Markers of cognitive function in individuals with metabolic disease: Morquio Syndrome and Tyrosinemia Type III

We characterized cognitive function in two metabolic diseases. MPS–IVa (mucopolysaccharidosis IVa, Morquio) and tyrosinemia type III individuals were assessed using tasks of attention, language and oculomotor function. MPS–IVa individuals were slower in visual search, but the display size effects were normal, and slowing was not due to long reaction times (ruling out slow item processing or distraction). Maintaining gaze in an oculomotor task was difficult. Results implicated sustained attention and task initiation or response processing. Shifting attention, accumulating evidence and selecting targets were unaffected. Visual search was also slowed in tyrosinemia type III, and patterns in visual search and fixation tasks pointed to sustained attention impairments, although there were differences from MPS–IVa. Language was impaired in tyrosinemia type III but not MPS–IVa. Metabolic diseases produced selective cognitive effects. Our results, incorporating new methods for developmental data and model selection, illustrate how cognitive data can contribute to understanding function in biochemical brain systems

Λs\Lambda_{\rm s}CDM model: A promising scenario for alleviation of cosmological tensions

We present a comprehensive analysis of the $\Lambda_{\rm s}$CDM model, which explores the recent conjecture suggesting a rapid transition of the Universe from anti-de Sitter vacua to de Sitter vacua (viz., the cosmological constant switches sign from negative to positive) at redshift ${z_\dagger\sim 2}$, inspired by the graduated dark energy (gDE) model. Our analysis shows that, predicting $z_\dagger\approx1.7$, $\Lambda_{\rm s}$CDM simultaneously addresses the major cosmological tensions of the standard $\Lambda$CDM model, viz., the Hubble constant $H_0$, the Type Ia Supernovae absolute magnitude $M_{\rm B}$, and the growth parameter $S_8$ tensions, along with other less significant tensions such as the BAO Lyman-$\alpha$ discrepancy.Comment: 7 pages, 3 figures, 1 table, and Supplemental material (7 pages, 8 figures, 2 tables

In silico evaluation of WHO-endorsed molecular methods to detect drug resistant tuberculosis

Universal drug susceptibility testing (DST) for tuberculosis is a major goal of the END TB strategy. PCR-based molecular diagnostic tests have been instrumental in increasing DST globally and several assays have now been endorsed by the World Health Organization (WHO) for use in the diagnosis of drug resistance. These endorsed assays, however, each interrogate a limited number of mutations associated with resistance, potentially limiting their sensitivity compared to sequencing-based methods. We applied an in silico method to compare the sensitivity and specificity of WHO-endorsed molecular based diagnostics to the mutation set identified by the WHO mutations catalogue using phenotypic DST as the reference. We found that, in silico, the mutation sets used by probe-based molecular diagnostic tests to identify rifampicin, isoniazid, pyrazinamide, levofloxacin, moxifloxacin, amikacin, capreomycin and kanamycin resistance produced similar sensitivities and specificities to the WHO mutation catalogue. PCR-based diagnostic tests were most sensitive for drugs where mechanisms of resistance are well established and localised to small genetic regions or a few prevalent mutations. Approaches using sequencing technologies can provide advantages for drugs where our knowledge of resistance is limited, or where complex resistance signatures exist

Ten simple rules for the sharing of bacterial genotype—Phenotype data on antimicrobial resistance

The increasing availability of high-throughput sequencing (frequently termed next-generation sequencing (NGS)) data has created opportunities to gain deeper insights into the mechanisms of a number of diseases and is already impacting many areas of medicine and public health. The area of infectious diseases stands somewhat apart from other human diseases insofar as the relevant genomic data comes from the microbes rather than their human hosts. A particular concern about the threat of antimicrobial resistance (AMR) has driven the collection and reporting of large-scale datasets containing information from microbial genomes together with antimicrobial susceptibility test (AST) results. Unfortunately, the lack of clear standards or guiding principles for the reporting of such data is hampering the field's advancement. We therefore present our recommendations for the publication and sharing of genotype and phenotype data on AMR, in the form of 10 simple rules. The adoption of these recommendations will enhance AMR data interoperability and help enable its large-scale analyses using computational biology tools, including mathematical modelling and machine learning. We hope that these rules can shed light on often overlooked but nonetheless very necessary aspects of AMR data sharing and enhance the field's ability to address the problems of understanding AMR mechanisms, tracking their emergence and spread in populations, and predicting microbial susceptibility to antimicrobials for diagnostic purposes

Defensins knowledgebase: a manually curated database and information source focused on the defensins family of antimicrobial peptides

The defensins knowledgebase is a manually curated database and information source focused on the defensin family of antimicrobial peptides. The current version of the database holds a comprehensive collection of over 350 defensin records each containing sequence, structure and activity information. A web-based interface provides access to the information and allows for text-based searching on the data fields. In addition, the website presents information on patents, grants, research laboratories and scientists, clinical studies and commercial entities pertaining to defensins. With the rapidly increasing interest in defensins, we hope that the knowledgebase will prove to be a valuable resource in the field of antimicrobial peptide research. The defensins knowledgebase is available at

A comparative evaluation of avidin-biotin ELISA and micro SNT for detection of antibodies to infectious bovine rhinotracheitis in cattle population of Odisha, India

