Statistical analysis of pair-wise compatibility of spatially nearest neighbor and adjacent residues in alpha-helix and beta-strands: application to a minimal model for secondary structure prediction

Secondary structural elements like alpha-helix and beta-strands possess distinctly different structural features and thus the relative positioning of the nearest neighbor residues, and also the sequence-wise adjacent residues is important in determining the structural preference. In the present work we have statistically examined the pair-wise compatibility pattern of physically nearest neighbors and separately the adjacent residue pairs along the sequence in between the nearest neighbor partners in alpha-helices and beta-strands. It has been demonstrated that the patterns and hence, the physical basis of the compatibility of adjacent residue pairs and the spatially nearest neighbors are significantly different in most cases. The influence of tertiary contacts on the pair-wise compatibility is shown to be significant for beta-strands while it is small for alpha-helices. Based on the compatibility of physically nearest neighbors and the sequence-wise adjacent residue pairs, a minimal model has been constructed to predict the alpha-helices, beta-strands and coils of a protein from its sequence. Application of this method to 100 sequences shows that it has a predictive capability comparable to that of other more sophisticated statistical methods.     

Asymmetry of the acceleration and deceleration capacity of heart rate is strongly dependent on ventricular premature complexes.

In this letter, we explain the role of acceleration and deceleration capacities as novel risk predictors after myocardial infarction and their relation to the occurrence of ventricular premature complexes.     

Development of a Quantitative Competitive Reverse Transcription Polymerase Chain Reaction (QC-RT–PCR) for Detection and Quantitation of Chikungunya Virus

Chikungunya is one of the most important emerging arboviral infections of public health significance. Due to lack of a licensed vaccine, rapid diagnosis plays an important role in early management of patients. In this study, a QC-RT–PCR assay was developed to quantify Chikungunya virus (CHIKV) RNA by targeting the conserved region of E1 gene. A competitor molecule containing an internal insertion was generated, which provided a stringent control of the quantification process. The introduction of 10-fold serially diluted competitor in each reaction was further used to determine sensitivity. The applicability of this assay for quantification of CHIKV RNA was evaluated with human clinical samples, and the results were compared with real-time quantitative RT–PCR. The sensitivity of this assay was estimated to be 100 RNA copies per reaction with a dynamic detection range of 10² to 10¹⁰ copies. Specificity was confirmed using closely related alpha and flaviviruses. The comparison of QC-RT–PCR result with real-time RT–PCR revealed 100% concordance for the detection of CHIKV in clinical samples. These findings demonstrated that the reported assay is convenient, sensitive and accurate method and has the potential usefulness for clinical diagnosis due to simultaneous detection and quantification of CHIKV in acute-phase serum samples.     

Degradation Kinetics of Caffeine and Related Methylxanthines by Induced Cells of <Emphasis Type="Italic">Pseudomonas</Emphasis> sp.

In this study, the kinetics of degradation of caffeine and related methylxanthines by induced cells of Pseudomonas sp. was performed. The kinetics data showed that degradation of caffeine, theobromine, and 7-methylxanthine followed Michealis–Menten kinetics. The values of K _m are low for caffeine and 7-methylxanthine and high for theobromine. Degradation of caffeine and theobromine was enhanced in the presence of NADH and NADPH, whereas the degradation of 7-methylxanthine was unaffected. Among the various metal ions tested, Fe²⁺ was found to enhance the rate of degradation for all three substrates, whereas Zn²⁺ and Cu²⁺ inhibited the degradation of caffeine and theobromine but not 7-methylxanthine. The differences in kinetic parameters and cofactor requirement suggest the possibility of the involvement of more than one N-demethylases in the caffeine catabolic pathway in Pseudomonas sp. The induced cells can serve as effective biocatalysts for the development of biodecaffeination techniques.     

Role of intrinsic disorder in transient interactions of hub proteins

Hubs in the protein-protein interaction network have been classified as "party" hubs, which are highly correlated in their mRNA expression with their partners while "date" hubs show lesser correlation. In this study, we explored the role of intrinsic disorder in date and party hub interactions. The data reveals that intrinsic disorder is significantly enriched in date hub proteins when compared with party hub proteins. Intrinsic disorder has been largely implicated in transient binding interactions. The disorder to order transition, which occurs during binding interactions in disordered regions, renders the interaction highly reversible while maintaining the high specificity. The enrichment of intrinsic disorder in date hubs may facilitate transient interactions, which might be required for date hubs to interact with different partners at different times.     

A computational model of skeletal muscle metabolism linking cellular adaptations induced by altered loading states to metabolic responses during exercise

Background  

The alterations in skeletal muscle structure and function after prolonged periods of unloading are initiated by the chronic lack of mechanical stimulus of sufficient intensity, which is the result of a series of biochemical and metabolic interactions spanning from cellular to tissue/organ level. Reduced activation of skeletal muscle alters the gene expression of myosin heavy chain isoforms to meet the functional demands of reduced mechanical load, which results in muscle atrophy and reduced capacity to process fatty acids. In contrast, chronic loading results in the opposite pattern of adaptations.