Evidence That Cytochrome \u3cem\u3eb\u3csub\u3e5\u3c/sub\u3e\u3c/em\u3e Acts as a Redox Donor in CYP17A1 Mediated Androgen Synthesis

Cytochrome P450 17A1 (CYP17A1) is an important drug target for castration resistant prostate cancer. It is a bi-functional enzyme, catalyzing production of glucocorticoid precursors by hydroxylation of pregnene-nucleus, and androgen biosynthesis by a second C--C lyase step, at the expense of glucocorticoid production. Cytochrome b5(cyt b5) is known to be a key regulator of the androgen synthesis reaction in vivo, by a mechanism that is not well understood. Two hypotheses have been proposed for the mechanism by which cyt b5 increases androgen biosynthesis. Cyt b5 could act as an allosteric effector, binding to CYP17A1 and either changing its selective substrate affinity or altering the conformation of the P450 to increase the catalytic rate or decrease unproductive uncoupling channels. Alternatively, cyt b5 could act as a redox donor for supply of the second electron in the P450 cycle, reducing the oxyferrous complex to form the reactive peroxo-intermediate. To understand the mechanism of lyase enhancement by cyt b5, we generated a redox-inactive form of cyt b5, in which the heme is replaced with a Manganese-protoporphyrin IX (Mn-b5), and investigated enhancement of androgen producing lyase reaction by CYP17A1. Given the critical significance of a stable membrane anchor for all of the proteins involved and the need for controlled stoichiometric ratios, we employed the Nanodisc system for this study. The redox inactive form was observed to have no effect on the lyase reaction, while reactions with the normal heme-iron containing cyt b5 were enhanced ∼5 fold as compared to reactions in the absence of cyt b5. We also performed resonance Raman measurements on ferric CYP17A1 bound to Mn-b5. Upon addition of Mn-b5 to Nanodisc reconstituted CYP17A1, we observed clear evidence for the formation of a b5-CYP17A1 complex, as noted by changes in the porphyrin modes and alteration in the proximal Fe--S vibrational frequency. Thus, although Mn-b5 binds to CYP17A1, it is unable to enhance the lyase reaction, strongly suggesting that cyt b5 has a redox effector role in enhancement of the CYP17A1 mediated lyase reaction necessary for androgen synthesis

Image Exploitation-A Forefront Area for UAV Application

Image exploitation, an innovative image utilisation program uses high revisit multisensor, multiresolution imagery from unmanned air vehicle or other reconnaissance platform for intelligent information gathering. This paper describes the imagc exploitation system developed at the Aeronautical Dcvclopment Establishment, Bangalore, for the remotely piloted vehicle (RPV) Nishonr and highlights two major areas (i) In-flight imagc exploitation, and (ii) post-flight imagc cxploitatlon. In-flight imagc study includes real-timeenhancement of images frames during RPV flight. target acquisition. calculation of geo-location of targets, distance and area computation, and image-to-map correspondence. Post-flight image exploitation study includes image restoration, classtfication of terrain, 3-D depth computation using stereo vision and shape from shading techniques. The paper shows results obtained in each of these areas from actual flight trials

An Interdental Radiolucent Lesion of Mandible: A Case Report and Differential Diagnosis

Aim: The present article discusses a case which was an accidental finding in uncommon location. Case Report: A 70-year-old apparently healthy woman presented with proximal caries on mesial surface of canine and exhibited mild sensitivity to percussion. An intraoral periapical radiograph demonstrated interdental bone loss along with a diffuse unilocular radiolucent lesion between the canine and premolar region. Pathologies such as Radicular cyst,  Lateral Periodontal Cyst, Collateral Keratocystic Odontogenic Tumor (KCOT), Squamous Odontogenic Tumor (SOT), Central Giant Cell Granuloma (CGCG), Extrafollicular Adenomatoid Odontogenic Tumor (AOT), other possible odontogenic and mesenchymal lesions with similar presentation in the anterior jaw were considered and discussed in our differential diagnosis. Conclusion: After histopathological examination of the incisional biopsy, the lesion was diagnosed of KCOT. The lesion was treated with carnoy’s solution prior to surgical enucleation. The patient had been under regular follow-up for 2 years and showed no recurrence

Spacelike Ricci Inheritance Vectors in a Model of String Cloud and String Fluid Stress Tensor

