Identification of Small-Molecule Inhibitors against Meso-2, 6-Diaminopimelate Dehydrogenase from Porphyromonas gingivalis

Species-specific antimicrobial therapy has the potential to combat the increasing threat of antibiotic resistance and alteration of the human microbiome. We therefore set out to demonstrate the beginning of a pathogen-selective drug discovery method using the periodontal pathogen Porphyromonas gingivalis as a model. Through our knowledge of metabolic networks and essential genes we identified a “druggable” essential target, meso-diaminopimelate dehydrogenase, which is found in a limited number of species. We adopted a high-throughput virtual screen method on the ZINC chemical library to select a group of potential small-molecule inhibitors. Meso-diaminopimelate dehydrogenase from P. gingivaliswas first expressed and purified in Escherichia coli then characterized for enzymatic inhibitor screening studies. Several inhibitors with similar structural scaffolds containing a sulfonamide core and aromatic substituents showed dose-dependent inhibition. These compounds were further assayed showing reasonable whole-cell activity and the inhibition mechanism was determined. We conclude that the establishment of this target and screening strategy provides a model for the future development of new antimicrobials

"Charged" Particle's Tunneling from Rotating Black Holes

The behavior of a scalar field theory near the event horizon in a rotating black hole background can be effectively described by a two dimensional field theory in a gauge field background. Based on this fact, we proposal that the quantum tunneling from rotating black hole can be treated as "charged" particle' s tunneling process in its effectively two dimensional metric. Using this viewpoint and considering the corresponding "gauge charge" conservation, we calculate the non-thermal tunneling rate of Kerr black hole and Myers-Perry black hole, and results are consistent with Parikh-Wilczek's original result for spherically symmetric black holes. Especially for Myers-Perry black hole which has multi-rotation parameters, our calculation fills in the gap existing in the literature applying Parikh-Wilczek's tunneling method to various types black holes. Our derivation further illuminates the essential role of effective gauge symmetry in Hawking radiation from rotating black holes.Comment: 15 pages, no figure; any comments are welcome

Spectral fluctuation characterization of random matrix ensembles through wavelets

A recently developed wavelet based approach is employed to characterize the scaling behavior of spectral fluctuations of random matrix ensembles, as well as complex atomic systems. Our study clearly reveals anti-persistent behavior and supports the Fourier power spectral analysis. It also finds evidence for multi-fractal nature in the atomic spectra. The multi-resolution and localization nature of the discrete wavelets ideally characterizes the fluctuations in these time series, some of which are not stationary.Comment: 7 pages, 2 eps figure

GM crops and gender issues

Correspondence in the December issue by Jonathan Gressel not only states that gender issues in rural settings have not been adequately addressed with respect to weed control biotech but also asserts that such technology can increase the quality of life of rural women in developing countries. Improved weed control is a labor-saving technology that can result in less employment in a labor surplus rural economy. Often in rural areas, wage income is the main source of income and an important determinant of the quality of life, particularly where employment opportunities are generally limited. Apart from soil preparation, planting and weeding, harvesting is also 'femanual' work that can generate more employment if yields are higher. Biotech can enhance the quality of life of women but only if the technology is associated with overall generation of rural employment

Network Analysis of Breast Cancer Progression and Reversal Using a Tree-Evolving Network Algorithm

The HMT3522 progression series of human breast cells have been used to discover how tissue architecture, microenvironment and signaling molecules affect breast cell growth and behaviors. However, much remains to be elucidated about malignant and phenotypic reversion behaviors of the HMT3522-T4-2 cells of this series. We employed a "pan-cell-state" strategy, and analyzed jointly microarray profiles obtained from different state-specific cell populations from this progression and reversion model of the breast cells using a tree-lineage multi-network inference algorithm, Treegl. We found that different breast cell states contain distinct gene networks. The network specific to non-malignant HMT3522-S1 cells is dominated by genes involved in normal processes, whereas the T4-2-specific network is enriched with cancer-related genes. The networks specific to various conditions of the reverted T4-2 cells are enriched with pathways suggestive of compensatory effects, consistent with clinical data showing patient resistance to anticancer drugs. We validated the findings using an external dataset, and showed that aberrant expression values of certain hubs in the identified networks are associated with poor clinical outcomes. Thus, analysis of various reversion conditions (including non-reverted) of HMT3522 cells using Treegl can be a good model system to study drug effects on breast cancer. © 2014 Parikh et al

Adaptation to Variable Environments, Resilience to Climate Change: Investigating Land, Water and Settlement in Indus Northwest India

This paper explores the nature and dynamics of adaptation and resilience in the face of a diverse and varied environmental and ecological context using the case study of South Asia’s Indus Civilization (ca. 3000–1300 BC). Most early complex societies developed in regions where the climatic parameters faced by ancient subsistence farmers were varied but rain falls primarily in one season. In contrast, the Indus Civilization developed in a specific environmental context that spanned a very distinct environmental threshold, where winter and summer rainfall systems overlap. There is now evidence to show that this region was directly subject to climate change during the period when the Indus Civilization was at its height (ca. 2500–1900 BC). The Indus Civilization, therefore, provides a unique opportunity to understand how an ancient society coped with diverse and varied ecologies and change in the fundamental environmental parameters. This paper integrates research carried out as part of the Land, Water and Settlement project in northwest India between 2007 and 2014. Although coming from only one of the regions occupied by Indus populations, these data necessitate the reconsideration of several prevailing views about the Indus Civilization as a whole and invigorate discussion about human-environment interactions and their relationship to processes of cultural transformation

Incompressible Fluids of the de Sitter Horizon and Beyond

There are (at least) two surfaces of particular interest in eternal de Sitter space. One is the timelike hypersurface constituting the lab wall of a static patch observer and the other is the future boundary of global de Sitter space. We study both linear and non-linear deformations of four-dimensional de Sitter space which obey the Einstein equation. Our deformations leave the induced conformal metric and trace of the extrinsic curvature unchanged for a fixed hypersurface. This hypersurface is either timelike within the static patch or spacelike in the future diamond. We require the deformations to be regular at the future horizon of the static patch observer. For linearized perturbations in the future diamond, this corresponds to imposing incoming flux solely from the future horizon of a single static patch observer. When the slices are arbitrarily close to the cosmological horizon, the finite deformations are characterized by solutions to the incompressible Navier-Stokes equation for both spacelike and timelike hypersurfaces. We then study, at the level of linearized gravity, the change in the discrete dispersion relation as we push the timelike hypersurface toward the worldline of the static patch. Finally, we study the spectrum of linearized solutions as the spacelike slices are pushed to future infinity and relate our calculations to analogous ones in the context of massless topological black holes in AdS$_4$.Comment: 27 pages, 8 figure