Adaptive Evolution in the Glucose Transporter 4 Gene Slc2a4 in Old World Fruit Bats (Family: Pteropodidae)

Frugivorous and nectarivorous bats are able to ingest large quantities of sugar in a short time span while avoiding the potentially adverse side-effects of elevated blood glucose. The glucose transporter 4 protein (GLUT4) encoded by the Slc2a4 gene plays a critical role in transmembrane skeletal muscle glucose uptake and thus glucose homeostasis. To test whether the Slc2a4 gene has undergone adaptive evolution in bats with carbohydrate-rich diets in relation to their insect-eating sister taxa, we sequenced the coding region of the Slc2a4 gene in a number of bat species, including four Old World fruit bats (Pteropodidae) and three New World fruit bats (Phyllostomidae). Our molecular evolutionary analyses revealed evidence that Slc2a4 has undergone a change in selection pressure in Old World fruit bats with 11 amino acid substitutions detected on the ancestral branch, whereas, no positive selection was detected in the New World fruit bats. We noted that in the former group, amino acid replacements were biased towards either Serine or Isoleucine, and, of the 11 changes, six were specific to Old World fruit bats (A133S, A164S, V377F, V386I, V441I and G459S). Our study presents preliminary evidence that the Slc2a4 gene has undergone adaptive changes in Old World fruit bats in relation to their ability to meet the demands of a high sugar diet

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

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

Protecting against threats to information security : an attitudinal ambivalence perspective

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Adipose tissue imaging as nutritional predictors in patients undergoing enterocutaneous fistula repair

Objectives: The management of enterocutaneous fistulae (ECF) is complex, challenging, and often associated with metabolic, septic, and nutritional complications. Radiographic quantification of body composition such as fat or lean body mass distribution is a potentially valuable preoperative assessment tool to optimize nutritional status. The aim of this study was to investigate the correlation between total adipose tissue (fat) area (TFA), assessed by computed tomography and magnetic resonance imaging radiology tests, with body weight, body mass index (BMI), various biochemical parameters, need for nutritional support, and survival in patients undergoing ECF repair. / Methods: Biochemical and anthropometric parameters at the time of ECF surgery were retrospectively collected for adult patients undergoing ECF repair at University College London Hospital, UK. Visceral and subcutaneous adiposity was measured at the level of the third lumbar vertebra (Image J) at computed tomography or magnetic resonance imaging. Statistical analysis included descriptives, univariate and multivariate analysis between TFA and various parameters, and their influence on postoperative survival. / Results: A complete set of data was available for 85 patients (51 women, 56.9 ± 14.5 y of age) who underwent ECF repair. ECF originated mainly as a surgical complication (86%) while 14% were undergoing a second ECF repair. Median BMI was 22.8 kg/m2 and mean TFA was 361 ± 174.9 cm2, with a higher visceral fat content in men than in women (183.8 ± 99.2 versus 99 ± 59.7 cm2, P 60 y of age (hazard ratio [HR], 2.69, P < 0.02) and use of parenteral nutrition (HR, 3.90, P < 0.02) were associated with worse overall survival. / Conclusion: Abdominal adiposity was strongly correlated with anthropometric parameters at the time of surgery. Earlier identification of patients requiring artificial nutrition at standard preoperative imaging might allow integration of nutritional optimization into initial clinical management plans reducing length of stay and improving clinical outcomes

<it>Streptobacillus moniliformis </it>septic arthritis: a clinical entity distinct from rat-bite fever?

<p>Abstract</p> <p>Background</p> <p><it>Streptobacillus moniliformis </it>is a zoonotic agent associated with rodent contacts. Although it is more commonly reported to cause rat-bite fever with reactive arthritides, it can also lead to pyogenic infection of the joints.</p> <p>Case presentation</p> <p>We present a lady with past history of osteoarthritis developing streptobacillary septic arthritides of the right knee and left wrist, and required antibiotic and arthrotomy for treatment. We also review 11 previously reported cases of streptobacillary septic arthritis to discuss the characteristics, treatment, prognosis of the infection, and illustrates the differences between streptobacillary rat-bite fever and septic arthritis. Among this patient population, most patients had potential contact with rats (91.6%). The knee is the most commonly affected joint (58.3%), and 83.3% patients having polyarticular involvement. As opposed to rat-bite fever, fever and rash was only present in 58.3% and 16.7% of patients respectively. <it>S. moniliformis </it>bacteremia is uncommon (8.4%) and the prognosis is good.</p> <p>Conclusion</p> <p>Arthrocentesis is useful in distinguishing streptobacillary septic arthritis from reactive arthritis of rat-bite fever. The sole use of commercial media containing sodium polyanethol sulfonate may render the bacterial culture negative. A detailed history of possible exposure to rodents should be elicited from patients with arthritis in order to facilitate microbiologic diagnosis.</p