A Stoichiometry Driven Universal Spatial Organization of Backbones of Folded Proteins: Are there Chargaff's Rules for Protein Folding?

Abstract

Protein folding is at least a six decade old problem, since the times of Pauling and Anfinsen. However, rules of protein folding remain elusive till date. In this work, rigorous analyses of several thousand crystal structures of folded proteins reveal a surprisingly simple unifying principle of backbone organization in protein folding. We find that protein folding is a direct consequence of a narrow band of stoichiometric occurrences of amino-acids in primary sequences, regardless of the size and the fold of a protein. We observe that “preferential interactions” between amino-acids do not drive protein folding, contrary to all prevalent views. We dedicate our discovery to the seminal contribution of Chargaff which was one of the major keys to elucidation of the stoichiometry-driven spatially organized double helical structure of DNA.     

A facile enzymatic method for the location of radioactivity associated with the carbons of L-aspartic acid, L-asparagine, and beta-cyano-L-alanine.

A radiometric enzymatic technique has been devised for locating radioactivity in the carbon skeleton of l-aspartic acid, l-asparagine, and β-cyano-l-alanine. l-Asparaginase at demonstrably discriminant concentrations is used to hydrolyze l-asparagine and/or β-cyano-l-alanine to l-aspartic acid, which in turn is transaminated to oxaloacetic acid by l-glutamate oxaloacetate transaminase. The β-carboxyl group of oxaloacetate is detached by zinc ions, and the radiolabeled CO₂ is collected in alkali after diffusion. The residual pyruvic acid is α-decarboxylated by pyruvate decarboxylase to CO₂, which is collected in a second alkaline trap, and the other product of decarboxylation, acetaldehyde, diffuses into a separate semicarbazide trap. Carbons 4, 1, and 3 plus 2 are located in this order. This method is shown to be facile, sensitive, reliable, and applicable to samples of biological origin.     

Strengthening individual and family resilience against leprosy-related discrimination: A pilot intervention study

BackgroundLeprosy and leprosy-related stigma can have a major impact on psychosocial wellbeing of persons affected and their family members. Resilience is a process that incorporates many of the core skills and abilities which may enable people to address stigma and discrimination. The current study aimed to develop and pilot an intervention to strengthen individual and family resilience against leprosy-related discrimination.MethodologyWe used a quasi-experimental, before-after study design with a mixed methods approach. The 10-week family-based intervention was designed to strengthen the resilience of individuals and families by enhancing their protective abilities and capacity to overcome adversity. The study was conducted in two sites, urban areas in Telangana state, and in rural areas in Odisha state, India. Persons affected and their family members were included using purposive sampling. Two questionnaires were used pre-and post-intervention: the Connor-Davidson Resilience Scale (CD-RISC, maximum score 100, with high scores reflecting greater resilience) and the WHOQOL-BREF (maximum score of 130, with higher scores reflecting higher quality of life). In addition, semi-structured interviews were conducted post-intervention. Data were collected at baseline, a few weeks after completion of the intervention, and in the Odisha cohort again at six months after completion. Paired t-tests measured differences pre- and post- intervention. Qualitative data were thematically analysed.FindingsEighty participants across 20 families were included in the study (23 persons affected and 57 family members). We found a significant increase in CD-RISC scores for persons affected and family members from Odisha state (baseline 46.5, first follow-up 77.0, second follow-up 70.0), this improvement was maintained at six-month follow-up. There was no increase in CD-RISC scores post-intervention among participants from Telangana state. WHOQOL-BREF scores were significantly higher at follow-up for persons affected in both states, and for family members in Odisha state. No families dropped out of the study. In the qualitative feedback, all participants described drawing benefit from the programme. Participants especially appreciated the social dimensions of the intervention.ConclusionThis pilot study showed that the 10-week family-based intervention to strengthen resilience among persons affected by leprosy and their family members was feasible, and has the potential to improve resilience and quality of life. A large-scale efficacy trial is necessary to determine the effectiveness and long-term sustainability of the intervention.     

Fine needle aspiration cytology of well-differentiated papillary peritoneal mesothelioma. Report of a case

The fine needle aspiration cytologic findings in a well-differentiated multifocal papillary peritoneal mesothelioma in a young man presenting with abdominal pain and mass are described. The patient is alive and well 50 months after the onset of symptomatology. The cytologic and histologic appearance as well as the clinical course of the patient point to a benign multifocal mesothelioma.     

Inhibition of L-asparagine synthetase by mucochloric and mucobromic acids.

Mucochloric and mucobromic acids are powerful inhibitors of tumoral and pancreatic L-asparagine synthetases. Two nitrogen donors, L-glutamine and ammonia, can be used by these enzymes; at a concentration of 1 mmol/l, mucochloric and mucobromic acids preferentially inhibit the utilization of ammonia as opposed to L-glutamine in vitro. Using the tumoral enzyme, kinetic analysis revealed that mucochloric acid produced inhibition which was apparently noncompetitive with ammonia but competitive with L-glutamine. In molar excess, L-glutamine and dithiothreitol effectively antagonized such inhibition; dialysis, however, failed to reverse established inhibition. These findings, suggest that the drugs operate by covalent attachment to crucial sulfhydryl functions on the enzyme.