Global biogeography of warning coloration in the butterfly Danaus chrysippus

Warning coloration provides a textbook example of natural selection, but the frequent observation of polymorphism in aposematic species presents an evolutionary puzzle. We investigated biogeography and polymorphism of warning patterns in the widespread butterfly Danaus chrysippus using records from citizen science (n = 5467), museums (n = 8864) and fieldwork (n = 2586). We find that polymorphism in three traits controlled by known mendelian loci is extensive. Broad allele frequency clines, hundreds of kilometres wide, suggest a balance between long-range dispersal and predation of unfamiliar morphs. Mismatched clines for the white hindwing and forewing tip in East Africa are consistent with a previous finding that the black wingtip allele has spread recently in the region through hitchhiking with a heritable endosymbiont. Light/dark background coloration shows more extensive polymorphism. The darker genotype is more common in cooler regions, possibly reflecting a trade-off between thermoregulation and predator warning. Overall, our findings show how studying local adaptation at the global scale provides a more complete picture of the evolutionary forces involved.     

The potential of Cystatin C and small dense LDL as biomarkers of coronary artery disease risk in a young Indian population

Coronary artery disease (CAD) affects Indians 5–6 years earlier than in the west, is diffuse and malignant, and poses a heavy burden on India’s developing economy. Traditional risk factors have failed to explain this high incidence of premature CAD and hence this study investigated the association of two novel risk biomarkers, cystatin C and small dense LDL (sdLDL) with the presence and severity of CAD. Cystatin C and sdLDL were estimated in 204 CAD patients ≤45 years of age and compared with 161 age-matched healthy controls. The traditional lipid profile parameters, i.e., cholesterol, LDL, HDL, triglycerides, apolipoproteins A1 and B, and Lp(a) were also measured in both groups. Cystatin C was significantly raised and mean LDL particle size significantly reduced in CAD patients as compared to controls. 62.7 % of CAD patients showed pattern B while 37.3 % patients showed pattern A. Of the traditional lipid tests, only HDL and apolipoprotein A1 showed a significant decrease in the CAD group. sdLDL was significantly associated with the severity of CAD, while cystatin C was not. Both cystatin C and sdLDL emerged as independent risk factors, however, of the two, sdLDL was a more sensitive predictor of CAD events. Cystatin C and mean LDL particle size are significantly and independently associated with the presence of CAD events in patients ≤45 years with normal kidney function. Hence, these novel risk biomarkers can be useful tools in reducing the morbidity and mortality associated with CAD in the productive Indian workforce.     

Redox-active iron mediates amyloid-beta toxicity

While amyloid-beta toxicity is mediated by oxidative stress and can be attenuated by antioxidants, the actual biochemical mechanism underlying neurotoxicity remains to be established. However, since aggregated amyloid-beta can interact with transition metals, such as iron, both in vitro and in vivo, we suspected that bound iron might be the mediator of toxicity such that holo- and apo-amyloid would have differential effects on cellular viability. Here we demonstrate that when amyloid-beta is pretreated with the iron chelator deferoxamine, neuronal toxicity is significantly attenuated while conversely, incubation of holo-amyloid-beta with excess free iron restores toxicity to original levels. These data, taken together with the known sequelae of amyloid-beta, suggest that the toxicity of amyloid-beta is mediated, at least in part, via redox-active iron that precipitates lipid peroxidation and cellular oxidative stress.     

Spotiton: a prototype for an integrated inkjet dispense and vitrification system for cryo-TEM

Over the last three decades, Cryo-TEM has developed into a powerful technique for high-resolution imaging of biological macromolecules in their native vitrified state. However, the method for vitrifying specimens onto EM grids is essentially unchanged - application of ～3 μL sample to a grid, followed by blotting and rapid plunge freezing into liquid ethane. Several trials are often required to obtain suitable thin (few hundred nanometers or less) vitrified layers amenable for cryo-TEM imaging, which results in waste of precious sample and resources. While commercially available instruments provide some level of automation to control the vitrification process in an effort to increase quality and reproducibility, obtaining satisfactory vitrified specimens remains a bottleneck in the Cryo-TEM pipeline. We describe here a completely novel method for EM specimen preparation based on small volume (picoliter to nanoliter) dispensing using inkjet technology. A first prototype system (Spotiton v0.5) demonstrates feasibility of this new approach for specimen vitrification. A piezo-electric inkjet dispenser is integrated with optical real-time cameras (100 Hz frame rate) to analyze picoliter to nanoliter droplet profiles in-flight and spreading dynamics on the grid, and thus provides a method to optimize timing of the process. Using TEM imaging and biochemical assays we demonstrate that the piezo-electric inkjet mechanism does not disrupt the structural or functional integrity of macromolecules. These preliminary studies provide insight into the factors and components that will need further development to enable a robust and repeatable technique for specimen vitrification using this novel approach.     

