Search

Blood-feeding behavior has independently evolved in arthropods multiple times. Unlike hard ticks, soft ticks employ a rapid-feeding strategy for hematophagy, and there are comparatively limited studies on the transcriptomes of these organisms. This study investigates the soft tick Ornithodoros hermsi, conducting histopathological examinations at bitten skin sites and tick whole-body transcriptomic analyses across various developmental and feeding stages, including larvae, 1st-nymphal, and 2nd-nymphal stages. The results revealed the ability of O. hermsi to induce skin hemorrhage at the bite sites. Transcriptomic analyses identified three consistent transcriptional profiles: unfed, early-fed (6 h, 12 h, 24 h), and late-fed (5 days). The unfed profile exhibited high transcriptional activity across most of the functional classes annotated. In contrast, early-fed stages exhibited decreased expression of most functional classes, except for the unknown, which is highly expressed. Finally, transcriptional expression of most functional classes increased in the late-fed groups, resembling the baseline expression observed in the unfed groups. These findings highlight intense pre-feeding transcriptional activity in O. hermsi ticks, aligning with their rapid-feeding strategy. Moreover, besides shedding light on the temporal dynamics of key pathways during blood meal processing and tick development, this study contributes significantly to the transcriptome repertoire of a medically relevant soft tick species with relatively limited prior knowledge. [ABSTRACT FROM AUTHOR]

While Heinrich Melchior Mühlenberg and his pastor colleagues from Halle have gone down in history for their pioneering work – organizing the Lutheran Church on North American soil – they are not known for missionary projects to Native Americans. This article examines how things changed after a second generation of Halle pastors arrived in Pennsylvania in the 1760s. It was, above all, down to Mühlenberg's later son-in-law Johann Christoph Kunze, who had a rather different view on America's indigenous people. During his whole lifespan in America, Kunze pursued his goal of establishing a mission to Native Americans. This engagement contributed to a paradigm shift in the Lutheran Church. In contrast to Mühlenberg and the first generation of Halle pastors, Kunze sought transnational support that was no longer exclusively centered in Halle's Glaucha Institutions but based on pan-Protestant, maritime networks. [ABSTRACT FROM AUTHOR]

Cryptococcus gattii is a primary pathogenic fungus that causes pneumonia. This species is also responsible for an outbreak in Vancouver, Canada, and spreading to the mainland and United States. The use of medical devices is often complicated by infections with biofilm-forming microbes with increased resistance to antimicrobial agents and host defense mechanisms. This study investigated the comparative proteome of C. gattii R265 (VGIIa) grown under planktonic and biofilm conditions. A brief comparison with C. neoformans H99 biofilm and the use of different culture medium and surface were also evaluated. Using Multidimensional Protein Identification Technology (MudPIT), 1819 proteins were identified for both conditions, where 150 (8.2%) were considered differentially regulated (up- or down-regulated and unique in biofilm cells). Overall, the proteomic approach suggests that C. gattii R265 biofilm cells are maintained by the induction of electron transport chain for reoxidation, and by alternative energy metabolites, such as succinate and acetate. Since C. gattii is considered a primary pathogen and is one of the most virulent and less susceptible to antifungals, understanding how biofilms are maintained is fundamental to search for new targets to control this important mode of growth that is difficult to eradicate. [Display omitted] • A comparative proteome analysis of C. gattii biofilm was made against planktonic cells. • Metabolic alterations were observed in biofilm, with down-regulation of carbohydrate metabolism. • The electron transport chain seems to be activated in C. gattii biofilm. • Succinate and acetate might support cell maintenance in biofilm. [ABSTRACT FROM AUTHOR]

• Cisplatin group presented a greater number of atretic follicles (p = 0.014). • Cisplatin triggered plasma and ovarian tissue kallikrein generation. • The main product of kinin receptor activation, nitric oxide, increased. • Neutrophil and macrophage infiltration markers increased. • Superoxide anion generation was higher and reduced glutathione levels were lower. Kallikrein-kinin system (KKS) is involved in vascular reactivity and inflammatory response to cytotoxic drugs. Since cisplatin is a widely used chemotherapy and its cytotoxic mechanism can trigger inflammation and oxidative damage, in this work we evaluated the role of KKS in an animal model of cisplatin-induced ovarian toxicity. Biomarkers of ovarian stem cells, activity of KKS, inflammation and oxidative damage were measured in ovarian tissue of C57BL/6 female mice treated with vehicle or cisplatin (2.5 mg/kg). Cisplatin group presented greater number of atretic follicles, and lower numbers of antral and total viable follicles. Ki67, DDX4 and OCT-4 markers were similar between groups. Cisplatin triggered plasma and ovarian tissue kallikrein generation; and increased expression of bradykinin receptors B1 and B2. Neutrophil and macrophage infiltration markers increased. Superoxide anion generation also increased, while reduced glutathione levels decreased. These results suggest that KKS is activated and contributes to ovarian injury during cisplatin treatment. [ABSTRACT FROM AUTHOR]

Background: Lonomia obliqua venom is nephrotoxic and acute kidney injury (AKI) is the main cause of death among envenomed victims. Mechanism underlying L. obliqua-induced AKI involves renal hypoperfusion, inflammation, tubular necrosis and loss of glomerular filtration and tubular reabsorption capacities. In the present study, we aimed to investigate the contribution of kallikrein to the hemodynamic instability, inflammation and consequent renal and vascular impairment Methodology/Principal findings: Addition of L. obliqua venom to purified prekallikrein and human plasma in vitro or to vascular smooth muscle cells (VSMC) in culture, was able to generate kallikrein in a dose-dependent manner. Injected in rats, the venom induced AKI and increased kallikrein levels in plasma and kidney. Kallikrein inhibition by aprotinin prevented glomerular injury and the decrease in glomerular filtration rate, restoring fluid and electrolyte homeostasis. The mechanism underlying these effects was associated to lowering renal inflammation, with decrease in pro-inflammatory cytokines and matrix metalloproteinase expression, reduced tubular degeneration, and protection against oxidative stress. Supporting the key role of kallikrein, we demonstrated that aprotinin inhibited effects directly associated with vascular injury, such as the generation of intracellular reactive oxygen species (ROS) and migration of VSMC induced by L. obliqua venom or by diluted plasma obtained from envenomed rats. In addition, kallikrein inhibition also ameliorated venom-induced blood incoagulability and decreased kidney tissue factor expression Conclusions/Significance: These data indicated that kallikrein and consequently kinin release have a key role in kidney injury and vascular remodeling. Thus, blocking kallikrein may be a therapeutic alternative to control the progression of venom-induced AKI and vascular disturbances. [ABSTRACT FROM AUTHOR]

