The alpha helix dipole: screened out?

Aligned alpha helix peptide dipoles sum to a "macroscopic" dipole parallel to the helix axis that has been implicated in protein folding and function. However, in aqueous solution the dipole is counteracted by an electrostatic reaction field generated by the solvent, and the strength of the helix dipole may reduce drastically from its value in vacuum. Here, using atomic-detail helix models and Poisson-Boltzmann continuum electrostatics calculations, the net effective dipole moment, mu(eff), is calculated. Some initially surprising results are found. Whereas in vacuum mu(eff) increases with helix length, the opposite is found to be the case for transmembrane helices. In soluble proteins, mu(eff) is found to vary strongly with the orientation and position of the helix relative to the aqueous medium. A set of rules is established to estimate of the strength of mu(eff) from graphical inspection of protein structures.     

Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene

Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory tract infection for which no vaccine or antiviral treatment is available. The RSV NS1 protein seems to antagonize the host interferon (IFN) response; however, its mechanism is unknown. Here, we used a plasmid-borne small interfering RNA targeting the NS1 gene (siNS1) to examine the role of NS1 in modulating RSV infection. RSV replication was reduced in A549 cells, but not IFN-deficient Vero cells, transfected with siNS1. siNS1 induced upregulated expression of IFN-beta and IFN-inducible genes in A549 cells. siNS1-transfected human dendritic cells, upon RSV infection, produced elevated type-1 IFN and induced differentiation of naive CD4+ T cells to T helper type 1 (TH1) cells. Mice treated intranasally with siNS1 nanoparticles before or after infection with RSV showed substantially decreased virus titers in the lung and decreased inflammation and airway reactivity compared to controls. Thus, siNS1 nanoparticles may provide an effective inhibition of RSV infection in humans.     

Evolution of mutualism through spatial effects

Mutualism among species is ubiquitous in natural ecosystems but its evolution is not well understood. We provided a simple lattice model to clarify the importance of spatial structure for the evolution of mutualism. We assumed reproductive rates of two species are modified through interaction between species and examine conditions where mutualists of both species, that give some benefit to the other species with their own cost, invade non-mutualists populations. When dispersal of offspring is unlimited, we verified the evolution of mutualism is impossible under any condition. On the other hand, when the dispersal is limited to neighboring lattice sites, mutualists can invade if the ratio of cost to benefit is low and the intrinsic reproductive rate is low in case where the parameter values are symmetric between species. Under the same conditions, non-mutualists cannot invade mutualist populations, that is, the latter are evolutionarily stable. In case of asymmetric parameters, mutualists tend to invade if the average value of costs to two species is low or that of benefits is high, and if the intrinsic reproductive rate is low for one of the two species. A mechanistic explanation of why mutualists increase when the dispersal is limited is given by showing that mutualist pairs of the two species at the same lattice site rapidly increase at the initial phase of the invasion.     

On the relationships among diversity,productivity and climate from an Indian tropical ecosystem: a preliminary investigation

The relationships among diversity, productivity and climate are complex, especially in tropical ecosystems; and are less studied. We studied here the bi- and tri-partite relationships between and among the plant diversity, productivity and climate variables (i.e., temperature, precipitation and moisture) in a tropical ecosystem in India by analyzing three forest types for the year 2010. Comparison of productivity (Carnegie–Ames–Stanford Approach model derived-net primary productivity, NPP) and climate condition with respect to 2001 showed significant increase in NPP and temperature and overall decrease in precipitation and moisture condition in last decade. The NPP for sal forest ranged from 579.4 to 1,142 for the year 2001 and 557.2 to 1231.6 g Cm⁻² year⁻¹ for the year 2010. The mean monthly temperature varied from 18 to 21.8°C and 26 to 27°C; and the annual precipitation varied from 15 to 45 and 32 to 76 cm/year for the year 2001 and 2010 respectively. Strong correlation was observed between monthly mean temperature and productivity during 2001, while a decrease was observed during the year 2010. The ecosystem has shown a trend of rapid drying in last decade, triggering more detail studies for understanding of the eco-climatology. In general, sal forest, a natural forest sowed higher diversity and productivity followed by mixed deciduous (MD) forest and teak plantation. Though, areas with higher NPP are well correlated with higher temperature, precipitation and moisture; they seem to be related to species density rather than diversity. However, there is a need to have year-on-year assessments in order to ascertain if this difference represents a real phenomenon rather than an artefact of sampling. The pilot study helps in understanding the complex relationships and is very useful in the fast changing climate.     

