake of energetic food has made obesity a current worldwide health problem. Despite great efforts to study the obesity and its related diseases, the mechanisms underlying the development of these diseases are not well understood. Therefore, identifying novel strategies to slow the progression of these diseases is urgently needed. Experimental observations indicate that melatonin has an important role in energy metabolism and cell signalling; thus, the use of this molecule may counteract the pathologies of obesity. In this study, wild-type and obese (ob/ob) mice received daily intraperitoneal injections of melatonin at a dose of 500 µg/kg body weight for 4 weeks, and the livers of these mice were used to evaluate the oxidative stress status, proteolytic (autophagy and proteasome) activity, unfolded protein response, inflammation and insulin signalling. Our results show, for the first time, that melatonin could significantly reduce endoplasmic reticulum stress in leptin-deficient obese animals and ameliorate several symptoms that characterize this disease. Our study supports the potential of melatonin as a therapeutic treatment for the most common type of obesity and its liver-associated disorders.

Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in-tissue multiscale 3D electron microscopy.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the coding sequence of huntingtin protein. Initially, it predominantly affects medium-sized spiny neurons (MSSNs) of the corpus striatum. No effective treatment is still available, thus urging the identification of potential therapeutic targets. While evidence of mitochondrial structural alterations in HD exists, previous studies mainly employed 2D approaches and were performed outside the strictly native brain context. In this study, we adopted a novel multiscale approach to conduct a comprehensive 3D in situ structural analysis of mitochondrial disturbances in a mouse model of HD. We investigated MSSNs within brain tissue under optimal structural conditions utilizing state-of-the-art 3D imaging technologies, specifically FIB/SEM for the complete imaging of neuronal somas and Electron Tomography for detailed morphological examination, and image processing-based quantitative analysis. Our findings suggest a disruption of the mitochondrial network towards fragmentation in HD. The network of interlaced, slim and long mitochondria observed in healthy conditions transforms into isolated, swollen and short entities, with internal cristae disorganization, cavities and abnormally large matrix granules.

The impact of teleworking technostress on satisfaction, anxiety and performance.

The aim of the research project is to find out how technostress influences the satisfaction, anxiety and performance of teleworkers and university students. The growth of technology and the use of digital platforms has given rise to a phenomenon called teleworking, a modality of work that involves remote work with the use of ICTs. However, the faster the use of ICTs in organisations grows, the more difficult it becomes for teleworkers, leading to anxiety and stress. This feeling is known as technostress, and knowing its impact on workers is of vital importance for organizational success. The study was conducted through a literature review and the dissemination of an online questionnaire using PLS software. The analysis validated the measurement scale and analysed the structural model at different stages, which confirmed its validity and reliability. The research concludes by affirming the high relationship between technostress, satisfaction, anxiety and performance. It is highlighted that the lower the technostress, the higher the satisfaction and performance, and the higher the technostress, the higher the anxiety and the lower the satisfaction. This research brings as an added value the validation of a scale of technostress together with the variables satisfaction, anxiety and performance not previously analysed by other researches. In addition, the research provides a series of measures to mitigate the effects of technostress and suggests future lines of research. Thus, it highlights the importance of understanding the impact of technostress on teleworkers, to provide effective measures to mitigate it and thus increase the satisfaction and performance of workers.

Problem based learning approaches to the technology education of physical therapy students.

BACKGROUND: Problem-Based Learning (PBL) is a whole-curriculum concept. AIM: This study aimed to compare learning preferences and strategies between physical therapy students taught by PBL and those receiving conventional lectures on massage therapy, trauma physical therapy, and electrotherapy, hydrotherapy, and thermotherapy. METHODS: This quasi-experimental study included 182 male and female students on physical therapy diploma courses at three universities in Andalusia (Spain). The Canfield Learning Skills Inventory (CLSI) was used to assess learning strategies and the Approaches to Study Skills Inventory for Students (ASSIST) to analyze study preferences. RESULTS: At the end of the academic year 2009/10, physical therapy students taught by PBL considered the most important learning strategies to be group work, study organization, relationship of ideas, and academic results. In comparison to conventionally taught counterparts, they considered that PBL reduced lack of purpose, memorizing without relating, the law of minimum effort, and fear of failure. Among these PBL students, the most highly rated study preferences were: organization of course tasks, cordial interaction with the teacher, learning by reading and images, and direct hands-on experience. CONCLUSION: For these physical therapy students, PBL facilitates learning strategies and study preferences in comparison to conventional teaching.

Role of laccase and low molecular weight metabolites from Trametes versicolor in dye decolorization.

The studies regarding decolorization of dyes by laccase may not only inform about the possible application of this enzyme for environmental purposes, but also may provide important information about its reaction mechanism and the influence of several factors that could be involved. In this paper, decolorization of crystal violet and phenol red was carried out with different fractions of extracellular liquids from Trametes versicolor cultures, in order to describe the role of laccase in this reaction. Moreover, the possible role of the low molecular weight metabolites (LMWMs) also produced by the fungus was evaluated. The results confirm the existence of a nonenzymatic decolorization factor, since the nonprotein fraction of the extracellular liquids from cultures of T. versicolor has shown decolorization capability. Several experiments were performed in order to identify the main compounds related to this ability, which are probably low molecular weight peroxide compounds.

Impaired ATF6α processing, decreased Rheb and neuronal cell cycle re-entry in Huntington's disease.