Summary: The current focus on the use phase in automotive carbon dioxide (CO2) legislation bares a risk of unintended consequences as often reductions in the use phase come along with increasing CO2 emissions in other life cycle (LC) phases. This study presents voluntary policy options in form of LC‐based CO2 emission credits. They were developed by desk research considering existing applications of LCA in practice (e.g., environmental reports) and feedback obtained in a structured stakeholder dialogue. A variety of credit options were identified, including rather simple ones based on life cycle thinking (LCT) and more advanced options which rely on quantitative LCA: LCT options that reward innovations leading to CO2 reductions, for example, in the production phase. LCA‐based options reward CO2 reductions along the LC (credits for an International Organization for Standardization [ISO] 14044 conforming externally reviewed LCA showing a continuous improvement) or reductions of other environmental impacts. It was shown that the credit options can be implemented throughout a simplified and robust methodology, for example, with defined rules for conducting the LCA based on international standards and established industry practice, and for calculating the credits (e.g., a credit of 1 gram [g] of CO2/km [kilometer] for savings of 10 g of CO2/km). Voluntary credit options as a complementary modality to the current automotive tailpipe‐based CO2 regulations would help to improve its efficiency and effectiveness and support and reward efforts on achieving real net CO2 emission reductions. The credit options were developed with a first focus on CO2 and automotive industry, but can generally be transferred to other environmental impacts and sectors as well. [ABSTRACT FROM AUTHOR]

Due to steadily increasing resource demand and accompanying raising public awareness, a variety of assessment methodologies evaluating resource use and its consequences were published in the last years. Existing methodologies are typically developed considering the specific characteristics of one particular resource type and as consequence are not suitable for cross-cutting assessment of different resource types. This paper proposes an 3-step approach for combining different resource use assessment methodologies allowing for a consistent assessment of product systems using different resource types. The first steps evaluate if the considered dimensions, categories, indicators, indicator models and underlying data are consistent. When this is the case, they can be included in the combined methodology without further adjustments. Differences are identified simultaneously and addressed in the subsequent steps. Within the steps guidance is provided on how the dimensions, categories and indicators of the methodologies can be adjusted to fit in the combined methodology. In a case study the proposed approach is applied to two methodologies developed by the authors assessing abiotic (ESSENZ method) and biotic resources and raw materials (BIRD method). The ESSENZ method consists of four dimensions, which are quantified by overall 21 categories and indicators. The BIRD method takes into account five dimensions and 24 corresponding categories and indicators. As none of the considered dimension of the two methodologies match, comparison of the considered resource types as well as application in a case study is not possible. By applying the proposed approach all five dimensions and 25 of the overall 27 categories and indicators can be integrated in the combined approach for a consistent assessment of abiotic and biotic resources and raw materials. The obtained combined methodology is then applied to three shelves made out of metal, wood and plastic. It could be shown that the introduced approach provides meaningful guidance on how to combine different resource use assessment methodologies and increases the findings gained from a combined and consistent assessment. [ABSTRACT FROM AUTHOR]

The supply of water, food, and energy in our global economy is highly interlinked. Virtual blue water embedded into internationally traded food crops has therefore been extensively researched in recent years. This study focuses on the often neglected energy needed to supply this blue irrigation water. It provides a globally applicable and spatially explicit approach to the watershed level for water source specific quantification of energy consumption and related greenhouse gas (GHG) emissions of irrigation water supply. The approach is applied to Israel's total domestic and imported food crop supply of 105 crops by additionally including import‐related transportation energy and emissions. Total energy use and related emissions of domestic crop production were much lower (551 GWh/422 kt CO2‐equivalents [CO2e]) than those embedded into crop imports (1639 GWh/649 kt CO2e). Domestic energy and emissions were mainly attributable to the irrigation water supply with artificial water sources (treated domestic wastewater and desalinated water, 84%). Transport accounted for 79% and 66% of virtually imported energy and emissions, respectively. Despite transport, specific GHG emissions (CO2e per ton of crop) were significantly lower for several crops (e.g., olives, almonds, chickpeas) compared to domestic production. This could be attributed to the high share of energy‐intensive artificial water supply in combination with higher irrigation water demands in Israel. In the course of an increasing demand for artificial water supply in arid and semi‐arid regions, our findings point to the importance of including "energy for water" into comparative environmental assessment of crop supply to support decision‐making related to the water–energy–food nexus. [ABSTRACT FROM AUTHOR]

We report on the discovery of two new lead series for the development of glucocorticoid receptor agonists. Firstly, the discovery of tetrahydronaphthalenes led to metabolically stable and dissociated compounds. Their binding mode to the glucocorticoid receptor could be elucidated through an X-ray structure. Closer inspection into the reaction path and analyses of side products revealed a new amino alcohol series also addressing the glucocorticoid receptor and demonstrating strong anti-inflammatory activity in vitro . [ABSTRACT FROM AUTHOR]

With increasing demand of abiotic resources also the pollution of natural resources like water and soil has risen in the last decades due to global industrial and technological development. Thus, enhancing resource efficiency is a key goal of national and international strategies. For a comprehensive assessment of all related impacts of resource extraction and use all three sustainability dimensions have to be taken into account: economic, environmental and social aspects. Furthermore, to avoid burden shifting life cycle based methods should be applied. As companies need operational tools and approaches, a comprehensive method has been developed to measure resource efficiency of products, processes and services in the context of sustainable development (ESSENZ). Overall 21 categories are established to measure impacts on the environment, physical and socio-economic availability of the used resources as well as their societal acceptance. For the categories socio-economic availability and societal acceptance new approaches are developed and characterization factors are provided for a portfolio of 36 metals and four fossil raw materials. The introduced approach has been tested on several case studies, demonstrating that it enhances the applicability of resource efficiency to assess product systems significantly by providing an overall framework that can be adopted across sectors, using indicators and methods which are applicable and can be integrated into existing life cycle assessment based schemes. [ABSTRACT FROM AUTHOR]

Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. To characterize L. obliqua venom effects, we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery-based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman's space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increase the expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. In conclusion, the mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia's envenomation. [ABSTRACT FROM AUTHOR]

Aiming to enhance the analysis of water consumption and resulting consequences along the supply chain of products, the water accounting and vulnerability evaluation (WAVE) model is introduced. On the accounting level, atmospheric evaporation recycling within drainage basins is considered for the first time, which can reduce water consumption volumes by up to 32%. Rather than predicting impacts, WAVE analyzes the vulnerability of basins to freshwater depletion. Based on local blue water scarcity, the water depletion index (WDI) denotes the risk that water consumption can lead to depletion of freshwater resources. Water scarcity is determined by relating annual water consumption to availability in more than 11?000 basins. Additionally, WDI accounts for the presence of lakes and aquifers which have been neglected in water scarcity assessments so far. By setting WDI to the highest value in (semi)arid basins, absolute freshwater shortage is taken into account in addition to relative scarcity. This avoids mathematical artifacts of previous indicators which turn zero in deserts if consumption is zero. As illustrated in a case study of biofuels, WAVE can help to interpret volumetric water footprint figures and, thus, promotes a sustainable use of global freshwater resources. [ABSTRACT FROM AUTHOR]