Comparison of two ferns (Adiantum capillus-veneris Linn. and Microsorium punctatum (Linn.) Copel) for their Cr accumulation potential and antioxidant responses

Study was undertaken to compare Cr accumulation in two ferns (Adiantum capillus-veneris Linn. and Microsorium punctatum (Linn.) Copel) and the role of antioxidants were also investigated towards metal tolerance in order to assess the use of ferns in phytomediation/ phytostabilization. Different concentrations (0, 50, 100, 150 microg g(-1) dw) of Cr were added to fern planted in pot containing 1 kg soil. In both the ferns, Cr accumulation increased with increase in metal concentration and maximum accumulation of 800.5 microg g(-1) (fronds) and 1457.4 microg g(-1) (roots) in M. punctatum and 660.8 microg g(-1) (fronds) and 1259.6 microg g(-1) (roots) in A. capillus-veneris was recorded. The increase in the levels of malondialdehyde, antioxidants and antioxidant enzymes (superoxide dismutase, glutathione peroxidase) in A. capillus-veneris was less pronounced than M. punctatum under Cr exposure as compared to their respective controls. In view of less decrease in chlorophyll content and antioxidants along with higher accumulation of Cr in the fronds M. punctatum, is indicative of its higher tolerance towards Cr. However, bioaccumulation factor (concentration of Cr in fronds/concentration of Cr in the soil) of both the ferns was recorded > 1 which qualifies the plants as potential Cr hyperaccumulator and suitable for phytoremediaton.     

Fine needle aspiration in aspergilloma of frontal sinus: a case report

BACKGROUND: The increased incidence of fungal diseases in humans is most likely due to indiscriminate use of broad-spectrum antibiotics and increased numbers of immunocompromised patients. Although Aspergillus species are ubiquitous and normally nonpathogenic, they can be opportunistic pathogens in immunocompromised individuals. CASE: A 22-year-old immunocompetent man presented with a gradually increasing subcutaneous swelling near the root of his nose for previous 6 months. The mass was soft to firm, solid, nontender and immobile. There was no superficial skin ulceration and no local signs of inflammation. Proptosis of the left eye was present without any visual impairment. An osteolytic lesion that was contiguous with the subcutaneous mass, with the opacities of both the fontal sinuses was observed radiographically. Fine needle aspiration cytology (FNAC) demonstrated presence of branching hyphae in the cytoplasm of multinucleated giant cells along with mixed inflammatory cells. The species was identified by culture in Sabouraud's agar with chloramphenicol and wet mount with lactophenol cotton blue stain. CONCLUSION: Aspergillosis can remain dormant over a long period. Although uncommon, it can occur in immunocompetent patients. FNA is a very useful tool in establishing the diagnosis     

Association of <Emphasis Type="Italic">p</Emphasis>53 codon 72 polymorphism and survival of North Indian lung cancer patients treated with platinum-based chemotherapy

