Recent Developments in the Chemistry and Biology of G-Quadruplexes with Reference to the DNA Groove Binders

DNA is the chemotherapeutic target for treating diseases of genetic origin. Besides well-known double-helical structures (A, B, Z, parallel stranded-DNA etc.), DNA is capable of forming several multi-stranded structures (triplex, tetraplex, i-motif etc.) which have unique biological significance. The G-rich 3'-ends of chromosomes, called telomeres, are synthesized by telomerase, a ribonucleoprotein, and over-expression of telomerase is associated with cancer. The activity of telomerase is suppressed if the G-rich region is folded into the four stranded structures, called G-quadruplexes (G4-DNAs) using small synthetic ligands. Thus design and synthesis of new G4-DNA ligands is an attractive strategy to combat cancer. G4-DNA forming sequences are also prevalent in other genomic regions of biological significance including promoter regions of several oncogenes. Effective gene regulation may be achieved by inducing a G4-DNA structure within the G-rich promoter sequences. To date, several G4-DNA stabilizing ligands are known. DNA groove binders interact with the duplex B-DNA through the grooves (major and minor groove) in a sequence-specific manner. Some of the groove binders are known to stabilize the G4-DNA. However, this is a relatively under explored field of research. In this review, we focus on the recent advances in the understanding of the G4-DNA structures, particularly made from the human telomeric DNA stretches. We summarize the results of various investigations of the interaction of various organic ligands with the G4-DNA while highlighting the importance of groove binder-G4-DNA interactions.

Averting biodiversity collapse in tropical forest protected areas

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon(1-3). With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses(4-9). As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve `health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.

Control of a Duct Flow Network for Wind Display in a Virtual Environment

Control of flow in duct networks has a myriad of applications ranging from heating, ventilation, and air-conditioning to blood flow networks. The system considered here provides vent velocity inputs to a novel 3-D wind display device called the TreadPort Active Wind Tunnel. An error-based robust decentralized sliding-mode control method with nominal feedforward terms is developed for individual ducts while considering cross coupling between ducts and model uncertainty as external disturbances in the output. This approach is important due to limited measurements, geometric complexities, and turbulent flow conditions. Methods for resolving challenges such as turbulence, electrical noise, valve actuator design, and sensor placement are presented. The efficacy of the controller and the importance of feedforward terms are demonstrated with simulations based upon an experimentally validated lumped parameter model and experiments on the physical system. Results show significant improvement over traditional control methods and validate prior assertions regarding the importance of decentralized control in practice.

Report on the IUTAM Symposium on Mobile Particulate Systems: Kinematics, Rheology, and Complex Phenomena, Bangalore, India, 2012

This report summarizes the presentations and discussions conducted during the symposium, which was held under the aegis of the International Union of Theoretical and Applied Mechanics during 23-27 January 2012 in Bangalore, India. (C) 2013 AIP Publishing LLC.

EFFECT OF OFF-STOICHIOMETRY AND TERNARY ADDITIONS ON PLANAR FAULT ENERGIES IN Ni3Al

First principles calculations were done to evaluate the lattice parameter, cohesive energy and stacking fault energies of ordered gamma' (Ll(2)) precipitates in superalloys as a function of composition. It was found that addition of Ti and Ta lead to an increase in lattice parameter and decrease in cohesive energy, while Ni antisites had the opposite effect. Ta and Ti addition to stoichiometric Ni3Al resulted in an initial increase in the energies of APB((111)), CSF(111), APB((001)) and SISF(111). However, at higher concentrations, the fault energies decreased. Addition of Ni antisites decreased the energy of all four faults monotonically. A model based on nearest neighbor bonding was used for Ni-3(Al, Ta), Ni-3(Al, Ti) and Ni-3(Al, Ni) pseudo-binary systems and extended to pseudo- ternary Ni-3(Al, Ta, Ni) and Ni-3(Al, Ti, Ni) systems. Recipes were developed for predicting lattice parameters, cohesive energies and fault energies in pseudo- ternary systems on the basis of coefficients derived from simpler pseudobinary systems. The model predictions were found to be in good agreement with first principles calculations for lattice parameters, cohesive energies, and energies of APB((111)) and CSF(111).