Abstract: The clinical manifestations of Lonomia obliqua caterpillar envenomation are systemic hemorrhage and acute kidney injury. In an effort to better understand the physiopathological mechanisms of envenomation, a rat model was established to study systemic tissue damage during L. obliqua envenomation. An array of acute venom effects was characterized, including biochemical, hematological, histopathological, myotoxic and genotoxic alterations. Rapid increases in serum alanine and aspartate transaminases, γ-glutamyl transferase, lactate dehydrogenase, hemoglobin, bilirubin, creatinine, urea and uric acid were observed, indicating that intravascular hemolysis and liver and kidney damage had occurred. Treatment with a specific antivenom (antilonomic serum) for up to 2 h post-venom injection neutralized the biochemical alterations. However, treatment after 6 h post-venom injection failed to normalize all biochemical parameters, despite its efficacy in reversing coagulation dysfunction. The hematological findings were consistent with hemolytic anemia and neutrophilic leukocytosis. The histopathological alterations were mainly related to hemorrhage and inflammation in the subcutaneous tissue, lung, heart and kidneys. Signs of congestion and hemosiderosis were evident in the spleen, and hemoglobin and/or myoglobin casts were also detected in the renal tubules. Increased levels of creatine kinase and creatine kinase-MB were correlated with the myocardial necrosis observed in vivo and confirmed the myotoxicity detected in vitro in isolated extensor digitorum longus muscles. Significant DNA damage was observed in the kidneys, heart, lung, liver and lymphocytes. The majority of the DNA lesions in the kidney were due to oxidative damage. The results presented here will aid in understanding the pathology underlying Lonomia's envenomation. [Copyright &y& Elsevier]

This work identifies shortcomings in water footprinting and discusses whether the water footprint should be a volumetric or impact-oriented index. A key challenge is the current definition of water consumption according to which evaporated water is regarded as lost for the originating watershed per se. Continental evaporation recycling rates of up to 100% within short time and length scales show that this definition is not generally valid. Also, the inclusion of land use effects on the hydrological balance is questionable, as land transformation often leads to higher water availability due to locally increased runoff. Unless potentially negative consequences, such as flooding or waterlogging, and adverse effects on the global water cycle are considered, water credits from land transformation seem unjustified. Most impact assessment methods use ratios of annual withdrawal or consumption to renewability rates to denote local water scarcity. As these ratios are influenced by two metrics-withdrawal and availability-arid regions can be regarded as uncritical if only small fractions of the limited renewable supplies are used. Besides neglecting sensitivities to additional water uses, such indicators consider neither ground nor surface water stocks, which can buffer water shortages temporally. Authors favoring volumetric indicators claim that global freshwater appropriation is more important than local impacts, easier to determine, and less error prone than putting complex ecological interaction into mathematical models. As shown in an example, volumetric water footprints can be misleading without additional interpretation because numerically smaller footprints can cause higher impacts. [ABSTRACT FROM AUTHOR]

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients. [ABSTRACT FROM AUTHOR]

Due to global increase of freshwater scarcity, knowledge about water consumption in product life cycles is important This study analyzes water consumption and the resulting impacts of Volkswagen's car models Polo, Golf and Passat and represents the first application of impact-oriented water footprint methods on complex industrial products. Freshwater consumption throughout the cars' life cycles is allocated to material groups and assigned to countries according to import mix shares or location of production sites. Based on these regionalized water inventories, consequences for human health, ecosystems, and resources are determined by using recently developed impact assessment methods. Water consumption along the life cycles of the three cars ranges from 52 to 83 m3/car, of which more than 95% is consumed in the production phase, mainly resulting from producing iron, steel, precious metals, and polymers. Results show that water consumption takes place in 43 countries worldwide and that only 10% is consumed directly at Volkswagen's production sites. Although impacts on health tend to be dominated by water consumption in South Africa and Mozambique, resulting from the production of precious metals and aluminum, consequences for ecosystems and resources are mainly caused by water consumption of material production in Europe. [ABSTRACT FROM AUTHOR]

Abstract: Caterpillar envenomation has been an emergent health issue. Lonomia obliqua is a medically important animal that causes a hemorrhagic syndrome that can progress to acute renal failure, intracranial hemorrhage and death. In the past few years the molecular characterization of L. obliqua venom in addition to experimental models has provided fundamental information to the understanding of the envenomation syndrome. Herein studies from several authors which characterized the complex toxic-pharmacological actions of whole venom are reviewed. [ABSTRACT FROM AUTHOR]

Abstract: The dissociated glucocorticoid receptor (GR) agonist ZK 216348 is rendered GR-selective over other nuclear hormone receptors through replacing the methylbenzoxazine with a quinoline moiety. Compounds were shown to be efficacious in cell assays with respect to inflammation endpoints, along with reduced activity in a transactivation assay, hinting at an improved therapeutic window over corticosteroids. [Copyright &y& Elsevier]

Abstract: Envenomation caused by Lonomia obliqua is a public health hazard in Southern Brazil. Envenomed victims present severe hemorrhagic syndrome that can progress to intracranial hemorrhage and death. To understand the mechanisms that lead to hemorrhage, we investigated the platelet dysfunction and blood coagulation disturbances following experimental envenomation in rats. L. obliqua bristle extract was injected (s.c.) and blood collected at different times post-venom administration for determination of platelet response and analysis of blood coagulation. Rats presented hypofibrinogenemia and platelet hypoaggregation in platelet rich plasma (PRP). After addition of exogenous fibrinogen to PRP, platelet hypoaggregation was not corrected. Interestingly, normoaggregation was observed when platelets were separated from plasma. In addition, incubation of plasma from envenomed rats inhibits aggregation response of normal washed platelets. These results indicate that an aggregation inhibitor is generated in plasma during envenomation. Moreover, rats presented an increase in nitric oxide plasmatic levels which coincided with maximum inhibition in platelet aggregation. Animals also showed blood incoagulability and a significant increase in thrombin, plasmin and urokinase plasmatic activities. Despite this intravascular thrombin generation, only a slight decrease in platelet numbers was detected. Certainly, the platelet hypoaggregation and blood incoagulability described herein contribute to systemic bleeding observed in patients. [Copyright &y& Elsevier]

