Typical and atypical domain combinations in human protein kinases: functions, disease causing mutations and conservation in other primates

Ser/Thr and Tyr protein kinases orchestrate many signalling pathways and hence loss in this balance leads to many disease phenotypes. Due to their high abundance, diversity and importance, efforts have been made in the past to classify kinases and annotate their functions at both gross and fine levels. These kinases are conventionally classified into subfamilies based on the sequences of catalytic domains. Usually the domain architecture of a full-length kinase is consistent with the subfamily classification made based on the sequence of kinase domain. Important contributions of modular domains to the overall function of the kinase are well known. Recently occurrence of two kinds of outlier kinases-''Hybrid'' and ``Rogue'' has been reported. These show considerable deviations in their domain architectures from the typical domain architecture known for the classical kinase subfamilies. This article provides an overview of the different subfamilies of human kinases and the role of non-kinase domains in functions and diseases. Importantly this article provides analysis of hybrid and rogue kinases encoded in the human genome and highlights their conservation in closely related primate species. These kinases are examples of elegant rewiring to bring about subtle functional differences compared to canonical variants.

Looking beyond parks: the conservation value of unprotected areas for hornbills in Arunachal Pradesh, Eastern Himalaya

The loss of tropical forests and associated biodiversity is a global concern. Conservation efforts in tropical countries such as India have mostly focused on state-administered protected areas despite the existence of vast tracts of forest outside these areas. We studied hornbills (Bucerotidae), an ecologically important vertebrate group and a flagship for tropical forest conservation, to assess the importance of forests outside protected areas in Arunachal Pradesh, north-east India. We conducted a state-wide survey to record encounters with hornbills in seven protected areas, six state-managed reserved forests and six community-managed unclassed forests. We estimated the density of hornbills in one protected area, four reserved forests and two unclassed forests in eastern Arunachal Pradesh. The state-wide survey showed that the mean rate of encounter of rufous-necked hornbills Aceros nipalensis was four times higher in protected areas than in reserved forests and 22 times higher in protected areas than in unclassed forests. The mean rate of encounter of wreathed hornbills Rhyticeros undulatus was twice as high in protected areas as in reserved forests and eight times higher in protected areas than in unclassed forests. The densities of rufous-necked hornbill were higher inside protected areas, whereas the densities of great hornbill Buceros bicornis and wreathed hornbill were similar inside and outside protected areas. Key informant surveys revealed possible extirpation of some hornbill species at sites in two protected areas and three unclassed forests. These results highlight a paradoxical situation where individual populations of hornbills are being lost even in some legally protected habitat, whereas they continue to persist over most of the landscape. Better protection within protected areas and creative community-based conservation efforts elsewhere are necessary to maintain hornbill populations in this biodiversity-rich region.

Hemagglutinin sequence conservation guided stem immunogen design from influenza A H3 subtype

Seasonal epidemics caused by influenza A (H1 and H3 subtypes) and B viruses are a major global health threat. The traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. This antigenic variability mediates viral escape from the host immune responses, necessitating annual vaccine updates. Influenza vaccines elicit a protective antibody response, primarily targeting the viral surface glycoprotein hemagglutinin (HA). However, the predominant humoral response is against the hypervariable head domain of HA, thereby restricting the breadth of protection. In contrast, the conserved, subdominant stem domain of HA is a potential ``universal'' vaccine candidate. We designed an HA stem-fragment immunogen from the 1968 pandemic H3N2 strain (A/Hong Kong/1/68) guided by a comprehensive H3 HA sequence conservation analysis. The biophysical properties of the designed immunogen were further improved by C-terminal fusion of a trimerization motif, ``isoleucine-zipper'', or ``foldon''. These immunogens elicited cross-reactive, antiviral antibodies and conferred partial protection against a lethal, homologous HK68 virus challenge in vivo. Furthermore, bacterial expression of these immunogens is economical and facilitates rapid scale-up.

Volume conservation issues in incompressible smoothed particle hydrodynamics

A divergence-free velocity field is usually sought in numerical simulations of incompressible fluids. We show that the particle methods that compute a divergence-free velocity field to achieve incompressibility suffer from a volume conservation issue when a finite time-step position update scheme is used. Further, we propose a deformation gradient based approach to arrive at a velocity field that reduces the volume conservation issues in free surface flows and maintains density uniformity in internal flows while retaining the simplicity of first order time updates. (C) 2015 Elsevier Inc. All rights reserved.

