Comparative Evaluation of Zoledronic Acid, Alfacalcidol and Propranolol in Pharmacological Correction of Experimental Osteoporosis

Propranolol, a beta-adrenergic receptor blocker, is presently considered to be a potential therapeutic intervention under investigation for its role in prevention and treatment of osteoporosis. However, no studies have compared the osteoprotective properties of propranolol with well accepted therapeu-tic interventions for the treatment of osteoporosis. To address this question, this study was designed to evaluate the bone protective effects of zoledronic acid, alfacalcidol and propranolol in an animal model of postmenopausal osteoporosis. Five days after ovariectomy, 36 ovariectomized (OVX) rats were divided in- to 6 equal groups, randomized to treatments zoledronic acid (100 μg/kg, intravenous single dose); alfacal-cidol (0.5 μg/kg, oral gauge daily); propranolol (0.1mg/kg, subcutaneously 5 days per week) for 12 weeks. Untreated OVX and sham OVX were used as controls. At the end of the study, rats were killed under anesthesia. For bone porosity evaluation, whole fourth lumbar vertebrae (LV4) were removed. LV4 were also used to measure bone mechanical propeties. Left femurs were used for bone histology. Propranolol showed a significant decrease in bone porosity in comparison to OVX control. Moreover, propranolol sig- nificantly improved bone mechanical properties and bone quality when compared with OVX control. The osteoprotective effect of propranolol was comparable with zoledronic acid and alfacalcidol. Based on this comparative study, the results strongly suggest that propranolol might be new therapeutic intervention for the management of postmenopausal osteoporosis in humans.

A simple model for spatial disaggregation of evaporative fraction: Comparative study with thermal sharpened land surface temperature data over India

[1] Evaporative fraction (EF) is a measure of the amount of available energy at the earth surface that is partitioned into latent heat flux. The currently operational thermal sensors like the Moderate Resolution Imaging Spectroradiometer (MODIS) on satellite platforms provide data only at 1000 m, which constraints the spatial resolution of EF estimates. A simple model (disaggregation of evaporative fraction (DEFrac)) based on the observed relationship between EF and the normalized difference vegetation index is proposed to spatially disaggregate EF. The DEFrac model was tested with EF estimated from the triangle method using 113 clear sky data sets from the MODIS sensor aboard Terra and Aqua satellites. Validation was done using the data at four micrometeorological tower sites across varied agro-climatic zones possessing different land cover conditions in India using Bowen ratio energy balance method. The root-mean-square error (RMSE) of EF estimated at 1000 m resolution using the triangle method was 0.09 for all the four sites put together. The RMSE of DEFrac disaggregated EF was 0.09 for 250 m resolution. Two models of input disaggregation were also tried with thermal data sharpened using two thermal sharpening models DisTrad and TsHARP. The RMSE of disaggregated EF was 0.14 for both the input disaggregation models for 250 m resolution. Moreover, spatial analysis of disaggregation was performed using Landsat-7 (Enhanced Thematic Mapper) ETM+ data over four grids in India for contrasted seasons. It was observed that the DEFrac model performed better than the input disaggregation models under cropped conditions while they were marginally similar under non-cropped conditions.

Comparative Study of Protein Unfolding in Aqueous Urea and Dimethyl Sulfoxide Solutions: Surface Polarity, Solvent Specificity, and Sequence of Secondary Structure Melting

Elucidation of possible pathways between folded (native) and unfolded states of a protein is a challenging task, as the intermediates are often hard to detect. Here, we alter the solvent environment in a controlled manner by choosing two different cosolvents of water, urea, and dimethyl sulfoxide (DMSO) and study unfolding of four different proteins to understand the respective sequence of melting by computer simulation methods. We indeed find interesting differences in the sequence of melting of alpha helices and beta sheets in these two solvents. For example, in 8 M urea solution, beta-sheet parts of a protein are found to unfold preferentially, followed by the unfolding of alpha helices. In contrast, 8 M DMSO solution unfolds alpha helices first, followed by the separation of beta sheets for the majority of proteins. Sequence of unfolding events in four different alpha/beta proteins and also in chicken villin head piece (HP-36) both in urea and DMSO solutions demonstrate that the unfolding pathways are determined jointly by relative exposure of polar and nonpolar residues of a protein and the mode of molecular action of a solvent on that protein.