Phylogeography unplugged: comparative surveys in the genomic era

In March 2012, the authors met at the National Evolutionary Synthesis Center (NESCent) in Durham, North Carolina, USA, to discuss approaches and cooperative ventures in Indo-Pacific phylogeography. The group emerged with a series of findings: (1) Marine population structure is complex, but single locus mtDNA studies continue to provide powerful first assessment of phylogeographic patterns. (2) These patterns gain greater significance/power when resolved in a diversity of taxa. New analytical tools are emerging to address these analyses with multi-taxon approaches. (3) Genome-wide analyses are warranted if selection is indicated by surveys of standard markers. Such indicators can include discordance between genetic loci, or between genetic loci and morphology. Phylogeographic information provides a valuable context for studies of selection and adaptation. (4) Phylogeographic inferences are greatly enhanced by an understanding of the biology and ecology of study organisms. (5) Thorough, range-wide sampling of taxa is the foundation for robust phylogeographic inference. (6) Congruent geographic and taxonomic sampling by the Indo-Pacific community of scientists would facilitate better comparative analyses. The group concluded that at this stage of technology and software development, judicious rather than wholesale application of genomics appears to be the most robust course for marine phylogeographic studies. Therefore, our group intends to affirm the value of traditional (''unplugged'') approaches, such as those based on mtDNA sequencing and microsatellites, along with essential field studies, in an era with increasing emphasis on genomic approaches.

Advancing biodiversity research in developing countries: the need for changing paradigms

The world is in the midst of a biodiversity crisis, threatening essential goods and services on which humanity depends. While there is an urgent need globally for biodiversity research, growing obstacles are severely limiting biodiversity research throughout the developing world, particularly in Southeast Asia. Facilities, funding, and expertise are often limited throughout this region, reducing the capacity for local biodiversity research. Although western scientists generally have more expertise and capacity, international research has sometimes been exploitative ``parachute science,'' creating a culture of suspicion and mistrust. These issues, combined with misplaced fears of biopiracy, have resulted in severe roadblocks to biodiversity research in the very countries that need it the most. Here, we present an overview of challenges to biodiversity research and case studies that provide productive models for advancing biodiversity research in developing countries. Key to success is integration of research and education, a model that fosters sustained collaboration by focusing on the process of conducting biodiversity research as well as research results. This model simultaneously expands biodiversity research capacity while building trust across national borders. It is critical that developing countries enact policies that protect their biodiversity capital without shutting down international and local biodiversity research that is essential to achieve the long-term sustainability of biodiversity, promoting food security and economic development.

The April 2012 Indian Ocean earthquakes: Seismotectonic context and implications for their mechanisms

The 11 April 2012 earthquakes (M-w 8.6 and M-w 8.2) were sourced within the Northern Wharton Basin in the northeastern part of the Indo-Australian diffuse plate boundary. This unusually active oceanic intraplate region has generated many large earthquakes in the past, most of which are believed to have occurred by strike-slip motion, triggered by the NW-SE oriented compressional stresses acting across the Indian and Australian plates. In the aftermath of the 2004 megathrust earthquake along the nearby Sunda Trench, increased seismicity in the Northern Wharton Basin is attributed to the stress transfer from the Sumatra-Andaman plate boundary. Models proposed for the April 2012 earthquakes differ somewhat in details but partly attribute their complex rupture to the reactivation of pre-existing structures. These structures include previously mapped N-S trending fracture zones within the Northern Wharton Basin and E-W lineations across the Ninetyeast Ridge. In this paper, we review the regional tectonics and past seismicity on the Indo-Australian Plate in order to understand the seismotectonic setting of the April 2012 Indian Ocean earthquakes. (c) 2014 Elsevier B.V. All rights reserved.

Slow Slip Acceleration beneath Andaman Islands Triggered by the 11 April 2012 Indian Ocean Earthquakes

The M-w 8.6 and 8.2 strike-slip earthquakes that struck the northeast Indian Ocean on 11 April 2012 resulted in coseismic deformation both at near and distant sites. The slip distribution, deduced using seismic-wave analysis for the orthogonal faults that ruptured during these earthquakes, is sufficient to predict the coseismic displacements at the Global Positioning System (GPS) sites, such as NTUS, PALK, and CUSV, but fall short at four continuous sites in the Andaman Islands region. Slip modeling, for times prior to the events, suggests that the lower portion of the thrust fault beneath the Andaman Islands has been slipping at least at the rate of 40 cm/yr, in response to the 2004 Sumatra-Andaman coseismic stress change. Modeling of GPS displacements suggests that the en echelon and orthogonal fault ruptures of the 2012 intraplate oceanic earthquakes could have possibly accelerated the ongoing slow slip, along the lower portion of the thrust fault beneath the islands with a month-long slip of 4-10 cm. The misfit to the coseismic GPS displacements along the Andaman Islands could be improved with a better source model, assuming that no local process contributed to this anomaly.