Distribution, relative abundance, and conservation status of Asian elephants in Karnataka, southern India

Karnataka state in southern India supports a globally significant and the country's largest population of the Asian elephant Elephas maximus. A reliable map of Asian elephant distribution and measures of spatial variation in their abundance, both vital needs for conservation and management action, are unavailable not only in Karnataka, but across its global range. Here, we use various data gathered between 2000 and 2015 to map the distribution of elephants in Karnataka at the scale of the smallest forest management unit, the `beat', while also presenting data on elephant dung density for a subset of `elephant beats.' Elephants occurred in 972 out of 2855 forest beats of Karnataka. Sixty percent of these 972 beats and 55% of the forest habitat lay outside notified protected areas (PM), and included lands designated for agricultural production and human dwelling. While median elephant dung density inside protected areas was nearly thrice as much as outside, elephants routinely occurred in or used habitats outside PM where human density, land fraction under cultivation, and the interface between human-dominated areas and forests were greater. Based on our data, it is clear that India's framework for elephant conservation which legally protects the species wherever it occurs, but protects only some of its habitats while being appropriate in furthering their conservation within PM, seriously falters in situations where elephants reside in and/or seasonally use areas outside PAs. Attempts to further elephant conservation in production and dwelling areas have extracted high costs in human, elephant, material and monetary terms in Karnataka. In such settings, conservation planning exercises are necessary to determine where the needs of elephants or humans must take priority over the other, and to achieve that in a manner that is based not only on reliable scientific data but also on a process of public reasoning. (C) 2015 Elsevier Ltd. All rights reserved.

Perceptions of priority issues in the conservation of biodiversity and ecosystems in India

We report on the results of a country-wide survey of people's perceptions of issues relating to the conservation of biodiversity and ecosystems in India. Our survey, mainly conducted online, yielded 572 respondents, mostly among educated, urban and sub-urban citizens interested in ecological and environmental issues. 3160 ``raw'' questions generated by the survey were iteratively processed by a group of ecologists, environmental and conservation scientists to produce the primary result of this study: a summarized list of 152 priority questions for the conservation of India's biodiversity and ecosystems, which range across 17 broad thematic classes. Of these, three thematic classes-''Policy and Governance'', ``Biodiversity and Endangered Species'' and ``Protection and Conservation''-accounted for the largest number of questions. A comparative analysis of the results of this study with those from similar studies in other regions brought out interesting regional differences in the thematic classes of questions that were emphasized and suggest that local context plays a large role in determining emergent themes. We believe that the ready list of priority issues generated by this study can be a useful guiding framework for conservation practitioners, researchers, citizens, policy makers and funders to focus their resources and efforts in India's conservation research, action and funding landscape. (C) 2015 Elsevier Ltd. All rights reserved.

Weak conservation of structural features in the interfaces of homologous transient protein-protein complexes

Residue types at the interface of protein-protein complexes (PPCs) are known to be reasonably well conserved. However, we show, using a dataset of known 3-D structures of homologous transient PPCs, that the 3-D location of interfacial residues and their interaction patterns are only moderately and poorly conserved, respectively. Another surprising observation is that a residue at the interface that is conserved is not necessarily in the interface in the homolog. Such differences in homologous complexes are manifested by substitution of the residues that are spatially proximal to the conserved residue and structural differences at the interfaces as well as differences in spatial orientations of the interacting proteins. Conservation of interface location and the interaction pattern at the core of the interfaces is higher than at the periphery of the interface patch. Extents of variability of various structural features reported here for homologous transient PPCs are higher than the variation in homologous permanent homomers. Our findings suggest that straightforward extrapolation of interfacial nature and inter-residue interaction patterns from template to target could lead to serious errors in the modeled complex structure. Understanding the evolution of interfaces provides insights to improve comparative modeling of PPC structures.