Evaluation. of Transverse Piezoelectric Coefficient of ZnO Thin Films Deposited on Different Flexible Substrates: A Comparative Study on the Vibration Sensing Performance

We report on the systematic comparative study of highly c-axis oriented and crystalline piezoelectric ZnO thin films deposited on four different flexible substrates for vibration sensing application. The flexible substrates employed for present experimental study were namely a metal alloy (Phynox), metal (aluminum), polyimide (Kapton), and polyester (Mylar). ZnO thin films were deposited by an RF reactive magnetron sputtering technique. ZnO thin films of similar thicknesses of 700 +/- 30 nm were deposited on four different flexible substrates to have proper comparative studies. The crystallinity, surface morphology, chemical composition, and roughness of ZnO thin films were evaluated by respective material characterization techniques. The transverse piezoelectric coefficient (d(31)) value for assessing the piezoelectric property of ZnO thin films on different flexible substrates was measured by a four-point bending method. ZnO thin films deposited on Phynox alloy substrate showed relatively better material characterization results and a higher piezoelectric d(31) coefficient value as compared to ZnO films on metal and polymer substrates. In order to experimentally verify the above observations, vibration sensing studies were performed. As expected, the ZnO thin film deposited on Phynox alloy substrate showed better vibration sensing performance. It has generated the highest peak to peak output voltage amplitude of 256 mV as compared to that of aluminum (224 mV), Kapton (144 mV), and Mylar (46 mV). Therefore, metal alloy flexible substrate proves to be a more suitable, advantageous, and versatile choice for integrating ZnO thin films as compared to metal and polymer flexible substrates for vibration sensing applications. The present experimental study is extremely important and helpful for the selection of a suitable flexible substrate for various applications in the field of sensor and actuator technology.

DEFINING alpha-HELIX GEOMETRY BY C-alpha ATOM TRACE vs (phi-psi) TORSION ANGLES: A COMPARATIVE ANALYSIS

A regular secondary structure is described by a well defined set of values for the backbone dihedral angles (phi,psi and omega) in a polypeptide chain. However in real protein structures small local variations give rise to distortions from the ideal structures, which can lead to considerable variation in higher order organization. Protein structure analysis and accurate assignment of various structural elements, especially their terminii, are important first step in protein structure prediction and design. Various algorithms are available for assigning secondary structure elements in proteins but some lacunae still exist. In this study, results of a recently developed in-house program ASSP have been compared with those from STRIDE, in identification of alpha-helical regions in both globular and membrane proteins. It is found that, while a combination of hydrogen bond patterns and backbone torsional angles (phi-psi) are generally used to define secondary structure elements, the geometry of the C-alpha atom trace by itself is sufficient to define the parameters of helical structures in proteins. It is also possible to differentiate the various helical structures by their C-alpha trace and identify the deviations occurring both at mid-positions as well as at the terminii of alpha-helices, which often lead to occurrence of 3(10) and pi-helical fragments in both globular and membrane proteins.

Genomic mapping of cAMP receptor protein (CRPMt) in Mycobacterium tuberculosis: relation to transcriptional start sites and the role of CRPMt as a transcription factor

Chromatin immunoprecipitation identified 191 binding sites of Mycobacterium tuberculosis cAMP receptor protein (CRPMt) at endogenous expression levels using a specific alpha-CRPMt antibody. Under these native conditions an equal distribution between intragenic and intergenic locations was observed. CRPMt binding overlapped a palindromic consensus sequence. Analysis by RNA sequencing revealed widespread changes in transcriptional profile in a mutant strain lacking CRPMt during exponential growth, and in response to nutrient starvation. Differential expression of genes with a CRPMt-binding site represented only a minor portion of this transcriptional reprogramming with similar to 19% of those representing transcriptional regulators potentially controlled by CRPMt. The subset of genes that are differentially expressed in the deletion mutant under both culture conditions conformed to a pattern resembling canonical CRP regulation in Escherichia coli, with binding close to the transcriptional start site associated with repression and upstream binding with activation. CRPMt can function as a classical transcription factor in M. tuberculosis, though this occurs at only a subset of CRPMt-binding sites.

