Identification and Analysis of Novel Amino-Acid Sequence Repeats in Bacillus anthracis str. Ames Proteome Using Computational Tools

We have identified four repeats and ten domains that are novel in proteins encoded by the Bacillus anthracis str. Ames proteome using automated in silico methods. A “repeat” corresponds to a region comprising less than 55-amino-acid residues that occur more than once in the protein sequence and sometimes present in tandem. A “domain” corresponds to a conserved region with greater than 55-amino-acid residues and may be present as single or multiple copies in the protein sequence. These correspond to (1) 57-amino-acid-residue PxV domain, (2) 122-amino-acid-residue FxF domain, (3) 111-amino-acid-residue YEFF domain, (4) 109-amino-acid-residue IMxxH domain, (5) 103-amino-acid-residue VxxT domain, (6) 84-amino-acid-residue ExW domain, (7) 104-amino-acid-residue NTGFIG domain, (8) 36-amino-acid-residue NxGK repeat, (9) 95-amino-acid-residue VYV domain, (10) 75-amino-acid-residue KEWE domain, (11) 59-amino-acid-residue AFL domain, (12) 53-amino-acid-residue RIDVK repeat, (13) (a) 41-amino-acid-residue AGQF repeat and (b) 42-amino-acid-residue GSAL repeat. A repeat or domain type is characterized by specific conserved sequence motifs. We discuss the presence of these repeats and domains in proteins from other genomes and their probable secondary structure

Effect of lac treatment on mechanical properties of jute fabric /polyester resin based biocomposite

An attempt has been made to dissolve lac in methanol / sodium hydroxide solution and to use this lac solution as a coupling agent for jute fabric. Lac treated jute fabric has been used to reinforce the unsaturated polyester resin (USP). Flexural strength and inter-laminar shear strength (ILSS) of lac modified jute/USP biocomposite have been evaluated and then compared with sodium hydroxide treated jute as well as untreated jute based biocomposites. Lac treated jute fabric shows higher flexural properties of the biocomposite than that of untreated jute fabric, which infers that lac acts as a good compatibliser between jute fibre and USP. Lac treatment on jute fabric enhances the flexural properties of biocomposite better in alkaline medium than in solvent medium. It is concluded that lac treatment can be used to improve the flexural and ILSS properties of jute / thermoset resin based biocomposite

The Feasibility and Acceptability of a Smartphone-Based Music Intervention for Acute Pain

Pain is an unpleasant experience the neurobiology of which is influenced by psychosocial factors including negative affect. Music is a ubiquitous experience that can improve affect, potentially decreasing anxiety and catastrophizing, both of which are associated with greater pain severity. We hypothesized that a machine-learning generative music intervention in the form of a smartphone web app (Unwind) could be used to modulate the experience of pain. In this pilot study, we recruited 15 individuals with acute pain who were admitted to an observation unit in the emergency department, and were being treated with opioids. Participants used the music intervention (Unwind) during this brief hospitalization, after which we assessed their response to its use through a semi- structured qualitative interview. Overall, participants responded positively to Unwind. While some reported some technical challenges, participants were willing to continue using it at home. In particular, participants reported using Unwind to address their anxiety, and many used it to facilitate sleep in the presence of pain. This study demonstrates that individuals with acute pain will accept and use a smartphone-based music protocol

Plasma Sphingoid Base Profiles of Patients Diagnosed with Intrinsic or Idiosyncratic Drug-induced Liver Injury

Sphingolipids are exceptionally diverse, comprising hundreds of unique species. The bulk of circulating sphingolipids are synthesized in the liver, thereby plasma sphingolipid profiles represent reliable surrogates of hepatic sphingolipid metabolism and content. As changes in plasma sphingolipid content have been associated to exposure to drugs inducing hepatotoxicity both in vitro and in rodents, in the present study the translatability of the preclinical data was assessed by analyzing the plasma of patients with suspected drug-induced liver injury (DILI) and control subjects. DILI patients, whether intrinsic or idiosyncratic cases, had no alterations in total sphingoid base levels and profile composition compared to controls, whereby cardiovascular disease (CVD) was a confounding factor. Upon exclusion of CVD individuals, elevation of 1-deoxysphingosine (1-deoxySO) in the DILI group emerged. Notably, 1-deoxySO values did not correlate with ALT values. While 1-deoxySO was elevated in all DILI cases, only intrinsic DILI cases concomitantly displayed reduction of select shorter chain sphingoid bases. Significant perturbation of the sphingolipid metabolism observed in this small exploratory clinical study is discussed and put into context, in the consideration that sphingolipids might contribute to the onset and progression of DILI, and that circulating sphingoid bases may function as mechanistic markers to study DILI pathophysiology

Biomarkers of idiosyncratic drug-induced liver injury (DILI) - a systematic review

Introduction: Idiosyncratic drug-induced liver injury (DILI) is an unpredictable event, and there are no specific biomarkers that can distinguish DILI from alternative explanations or predict its clinical outcomes. Areas covered: This systematic review summarizes the available evidence for all biomarkers proposed to have a role in the diagnosis or prognosis of DILI. Following a comprehensive search, we included all types of studies in humans. We included DILI cases based on any threshold criteria but excluded intrinsic DILI, commonly caused by paracetamol overdose. We classified studies into diagnostic and prognostic categories and assessed their methodological quality. After reviewing the literature, 14 studies were eligible. Expert Opinion: Diagnostic studies were heterogeneous with regard to the study population and outcomes measured. Prognostic models were developed by integrating novel biomarkers, risk scores, and traditional biomarkers, which increased their prognostic ability to predict death or transplantation by 6 months. This systematic review highlights the case of need for non-genetic biomarkers that distinguish DILI from acute liver injury related to alternative etiology. Biomarkers with the potential to identify serious adverse outcomes from acute DILI should be validated in independent prospective cohorts with a substantial number of cases.This paper was funded by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 821283 (www.imi.europa.eu). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. Translational Safety Biomarker Pipeline (TransBioLine): Enabling develop- ment and implementation of novel safety biomarkers in clinical trials and diagnosis of disease’ — ‘TransBioLine’ (‘action’). Grant Number: 821283

Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community

AbstractObjectivesThe goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) outcomes in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of subjects aged 45 to 64 years.BackgroundThe level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD, but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community.MethodsCox proportional-hazards regression was used to evaluate the association of glomerular filtration rate (GFR) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects. We searched for nonlinear relationships between GFR and ASCVD.ResultsDuring a mean follow-up time of 6.2 years, 965 (6.3%) of subjects had ASCVD events. Subjects with GFR of 15 to 59 ml/min/1.73 m2(n = 444, hazard ratio 1.38 [1.02, 1.87]) and 60 to 89 ml/min/1.73 m2(n = 7,665, hazard ratio 1.16 [1.00, 1.34]) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m2. Each 10 ml/min/1.73 m2lower GFR was associated with an adjusted hazard ratio of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), and 1.06 (0.99, 1.13) for ASCVD, de novo ASCVD, and recurrent ASCVD, respectively. A nonlinear model did not fit the data better than a linear model.ConclusionsThe level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study

Decomposable representations and Lagrangian submanifolds of moduli spaces associated to surface groups

In this paper, we construct a Lagrangian submanifold of the moduli space associated to the fundamental group of a punctured Riemann surface (the space of representations of this fundamental group into a compact connected Lie group). This Lagrangian submanifold is obtained as the fixed-point set of an anti-symplectic involution defined on the moduli space. The notion of decomposable representation provides a geometric interpretation of this Lagrangian submanifold