AmylPepPred: Amyloidogenic Peptide Prediction tool

We present an efficient computational architecture designed using supervised machine learning model to predict amyloid fibril forming protein segments, named AmylPepPred. The proposed prediction model is based on bio-physio-chemical properties of primary sequences and auto-correlation function of their amino acid indices. AmylPepPred provides a user friendly web interface for the researchers to easily observe the fibril forming and non-fibril forming hexmers in a given protein sequence. We expect that this stratagem will be highly encouraging in discovering fibril forming regions in proteins thereby benefit in finding therapeutic agents that specifically aim these sequences for the inhibition and cure of amyloid illnesses.

Availability

AmylPepPred is available freely for academic use at www.zoommicro.in/amylpeppred     

Laboratory bioassays and field-cage trials of <Emphasis Type="Italic">Metarhizium</Emphasis> spp. isolates with field-collected Mormon crickets (<Emphasis Type="Italic">Anabrus simplex</Emphasis>)

The Mormon cricket (MC) is an important pest in the western United States. This study evaluated the virulence in the laboratory of 32 isolates of Metarhizium spp. towards field-collected MCs. Additionally, four isolates were tested in outdoor field-cage studies. All 32 Metarhizium isolates were pathogenic towards the MC (could induce some mortality in the laboratory), including four isolates of the grasshopper-specialist species M. acridum. Virulence varied considerably among the isolates. Field studies, conducted in 2008–2009, showed a statistically significant effect of fungal treatments in both years. Pairwise comparison of the survival curves, however, revealed that, in 2008, three of the isolates did not differ statistically from the non-fungus control treatment. In 2009, all three of the isolates tested had significantly lower survival rates than the control treatment: MCs exposed to M. robertsii isolate DWR 346 had the lowest survival with a LT₅₀ of 16 days. We hypothesize that the poor field performance resulted from a combination of negative environmental effects and isolate selection, and propose that further field studies with additional isolates are needed to identify an efficacious fungal agent for MC biocontrol.     

MtnK, methylthioribose kinase, is a starvation-induced protein in Bacillus subtilis

Background  

Methylthioadenosine, the main by-product of spermidine synthesis, is degraded inBacillus subtilisas adenine and methylthioribose. The latter is an excellent sulfur source and the precursor of quorum-sensing signalling molecules. Nothing was known about methylthioribose recycling in this organism.     

Inducible cytochrome P450 activities in renal glomerular mesangial cells: biochemical basis for antagonistic interactions among nephrocarcinogenic polycyclic aromatic hydrocarbons

BACKGROUND: Benzo(a)pyrene (BaP), anthracene (ANTH) and chrysene (CHRY) are polynuclear aromatic hydrocarbons (PAHs) implicated in renal toxicity and carcinogenesis. These PAHs elicit cell type-specific effects that help predict toxicity outcomes in vitro and in vivo. While BaP and ANTH selectively injure glomerular mesangial cells, and CHRY targets cortico-tubular epithelial cells, binary or ternary mixtures of these hydrocarbons markedly reduce the overall cytotoxic potential of individual hydrocarbons. METHODS: To study the biochemical basis of these antagonistic interactions, renal glomerular mesangial cells were challenged with BaP alone (0.03 - 30 microM) or in the presence of ANTH (3 microM) or CHRY (3 microM) for 24 hr. Total RNA and protein will be harvested for Northern analysis and measurements of aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (EROD) activity, respectively, to evaluate cytochrome P450 mRNA and protein inducibility. Cellular hydrocarbon uptake and metabolic profiles of PAHs were analyzed by high performance liquid chromatography (HPLC). RESULTS: Combined hydrocarbon treatments did not influence the cellular uptake of individual hydrocarbons. ANTH or CHRY strongly repressed BaP-inducible cytochrome P450 mRNA and protein expression, and markedly inhibited oxidative BaP metabolism. CONCLUSION: These findings indicate that antagonistic interactions among nephrocarcinogenic PAHs involve altered expression of cytochrome P450s that modulate bioactivation profiles and nephrotoxic/ nephrocarcinogenic potential.     

Intensive cannibalism and feeding on bregmacerotids in <Emphasis Type="Italic">Champsodon snyderi</Emphasis> (Champsodontidae): evidence for pelagic predation

Analysis of the stomach contents of 1002 specimens of Champsodon snyderi (Champsodontidae) (17.3–91.2mm SL) from Tosa Bay, southern Japan, showed that species to primarily feed on crustaceans and fishes (87.9% by frequency, 37.6% by weight for the former; 17.3% and 60.7% for the latter, respectively), although fishes occurred more often in stomachs of individuals larger than 50mm SL. Champsodon snyderi ingested large prey fishes (60.5–101.0% of predator SL), the maximum weight recorded for a single ingested specimen being 50.9% of the predator weight. Mesopelagic Bregmaceros nectabanus were by far the dominant prey fish, followed by C. snyderi (cannibalism), indicating that C. snyderi leaves the bottom to feed in the pelagic environment during the night.     