The endoplasmic reticulum-stress response is induced in several neurodegenerative diseases and in cellular models of Huntington's disease. However, here we report that the processing of ATF6α to its active nuclear form, one of the three branches of endoplasmic reticulum-stress activation, is impaired in both animal models and Huntington's disease patients. ATF6α has been reported to be essential for the survival of dormant tumour cells that, like neurons, are arrested in the G0-G1 phase of the cell cycle. This effect is mediated by the small GTPase Rheb (Ras-homologue enriched in brain). Our results suggest that the ATF6α/Rheb pathway is altered in Huntington's disease as the decrease in ATF6α processing is accompanied by a decrease in the accumulation of Rheb. These alterations correlate with the aberrant accumulation of cell cycle re-entry markers in post-mitotic neurons which is accompanied by death of a subset of neurons.

Chaperonins: Nanocarriers with Biotechnological Applications.

Chaperonins are molecular chaperones found in all kingdoms of life, and as such they assist in the folding of other proteins. Structurally, chaperonins are cylinders composed of two back-to-back rings, each of which is an oligomer of ~60-kDa proteins. Chaperonins are found in two main conformations, one in which the cavity is open and ready to recognise and trap unfolded client proteins, and a "closed" form in which folding takes place. The conspicuous properties of this structure (a cylinder containing a cavity that allows confinement) and the potential to control its closure and aperture have inspired a number of nanotechnological applications that will be described in this review.

The Role of INAPERTURATE POLLEN1 as a Pollen Aperture Factor Is Conserved in the Basal Eudicot Eschscholzia californica (Papaveraceae).

Pollen grains show an enormous variety of aperture systems. What genes are involved in the aperture formation pathway and how conserved this pathway is in angiosperms remains largely unknown. INAPERTURATE POLLEN1 (INP1) encodes a protein of unknown function, essential for aperture formation in Arabidopsis, rice and maize. Yet, because INP1 sequences are quite divergent, it is unclear if their function is conserved across angiosperms. Here, we conducted a functional study of the INP1 ortholog from the basal eudicot Eschscholzia californica (EcINP1) using expression analyses, virus-induced gene silencing, pollen germination assay, and transcriptomics. We found that EcINP1 expression peaks at the tetrad stage of pollen development, consistent with its role in aperture formation, which occurs at that stage, and showed, via gene silencing, that the role of INP1 as an important aperture factor extends to basal eudicots. Using germination assays, we demonstrated that, in Eschscholzia, apertures are dispensable for pollen germination. Our comparative transcriptome analysis of wild-type and silenced plants identified over 900 differentially expressed genes, many of them potential candidates for the aperture pathway. Our study substantiates the importance of INP1 homologs for aperture formation across angiosperms and opens up new avenues for functional studies of other aperture candidate genes.

Dating historical droughts from religious ceremonies, the international pro pluvia rogation database.

Climate proxy data are required for improved understanding of climate variability and change in the pre-instrumental period. We present the first international initiative to compile and share information on pro pluvia rogation ceremonies, which is a well-studied proxy of agricultural drought. Currently, the database has more than 3500 dates of celebration of rogation ceremonies, providing information for 153 locations across 11 countries spanning the period from 1333 to 1949. This product provides data for better understanding of the pre-instrumental drought variability, validating natural proxies and model simulations, and multi-proxy rainfall reconstructions, amongst other climatic exercises. The database is freely available and can be easily accessed and visualized via http://inpro.unizar.es/ .

Characterization of a family GH5 xylanase with activity on neutral oligosaccharides and evaluation as a pulp bleaching aid.

A new bacterial xylanase belonging to family 5 of glycosyl hydrolases was identified and characterized. The xylanase, Xyn5B from Bacillus sp. strain BP-7, was active on neutral, nonsubstituted xylooligosaccharides, showing a clear difference from other GH5 xylanases characterized to date that show a requirement for methyl-glucuronic acid side chains for catalysis. The enzyme was evaluated on Eucalyptus kraft pulp, showing its effectiveness as a bleaching aid.

Expression of LAIR-1 (CD305) on Human Blood Monocytes as a Marker of Hepatic Cirrhosis Progression.

BACKGROUND AND AIM: The presumed role of the inhibitory receptor LAIR-1 (CD305) in the inflammatory response suggests that it might contribute to the pathophysiology of chronic inflammatory diseases such as liver cirrhosis. We studied the LAIR-1 expression on liver macrophages and blood monocytes related to the progression of liver cirrhosis. METHODS: The expression of LAIR-1 was analyzed by immunohistochemistry, flow cytometry, and Western blot. RESULTS: We found a decreased number of macrophages expressing LAIR-1 in cirrhotic liver that could be due to a high presence of collagen, ligand of LAIR-1, in the fibrotic tissue which could downregulate its expression or interfere with the immunostaining. The expression of LAIR-1 decreased after cell differentiation, and the total content, but not the cell surface expression, increased after activation in the HL-60 human macrophage in vitro model. Blood monocytes exhibited higher LAIR-1 expression levels in cirrhotic patients, which were evident even in early clinical stages in all monocyte subsets, and greater in the "intermediate" inflammatory monocyte subpopulation. The in vitro activation of human blood monocytes did not increase its expression on the cell surface suggesting that the in vivo increase of LAIR-1 must be the result of a specific combination of stimuli present in cirrhotic patients. This represents an exclusive feature of liver cirrhosis, since blood monocytes from other chronic inflammatory pathologies showed similar or lower LAIR-1 levels compared with those of healthy controls. CONCLUSIONS: These results may indicate that monocyte LAIR-1 expression is a new biomarker to early detect liver damage caused by chronic inflammation in liver cirrhosis.