47 research outputs found

    Efficient long-range conduction in cable bacteria through nickel protein wires

    Get PDF
    Filamentous cable bacteria display long-range electron transport, generating electrical currents over centimeter distances through a highly ordered network of fibers embedded in their cell envelope. The conductivity of these periplasmic wires is exceptionally high for a biological material, but their chemical structure and underlying electron transport mechanism remain unresolved. Here, we combine high-resolution microscopy, spectroscopy, and chemical imaging on individual cable bacterium filaments to demonstrate that the periplasmic wires consist of a conductive protein core surrounded by an insulating protein shell layer. The core proteins contain a sulfur-ligated nickel cofactor, and conductivity decreases when nickel is oxidized or selectively removed. The involvement of nickel as the active metal in biological conduction is remarkable, and suggests a hitherto unknown form of electron transport that enables efficient conduction in centimeter-long protein structures

    The NS1 Glycoprotein Can Generate Dramatic Antibody-Enhanced Dengue Viral Replication in Normal Out-Bred Mice Resulting in Lethal Multi-Organ Disease

    Get PDF
    Antibody-enhanced replication (AER) of dengue type-2 virus (DENV-2) strains and production of antibody-enhanced disease (AED) was tested in out-bred mice. Polyclonal antibodies (PAbs) generated against the nonstructural-1 (NS1) glycoprotein candidate vaccine of the New Guinea-C (NG-C) or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E) glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (<0.5 LD50) of the DENV-2 NSx strain, but not the NG-C strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice developed life-threatening acute respiratory distress syndrome (ARDS), displayed by diffuse alveolar damage (DAD) resulting from i) dramatic interstitial alveolar septa-thickening with mononuclear cells, ii) some hyperplasia of alveolar type-II pneumocytes, iii) copious intra-alveolar protein secretion, iv) some hyaline membrane-covered alveolar walls, and v) DENV-2 antigen-positive alveolar macrophages. These mice also developed meningo-encephalitis, with greater than 90,000-fold DENV-2 AER titers in microglial cells located throughout their brain parenchyma, some of which formed nodules around dead neurons. Their spleens contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp macrophages, while their livers displayed extensive necrosis, apoptosis and macro- and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes. Their infections were confirmed by DENV-2 isolations from their lungs, spleens and livers. These findings accord with those reported in fatal human “severe dengue” cases. This DENV-2 AER/AED was blocked by high concentrations of only the NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1 glycoprotein-based vaccines, particularly against DENV strains that contain multiple mutations or genetic recombination within or between their DENV E and NS1 glycoprotein-encoding genes. The model provides potential for assessing DENV strain pathogenicity and anti-DENV therapies in normal mice

    Adverse effects of extra-articular corticosteroid injections: a systematic review

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection.</p> <p>Methods</p> <p>A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention).</p> <p>Results</p> <p>The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting.</p> <p>Conclusion</p> <p>In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported.</p

    Socialization, legitimation and the transfer of biomedical knowledge to low- and middle-income countries: analyzing the case of emergency medicine in India

    Get PDF
    BACKGROUND: Medical specialization is a key feature of biomedicine, and is a growing, but weakly understood aspect of health systems in many low- and middle-income countries (LMICs), including India. Emergency medicine is an example of a medical specialty that has been promoted in India by several high-income country stakeholders, including the Indian diaspora, through transnational and institutional partnerships. Despite the rapid evolution of emergency medicine in comparison to other specialties, this specialty has seen fragmentation in the stakeholder network and divergent training and policy objectives. Few empirical studies have examined the influence of stakeholders from high-income countries broadly, or of diasporas specifically, in transferring knowledge of medical specialization to LMICs. Using the concepts of socialization and legitimation, our goal is to examine the transfer of medical knowledge from high-income countries to LMICs through domestic, diasporic and foreign stakeholders, and the perceived impact of this knowledge on shaping health priorities in India. METHODS: This analysis was conducted as part of a broader study on the development of emergency medicine in India. We designed a qualitative case study focused on the early 1990s until 2015, analyzing data from in-depth interviewing (n = 87), document review (n = 248), and non-participant observation of conferences and meetings (n = 6). RESULTS: From the early 1990s, domestic stakeholders with exposure to emergency medicine in high-income countries began to establish Emergency Departments and initiate specialist training in the field. Their efforts were amplified by the active legitimation of emergency medicine by diasporic and foreign stakeholders, who formed transnational partnerships with domestic stakeholders and organized conferences, training programs and other activities to promote the field in India. However, despite a broad commitment to expanding specialist training, the network of domestic, diasporic and foreign stakeholders was highly fragmented, resulting in myriad unstandardized postgraduate training programs and duplicative policy agendas. Further, the focus in this time period was largely on training specialists, resulting in more emphasis on a medicalized, tertiary-level form of care. CONCLUSIONS: This analysis reveals the complexities of the roles and dynamics of domestic, diasporic and foreign stakeholders in the evolution of emergency medicine in India. More research and critical analyses are required to explore the transfer of medical knowledge, such as other medical specialties, models of clinical care, and medical technologies, from high-income countries to India

    SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

    Get PDF
    Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

    A novel hybrid organosolv: steam explosion method for the efficient fractionation and pretreatment of birch biomass

    Get PDF
    Background: The main role of pretreatment is to reduce the natural biomass recalcitrance and thus enhance sac- charification yield. A further prerequisite for efficient utilization of all biomass components is their efficient fractiona- tion into well-defined process streams. Currently available pretreatment methods only partially fulfill these criteria. Steam explosion, for example, excels as a pretreatment method but has limited potential for fractionation, whereas organosolv is excellent for delignification but offers poor biomass deconstruction. Results: In this article, a hybrid method combining the cooking and fractionation of conventional organosolv pre - treatment with the implementation of an explosive discharge of the cooking mixture at the end of pretreatment was developed. The effects of various pretreatment parameters (ethanol content, duration, and addition of sulfuric acid) were evaluated. Pretreatment of birch at 200 °C with 60% v/v ethanol and 1% w/w biomass H 2 SO 4 was proven to be the most efficient pretreatment condition yielding pretreated solids with 77.9% w/w cellulose, 8.9% w/w hemicellulose, and 7.0 w/w lignin content. Under these conditions, high delignification of 86.2% was demonstrated. The recovered lignin was of high purity, with cellulose and hemicellulose contents not exceeding 0.31 and 3.25% w/w, respectively, and ash to be < 0.17% w/w in all cases, making it suitable for various applications. The pretreated solids presented high saccharification yields, reaching 68% at low enzyme load (6 FPU/g) and complete saccharification at high enzyme load (22.5 FPU/g). Finally, simultaneous saccharification and fermentation (SSF) at 20% w/w solids yielded an ethanol titer of 80 g/L after 192 h, corresponding to 90% of the theoretical maximum. Conclusions: The novel hybrid method developed in this study allowed for the efficient fractionation of birch biomass and production of pretreated solids with high cellulose and low lignin contents. Moreover, the explosive dis- charge at the end of pretreatment had a positive effect on enzymatic saccharification, resulting in high hydrolyzability of the pretreated solids and elevated ethanol titers in the following high-gravity SSF. To the best of our knowledge, the ethanol concentration obtained with this method is the highest so far for birch biomass

    Anaerobiosis revisited: growth of Saccharomyces cerevisiae under extremely low oxygen availability

    Get PDF
    The budding yeast Saccharomyces cerevisiae plays an important role in biotechnological applications, ranging from fuel ethanol to recombinant protein production. It is also a model organism for studies on cell physiology and genetic regulation. Its ability to grow under anaerobic conditions is of interest in many industrial applications. Unlike industrial bioreactors with their low surface area relative to volume, ensuring a complete anaerobic atmosphere during microbial cultivations in the laboratory is rather difficult. Tiny amounts of O2 that enter the system can vastly influence product yields and microbial physiology. A common procedure in the laboratory is to sparge the culture vessel with ultrapure N2 gas; together with the use of butyl rubber stoppers and norprene tubing, O2 diffusion into the system can be strongly minimized. With insights from some studies conducted in our laboratory, we explore the question ‘how anaerobic is anaerobiosis?’. We briefly discuss the role of O2 in non-respiratory pathways in S. cerevisiae and provide a systematic survey of the attempts made thus far to cultivate yeast under anaerobic conditions. We conclude that very few data exist on the physiology of S. cerevisiae under anaerobiosis in the absence of the anaerobic growth factors ergosterol and unsaturated fatty acids. Anaerobicity should be treated as a relative condition since complete anaerobiosis is hardly achievable in the laboratory. Ideally, researchers should provide all the details of their anaerobic set-up, to ensure reproducibility of results among different laboratories. A correction to this article is available online at http://eprints.whiterose.ac.uk/131930/ https://doi.org/10.1007/s00253-018-9036-

    A first update on mapping the human genetic architecture of COVID-19

    Get PDF
    peer reviewe

    Elucidating the Importance of Numeracy Skills for Undergraduate Students in Life Sciences Using the Oxygen Requirement in Yeast as an Example

    No full text
    Current education in biology is devoid of mathematics in many countries, probably because many relevant biological processes are explained from a qualitative point of view rather than addressing the quantitative aspects of these phenomena. Here, we employ a case study from the yeast physiology to illustrate the importance of numeracy skills for a deeper understanding of relevant biological problems. Yeast anaerobic growth on sugars is a widespread process as it is the basis for beer, bread, and winemaking and it is much akin to lactic acid fermentation in muscle cells in response to an increased energy demand. To study the physiology of yeasts under controlled conditions and being able to compare the results quantitatively, one ought to perform measurements and calculations involving concentrations of oxygen, biomass, and organic compounds. To set-up an “anaerobic” culture of Saccharomyces cerevisiae in a defined medium, one needs to calculate how much oxygen must enter the cultivation system, to meet the requirements for ergosterol and oleic acid biosyntheses, both of which require oxygen. Using basic physicochemical principles and simple mathematical skills, students will be able to compute the oxygen requirement for yeast growth under such “anaerobic” conditions
    corecore