Comparative study of different nonconserving time integrators for wave propagation in hyperelastic waveguides

This paper addresses the formulation and numerical efficiency of various numerical models of different nonconserving time integrators for studying wave propagation in nonlinear hyperelastic waveguides. The study includes different nonlinear finite element formulations based on standard Galerkin finite element model, time domain spectral finite element model, Taylor-Galerkin finite element model, generalized Galerkin finite element model and frequency domain spectral finite element model. A comparative study on the computational efficiency of these different models is made using a hyperelastic rod model, and the optimal computational scheme is identified. The identified scheme is then used to study the propagation of transverse and longitudinal waves in a Timoshenko beam with Murnaghan material nonlinearity.

A Comparative Assessment of Hand Preference in Captive Red Howler Monkeys, Alouatta seniculus and Yellow-Breasted Capuchin Monkeys, Sapajus xanthosternos

There are two major theories that attempt to explain hand preference in non-human primates-the `task complexity' theory and the `postural origins' theory. In the present study, we proposed a third hypothesis to explain the evolutionary origin of hand preference in non-human primates, stating that it could have evolved owing to structural and functional adaptations to feeding, which we refer to as the `niche structure' hypothesis. We attempted to explore this hypothesis by comparing hand preference across species that differ in the feeding ecology and niche structure: red howler monkeys, Alouatta seniculus and yellow-breasted capuchin monkeys, Sapajus xanthosternos. The red howler monkeys used the mouth to obtain food more frequently than the yellow-breasted capuchin monkeys. The red howler monkeys almost never reached for food presented on the opposite side of a wire mesh or inside a portable container, whereas the yellow-breasted capuchin monkeys reached for food presented in all four spatial arrangements (scattered, on the opposite side of a wire mesh, inside a suspended container, and inside a portable container). In contrast to the red howler monkeys that almost never acquired bipedal and clinging posture, the yellow-breasted capuchin monkeys acquired all five body postures (sitting, bipedal, tripedal, clinging, and hanging). Although there was no difference between the proportion of the red howler monkeys and the yellow-breasted capuchin monkeys that preferentially used one hand, the yellow-breasted capuchin monkeys exhibited an overall weaker hand preference than the red howler monkeys. Differences in hand preference diminished with the increasing complexity of the reaching-for-food tasks, i.e., the relatively more complex tasks were perceived as equally complex by both the red howler monkeys and the yellow-breasted capuchin monkeys. These findings suggest that species-specific differences in feeding ecology and niche structure can influence the perception of the complexity of the task and, consequently, hand preference.

Comparative Studies on the Bioremediation of Hexavalent and Trivalent Chromium using Citrobacter freundii: Part I-Effect of parameters controlling Biosorption

The potential of Citrobacter freundii, a Gram negative bacteria for the remediation of hexavalent chromium (Cr(VI)) and trivalent chromium (Cr(III))) from aqueous solutions was investigated. Bioremediation of Cr(VI) involved both biosorption and bioreduction processes, as compared to only biosorption process observed with respect to Cr(III) bioremediation. In the case of Cr(VI) bioremediation studies, about 59 % biosorption was achieved at an equilibrium time of 2 h, initial Cr(VI) concentration of 4 mg/L, pH 1 and a biomass loading of 5x10(11) cells/mL. The remainder, 41 %, was found to be in the form of Cr(111) ions owing to bioreduction of Cr(VI) by the bacteria resulting in the absence of Cr(VI) ions in the residue, there by meeting the USEPA specifications. Similar studies were carried out using Cr(III) solution for an equilibrium time of 2 h, Cr(III) concentration of 4 mg/L, pH 3 and a biomass loading of 6.3x10(11) cells/mL., wherein a maximum biosorption of about 30 % was achieved.

