Focused Proteomics Analysis of Habu Snake (Protobothrops flavoviridis) Venom Using Antivenom-Based Affinity Chromatography Reveals Novel Myonecrosis-Enhancing Activity of Thrombin-Like Serine Proteases

Snakebites are one of the major causes of death and long-term disability in the developing countries due to the presence of various bioactive peptides and proteins in snake venom. In Japan, the venom of the habu snake (Protobothrops flavoviridis) causes severe permanent damage due to its myonecrotic toxins. Antivenom immunoglobulins are an effective therapy for snakebites, and antivenom was recently developed with effective suppressive activity against myonecrosis induced by snake venom. To compare the properties of an antivenom having anti-myonecrotic activity with those of conventional antivenom with no anti-myonecrotic activity, this study applied focused proteomics analysis of habu venom proteins using 2D gel electrophoresis. As a target protein for antivenom immunoglobulins with anti-myonecrotic activity, we identified a thrombin-like serine protease, TLSP2 (TLf2), which was an inactive proteolytic isoform due to the replacement of the active site, His43 with Arg. Additionally, we identified the unique properties and a novel synergistic function of pseudoenzyme TLf2 as a myonecrosis-enhancing factor. To our knowledge, this is the first report of a function of a catalytically inactive snake serine protease.

On the Relationship Between Placental Opioid-Enhancing Factor and Neuropeptide FF

Both ingested placenta and Neuropeptide FF (NPFF) are known to modify opioid activity. The following mini-review highlights the similarities in the function of ingested placenta and NPFF, and suggests that NPFF may be a key peptide mediating the CNS-based actions of ingested placenta. There is an advantage to understanding the mechanism of ingested placenta’s modification of opioid activity, in that such understanding may contribute to alternate painmanagement strategies.

Integrating a Polygenic Risk Score for Coronary Artery Disease as a Risk Enhancing Factor in the Pooled Cohort Equation is Cost-effective in a US Health System

Importance: The pooled cohort equation (PCE) is used to determine an individual's 10-year risk (low, borderline, intermediate, or high) of atherosclerotic cardiovascular disease (ASCVD) but it fails to identify all individuals at high risk. Those with borderline or intermediate risk require additional risk enhancing factors to guide preventive therapy decisions. Including a polygenic risk score (PRS) for coronary artery disease as a risk enhancing factor improves precision in determining the risk of ASCVD and informs decisions for prevention therapy. Objective: To assess the cost-effectiveness of integrating PRS for coronary artery disease with the PCE to determine an individual's 10-year risk for ASCVD compared to the PCE-alone. Design, setting, and population: A Markov model was developed on a hypothetical cohort of 40-year-old individuals in the US with borderline or intermediate PCE 10-year risk for ASCVD who fall in the top quintile of the PRS distribution and are not on preventive therapy (e.g., statins). Model transition probabilities and economic costs came from existing literature with costs reflecting a payer perspective and inflation-adjusted to 2019 US$. Interventions: The modeled strategies were: (1) the PCE-alone and (2) the PCE with PRS for coronary artery disease as a risk enhancing factor. Analyses were performed at 5 year, 10 year, and lifetime time horizons. Main outcomes and measures: Quality-adjusted life-years (QALYs) gained, acute coronary syndromes and ischemic stroke events prevented, mean costs, and incremental cost-effectiveness ratios (ICER) were measured. One-way, two-way, and probabilistic sensitivity analyses were used to assess uncertainty in parameter estimates. Future costs and health benefits were discounted at an annual rate of 3%. Results: Compared to the PCE-alone, PCE+PRS was cost-saving, effective and cost-effective (dominant). A health system would save more than $500, $2,300, and $9,000 per additional high-risk individual identified using PCE+PRS and prevent 27, 47 and 83 acute CAD or ischemic stroke events per 1,000 persons in 5 year, 10 year, and lifetime time horizons, respectively. Conclusions and relevance: Implementing PRS as a risk enhancing factor for CAD among individuals with borderline or intermediate 10-year risk reclassifies individuals as high-risk who would otherwise remain unidentified, prevents future acute CAD and ischemic stroke events, and both saves money and is cost-effective for health systems.

