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

Relaxing cosmological tensions with a sign switching cosmological constant: Improved results with Planck, BAO, and Pantheon data

We present a further observational analysis of the $\Lambda_{\rm s}$CDM model proposed in Akarsu et al. [Phys. Rev. D 104, 123512 (2021)]. This model is based on the recent conjecture suggesting the Universe has transitioned from anti-de Sitter vacua to de Sitter vacua (viz., the cosmological constant switches sign from negative to positive), at redshift ${z_\dagger\sim2}$, inspired by the graduated dark energy model proposed in Akarsu et al. [Phys. Rev. D 101, 063528 (2020)]. $\Lambda_{\rm s}$CDM was previously claimed to simultaneously relax five cosmological discrepancies, namely, the $H_0$, $S_8$, and $M_B$ tensions along with the Ly-$\alpha$ and $\omega_{\rm b}$ anomalies, which prevail within the standard $\Lambda$CDM model as well as its canonical/simple extensions. In the present work, we extend the previous analysis by constraining the model using the Pantheon data (with and without the SH0ES $M_B$ prior) and/or the completed BAO data along with the full Planck CMB data. We find that $\Lambda_{\rm s}$CDM exhibits a better fit to the data compared to $\Lambda$CDM, and simultaneously relaxes the six discrepancies of $\Lambda$CDM, viz., the $H_0$, $M_B$, $S_8$, Ly-$\alpha$, $t_0$, and $\omega_{\rm b}$ discrepancies, all of which are discussed in detail. When the $M_B$ prior is included in the analyses, $\Lambda_{\rm s}$CDM performs significantly better in relaxing the $H_0$, $M_B$, and $S_8$ tensions with the constraint ${z_\dagger\sim1.8}$ even when the Ly-$\alpha$ data (which imposed the $z_\dagger\sim2$ constraint in the previous studies) are excluded. In contrast, the presence of the $M_B$ prior causes only negligible improvements for $\Lambda$CDM. Thus, the $\Lambda_{\rm s}$CDM model provides remedy to various cosmological tensions simultaneously, only that the galaxy BAO data hinder its success to some extent.Comment: 27 pages, 11 figures, 5 tables; matches the version published in Physical Review

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

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

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

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

Recent advances in natural polymer-based hydroxyapatite scaffolds:Properties and applications

New materials that mimic natural bone properties, matching functional, mechanical, and biological properties have been continuously developed to rehabilitate bone defects. Desirably, 'tissue engineering' has been a multidisciplinary ground that uses the principles of life sciences and engineering for the biological replacements that restore or replace the tissue function or a whole organ. Nevertheless, the bone grafting treatment has numerous restrictions, counting the major hazards of morbidity from the sites where donor bone grafts are removed, the likelihood for an immune rejection or bacterial transport from the donor site (in case of allogeneic grafting), and the inadequate availability of donor bone grafts that can meet the current demands. Since the proper growth of synthetic materials for implantable bones encourages the reconstruction of bone tissues by providing strong structural support without any damages to the interferences of biological tissue. To serve for such behavior, the biodegradable matrices provide temporary scaffolds within which the bone tissues can be regenerated. Typically, the thermoplastic aliphatic polyesters are found to serve this purpose. The great significance of this field lies in the in vitro growth of precise cells on porous matrices (scaffolds) to generate three-dimensional (3D) tissues that can be entrenched into the location of tissue/bone damage. Numerous gifts have been gifted by our nature to advance and preserve the well-being of all living things either directly or indirectly. This review focuses on the recent advances in polymer-based hydroxyapatite scaffolds including their properties and applications