The X Chromosome of Hemipteran Insects: Conservation, Dosage Compensation and Sex-Biased Expression

Insects of the order Hemiptera (true bugs) use a wide range of mechanisms of sex determination, including genetic sex determination, paternal genome elimination, and haplodiploidy. Genetic sex determination, the prevalent mode, is generally controlled by a pair of XY sex chromosomes or by an XX/XO system, but different configurations that include additional sex chromosomes are also present. Although this diversity of sex determining systems has been extensively studied at the cytogenetic level, only the X chromosome of the model pea aphid Acyrthosiphon pisum has been analyzed at the genomic level, and little is known about X chromosome biology in the rest of the order. In this study, we take advantage of published DNA- and RNA-seq data from three additional Hemiptera species to perform a comparative analysis of the gene content and expression of the X chromosome throughout this clade. We find that, despite showing evidence of dosage compensation, the X chromosomes of these species show female-biased expression, and a deficit of male-biased genes, in direct contrast to the pea aphid X. We further detect an excess of shared gene content between these very distant species, suggesting that despite the diversity of sex determining systems, the same chromosomal element is used as the X throughout a large portion of the order.

High-Resolution Finite Compact Difference Schemes for Hyperbolic Conservation Laws

A finite compact (FC) difference scheme requiring only bi-diagonal matrix inversion is proposed by using the known high-resolution flux. Introducing TVD or ENO limiters in the numerical flux, several high-resolution FC-schemes of hyperbolic conservation law are developed, including the FC-TVD, third-order FC-ENO and fifth-order FC-ENO schemes. Boundary conditions formulated need only one unknown variable for third-order FC-ENO scheme and two unknown variables for fifth-order FC-ENO scheme. Numerical test results of the proposed FC-scheme were compared with traditional TVD, ENO and WENO schemes to demonstrate its high-order accuracy and high-resolution.

The impact of architectural uncertainty on product introduction in dispersed environments

This research addresses product introduction dispersed across locations and companies. Mechanisms appropriate to integrate activities in collocated teams may not serve dispersed teams well. A semiconductor design licensor was studied in depth to explore how dispersed product introduction varies with uncertainty. We found that autonomous teams focused on sub-products (micro-products) were used rather than cross-functional teams in departments with high architectural uncertainty. Both types of teams were effectively dispersed across locations and companies. This suggests that small high-technology companies may find it easier to expand into new geographies and product lines than was previously believed.

Charting multidisciplinary research and action priorities towards the conservation and sustainable management of sea turtles in the Pacific Ocean: a focus on Malaysia

The four sea turtle species found in Malaysia are the leatherback, olive ridley, green and hawksbill. The threats to these species are acute. Populations of leatherback, olive ridley and hawksbill turtles are on the brink of collapse – threatening a biodiversity crisis in Malaysia and the region. This proceedings contains 8 technical papers presented at a workshop convened in Kijal, Terengganu to chart new directions in the conservation of Malaysia's critically endangered sea turtles and to reverse population decline. They represent a wide range of issues from aspects of biology to a review of 40 years of sea turtle conservation. A paper on the socioeconomic linkages and impacts of fisheries was also included as the workshop adopted a multidisciplinary approach to address the issues. Two case studies, including successful restoration examples from international experiences and restoration efforts in Sabah, pave the way for enhancing turtle conservation in the country.

Strategic planning for long-term financing of Pacific leatherback conservation and recovery:Proceedings of the Bellagio Sea Turtle Conservation Initiative, Terengganu, Malaysia; July 2007

On 17-20 July 2007, 45 experts on sea turtles, fisheries, conservation and finance from 10 countries convened at the Bellagio Sea Turtle Conservation Initiative workshop in Terengganu to focus on methods to save the imperiled Pacific leatherback from extinction. The group developed a strategic plan to guide the prioritization and long term financing of Pacific leatherback turtle conservation and recovery objectives. Participants identified critical conservation actions and agreed that a business plan is urgently needed to reverse the trajectory towards extinction of the Pacific leatherback. The conservation actions prioritized by the participants encompassed protecting nesting beaches including eggs and nesting females; reducing direct and indirect turtle take in coastal fisheries; and strengthening regional and sub-regional cooperation. The group committed to work together on fundraising and implementation of these urgent conservation actions. This report presents outputs and the plan that was produced from the workshop.