Aim: The present study was undertaken to serologically detect Infectious Bovine Rhinotracheitis (IBR) in the cattle population of Odisha, India using micro-Serum neutralization test (micro SNT) and Avidin-Biotin Enzyme linked immuno sorbent assay (AB ELISA) and finding out their comparative efficacy to serve as a suitable diagnostic tool in field condition. Materials and Methods: The study was carried out using serum samples (n=180) collected randomly from cattle populations of nine districts of Odisha. Similarly vaginal swabs (n=26) from cattle having history of repeat breeding, abortion, vulvo-vaginitis and nasal swabs (n=8) from calves with respiratory symptoms and nasal discharge were collected aseptically, to ascertain the circulation of virus among the cattle population. Results: Virus isolation by cell culture and subsequent confirmation by polymerase chain reaction confirmed four isolates. Screening of serum samples revealed 9.44% and 12.22% samples positive for IBR antibodies in micro SNT and AB ELISA respectively. The sensitivity and specificity of AB ELISA test was found to be 88.23% and 95.70% respectively taking micro SNT as gold standard and the kappa value between the two tests was 0.75. Conclusion: Screening of serum samples revealed 9.44% and 12.22% samples positive for IBR antibodies in micro SNT and AB ELISA respectively, thus highlighting the circulation of virus among the livestock population of Odisha and that AB ELISA could be more efficiently applied for the sero-diagnosis of IBR virus infections at field conditions, with demand for more study on faster, efficient and large scale screening of the infected animals

Chicken and duck myotubes are highly susceptible and permissive to influenza virus infection

Skeletal muscle, at 30 to 40% of body mass, is the most abundant soft tissue in the body. Besides its primary function in movement and posture, skeletal muscle is a significant innate immune organ with the capacity to produce cytokines and chemokines and respond to proinflammatory cytokines. Little is known about the role of skeletal muscle during systemic influenza A virus infection in any host and particularly avian species. Here we used primary chicken and duck multinucleated myotubes to examine their susceptibility and innate immune response to influenza virus infections. Both chicken and duck myotubes expressed avian and human sialic acid receptors and were readily susceptible to low-pathogenicity (H2N3 A/mallard duck/England/7277/06) and high-pathogenicity (H5N1 A/turkey/England/50-92/91 and H5N1 A/turkey/Turkey/1/05) avian and human H1N1 (A/USSR/77) influenza viruses. Both avian host species produced comparable levels of progeny H5N1 A/turkey/Turkey/1/05 virus.Notably, the rapid accumulation of viral nucleoprotein and matrix (M) gene RNA in chicken and duck myotubes was accompanied by extensive cytopathic damage with marked myotube apoptosis (widespread microscopic blebs, caspase 3/7 activation, and annexin V binding at the plasma membrane). Infected chicken myotubes produced significantly higher levels of proinflammatory cytokines than did the corresponding duck cells. Additionally, in chicken myotubes infected with H5N1 viruses, the induction of interferon beta (IFN-beta) and IFN-inducible genes, including the melanoma differentiation-associated protein 5 (MDA-5) gene, was relatively weak compared to infection with the corresponding H2N3 virus. Our findings highlight that avian skeletal muscle fibers are capable of productive influenza virus replication and are a potential tissue source of infection

Anemia, diet and therapeutic iron among children living with HIV: a prospective cohort study

BACKGROUND: Children living with HIV have higher-than-normal prevalence of anemia. The beneficial effect of therapeutic iron has been questioned in the setting of high prevalence of infections. This study examines anemia prevalence and effect of standard therapeutic iron on HIV disease progression among children. METHODS: Perinatally-infected children aged 2–12 years were enrolled at three sites in southern India, and were followed for 1 year with clinical assessments, dietary recall and anthropometry. Laboratory parameters included iron markers (ferritin, soluble transferrin receptor) and other micronutrient levels (vitamin A, B(12), folate). Iron was given to anemic children based on WHO guidelines. Statistical analyses including frequency distributions, chi square tests and multivariate logistic regression were performed using Stata v13.0. RESULTS: Among 240 children enrolled (mean age 7.7 years, 54.6 % males), median CD4 was 25 %, 19.2 % had advanced disease, 45.5 % had malnutrition, and 43.3 % were on antiretroviral treatment (ART) at baseline. Anemia was prevalent in 47.1 % (113/240) children. Iron deficiency was present in 65.5 %; vitamin A and vitamin B(12) deficiency in 26.6 % and 8.0 % respectively; and anemia of inflammation in 58.4 %. Independent risk factors for anemia were stunting, CD4 < 25 %, detectable viral load ≥400 copies/ml and vitamin A deficiency. Inadequate dietary iron was prominent; 77.9 % obtained less than two-thirds of recommended daily iron. Among clinically anemic children who took iron, overall adherence to iron therapy was good, and only minor self-limiting adverse events were reported. Median hemoglobin rose from 10.4 g/dl to 10.9 mg/dl among those who took iron for 3 months, and peaked at 11.3 mg/dl with iron taken for up to 6 months. Iron was also associated with a greater fall in clinical severity of HIV stage; however when adjusted for use of ART, was not associated with improvement in growth, inflammatory and CD4 parameters. CONCLUSIONS: Children living with HIV in India have a high prevalence of anemia mediated by iron deficiency, vitamin A deficiency and chronic inflammation. The use of therapeutic iron for durations up to 6 months appears to be safe in this setting, and is associated with beneficial effects on anemia, iron deficiency and HIV disease progression