p53 helps in maintaining genomic stability by undergoing cellular arrest, DNA repair or cellular apoptosis during DNA damage. So, as to find the association of p53Arg ⁷² Pro towards lung carcinogenesis and overall survival of North Indian lung cancer patients, single nucleotide polymorphic variant (rs1042522) was analyzed. 840 subjects including 420 cases and 420 controls were recruited and genotyped using PCR-RFLP technique for p53Arg ⁷² Pro polymorphic site. Association was analyzed using adjusted odds ratio along with its confidence intervals (95?% CI) and p value predicted from logistic regression whereas overall survival for lung cancer patients was obtained using Kaplan–Meir and Cox regression model for different parameters to obtain hazard ratio and survival time with statistical significance (log-rank p value). None of the variant genotypes for p53Arg ⁷² Pro showed any association towards lung cancer risk or any specific histological subtype. Lung cancer subjects with Pro/Pro genotype had better median survival time as compared to Arg/Pro genotype (10 months; HR?=?0.65; 95?% CI?=?0.45–0.95; p?=?0.03). Furthermore, female lung cancer patients with Arg/Pro (HR?=?0.08; 95?% CI?=?0.02–0.34; p?=?0.0005) and Pro/Pro (HR?=?0.21; 95?% CI?=?0.06–0.67; p?=?0.008) genotypes showed a better overall survival and hence a better prognosis as compared to males. Our data also reveals that lung cancer patients with ECOG scores between 0 and 1 and carrying the Pro/Pro had better chances of survival. p53 codon 72 polymorphism could play a role as a prognostic marker in lung cancer patients.     

Pareto-based multi-objective optimization for classification in data mining

This paper explores the possibility of classification based on Pareto multi-objective optimization. The efforts on solving optimization problems using the Pareto-based MOO methodology have gained increasing impetus on comparison of selected constraints. Moreover we have different types of classification problem based on optimization model like single objective optimization, MOO, Pareto optimization and convex optimization. All above techniques fail to generate distinguished class/subclass from existing class based on sensitive data. However, in this regard Pareto-based MOO approach is more powerful and effective in addressing various data mining tasks such as clustering, feature selection, classification, and knowledge extraction. The primary contribution of this paper is to solve such noble classification problem. Our work provides an overview of the existing research on MOO and contribution of Pareto based MOO focusing on classification. Particularly, the entire work deals with association of sub-features for noble classification. Moreover potentially interesting sub-features in MOO for classification are used to strengthen the concept of Pareto based MOO. Experiment has been carried out to validate the theory with different real world data sets which are more sensitive in nature. Finally, experimental results provide effectiveness of the proposed method using sensitive data.     

Tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives as microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors: SAR and in vivo efficacy in hyperalgesia pain model

A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE₂ release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity. Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic stability in liver microsomes, high plasma protein binding (PPB) and no significant inhibition observed in clinically relevant CYP isoforms. Besides, selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic profile and oral bioavailability (%F = 33 and 85). Additionally, the representative mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS-induced thermal hyperalgesia guinea pig pain model.     

Energy determines broad pattern of plant distribution in Western Himalaya

Several factors describe the broad pattern of diversity in plant species distribution. We explore these determinants of species richness in Western Himalayas using high‐resolution species data available for the area to energy, water, physiography and anthropogenic disturbance. The floral data involves 1279 species from 1178 spatial locations and 738 sample plots of a national database. We evaluated their correlation with 8‐environmental variables, selected on the basis of correlation coefficients and principal component loadings, using both linear (structural equation model) and nonlinear (generalised additive model) techniques. There were 645 genera and 176 families including 815 herbs, 213 shrubs, 190 trees, and 61 lianas. The nonlinear model explained the maximum deviance of 67.4% and showed the dominant contribution of climate on species richness with a 59% share. Energy variables (potential evapotranspiration and temperature seasonality) explained the deviance better than did water variables (aridity index and precipitation of the driest quarter). Temperature seasonality had the maximum impact on the species richness. The structural equation model confirmed the results of the nonlinear model but less efficiently. The mutual influences of the climatic variables were found to affect the predictions of the model significantly. To our knowledge, the 67.4% deviance found in the species richness pattern is one of the highest values reported in mountain studies. Broadly, climate described by water–energy dynamics provides the best explanation for the species richness pattern. Both modeling approaches supported the same conclusion that energy is the best predictor of species richness. The dry and cold conditions of the region account for the dominant contribution of energy on species richness.