ABSTRACT: Saturation transfer difference (STD) NMR experiments on human N-acetylglucosamine kinase (GlcNAc kinase) have been used to determine binding epitopes for the G1cNAc and ATP substrates and their analogues. The study reveals that during the enzyme reaction the binding mode of both substrates is conserved, although the binding affinity of the sugar is reduced. This suggests that the protein does not undergo any significant structural changes during catalysis. Our experiments also demonstrate that G1cNAc kinase has residual activity in the absence of Mg2+. Furthermore, our experiments clearly show that the GlcNAc kinase predominately, if not exclusively, produces the α anomer of phosphorylated sugars. To identify the minimum requirements for substrate binding, a detailed analysis of different natural occurring as well as synthetic sugars was employed. Modifications at the 1, 2, 3, 4 and 6 position as well as the N-acetyl group greatly reduce the binding affinity. In addition, the binding mode of these substrate analogues is often also changed. The high β anomeric preference of G1cNAc kinase along with the drastically reduced binding affinity for sugars other than G1cNAc, suggests that GlcNAc kinase phosphorylates fi-G1cNAc in cells. [ABSTRACT FROM AUTHOR]

Abstract: Spinal cord injury (SCI) is associated with a marked and rapid sublesional bone loss. So far, reports about the time course of adaptive changes in bone mass and structure in people with chronic and complete SCI are conflicting. Both, a continuous decline of bone parameters throughout the chronic phase of immobilisation as well as stabilisation of bone status on a low level have been documented. In our recently published cross-sectional study we suggested that subjects with a complete SCI reach a new bone steady-state in the paralysed limbs after extensive bone loss was complete. In addition, we described a time loss curve for each measured bone mineral density and geometry parameter and calculated its individual time to reach steady-state (t steady-state). The aim of the present study was to test the findings of our cross-sectional study in a longitudinal design. Thirty-nine male subjects of the original cross-sectional study with complete SCI and paralysis duration between 0.9 and 34 years were included. Two follow-up pQCT measurements at 15 and 30 months after baseline measurement were performed at the distal epiphyses and mid shafts of the femur, tibia and radius. From the epiphyseal scans, bone mass, trabecular and total BMD were calculated. From the shaft scans, bone mass and cortical BMD, total and cortical cross-sectional areas and cortical thickness were determined. Repeated measures ANOVAs were performed with bone data at baseline, after 15 months and 30 months. Analyses were performed including only subjects with a lesion duration ≥ t steady-state for each particular bone parameter. Bone parameters of tibial and femoral epi- and diaphyses were found to show no statistically significant differences between the three time points. Relative changes in bone parameters were small and ranged from −1.72% to +0.51% in the femur and from −1.67% to +0.42% in the tibia within 30 months of monitoring. Our data confirm the temporal limitation of the bone loss after complete SCI with stabilisation of BMD and geometric properties on a lower level—a finding of clinical importance considering the treatment strategies of bone loss after SCI with respect to lesion duration. [Copyright &y& Elsevier]

Abstract: Bleeding at the site of bite and/or systemic hemorrhage are symptoms frequently observed in envenomation by Bothrops jararaca snakes. In this study, we purified and characterized a prothrombin activator from B. jararaca that is probably involved in these clinical manifestations. The enzyme was isolated by a combination of gel filtration and ion exchange chromatographies and named bothrojaractivase. It has a single polypeptide chain with a molecular weight of 22,829Da as measured by mass spectroscopy. Bothrojaractivase generates active thrombin from prothrombin, independently of cofactors. SDS-PAGE analysis of the prothrombin activation products shows that bothrojaractivase converts prothrombin into meizothrombin producing similar fragments to those generated by group A prothrombin''s activators. In addition, bothrojaractivase degraded fibrinogen and fibrin. Chelating agents completely inhibited the enzymatic activity, whereas inhibitors of serine and cysteine proteinases had no effect. Amino acid sequence of four peptides demonstrated high similarity of bothrojaractivase with P-I class of snake venom metalloproteinases. Thus, our results indicate that bothrojaractivase is a new metalloproteinase that acts on different protein factors of the clotting cascade especially displaying a key and most relevant functional action in the generation of thrombin through prothrombin activation in a similar mode of action as that of group A activators. [Copyright &y& Elsevier]

Abstract: Glucocorticoids are among the most successful therapies in the treatment of chronic inflammatory and autoimmune diseases. Their efficacy seems to be caused by the interference of the ligand-activated glucocorticoid receptor with many pro-inflammatory pathways via different mechanisms. The ubiquitous expression of the glucocorticoid receptor is a prerequisite for efficacy. Their main drawback, however, is due to their potential to induce adverse effects, in particular upon high dosage and prolonged usage. For the purpose reducing systemic side effects, topical glucocorticoids that act locally have been developed. Nevertheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. Therefore a high medical need exists for drugs as effective as glucocorticoids but with a reduced side effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor which positively or negatively regulates the expression of specific genes. Several experiments suggest that negative regulation of gene expression by the glucocorticoid receptor accounts for its anti-inflammatory action. This occurs through direct or indirect binding of the receptor to pro-inflammatory transcription factors that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the ligand receptor complex to discrete nucleotide sequences and this contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show an improved therapeutic index. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, recent understanding of the molecular mechanisms of the GR has triggered several drug discovery programs and these have led to the identification of dissociated GR-ligands. Such selective GR agonists (SEGRAs) are likely to enter clinical testing soon. [Copyright &y& Elsevier]

Abstract: N-Acetylglucosamine (GlcNAc), a major component of complex carbohydrates, is synthesized de novo or salvaged from lysosomally degraded glycoconjugates and from nutritional sources. The salvage pathway requires that GlcNAc kinase converts GlcNAc to GlcNAc-6-phosphate, a component utilized in UDP-GlcNAc biosynthesis or energy metabolism. GlcNAc kinase belongs to the sugar kinase/Hsp70/actin superfamily that catalyze phosphoryl transfer from ATP to their respective substrates, and in most cases catalysis is associated with a large conformational change in which the N-terminal small and C-terminal large domains enclose the substrates. Here we report two crystal structures of homodimeric human GlcNAc kinase, one in complex with GlcNAc and the other in complex with ADP and glucose. The active site of GlcNAc kinase is located in a deep cleft between the two domains of the V-shaped monomer. The enzyme adopts a “closed” configuration in the GlcNAc-bound complex and GlcNAc interacts with residues of both domains. In addition, the N-acetyl methyl group contacts residues of the other monomer in the homodimer, a unique feature compared to other members of the sugar kinase/Hsp70/actin superfamily. This contrasts an “open” configuration in the ADP/glucose-bound structure, where glucose cannot form these interactions, explaining its low binding affinity for GlcNAc kinase. Our results support functional implications derived from apo crystal structures of GlcNAc kinases from Chromobacter violaceum and Porphyromonas gingivalis and show that Tyr205, which is phosphorylated in thrombin-activated platelets, lines the GlcNAc binding pocket. This suggests that phosphorylation of Tyr205 may modulate GlcNAc kinase activity and/or specificity. [Copyright &y& Elsevier]

