Elastic Free Energy Drives the Shape of Prevascular Solid Tumors

It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progression of early solid tumors in vivo and is an important step in understanding the processes underlying solid tumor growth.     

Human neuroglobin functions as a redox-regulated nitrite reductase

Neuroglobin is a highly conserved hemoprotein of uncertain physiological function that evolved from a common ancestor to hemoglobin and myoglobin. It possesses a six-coordinate heme geometry with proximal and distal histidines directly bound to the heme iron, although coordination of the sixth ligand is reversible. We show that deoxygenated human neuroglobin reacts with nitrite to form nitric oxide (NO). This reaction is regulated by redox-sensitive surface thiols, cysteine 55 and 46, which regulate the fraction of the five-coordinated heme, nitrite binding, and NO formation. Replacement of the distal histidine by leucine or glutamine leads to a stable five-coordinated geometry; these neuroglobin mutants reduce nitrite to NO ～2000 times faster than the wild type, whereas mutation of either Cys-55 or Cys-46 to alanine stabilizes the six-coordinate structure and slows the reaction. Using lentivirus expression systems, we show that the nitrite reductase activity of neuroglobin inhibits cellular respiration via NO binding to cytochrome c oxidase and confirm that the six-to-five-coordinate status of neuroglobin regulates intracellular hypoxic NO-signaling pathways. These studies suggest that neuroglobin may function as a physiological oxidative stress sensor and a post-translationally redox-regulated nitrite reductase that generates NO under six-to-five-coordinate heme pocket control. We hypothesize that the six-coordinate heme globin superfamily may subserve a function as primordial hypoxic and redox-regulated NO-signaling proteins.     

Motivations for entry into sex work and HIV risk among mobile female sex workers in India

This paper assesses the reasons for entry into sex work and its association with HIV risk behaviours among mobile female sex workers (FSWs) in India. Data were collected from a cross-sectional survey conducted in 22 districts across four high HIV prevalence states in India during 2007-2008. Analyses were limited to 5498 eligible mobile FSWs. The reasons given by FSWs for entering sex work and associations with socio-demographic characteristics were assessed. Reported reasons for entering sex work include poor or deprived economic conditions; negative social circumstances in life; own choice; force by an external person; and family tradition. The results from multivariate analyses indicate that those FSWs who entered sex work due to poor economic conditions or negative social circumstances in life or force demonstrated elevated levels of current inconsistent condom use as well as in the past in comparison with those FSWs who reported entering sex work by choice or family tradition. This finding indicates the need for a careful assessment of the pre-entry contexts among HIV prevention interventions since these factors may continue to hinder the effectiveness of efforts to reduce the spread of HIV/AIDS in India and elsewhere.     

Diet composition and quality in indian bison (Bos gaurus) based on fecal analysis

Diet composition and quality of the Indian Bison (Bos gaurus) was estimated by fecal analysis. The results, together with studies in other parts of India, indicate that gaurs are primarily intermediate or adaptable mixed feeders. Fecal composition varied seasonally, with high proportion of grasses, forbs, and woody plant leaves, particularly Cynodon dactylon, Cyperus rotundus in monsoon and post monsoon, and Strobilanthes callosus, Strobilanthes ixiocephalus, Grewia tiliaefolia and Syzygium cumini in winter and summer. Gaur selected herbs, shrubs, and grasses, and avoided eating woody plants for most of the year. Seasonal changes in the chemical composition of the feces were related to changes in phenology. The levels of crude protein, within certain limitations, and lignin in the feces were probably the most reliable indicators of diet quality. The ratio of crude protein:lignin was highest in monsoon and winter, corresponding early growing and fruiting seasons respectively. The usefulness of feces in estimating the composition and quality of the diet of an intermediate feeder is assessed.     

Lampe1: an ENU-germline mutation causing spontaneous hepatosteatosis identified through targeted exon-enrichment and next-generation sequencing

Using a small scale ENU mutagenesis approach we identified a recessive germline mutant, designated Lampe1 that exhibited growth retardation and spontaneous hepatosteatosis. Low resolution mapping based on 20 intercrossed Lampe1 mice revealed linkage to a ～14 Mb interval on the distal site of chromosome 11 containing a total of 285 genes. Exons and 50 bp flanking sequences within the critical region were enriched with sequence capture microarrays and subsequently analyzed by next-generation sequencing. Using this approach 98.1 percent of the targeted DNA was covered with a depth of 10 or more reads per nucleotide and 3 homozygote mutations were identified. Two mutations represented intronic nucleotide changes whereas one mutation affected a splice donor site in intron 11-12 of Palmitoyl Acetyl-coenzyme A oxygenase-1 (Acox1), causing skipping of exon 12. Phenotyping of Acox1(Lampe1) mutants revealed a progression from hepatosteatosis to steatohepatitis, and ultimately hepatocellular carcinoma. The current approach provides a highly efficient and affordable method to identify causative mutations induced by ENU mutagenesis and animal models relevant to human pathology.     

siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468)

Molecular Biology Reports - CD44, as a superficial cellular glycoprotein, is an essential factor in cell–cell and cell–matrix interaction. The CD44 expression level has been...     

All-Optical Plasmonic Switches Based on Asymmetric Directional Couplers Incorporating Bragg Gratings

Plasmonics - In this paper, a novel technique for realization of all-optical plasmonic switches is presented. The proposed structure is based on an asymmetric metal-insulator-metal plasmonic...