1H NMR metabolomics reveals increased glutaminolysis upon overexpression of NSD3s or Pdp3 in Saccharomyces cerevisiae

NSD3s, the proline-tryptophan-tryptophan-proline (PWWP) domain-containing, short isoform of the human oncoprotein NSD3, displays high transforming properties. Overexpression of human NSD3s or the yeast protein Pdp3 in Saccharomyces cerevisiae induces similar metabolic changes, including increased growth rate and sensitivity to oxidative stress, accompanied by decreased oxygen consumption. Here, we set out to elucidate the biochemical pathways leading to the observed metabolic phenotype by analyzing the alterations in yeast metabolome in response to NSD3s or Pdp3 overexpression using ¹H nuclear magnetic resonance (NMR) metabolomics. We observed an increase in aspartate and alanine, together with a decrease in arginine levels, on overexpression of NSD3s or Pdp3, suggesting an increase in the rate of glutaminolysis. In addition, certain metabolites, including glutamate, valine, and phosphocholine were either NSD3s or Pdp3 specific, indicating that additional metabolic pathways are adapted in a protein-dependent manner. The observation that certain metabolic pathways are differentially regulated by NSD3s and Pdp3 suggests that, despite the structural similarity between their PWWP domains, the two proteins act by unique mechanisms and may recruit different downstream signaling complexes. This study establishes for the first time a functional link between the human oncoprotein NSD3s and cancer metabolic reprogramming.     

Hematological profiles of COVID-19 patients at the Ratlam district,Madhya Pradesh State,India

It is of interest to compare the hematological profile (using Complete blood count) of COVID patients admitted in ICU, private ward, and isolation ward with varying severity. This data will help predict the severity of infection at peripheries and rural areas.  Detailed history and CBC was performed for all the cases. Different ratios and indexes such as systemic inflammatory index (SII), Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) were assessed. A total of 862 cases with a mean age of 49.9 ±17.4 years were enrolled. Hemoglobin level, lymphocyte (count per liter and percentage) were significantly lower in patients admitted in ICU as compared to patients admitted in the isolation ward and private ward (p <0.05). However, TLC, neutrophils, platelet count were higher in patients admitted to ICU (p <0.05). The Various ratios such as SII, NLR, and PLR showed significantly higher value in cases admitted in ICU (p <0.05). The TLC, neutrophil count, neutrophil percentage, SII, NLR, and PLR were significant predictors of severe disease (admission in ICU) with high diagnostic accuracy. We show that complete blood count method is a simple, readily available, rapid, and inexpensive tool that can be utilized for diagnosis and can predicting the severity of COVID 19 where RTPCR or trained staff is not available. Thus, NLR (%), SII, PLR, and TLC can predict severe illness with high accuracy.     

Accounting for movement increases sensitivity in detecting brain activity in Parkinson's disease

Parkinson's disease (PD) is manifested by motor impairment, which may impede the ability to accurately perform motor tasks during functional magnetic resonance imaging (fMRI). Both temporal and amplitude deviations of movement performance affect the blood oxygenation level-dependent (BOLD) response. We present a general approach for assessing PD patients' movement control employing simultaneously recorded fMRI time series and behavioral data of the patients' kinematics using MR-compatible gloves. Twelve male patients with advanced PD were examined with fMRI at 1.5T during epoch-based visually paced finger tapping. MR-compatible gloves were utilized online to quantify motor outcome in two conditions with or without dopaminergic medication. Modeling of individual-level brain activity included (i) a predictor consisting of a condition-specific, constant-amplitude boxcar function convolved with the canonical hemodynamic response function (HRF) as commonly used in fMRI statistics (standard model), or (ii) a custom-made predictor computed from glove time series convolved with the HRF (kinematic model). Factorial statistics yielded a parametric map for each modeling technique, showing the medication effect on the group level. Patients showed bilateral response to levodopa in putamen and globus pallidus during the motor experiment. Interestingly, kinematic modeling produced significantly higher activation in terms of both the extent and amplitude of activity. Our results appear to account for movement performance in fMRI motor experiments with PD and increase sensitivity in detecting brain response to levodopa. We strongly advocate quantitatively controlling for motor performance to reach more reliable and robust analyses in fMRI with PD patients.