CINCINNATA in Antirrhinum majus directly modulates genes involved in cytokinin and auxin signaling

Mutations in the CINCINNATA (CIN) gene in Antirrhinum majus and its orthologs in Arabidopsis result in crinkly leaves as a result of excess growth towards the leaf margin. CIN homologs code for TCP (TEOSINTE-BRANCHED 1, CYCLOIDEA, PROLIFERATING CELL FACTOR 1 AND 2) transcription factors and are expressed in a broad zone in a growing leaf distal to the proliferation zone where they accelerate cell maturation. Although a few TCP targets are known, the functional basis of CIN-mediated leaf morphogenesis remains unclear. We compared the global transcription profiles of wild-type and the cin mutant of A. majus to identify the targets of CIN. We cloned and studied the direct targets using RNA in situ hybridization, DNA-protein interaction, chromatin immunoprecipitation and reporter gene analysis. Many of the genes involved in the auxin and cytokinin signaling pathways showed altered expression in the cin mutant. Further, we showed that CIN binds to genomic regions and directly promotes the transcription of a cytokinin receptor homolog HISTIDINE KINASE 4 (AmHK4) and an IAA3/SHY2 (INDOLE-3-ACETIC ACID INDUCIBLE 3/SHORT HYPOCOTYL 2) homolog in A. majus. Our results suggest that CIN limits excess cell proliferation and maintains the flatness of the leaf surface by directly modulating the hormone pathways involved in patterning cell proliferation and differentiation during leaf growth. 10.1111/(ISSN)1469-8137

Effect of alkyl substituents in BODIPYs: a comparative DFT computational investigation

Random changes in the alkyl substitution patterns of fluorescent dyes, e.g. BODIPYs, are often accompanied by significant changes in their photophysical properties. To understand such alterations in properties in closely related molecular systems, a comparative DFT (density functional theory) computational investigation was performed in order to comprehend the effects of alkyl substitution in controlling the structural and electronic nature of BODIPY dyes. In this context, a systematic strategy was utilized, considering all possible outcomes of constitutionally-isomeric molecules to understand the alkyl groups' effects on the BODIPY molecules. Four different computational methods {i.e. B3LYP/631G(d); B3LYP/6-311++ G(d,p); wb97xd/6-311++ G(d,p) and mpw1pw91/6-311++ G(d,p)} were employed to rationalize the agreement of the trends associated with the molecular properties. In line with experimental observations, it was found that alkyl substituents in BODIPY dyes situated at 3/5-positions effectively participate in stabilization as well as planarization of such molecules. Screening of all the possible isomeric molecular systems was used to understand the individual properties and overall effects of the typical alkyl substituents in controlling several basic properties of such BODIPY molecules.

Streptococcus pneumoniae Genome Database (SPGDB): A database for strain specific comparative analysis of Streptococcus pneumoniae genes and proteins

Streptococcus pneumoniae causes pneumonia, septicemia and meningitis. S. pneumoniae is responsible for significant mortality both in children and in the elderly. In recent years, the whole genome sequencing of various S. pneumoniae strains have increased manifold and there is an urgent need to provide organism specific annotations to the scientific community. This prompted us to develop the Streptococcus pneumoniae Genome Database (SPGDB) to integrate and analyze the completely sequenced and available S. pneumoniae genome sequences. Further, links to several tools are provided to compare the pool of gene and protein sequences, and proteins structure across different strains of S. pneumoniae. SPGDB aids in the analysis of phenotypic variations as well as to perform extensive genomics and evolutionary studies with reference to S. pneumoniae. (C) 2014 Elsevier Inc. All rights reserved.

Ligand 5,10,15,20-Tetra(N-methyl-4-pyridyl)porphine (TMPyP4) Prefers the Parallel Propeller-Type Human Telomeric G-Quadruplex DNA over Its Other Polymorphs

The binding of ligand 5,10,15,20-tetra(N-methyl-4-pyridyl)porphine (TMPyP4) with telomeric and genomic G-quadruplex DNA has been extensively studied. However, a comparative study of interactions of TMPyP4 with different conformations of human telomeric G-quadruplex DNA, namely, parallel propeller-type (PP), antiparallel basket-type (AB), and mixed hybrid-type (MH) G-quadruplex DNA, has not been done. We considered all the possible binding sites in each of the G-quadruplex DNA structures and docked TMPyP4 to each one of them. The resultant most potent sites for binding were analyzed from the mean binding free energy of the complexes. Molecular dynamics simulations were then carried out, and analysis of the binding free energy of the TMPyP4-G-quadruplex complex showed that the binding of TMPyP4 with parallel propeller-type G-quadruplex DNA is preferred over the other two G-quadruplex DNA conformations. The results obtained from the change in solvent excluded surface area (SESA) and solvent accessible surface area (SASA) also support the more pronounced binding of the ligand with the parallel propeller-type G-quadruplex DNA.