The first total synthesis of the boron-containing macrodiolide antibiotic tartrolon B is reported in full detail. Two convergent approaches to the target compound are described, the first of which eventually failed, due to sensitive functionality. In the second, successful route the key step was a stereoselective boron-mediated aldol addition of a bicyclic acetonide protected ketone to a dienealdehyde. In this case the synthesis could be completed without major problems, using a Yamaguchi dimerization macrolactonization endgame. [ABSTRACT FROM AUTHOR]

In this paper, we analyse the evolution of prices in deregulated electricity markets. We present a general model that simultaneously takes into account the following features: seasonal patterns, price spikes, mean reversion, price dependent volatilities and long term non-stationarity. We estimate the parameters of the model using historical data from the European Energy Exchange. Finally, we demonstrate how it can be used for pricing derivatives via Monte Carlo simulation. [ABSTRACT FROM AUTHOR]

N -Acetylglucosamine is a major component of complex carbohydrates. The mammalian salvage pathway of N -acetylglucosamine recruitment from glycoconjugate degradation or nutritional sources starts with phosphorylation by N -acetylglucosamine kinase. In this study we describe the identification of two active site cysteines of the sugar kinase by site-directed mutagenesis and computer-based structure prediction. Murine N -acetylglucosamine kinase contains six cysteine residues, all of which were mutated to serine residues. The strongest reduction of enzyme activity was found for the mutant C131S, followed by C143S. Determination of the kinetic properties of the cysteine mutants showed that the decreased enzyme activities were due to a strongly decreased affinity to either N -acetylglucosamine for C131S, or ATP for C143S. A secondary structure prediction of N -acetylglucosamine kinase showed a high homology to glucokinase. A model of the three-dimensional structure ofN -acetylglucosamine kinase based on the known structure of glucokinase was therefore generated. This model confirmed that both cysteines are located in the active site of N -acetylglucosamine kinase with a potential role in the binding of the transfered γ-phosphate group of ATP within the catalytic mechanism. [ABSTRACT FROM AUTHOR]

Fucose is a major component of complex carbohydrates. l-Fucose kinase (fucokinase) takes part in the salvage pathway for reutilization of fucose from the degradation of oligosaccharides. The amino acid sequence of human fucokinase was derived from a cDNA encoding a protein of hitherto unidentified function. Human fucokinase polypeptide chain consists of 990 amino acids with a predicted molecular mass of 107 kDa. The C-terminal part of its amino acid sequence showed sequence motifs typical for sugar kinases. Fucokinase full-length protein and a deletion mutant lacking the first 363 amino acids of the N-terminus were expressed in Escherichia coli BL21 cells. Both proteins displayed fucokinase activity. These results reveal that the discovered cDNA encodes the fucokinase protein and they confirm that a functional kinase domain is located in the C-terminal part of the enzyme. [Copyright &y& Elsevier]

Examines the stability and selectivity of unnatural DNA with five-membered-ring nucleobase analogues. Effort ot develop orthogonal third base pair for storage in genetic information; Identification of selective against mispairing against with native bases; Use of hydrophobic bases to circumvent hydrogen bonding pattern of natural nase pairs.

N-Acetylglucosamine is produced by the endogenous degradation of glycoconjugates and by the degradation of dietary glycoconjugates by glycosidases. It enters the pathways of aminosugar metabolism by the action of N-acetylglucosamine kinase. In this study we report the isolation and characterization of a cDNA clone encoding the murine enzyme. An open reading frame of 1029 base pairs encodes 343 amino acids with a predicted molecular mass of 37.3 kDa. The deduced amino-acid sequence contains matches of the sequences of eight peptides derived from tryptic cleavage of rat N-acetylglucosamine kinase. The recombinant murine enzyme was functionally expressed in Escherichia coli BL21 cells, where it displays N-acetylglucosamine kinase activity as well as N-acetylmannosamine kinase activity. The complete cDNA sequence of human N-acetylglucosamine kinase was derived from the nucleotide sequences of several expressed sequence tags. An open reading frame of 1032 base pairs encodes 344 amino acids and a protein with a predicted molecular mass of 37.4 kDa. Similarities between human and murine N-acetylglucosamine kinase were 86.6% on the nucleotide level and 91.6% on the amino-acid level. Amino-acid sequences of murine and human N-acetylglucosamine kinase show sequence similarities to other sugar kinases, and all five sequence motifs necessary for the binding of ATP by sugar kinases are present. Tissue distribution of murine N-acetylglucosamine kinase revealed an ubiquitous occurrence of the enzyme and a very high expression in testis. The size of the murine mRNA was 1.35 kb in all tissues investigated, with the exception of testis, where it was 1.45 kb mRNA of the murine enzyme was continuously expressed during mouse development. mRNA of the human enzyme was expressed in all investigated human tissues, as well as in cancer cell lines. In both the tissues and the cancer cell lines, the human mRNA was 1.35 kb in size. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo.Alt a 1‐RA complex formation was analyzed in silico and in vitro. PBMCs from Alternaria‐allergic donors were stimulated with Alt a 1 complexed with RA (holo‐Alt a 1) or empty apo‐Alt a 1 and analyzed for cytokine production and CD marker expression. Serum IgE‐binding and crosslinking assays to apo‐ and holo‐protein were correlated to B‐cell epitope analysis. Female BALB/c mice already sensitized to Alt a 1 were intranasally treated with apo‐Alt a 1, holo‐Alt a 1 or RA alone before measuring anaphylactic response, serum antibody levels, splenic cytokines and CD marker expression.In silico docking calculations and in vitro assays showed that the extent of RA binding depended on the higher quaternary state of Alt a 1. Holo‐Alt a 1 loaded with RA reduced IL‐13 released from PBMCs and CD3+CD4+CRTh2 cells. Complexing Alt a 1 to RA masked its IgE B‐cell epitopes and reduced its IgE‐binding capacity. In a therapeutic mouse model of Alternaria allergy nasal application of holo‐Alt a 1, but not of apo‐Alt a 1, significantly impeded the anaphylactic response, impaired splenic antigen‐presenting cells and induced IL‐10 production.Holo‐Alt a 1 binding to RA was able to alleviate Th2 immunity in vitro, modulate an ongoing Th2 response and prevent anaphylactic symptoms in vivo, presenting a novel option for improving allergen‐specific immunotherapy in Alternaria allergy. [ABSTRACT FROM AUTHOR]

