DynaMut: predicting the impact of mutations on protein conformation, flexibility and stability.

Proteins are highly dynamic molecules, whose function is intrinsically linked to their molecular motions. Despite the pivotal role of protein dynamics, their computational simulation cost has led to most structure-based approaches for assessing the impact of mutations on protein structure and function relying upon static structures. Here we present DynaMut, a web server implementing two distinct, well established normal mode approaches, which can be used to analyze and visualize protein dynamics by sampling conformations and assess the impact of mutations on protein dynamics and stability resulting from vibrational entropy changes. DynaMut integrates our graph-based signatures along with normal mode dynamics to generate a consensus prediction of the impact of a mutation on protein stability. We demonstrate our approach outperforms alternative approaches to predict the effects of mutations on protein stability and flexibility (P-value < 0.001), achieving a correlation of up to 0.70 on blind tests. DynaMut also provides a comprehensive suite for protein motion and flexibility analysis and visualization via a freely available, user friendly web server at http://biosig.unimelb.edu.au/dynamut/

mCSM-PPI2: predicting the effects of mutations on protein-protein interactions.

Protein-protein Interactions are involved in most fundamental biological processes, with disease causing mutations enriched at their interfaces. Here we present mCSM-PPI2, a novel machine learning computational tool designed to more accurately predict the effects of missense mutations on protein-protein interaction binding affinity. mCSM-PPI2 uses graph-based structural signatures to model effects of variations on the inter-residue interaction network, evolutionary information, complex network metrics and energetic terms to generate an optimised predictor. We demonstrate that our method outperforms previous methods, ranking first among 26 others on CAPRI blind tests. mCSM-PPI2 is freely available as a user friendly webserver at http://biosig.unimelb.edu.au/mcsm_ppi2/.This work was supported by the Australian Government Research Training Program Scholarship [to C.H.M.R and Y.M.]; the Jack Brockhoff Foundation [JBF 4186, 2016 to D.B.A.]; a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) [MR/M026302/1 to D.B.A. and D.E.V.P.]; the National Health and Medical Research Council of Australia [APP1072476 to D.B.A.]; the Victorian Life Sciences Computation Initiative (VLSCI), an initiative of the Victorian Government, Australia, on its Facility hosted at the University of Melbourne [UOM0017]; the Instituto René Rachou (IRR/FIOCRUZ Minas), Brazil and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [to D.E.V.P.] and the Department of Biochemistry and Molecular Biology, University of Melbourne [to D.B.A.]. Supported in part by the Victorian Government's OIS Program

Empirical ways to identify novel Bedaquiline resistance mutations in AtpE.

Clinical resistance against Bedaquiline, the first new anti-tuberculosis compound with a novel mechanism of action in over 40 years, has already been detected in Mycobacterium tuberculosis. As a new drug, however, there is currently insufficient clinical data to facilitate reliable and timely identification of genomic determinants of resistance. Here we investigate the structural basis for M. tuberculosis associated bedaquiline resistance in the drug target, AtpE. Together with the 9 previously identified resistance-associated variants in AtpE, 54 non-resistance-associated mutations were identified through comparisons of bedaquiline susceptibility across 23 different mycobacterial species. Computational analysis of the structural and functional consequences of these variants revealed that resistance associated variants were mainly localized at the drug binding site, disrupting key interactions with bedaquiline leading to reduced binding affinity. This was used to train a supervised predictive algorithm, which accurately identified likely resistance mutations (93.3% accuracy). Application of this model to circulating variants present in the Asia-Pacific region suggests that current circulating variants are likely to be susceptible to bedaquiline. We have made this model freely available through a user-friendly web interface called SUSPECT-BDQ, StrUctural Susceptibility PrEdiCTion for bedaquiline (http://biosig.unimelb.edu.au/suspect_bdq/). This tool could be useful for the rapid characterization of novel clinical variants, to help guide the effective use of bedaquiline, and to minimize the spread of clinical resistance.M.K was funded by the Melbourne Research Scholarship. D.B.A was funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (MR/M026302/1), the Jack Brockhoff Foundation (JBF 4186, 2016), and a C. J. Martin Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1072476). The Vietnam genomic dataset was funded by a NHMRC Australia grant (APP1056689) to SJD and KEH. Supported in part by the Victorian Government's OIS Program

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Effectiveness of protected areas in conserving tropical forest birds.

Protected areas (PAs) are the cornerstones of global biodiversity conservation efforts, but to fulfil this role they must be effective at conserving the ecosystems and species that occur within their boundaries. Adequate monitoring datasets that allow comparing biodiversity between protected and unprotected sites are lacking in tropical regions. Here we use the largest citizen science biodiversity dataset - eBird - to quantify the extent to which protected areas in eight tropical forest biodiversity hotspots are effective at retaining bird diversity. We find generally positive effects of protection on the diversity of bird species that are forest-dependent, endemic to the hotspots, or threatened or Near Threatened, but not on overall bird species richness. Furthermore, we show that in most of the hotspots examined this benefit is driven by protected areas preventing both forest loss and degradation. Our results provide evidence that, on average, protected areas contribute measurably to conserving bird species in some of the world's most diverse and threatened terrestrial ecosystems

Utilização de Hortas Orgânicas Como Ferramenta Para Educação Ambiental

Resumo: Hortas orgânicas constituem um modo de produção de alimentos sustentável que respeita o meio ambiente e a saúde humana. Trata-se de uma importante ferramenta para se trabalhar educação ambiental com diferentes faixas etárias. A educação ambiental não se resume a um conceito, mas a um processo que envolve a formação de um cidadão justo, consciente com os recursos que utiliza e responsável por suas ações. O objetivo deste trabalho foi de ensinar o modelo orgânico de produção de hortaliças, assim como a importância deste sistema de produção. A metodologia empregada neste trabalho consistiu em visitas na horta orgânica da Unespar, campus de Paranavaí­, para conhecer as etapas para a construção de uma horta, aplicação de questionários e construção de pequenas hortas nas escolas de Paranavaí­ e região. Durante a visita e a construção das hortas discutiu-se a metodologia de produção de alimentos com a redução de lixo principalmente orgânico, o conceito de segurança alimentar, evidenciado pela qualidade do alimento produzido nas hortas orgânicas, que são livres de toxinas e a educação ambiental. O projeto proporcionou o suporte necessário tanto de materiais como técnico para que as hortas pudessem ser construí­das e mantidas. A execução deste trabalho foi importante para contribuir com a formação de cidadãos responsáveis com o meio ambiente onde estão inseridos. Disseminou a construção de novas hortas orgânicas nas escolas e foi um instrumento para educação ambiental. Os alunos cuidam do espaço da horta na escola e relatam que foi um estí­mulo para construção das hortas em suas casas. As hortas orgânicas produzem mais que alimentos, elas são um modelo para que novas hortas sejam construí­das