We study the consequences of the existence of spacelike Ricci inheritance vectors (SpRIVs) parallel to $x^a$ for model of string cloud and string fluid stress tensor in the context of general relativity. Necessary and sufficient conditions are derived for a spacetime with a model of string cloud and string fluid stress tensor to admit a SpRIV and a SpRIV which is also a spacelike conformal Killing vector (SpCKV). Also, some results are obtained.Comment: 11 page

Competing mechanisms and scaling laws for carbon nanotube scission by ultrasonication

Dispersion of carbon nanotubes (CNTs) into liquids typically requires ultrasonication to exfoliate individuals CNTs from bundles. Experiments show that CNT length drops with sonication time (or energy) as a power law t?m. Yet the breakage mechanism is not well understood, and the experimentally reported power law exponent m ranges from approximately 0.2 to 0.5. Here we simulate the motion of CNTs around cavitating bubbles by coupling Brownian dynamics with the Rayleigh-Plesset equation. We observe that, during bubble growth, CNTs align tangentially to the bubble surface. Surprisingly, we find two dynamical regimes during the collapse: shorter CNTs align radially, longer ones buckle.We compute the phase diagram for CNT collapse dynamics as a function of CNT length, stiffness, and initial distance from the bubble nuclei and determine the transition from aligning to buckling. We conclude that, depending on their length, CNTs can break due to either buckling or stretching. These two mechanisms yield different power laws for the length decay (0.25 and 0.5, respectively), reconciling the apparent discrepancy in the experimental data

GeneLink: a database to facilitate genetic studies of complex traits

BACKGROUND: In contrast to gene-mapping studies of simple Mendelian disorders, genetic analyses of complex traits are far more challenging, and high quality data management systems are often critical to the success of these projects. To minimize the difficulties inherent in complex trait studies, we have developed GeneLink, a Web-accessible, password-protected Sybase database. RESULTS: GeneLink is a powerful tool for complex trait mapping, enabling genotypic data to be easily merged with pedigree and extensive phenotypic data. Specifically designed to facilitate large-scale (multi-center) genetic linkage or association studies, GeneLink securely and efficiently handles large amounts of data and provides additional features to facilitate data analysis by existing software packages and quality control. These include the ability to download chromosome-specific data files containing marker data in map order in various formats appropriate for downstream analyses (e.g., GAS and LINKAGE). Furthermore, an unlimited number of phenotypes (either qualitative or quantitative) can be stored and analyzed. Finally, GeneLink generates several quality assurance reports, including genotyping success rates of specified DNA samples or success and heterozygosity rates for specified markers. CONCLUSIONS: GeneLink has already proven an invaluable tool for complex trait mapping studies and is discussed primarily in the context of our large, multi-center study of hereditary prostate cancer (HPC). GeneLink is freely available at

Ricci Collineations for type B warped space-times

We present the general structure of proper Ricci Collineations (RC) for type B warped space-times. Within this framework, we give a detailed description of the most general proper RC for spherically symmetric metrics. As examples, static spherically symmetric and Friedmann-Robertson-Walker space-times are considered.Comment: 18 pages, Latex, To appear in GR

An auxin-inducible, GAL4-compatible, gene expression system for Drosophila

The ability to control transgene expression, both spatially and temporally, is essential for studying model organisms. In Drosophila, spatial control is primarily provided by the GAL4/UAS system, whilst temporal control relies on a temperature-sensitive GAL80 (which inhibits GAL4) and drug-inducible systems. However, these are not ideal. Shifting temperature can impact on many physiological and behavioural traits, and the current drug-inducible systems are either leaky, toxic, incompatible with existing GAL4-driver lines, or do not generate effective levels of expression. Here, we describe the auxin-inducible gene expression system (AGES). AGES relies on the auxin-dependent degradation of a ubiquitously expressed GAL80, and therefore, is compatible with existing GAL4-driver lines. Water-soluble auxin is added to fly food at a low, non-lethal, concentration, which induces expression comparable to uninhibited GAL4 expression. The system works in both larvae and adults, providing a stringent, non-lethal, cost-effective, and convenient method for temporally controlling GAL4 activity in Drosophila

On global models for isolated rotating axisymmetric charged bodies; uniqueness of the exterior field

A relatively recent study by Mars and Senovilla provided us with a uniqueness result for the exterior vacuum gravitational field generated by an isolated distribution of matter in axial rotation in equilibrium in General Relativity. The generalisation to exterior electrovacuum gravitational fields, to include charged rotating objects, is presented here.Comment: LaTeX, 21 pages, uses iopart styl