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person‐centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision‐making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried‐over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)—Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)—on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally‐enabled PCC in AIT. [ABSTRACT FROM AUTHOR]

Acmella oleracea (L.) R. K. Jansen (Asteraceae), known as jambú in Brazil, is used in traditional medicine as analgesic and for inflammatory conditions, characterized by the presence of N -alkylamides, mainly spilanthol. This bioactive compound is responsible for the above-described pharmacological properties, including sialagogue and anesthetic. This study aimed to characterize the anti-inflammatory effects of A. oleracea leaves (AOEE-L) and flowers (AOEE-F) extracts, including an isolated alkylamide (spilanthol), using in vitro and in vivo models. The mechanism underlying this effect was also investigated. Extracts were analyzed by HPLC-ESI-MS/MS in order to characterize the N -alkylamides content. AOEE-L, AOEE-F (25–100 μg/mL) and spilanthol (50–200 μM) were tested in vitro on VSMC after stimulation with hyperglycemic medium (25 mM glucose). Their effects over nitric oxide (NO) generation, chymase inhibition and expression, catalase (CAT), superoxide anion (SOD) radical activity were evaluated. After an acute administration of extracts (10–100 mg/mL) and spilanthol (6.2 mg/mL), the anti-inflammatory effects were evaluated by applying the formalin test in rats. Blood was collected to measure serum aminotransferases activities, NO activity, creatinine and urea. A number of distinct N -alkylamides were detected and quantified in AOEE-L and AOEE-F. Spilanthol was identified in both extracts and selected for experimental tests. Hyperglycemic stimulation in VSMC promoted the expression of inflammatory parameters, including chymase, NO, CAT and SOD activity and chymase expression, all of them attenuated by the presence of the extracts and spilanthol. The administration of extracts or spilanthol significantly inhibited edema formation, NO production and cell tissue infiltration in the formalin test, without causing kidney and liver toxicity. Taken together, these results provide evidence for the anti-inflammatory activity of leaves and flowers extracts of jambú associated distinctly with their chemical profile. The effects appear to be associated with the inhibition of chymase activity, suppression of the proinflammatory cytokine NO and antioxidant activities. Image 1 [ABSTRACT FROM AUTHOR]

• We present the first full review of research pertaining a water planetary boundary. • Initial shortcomings of the water planetary boundary have partly been resolved. • Input-output analysis may facilitate investigation into the exceedance of boundaries. • Spatiotemporal mismatches amid input-output and hydrological data pose a challenge. The water planetary boundary has been proposed to determine limits for a sustainable anthropogenic appropriation of freshwater. Aim of the present research was to summarise the water planetary boundary's development status and applications including its integration into Life Cycle Assessment and Environmentally-Extended Input-Output-Analysis. A systematic literature review was conducted for studies featuring the keywords "planetary boundary" and "water consumption". All pertinent studies were categorised as either revision, commentary, stand-alone application, the application within Life Cycle Assessment or application within Environmentally-Extended Input-Output Analysis and subsequently summarised and discussed. Overall, 35 studies from the period of 2009 until mid-2020 are subject of this review. Recent advancements such as spatially differentiated thresholds and refined sub-boundaries have addressed initial shortcomings of the concept of a water planetary boundary. Stand-alone applications of the water planetary boundary have either established local thresholds or allocated fair shares of afore-defined global thresholds. Several authors integrated the concept of a water planetary boundary into LCA e.g. via characterisation factors, weighting or normalisation, often under consideration of sharing principles. An application of the water planetary boundary into Environmentally-Extended Input-Output Analysis is less represented although some authors have demonstrated its powerfulness in investigating causes for the exceedance of local thresholds. For some of the reviewed studies, a link to the water planetary boundary remains rather vague as these studies merely investigate water availability in comparison to consumption. Although it should be applied with caution, the concept of a planetary boundary for freshwater use can contribute to understanding limits to sustainable freshwater consumption. Many studies established water use thresholds but refrained from analysing causative drivers in detail. Challenges for exploring this further include overcoming spatial and temporal mismatches of environmentally-extended economic accounts and hydrogeological data. [ABSTRACT FROM AUTHOR]

Investigates the inhibition of T cell signal transduction by polyunsaturated fatty acids (PUFA). Detergent-resistant membrane (DRM) domains involved in signal transduction; Enrichment of PUFA in T cells; Correlation of signal transduction in PUFA-enriched T cells with presence of Src family kinase Lck in DRM.

We report on the discovery of the new clinical candidate BAY 1003803 as glucocorticoid receptor agonist for the topical treatment of psoriasis or severe atopic dermatitis. In the course of optimizing the amino alcohol series as a highly potent new non-steroidal lead structure, considerations were made as to how physicochemical properties and safety concerns relate to structural motifs. BAY 1003803 demonstrates strong anti-inflammatory activity in vitro paired with a pharmacokinetic profile suitable for topical application. [ABSTRACT FROM AUTHOR]

The EOS™2D/3D system is a low-dose, 3D imaging system that utilizes two perpendicular X-ray beams to create simultaneous frontal and lateral images of the body. This is a useful modality to assess spinal pathologies. However, due to the slow imaging acquisition time up to 25 s, motion artifacts (MA) frequently occur. These artifacts may not be distinguishable from pathological findings, such as scoliosis, and may impair the diagnostic process. The aim of this study was to design a method to detect MA in EOS X-ray. We retrospectively analyzed EOS imaging from 40 patients wearing a radiopaque reference device during imaging. We drew a straight vertical line along the reference device. We measured deviations from it to quantify MA, presenting these findings through descriptive statistics. For a subset of patients with high MA, acquisitions were repeated after giving specific instructions to stand still. For these patients, we compared MA between the two acquisitions. In our study, a substantial proportion of patients exhibited MA ≥ 1 mm, with 80% in frontal projections and 87.9% in lateral projections. In the subjects who received a second acquisition, MA was significantly lower in the second images. Our method allows for a precise detection of MA on EOS images through a simple, yet reliable solution. Our method may improve the reliability of spine measurements, and reduce the risk of wrong diagnosis due to low imaging quality. [ABSTRACT FROM AUTHOR]

