Male- and female-specific variants of doublesex gene products have different roles to play towards regulation of Sex combs reduced expression and sex comb morphogenesis in Drosophila

Sexually dimorphic characters have two-fold complexities in pattern formation as they have to get input from both somatic sex determination as well as the positional determining regulators. Sex comb development in Drosophila requires functions of the somatic sex-determining gene doublesex and the homeotic gene Sex combs reduced. Attempts have not been made to decipher the role of dsx in imparting sexually dimorphic expression of SCR and the differential function of sex-specific variants of dsx products in sex comb development. Our results in this study indicate that male-like pattern of SCR expression is independent of dsx function, and dsx ^F must be responsible for bringing about dimorphism in SCR expression, whereas dsx ^M function is required with Scr for the morphogenesis of sex comb.     

Acute outcome of treating patients admitted with electrical storm in a tertiary care centre

Background

Electrical storm (ES) is a life threatening emergency. There is little data available regarding acute outcome of ES.

Aims

The study aimed to analyze the acute outcome of ES, various treatment modalities used, and the factors associated with mortality.

Methods

This is a retrospective observational study involving patients admitted with ES at our centre between 1/1/2007 and 31/12/2013.

Results

41 patients (mean age 54.61 ± 12.41 years; 86.7% males; mean ejection fraction (EF) 44.51 ± 16.48%) underwent treatment for ES. Hypokalemia (14.63%) and acute coronary syndrome (ACS) (14.63%) were the commonest identifiable triggers. Only 9 (21.95%) patients already had an ICD implanted. Apart from antiarrhythmic drugs (100%), deep sedation (87.8%), mechanical ventilation (24.39%) and neuraxial modulation using left sympathetic cardiac denervation (21.95%) were the common treatment modalities used. Thirty-three (80.49%) patients could be discharged after a mean duration of 14.2 ± 2.31 days. Eight (19.5%) patients died in hospital. The mortality was significantly higher in those with EF < 35% compared to those with a higher EF (8 (42.11% vs 0 (0%), p = 0.03)). There was no significant difference in mortality between those with versus without a structural heart disease (8 (21.1% vs 0 (0%), p = 0.32)). Comparison of mortality an ACS with ES versus ES of other aetiologies (3 (50%) vs 5 (14.29) %, p = 0.076)) showed a trend towards significance.

Conclusion

With comprehensive treatment, there is reasonable acute survival rate of ES. Hypokalemia and ACS are the commonest triggers of ES. Patients with low EF and ACS have higher mortality.     

Retroviral transfer of the p16INK4a cDNA inhibits C6 glioma formation in Wistar rats

BACKGROUND: The p16INK4A gene product halts cell proliferation by preventing phosphorylation of the Rb protein. The p16INK4a gene is often deleted in human glioblastoma multiforme, contributing to unchecked Rb phosphorylation and rapid cell division. We show here that transduction of the human p16INK4a cDNA using the pCL retroviral system is an efficient means of stopping the proliferation of the rat-derrived glioma cell line, C6, both in tissue culture and in an animal model. C6 cells were transduced with pCL retrovirus encoding the p16INK4a, p53, or Rb genes. These cells were analyzed by a colony formation assay. Expression of p16INK4a was confirmed by immunohistochemistry and Western blot analysis. The altered morphology of the p16-expressing cells was further characterized by the senescence-associated beta-galactosidase assay. C6 cells infected ex vivo were implanted by stereotaxic injection in order to assess tumor formation. RESULTS: The p16INK4a gene arrested C6 cells more efficiently than either p53 or Rb. Continued studies with the p16INK4a gene revealed that a large portion of infected cells expressed the p16INK4a protein and the morphology of these cells was altered. The enlarged, flat, and bi-polar shape indicated a senescence-like state, confirmed by the senescence-associated beta-galactosidase assay. The animal model revealed that cells infected with the pCLp16 virus did not form tumors. CONCLUSION: Our results show that retrovirus mediated transfer of p16INK4a halts glioma formation in a rat model. These results corroborate the idea that retrovirus-mediated transfer of the p16INK4a gene may be an effective means to arrest human glioma and glioblastoma.     

Species divergence in sexually selected traits: increase in song elaboration is related to decrease in plumage ornamentation in finches

Elaborate plumage and complex songs of male birds are two of the best-known examples of sexually selected traits, yet the interaction between these traits is poorly understood. Theory suggests that among a suite of potential displays, animals will emphasize traits that are most conspicuous, least costly, or best signal condition and reduce display of other traits. Here we examined the relationship between song and plumage elaborations in cardueline finches, songbirds that are highly variable in plumage displays and songs, but that share a similar mating system. We statistically controlled for body mass, habitat characteristics, and phylogenetic relationships and found that across species song complexity was strongly negatively related to elaboration of plumage ornamentation. When plumage coloration was partitioned into carotenoid-based and melanin-based components, song complexity was negatively related to elaboration of male carotenoid-based coloration but unrelated to elaboration of melanin-based coloration. These observations support the idea that, for condition-dependent traits, animal species trade off trait expression in response to changes in the costs or the information content of these traits. We discuss several alternative explanations for the observed pattern.     

Cytosolic thioredoxin reductase 1 is required for correct disulfide formation in the ER

Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so‐called non‐native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non‐native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non‐native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1). Inhibition of this reductive pathway prevents the correct folding and secretion of proteins that are known to form non‐native disulfides during their folding. Hence, we have shown for the first time that mammalian cells have a pathway for transferring reducing equivalents from the cytosol to the ER, which is required to ensure correct disulfide formation in proteins entering the secretory pathway.     

Total antioxidant capacity – a novel early bio-chemical marker of oxidative stress in HIV infected individuals

Background  

Oxidative stress induced by the production of reactive oxygen species may play a critical role in the stimulation of HIV replication and the development of immunodeficiency. This study was conducted as there are limited and inconclusive studies on the significance of a novel early marker of oxidative stress which can reflect the total antioxidant capacity in HIV patients,     

Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function

Endo- β-N-acetylgucosaminidases (ENGases) are the enzymes that catalyze both hydrolysis and transglycosylation reactions. It is of interest to study ENGases because of their ability to synthesize glycopeptides. Homology models of Human, Arabidopsis thaliana and Sorghum ENGases were developed and their active sites marked based on information available from Arthrobacter protophormiae (PDB ID: 3FHQ) ENGase. Further, these models were docked with the natural substrate GlcNAc-Asn and the inhibitor Man₃GlcNAc-thiazoline. The catalytic triad of Asn, Glu and Tyr (N171, E173 and Y205 of bacteria) were found to be conserved across the phyla. The crucial Y299F mutation showing 3 times higher transglycosylation activity than in wild type Endo-A is known. The hydrolytic activity remained unchanged in bacteria, while the transglycosylation activity increased. This Y to F change is found to be naturally evolved and should be attributing higher transglycosylation rates in human and Arabidopsis thaliana ENGases. Ligand interactions Ligplots revealed the interaction of amino acids with hydrophobic side chains and polar uncharged side chain amino acids. Thus, structure based molecular model-ligand interactions provide insights into the catalytic mechanism of ENGases and assist in the rational engineering of ENGases.