Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition

RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1

Who is in charge? A review and a research agenda on the 'human side' of the circular economy

The adoption of the circular economy (CE) at the firm level has rarely intersected with human resource management (HRM) – here called 'the human side of organizations' – and these two fields remain largely separate areas of knowledge. While the literature on the CE is expanding, discussion of its implementation in organizations is, so far, rare, along with exploration of the necessary alignment of the CE with green human resource management (GHRM). In this article, we extend the state-of-the-art literature on CE business models through the inclusion of the ‘human side’ of such issues. This goal is met by offering an original integrative GHRM framework for organizations developing CE. The theoretical lenses of stakeholders' theory and the resource based view (RBV) form the foundation of this framework, which represents a 'middle range theory'. We underline the practices and dimensions of the links between GHRM and the 'ReSOLVE' CE model. Through an exploration of this integrative framework, we propose a future research agenda along with original research propositions. Furthermore, the middle-range integrated theoretical framework we propose can serve both academics and practitioners in developing understanding of the human resource management (HRM) and change management aspects of the CE

Metabolic diseases affect male reproduction and induce signatures in gametes that may compromise the offspring health

The most prevalent diseases worldwide are non-communicable such as obesity and type 2 diabetes. Noteworthy, the prevalence of obesity and type 2 diabetes is expected to steadily increase in the next decades, mostly fueled by bad feeding habits, stress, and sedentarism. The reproductive function of individuals is severely affected by abnormal metabolic environments, both at mechanical and biochemical levels. Along with mechanical dysfunctions, and decreased sperm quality (promoted both directly and indirectly by metabolic abnormalities), several studies have already reported the potentially harmful effects of metabolic disorders in the genetic and epigenetic cargo of spermatozoa, and the epigenetic inheritance of molecular signatures induced by metabolic profile (paternal diet, obesity, and diabetes). The inheritance of epigenetic factors towards the development of metabolic abnormalities means that more people in reproductive age can potentially suffer from these disorders and for longer periods. In its turn, these individuals can also transmit this (epi)genetic information to future generations, creating a vicious cycle. In this review, we collect the reported harmful effects related to acquired metabolic disorders and diet in sperm parameters and male reproductive potential. Besides, we will discuss the novel findings regarding paternal epigenetic inheritance, particularly the ones induced by paternal diet rich in fats, obesity, and type 2 diabetes. We analyze the data attained with in vitro and animal models as well as in long-term trans generational population studies. Although the findings on this topic are very recent, epigenetic inheritance of metabolic disease has a huge societal impact, which may be crucial to tackle the `fat epidemic' efficiently

Glycerol and testicular activity: the good, the bad and the ugly

Over the past decades, there have been several studies suggesting that semen quality is declining. Interestingly, these observations are paired with a significant increase in the number of individuals diagnosed with metabolic diseases, including obesity and diabetes mellitus. Hence, it is tempting to hypothesize that obesity and its associated comorbidities and risk factors (such as a hypercaloric diets) impair the homeostasis of the male reproductive health, with a possible direct effect on the testes. The blood and interstitial fluids of obese individuals usually have increased levels of glycerol, notably due to triglyceride and phospholipid catabolism and high fructose intake. Glycerol is metabolized via intermediary metabolism by a group of reactions centred at the glycerol-3-phosphate shuttle, which links the metabolic pathway of glucose, lipids and oxidative phosphorylation, illustrating its high relevance for biological systems. Glycerol enters and exits the cells by the action of specialized carriers, known as aquaglyceroporins, whose functional importance for male reproductive health has emerged in the last few years. Notably, glycerol has antispermatogenic properties. When present in high concentration in the testis, it causes blood-testis barrier disruption, impairing tubular fluid homeostasis. Nevertheless, glycerol metabolism in testicular cells remains a matter of debate. Herein we discuss previous and current research concerning the role of glycerol and its metabolism in testicular cells, and how it can influence testicular activity

Valorisation of red beet waste: one-step extraction and separation of betalains and chlorophylls using thermoreversible aqueous biphasic systems

Globally, up to 50% of root crops, fruits and vegetables produced is wasted. Beetroot stems and leaves fit into this scenario, with only a small fraction being used in cattle food. One way of approaching this problem is through their valorisation, by extracting and recovering valuable compounds present in this type of waste that could be used in other applications, while contributing towards a circular economy. In this work, a new integrated process using thermoreversible aqueous biphasic systems (ABS) composed of quaternary ammonium-based ionic liquids (ILs) and polypropyleneglycol 400 g mol−1 (PPG) is shown to allow the one-step extraction and separation of two pigment classes—betalains and chlorophylls—from red beet stems and leaves. The pigment extraction was carried out with a monophasic aqueous solution of the IL and PPG, whose phase separation was then achieved by a temperature switch, resulting in the simultaneous separation of chlorophylls and betalains into opposite phases. A central composite design was used to optimise the extraction parameters (time, temperature, and solid : liquid (S/L) ratio) of both pigment extraction yields, reaching at 20 °C, 70 min and a S/L ratio of 0.12 a maximum extraction yield of 6.67 wt% for betalains and 1.82 wt% for chlorophylls (per weight of biomass). Moreover, it is shown that aqueous solutions of ILs better stabilise betalains than the gold standard solvent used for the extraction method. Among the studied systems, the ABS comprising the IL N-ethyl-N-methyl-N,N-bis(2-hydroxyethyl) bromide ([N21(2OH)(2OH)]Br) presented the best separation performance, with an extraction efficiency of 92% and 95% for chlorophylls and betalains, respectively, for opposite phases. The pigments were removed from the respective phases using affinity resins, with high recoveries: 96% for betalains and 98% for chlorophylls, further allowing the IL reuse. Finally, the cyto- and ecotoxicities of the quaternary ammonium-based ILs were determined. The obtained results disclosed low to negligible toxicity in the thousands of mg L−1 range, with [N21(2OH)(2OH)]Br being harmless from an ecotoxicological point of view. Overall, it is shown here that the developed process is an innovative approach for the one-step extraction and selective separation of pigments contributing to the valorisation of waste biomass