Due to the increasing relevance of analyzing water consumption along product life cycles, the method of Water Footprinting gained rising attention in the last years. In this context the water accounting and vulnerability evaluation model (WAVE+) was developed at the TU Berlin. Based on a consumption-to-availability ratio derived from the hydrological model WaterGap3, WAVE+ currently analyzes the vulnerability of basins to freshwater depletion in more than 8.000 basins. On the accounting level the atmospheric evaporation recycling within drainage basins is considered which can reduce the water consumption volumes within specific basins significantly. However, the model does not consider evaporation recycling patterns across basin boundaries until now.This research focuses on the enhancement of the method by including the latter point. In addition to the consideration of the basin internal evaporation recycling (BIER) the basin external evaporation recycling (BEER) is included for the first time. The main outcome are monthly and basin-specific recycling patterns which are able to show in which drainage basins evaporated water will finally re-precipitate. The results were gained from the atmospheric moisture tracking model WAM-2layers which was fed with climatic input data from the ERA-Interim reanalysis on a 1.5° latitude and 1.5° longitude grid for the period of 2001-2010. With regard to evaporation data, the Era-Interim data were replaced by data of the hydrological model WaterGap3 to ensure consistency with the WAVE+ model. The import and export of water flows were aggregated according to the basin delineation of the WAVE+ method.First results for the region around Berlin show that most of the evaporated water re-precipitates over land, mainly in basins located in Eastern Germany, Poland, Czech Republic, Slovakia and the Ukraine. With regards to the region of Central Borneo most of the re-precipitation takes place on the island itself as well as over the surrounding sea and East Indonesia. In addition to presenting basin-specific recycling patterns, the research discusses methodological aspects on how those results could potentially be used within the scope of Water Footprinting. In order to enable further application purposes, the un-aggregated raw data of the fate analysis of evaporated water will be provided on a 1.5° latitude and 1.5° longitude grid and be made publicly available. [ABSTRACT FROM AUTHOR]

Ticks inject serine protease inhibitors (serpins) into their feeding sites to evade serine protease-mediated host defenses against tick-feeding. This study describes two highly identitical (97%) but functionally different Amblyomma americanum tick saliva serpins (AAS41 and 46) that are secreted at the inception of tick-feeding. We show that AAS41, which encodes a leucine at the P1 site inhibits inflammation system proteases: chymase (SI = 3.23, Ka = 5.6 ± 3.7X103M−1 s−1) and α-chymotrypsin (SI = 3.18, Ka = 1.6 ± 4.1X104M−1 s−1), while AAS46, which encodes threonine has no inhibitory activity. Similary, rAAS41 inhibits rMCP-1 purified from rat peritonuem derived mast cells. Consistently, rAAS41 inhibits chymase-mediated inflammation induced by compound 48/80 in rat paw edema and vascular permeability models. Native AAS41/46 proteins are among tick saliva immunogens that provoke anti-tick immunity in repeatedly infested animals as revealed by specific reactivity with tick immune sera. Of significance, native AAS41/46 play critical tick-feeding functions in that RNAi-mediated silencing caused ticks to ingest significantly less blood. Importantly, monospecific antibodies to rAAS41 blocked inhibitory functions of rAAS41, suggesting potential for design of vaccine antigens that provokes immunity to neutralize functions of this protein at the tick-feeding site. We discuss our findings with reference to tick-feeding physiology and discovery of effective tick vaccine antigens. • Amblyomma americanum secretes two highly identical (97% identity) serpins (AAS 41 and 46) that have different functions • Amblyomma americanum utilizes AAS41 to block host inflammation defense by disrupting chymase and chymotrypsin functions • Functions of AAS 41 and 46 are critical to tick feeding success as revealed by RNAi mediated silencing • Both AAS 41 and 46 are among immunogens that provoke anti-tick immunity in repeatedly infested rabbits. [ABSTRACT FROM AUTHOR]

Various studies investigated the fate of evaporation and the origin of precipitation. The more recent studies among them were often carried out with the help of numerical moisture tracking. Many research questions could be answered within this context, such as dependencies of atmospheric moisture transfers between different regions, impacts of land cover changes on the hydrological cycle, sustainability-related questions, and questions regarding the seasonal and interannual variability of precipitation. In order to facilitate future applications, global datasets on the fate of evaporation and the sources of precipitation are needed. Since most studies are on a regional level and focus more on the sources of precipitation, the goal of this study is to provide a readily available global dataset on the fate of evaporation for a fine-meshed grid of source and receptor cells. The dataset was created through a global run of the numerical moisture tracking model Water Accounting Model-2layers (WAM-2layers) and focused on the fate of land evaporation. The tracking was conducted on a 1.5∘×1.5∘ grid and was based on reanalysis data from the ERA-Interim database. Climatic input data were incorporated in 3- to 6-hourly time steps and represent the time period from 2001 to 2018. Atmospheric moisture was tracked forward in time and the geographical borders of the model were located at ±79.5 ∘ latitude. As a result of the model run, the annual, the monthly and the interannual average fate of evaporation were determined for 8684 land grid cells (all land cells except those located within Greenland and Antarctica) and provided via source–receptor matrices. The gained dataset was complemented via an aggregation to country and basin scales in order to highlight possible usages for areas of interest larger than grid cells. This resulted in data for 265 countries and 8223 basins. Finally, five types of source–receptor matrices for average moisture transfers were chosen to build the core of the dataset: land grid cell to grid cell, country to grid cell, basin to grid cell, country to country, basin to basin. The dataset is, to our knowledge, the first ready-to-download dataset providing the overall fate of evaporation for land cells of a global fine-meshed grid in monthly resolution. At the same time, information on the sources of precipitation can be extracted from it. It could be used for investigations into average annual, seasonal, and interannual sink and source regions of atmospheric moisture from land masses for most of the regions in the world and shows various application possibilities for studying interactions between people and water, such as land cover changes or human water consumption patterns. The dataset is accessible under 10.1594/PANGAEA.908705 (Link et al., 2019a) and comes along with example scripts for reading and plotting the data. [ABSTRACT FROM AUTHOR]

The applied surface dose is a key parameter for the measurement of toxic effects of airborne particles by air liquid interface exposure of human lung cells. Besides online measurement of the deposited particle mass by quartz crystal microbalance frequently other dose metrics such as particle size distribution, surface and agglomeration state are required. These particle properties and their spatial distribution can be determined by digital processing of micrographs obtained by transmission electron microscopy (TEM). Here, we report the development and characterization of a novel holder for film coated TEM copper grids, which allows for sampling under identical geometric and ambient conditions as in a cell culture chamber. The sample holder avoids artefacts by reliable grounding of the grids and improves handling of the grids to prevent damage of the sensitive film. This sample holder is applied during exposure experiments with titanium dioxide nanoparticles. The measured dose of 0.2 µg/cm² corresponds well to the mass loading signal of the quartz crystal microbalance. Additionally, the spatial distribution of particles on the sampling surface shows a good homogeneity of deposition. This novel sampling method allows verifying other dosimetry methods and gives additional information about particle properties and homogeneity of the dose. [ABSTRACT FROM AUTHOR]