How does the yield variability in rainfed crops respond to climate variables? Evidence from pulses yields in Telangana, India

PurposeThis paper aims to evaluate the effects of climate variables on the mean yield and yield variability of major pulse crops in the Telangana state of India.Design/methodology/approachAuthors have estimated the Just and Pope (1978, 1979) production function using panel data at the district level of four major pulses in nine former districts of Telangana for 36 years during 1980–2015. A three-stage feasible generalized least squares estimation procedure has been followed. The mean yield and yield variance functions have been estimated individually for each of these study crops, namely, Bengal gram, green gram, red gram and horse gram.FindingsResults have shown that changes in climatic factors such as rainfall and temperature have significant influences on the mean yield levels and yield variance of pulses. The maximum temperature is observed to have a significant adverse impact on the mean yield of a majority of pulses, and it is also a risk-enhancing factor for a majority of pulses except horse gram. However, the minimum temperature is positively related to the mean yields of the study crops except for Bengal gram, and it is having a risk-reducing impact for a majority of study crops. Rainfall is observed to have a negative impact on the mean yields of all pulses, but it is a risk-enhancing factor for only one crop, i.e. Bengal gram. Thus, rising temperatures and excess rainfall are not favorable to the productivity of pulses in study districts.Research limitations/implicationsThe present study is based on the secondary data at the district level and is considering only one state. Season-wise primary data, including farm-specific characteristics, could have been better. The projected climate change and its impact on the mean yields and yield variance of pulses need to be considered in a future study.Originality/valueAccording to the best of our knowledge, this is the first study to empirically evaluate the impact of climatic variables on the mean yields and yield variability of major pulses in Telangana using a panel data for major pulses and nine districts of 36 years time-series during 1980–2015. The study has given useful policy recommendations.

A comparison of several media types and basic techniques used to assess outdoor airborne fungi in Melbourne, Australia

Despite the recent increase in interest in indoor air quality regarding mould, there is no universally accepted standard media for the detection of airborne fungi, nor verification of many commonly used techniques. Commonly used media including malt-extract agar (MEA), Sabouraud dextrose agar (Sab), potato dextrose agar (PDA) with and without antibiotics chloramphenicol & gentamycin (CG) were compared for their suitability in detecting a range of airborne fungi by collecting 150 L outdoor air on a number of different days and seasons via an Anderson 400-hole sampler in suburban Melbourne, Australia. There was relatively little variation in mean numbers of colony forming units (CFU) and types of fungi recovered between MEA, PDA, Sab media groups relative to variation within each group. There was a significant difference between Sab, Dichloran-18% glycerol (DG18) and V8® Original juice agar media, however. Antibiotics reliably prevented the growth of bacteria that typically interfered with the growth and appearance of fungal colonies. There was no significant evidence for a growth enhancing factor from potato, mineral supplements or various vegetable juices. Differing glucose concentrations had modest effects, showing a vague ideal at 2%-4% with peptone. Sanitisation of the aluminium Andersen 400-hole sampler top-plate by flame is possible, but not strictly required nor advisable. The use of SabCG as a standard medium was generally supported.

Visfatin: A Possible Role in Cardiovasculo-Metabolic Disorders

Visfatin/NAMPT (nicotinamide phosphoribosyltransferase) is an adipocytokine with several intriguing properties. It was first identified as pre-B-cell colony-enhancing factor but turned out to possess enzymatic functions in nicotinamide adenine dinucleotide biosynthesis, with ubiquitous expression in skeletal muscles, liver, cardiomyocytes, and brain cells. Visfatin exists in an intracellular (iNAMPT) and extracellular (eNAMPT) form. Intracellularly, visfatin/iNAMPT plays a regulatory role in NAD+ biosynthesis and thereby affects many NAD-dependent proteins such as sirtuins, PARPs, MARTs and CD38/157. Extracellularly, visfatin is associated with many hormone-like signaling pathways and activates some intracellular signaling cascades. Importantly, eNAMPT has been associated with several metabolic disorders including obesity and type 1 and 2 diabetes. In this review, a brief overview about visfatin is presented with special emphasis on its relevance to metabolic diseases. Visfatin/NAMPT appears to be a unique molecule with clinical significance with a prospective promising diagnostic, prognostic, and therapeutic applications in many cardiovasculo-metabolic disorders.