A Novel Folate-Targeted Nanoliposomal System of Doxorubicin for Cancer Targeting

Targeted drug delivery systems for cancer improves anti-tumor efficacy and reduces systemic toxicity by restricting availability of cytotoxic drugs within tumors. Targeting moieties, such as natural ligands (folic acid, transferrin, and biotin) which are overexpressed on tumors, have been used to enhance liposome-encapsulated drug accumulation within tumors and resulted in better control. In this report, we explored the scope of targeting ligand folic acid, which is incorporated in liposome systems using folic acid-modified cholesterol (CPF), enabled highly selective tumor-targeted delivery of liposome-encapsulated doxorubicin and resulted in increased cytotoxicity within tumors. Folate-tagged poloxamer-coated liposomes (FDL) were found to have significantly higher cellular uptake than conventional poloxamer-coated liposomes (DL), as confirmed by fluorometric analysis in B16F10 melanoma cells. Biodistribution study of the radiolabeled liposomal system indicated the significantly higher tumor uptake of FDL as compared to DL. Anti-tumor activity of FDL against murine B16F10 melanoma tumor-bearing mice revealed that FDL inhibited tumor growth more efficiently than the DL. Taken together, the results demonstrated the significant potential of the folate-conjugated nanoliposomal system for drug delivery to tumors.     

Distributed anomaly detection using concept drift detection based hybrid ensemble techniques in streamed network data

Cluster Computing - Ever since the internet became part of the everyday lives of humans providing network security has been considered of utmost importance. Over the years lot of time and energy...     

Cholesterol Diet Withdrawal Leads to an Initial Plaque Instability and Subsequent Regression of Accelerated Iliac Artery Atherosclerosis in Rabbits

Effect of long term cholesterol diet withdrawal on accelerated atherosclerosis in iliac artery of New Zealand White (NZW) rabbits has not been explored so far. Atherosclerosis was thus induced in rabbits by a combination of balloon injury and atherogenic diet (AD) (1% cholesterol and 6% peanut oil) feeding for 8 weeks (baseline) followed by chow diet (CD) feeding for 4, 8, 16, 32, 50 and 64 weeks. The plaque characterization was done using histology, real time RT-PCR and vasoreactivity studies. Significant elevation in plasma lipids with AD feeding was normalized following 16 weeks of CD feeding. However, baseline comparison showed advanced plaque features even after 8 weeks of CD period with significant elevation in intima/media thickness ratio and plaque area later showing reduction at 50 and 64 weeks CD periods. Lesion lipid accumulation and CD68 positivity was maintained till 16 weeks of CD feeding which significantly reduced from 32 to 64 weeks CD periods. Baseline comparison showed significant increase in ground substance, MMP-9 and significant decrease in α-actin and collagen content at 8 weeks CD period indicating features of unstable plaque. These features regressed up to 64 weeks of CD. Partial restoration of functional vasoconstriction and vasorelaxation was seen after 64 weeks of CD feeding. mRNA expression of MCP-1, VCAM-1, collagen type I and III, MMP-9, TIMP-1, IFN-γ, TNF-α, IL-10 and eNOS supported the above findings. The study thus reveals insights into initial plaque instability and subsequent regression on AD withdrawal in this model. These results are suggestive of an appropriate window for drug intervention for plaque stability/regression and restenosis as well as improves understanding of plaque regression phenomenon in this model.     

Lgr5 Identifies Progenitor Cells Capable of Taste Bud Regeneration after Injury

Taste buds are composed of a variety of taste receptor cell types that develop from tongue epithelium and are regularly replenished under normal homeostatic conditions as well as after injury. The characteristics of cells that give rise to regenerating taste buds are poorly understood. Recent studies have suggested that Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) identifies taste bud stem cells that contribute to homeostatic regeneration in adult circumvallate and foliate taste papillae, which are located in the posterior region of the tongue. Taste papillae in the adult anterior region of the tongue do not express Lgr5. Here, we confirm and extend these studies by demonstrating that Lgr5 cells give rise to both anterior and posterior taste buds during development, and are capable of regenerating posterior taste buds after injury induced by glossopharyngeal nerve transection.