The recent outbreak of Zika virus (ZIKV) in Brazil and other countries globally demonstrated the relevance of ZIKV studies. During and after this outbreak, there was an intense increase in scientific production on ZIKV infections, especially toward alterations promoted by the infection and related to clinical outcomes. Considering this massive amount of new data, mainly thousands of genes and proteins whose expression is impacted by ZIKV infection, the ZIKA Virus Infection Database (ZIKAVID) was created. ZIKAVID is an online database that comprises all genes or proteins, and associated information, for which expression was experimentally measured and found to be altered after ZIKV infection. The database, available at https://zikavid.org, contains 16,984 entries of gene expression measurements from a total of 7348 genes. It allows users to easily perform searches for different experimental hosts (cell lines, tissues, and animal models), ZIKV strains (African, Asian, and Brazilian), and target molecules (messenger RNA [mRNA] and protein), among others, used in differential expression studies regarding ZIKV infection. In this way, the ZIKAVID will serve as an additional and important resource to improve the characterization of the molecular impact and pathogenesis associated with ZIKV infection. [ABSTRACT FROM AUTHOR]

Ticks successfully feed and transmit pathogens by injecting pharmacological compounds in saliva to thwart host defenses. We have previously used LC-MS/MS to identify proteins that are present in saliva of unfed Amblyomma americanum ticks that were exposed to different hosts. Here we show that A. americanum serine protease inhibitor (serpin) 27 (AAS27) is an immunogenic saliva protein that is injected into the host within the first day of tick feeding and is an anti-inflammatory protein that might act by blocking plasmin and trypsin functions. Although AAS27 is injected into the host throughout tick feeding, qRT-PCR and western blotting analyses indicate that the respective transcript and protein are present in high amounts within the first 24 h of tick feeding. Biochemical screening of Pichia pastoris-expressed recombinant (r) AAS27 against mammalian proteases related to host defense shows it is an inhibitor of trypsin and plasmin, with stoichiometry of inhibition indices of 3.5 and 3.8, respectively. Consistent with typical inhibitory serpins, rAAS27 formed heat- and SDS-stable irreversible complexes with both proteases. We further demonstrate that rAAS27 inhibits trypsin with ka of 6.46 ± 1.24 x 104 M-1 s-1, comparable to serpins of other tick species. We show that native AAS27 is part of the repertoire of proteins responsible for the inhibitory activity against trypsin in crude tick saliva. AAS27 is likely utilized by the tick to evade the hosts inflammation defense since rAAS27 blocks both formalin and compound 48/80-induced inflammation in rats. Tick immune sera of rabbits that had acquired resistance against tick feeding following repeated infestations with A. americanum or Ixodes scapularis ticks reacts with rAAS27. Of significant interest, antibody to rAAS27 blocks this serpin inhibitory functions. Taken together, we conclude that AAS27 is an anti-inflammatory protein secreted into the host during feeding and may represent a potential candidate for development of an anti-tick vaccine. [ABSTRACT FROM AUTHOR]

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron–quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo– or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated Kd values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo– and holo–Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation. [ABSTRACT FROM AUTHOR]

The article reports on the effectiveness of antivibration (AV) gloves and mentions that AV gloves can provide adequate protection as long asthey are utilized within appropriate ranges. The gloves are used by workers who operate vibrating tools and machinery or handle vibrating work pieces are therefor exposed to intense vibration. The limitations and selection and of AV gloves are mentioned.

Abstract Evaluating the impacts on biodiversity by means of the life cycle assessment (LCA) is a task researchers are currently facing. One impact assessment method that aims to do so is the recently developed biodiversity impact assessment BIA+. The aim of the present paper is to test this method and to show its applicability and feasibility. Additionally opportunities and challenges of this method shall be revealed. For this purpose, a case study for assessing the impacts of biodiesel production on freshwater biodiversity is introduced. Two substances, namely phosphorus and 1,4-dichlorobenzene (DCB), which are used for the biodiesel production for fertilization and the usage of pesticides, are being considered. The inventory data needed for the case study is gathered through the grey water footprint of the crop production that forms the basis of the European biodiesel consumption. Further, the BIA+ method is applied in order to assess the impacts of the biodiesel consumption in Europe for the year 2010 on freshwater biodiversity. The results reveal that even though assumptions have to be made and the results are highly uncertain, this method helps to identify hotspots within production processes. By including the BIA+ as an impact assessment method into LCA, impacts of products can be assessed with regard to biodiversity including genetic, species and ecosystem diversity. The main impact hotspot occurs in France with a potential loss of the biodiversity of 0.5 points. The lowest loss of the biodiversity occurs in Brazil (loss of 8.05*10–06 points). The results are mainly influenced by the impact of the toxic substance 1,4-DCB. By means of the case study, it is shown that the BIA+ method is applicable. [ABSTRACT FROM AUTHOR]

Abstract This study investigates the water scarcity footprint (WSF) trend of German agricultural imports over recent years, following the principles of the ISO 14046 standard on water footprinting. For this purpose, the import statistics of agricultural goods for the years 2000, 2005, 2010, and 2015 was compiled and linked with the irrigation water consumption during their production as well as with the AWARE water scarcity factors of the country of production. Agricultural imports increased by 62% from 22 to 35 million tons during the analysed period. At the same time, the blue water consumption for agricultural production (i.e., irrigation water) decreased by 13% and the WSF declined by 20%, from 119 to 91 km3 world-equivalents (world-eq.). The decrease in WSF is caused by drop in the cotton imports, while the WSF associated with the imports of other crops increased by 45%. Product-wise, cotton, nuts, and rice contribute to more than half of the total WSF in all analysed years. Despite their high WSF, these products account for only 3% of the imports by mass confirming the relevance of impact based water footprint assessments. Country-wise, main contributors change along the analysed years. In the year 2000, one-quarter of the WSF occurs in Uzbekistan due to cotton imports. Afterwards, the highest WSF arises in Iran and Spain, while the imports from the US dominate the WSF in 2015. The changing trend follows the pattern of production of the hotspots identified on the product level, e.g. nuts, soybeans, and cotton. This study provides information on the water scarcity impacts that the German consumption creates in other countries and may be useful for decision-making processes aiming at optimising water scarcity footprints. Graphical abstract Unlabelled Image Highlights • Water Scarcity Footprint (WSF) of German agricultural imports was calculated. • WSF decreased from 119 to 91 km3 world-eq. between 2000 and 2015. • The imports increased from 22 to 35 million tons between 2000 and 2015. • Imports of cotton , nuts , and rice contribute to almost half of the total WSF. [ABSTRACT FROM AUTHOR]