Health-related quality of life in patients with venous leg ulcer treated in primary care in Brazil and Portugal

Background Venous ulcers constitute an important public health problem as they can cause disability with consequences for multiple dimensions of quality of life. Objective To describe the quality of life in patients with venous leg ulcer treated in primary care in two cities from Brazil and Portugal. Methods This was a cross-sectional comparative study with a non-probabilistic sample of 171 patients with venous leg ulcers who were treated in primary care in two cities from Brazil and Portugal, namely, Natal and Évora. A form covering sociodemographic and health data and the Medical Outcomes Study 36-Item Short-Form Health Survey were used, and descriptive and inferential analyses were performed. Results Significant differences in age and income were observed between the two samples. Patients with venous leg ulcer from Brazil had lower income and were younger than those from Portugal. Quality of life scores were significantly higher in Portugal for the physical aspects, pain, and social functioning, among domains, and for the physical health dimension and total score of QOL. Conclusion The quality of life was better in Portugal than in Brazil and the differences between the countries need further investigation

Disturbance and diversity at two spatial scales

The spatial scale of disturbance is a factor potentially influencing the relationship between disturbance and diversity. There has been discussion on whether disturbances that affect local communities and create a mosaic of patches in different successional stages have the same effect on diversity as regional disturbances that affect the whole landscape. In a microcosm experiment with metacommunities of aquatic protists, we compared the effect of local and regional disturbances on the disturbance–diversity relationship. Local disturbances destroyed entire local communities of the metacommunity and required reimmigration from neighboring communities, while regional disturbances affected the whole metacommunity but left part of each local community intact. Both disturbance types led to a negative relationship between disturbance intensity and Shannon diversity. With strong local disturbance, this decrease in diversity was due to species loss, while strong regional disturbance had no effect on species richness but reduced the evenness of the community. Growth rate appeared to be the most important trait for survival after strong local disturbance and dominance after strong regional disturbance. The pattern of the disturbance–diversity relationship was similar for both local and regional diversity. Although local disturbances at least temporally increased beta diversity by creating a mosaic of differently disturbed patches, this high dissimilarity did not result in regional diversity being increased relative to local diversity. The disturbance–diversity relationship was negative for both scales of diversity. The flat competitive hierarchy and absence of a trade-off between competition and colonization ability are a likely explanation for this pattern

Modeling Magnification and Anisotropy in the Primate Foveal Confluence

A basic organizational principle of the primate visual system is that it maps the visual environment repeatedly and retinotopically onto cortex. Simple algebraic models can be used to describe the projection from visual space to cortical space not only for V1, but also for the complex of areas V1, V2 and V3. Typically a conformal (angle-preserving) projection ensuring local isotropy is regarded as ideal and primate visual cortex is often regarded as an approximation of this ideal. However, empirical data show systematic deviations from this ideal that are especially relevant in the foveal projection. The aims of this study were to map the nature of anisotropy predicted by existing models, to investigate the optimization targets faced by different types of retino-cortical maps, and finally to propose a novel map that better models empirical data than other candidates. The retino-cortical map can be optimized towards a space-conserving homogenous representation or a quasi-conformal mapping. The latter would require a significantly enlarged representation of specific parts of the cortical maps. In particular it would require significant enlargement of parafoveal V2 and V3 which is not supported by empirical data. Further, the recently published principal layout of the foveal singularity cannot be explained by existing models. We suggest a new model that accurately describes foveal data, minimizing cortical surface area in the periphery but suggesting that local isotropy dominates the most foveal part at the expense of additional cortical surface. The foveal confluence is an important example of the detailed trade-offs between the compromises required for the mapping of environmental space to a complex of neighboring cortical areas. Our models demonstrate that the organization follows clear morphogenetic principles that are essential for our understanding of foveal vision in daily life

Impact of Space Weather on Climate and Habitability of Terrestrial Type Exoplanets

The current progress in the detection of terrestrial type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favorable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of astrospheric, atmospheric and surface environments of exoplanets in habitable zones around G-K-M dwarfs including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles, and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favorable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro) physical, chemical, and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the habitable zone to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.Comment: 206 pages, 24 figures, 1 table; Review paper. International Journal of Astrobiology (2019

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals