Accurate Protein Structure Annotation through Competitive Diffusion of Enzymatic Functions over a Network of Local Evolutionary Similarities

High-throughput Structural Genomics yields many new protein structures without known molecular function. This study aims to uncover these missing annotations by globally comparing select functional residues across the structural proteome. First, Evolutionary Trace Annotation, or ETA, identifies which proteins have local evolutionary and structural features in common; next, these proteins are linked together into a proteomic network of ETA similarities; then, starting from proteins with known functions, competing functional labels diffuse link-by-link over the entire network. Every node is thus assigned a likelihood z-score for every function, and the most significant one at each node wins and defines its annotation. In high-throughput controls, this competitive diffusion process recovered enzyme activity annotations with 99% and 97% accuracy at half-coverage for the third and fourth Enzyme Commission (EC) levels, respectively. This corresponds to false positive rates 4-fold lower than nearest-neighbor and 5-fold lower than sequence-based annotations. In practice, experimental validation of the predicted carboxylesterase activity in a protein from Staphylococcus aureus illustrated the effectiveness of this approach in the context of an increasingly drug-resistant microbe. This study further links molecular function to a small number of evolutionarily important residues recognizable by Evolutionary Tracing and it points to the specificity and sensitivity of functional annotation by competitive global network diffusion. A web server is at http://mammoth.bcm.tmc.edu/networks

Interstitial lung disease in children - genetic background and associated phenotypes

Interstitial lung disease in children represents a group of rare chronic respiratory disorders. There is growing evidence that mutations in the surfactant protein C gene play a role in the pathogenesis of certain forms of pediatric interstitial lung disease. Recently, mutations in the ABCA3 transporter were found as an underlying cause of fatal respiratory failure in neonates without surfactant protein B deficiency. Especially in familiar cases or in children of consanguineous parents, genetic diagnosis provides an useful tool to identify the underlying etiology of interstitial lung disease. The aim of this review is to summarize and to describe in detail the clinical features of hereditary interstitial lung disease in children. The knowledge of gene variants and associated phenotypes is crucial to identify relevant patients in clinical practice

The self-organizing fractal theory as a universal discovery method: the phenomenon of life

A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy

The topographic evolution of the Tibetan Region as revealed by palaeontology

The Tibetan Plateau was built through a succession of Gondwanan terranes colliding with Asia during the Mesozoic. These accretions produced a complex Paleogene topography of several predominantly east–west trending mountain ranges separated by deep valleys. Despite this piecemeal assembly and resultant complex relief, Tibet has traditionally been thought of as a coherent entity rising as one unit. This has led to the widely used phrase ‘the uplift of the Tibetan Plateau’, which is a false concept borne of simplistic modelling and confounds understanding the complex interactions between topography climate and biodiversity. Here, using the rich palaeontological record of the Tibetan region, we review what is known about the past topography of the Tibetan region using a combination of quantitative isotope and fossil palaeoaltimetric proxies, and present a new synthesis of the orography of Tibet throughout the Paleogene. We show why ‘the uplift of the Tibetan Plateau’ never occurred, and quantify a new pattern of topographic and landscape evolution that contributed to the development of today’s extraordinary Asian biodiversity

The gender gap in European neurosurgical conference presentations

OBJECTIVEWithin neurosurgery, there are fewer women than men at all levels. The authors aimed to assess whether opportunities and representation within neurosurgery are proportional to the existing gender gap.METHODSThe authors analyzed the program of the 2019 joint European Association of Neurosurgical Societies (EANS)/Society of British Neurological Surgeons (SBNS) conference to assess the proportions of presentations given through abstract submission and invitation by men and women. They compared proportions to the previous joint conference in 2007 and to the gender proportions of board-certified European neurosurgeons.RESULTSWomen delivered 75/577 (13%) presentations at the 2019 EANS/SBNS conference: 54/283 (19%) abstract submissions and 21/294 (7%) invited presentations. Fifteen of 152 (10%) session chairs were women. This increased significantly from 4/121 (3%) presentations delivered by women in 2007. When only presentations given by neurosurgeons (residents or consultants) were analyzed, the proportion of female speakers increased from 1/111 (1%) in 2007 to 60/545 (11%) in 2019. Pediatrics was the subspecialty with the highest proportion of invited female speakers. Across subspecialties, there were no differences in gender proportions for presentations from abstract submissions. Across the top 5 participating European countries, the proportion of female invited speakers (8%) and chairs (8%) was half the proportion of female board-certified neurosurgeons (16%).CONCLUSIONSThe proportion of women delivering invited presentations and chairing sessions at a European neurosurgical conference is lower than expected from the available pool of board-certified neurosurgeons. The proportion of women participating is higher through application (abstract submission) than through invitation. The higher proportion of presentations from abstract submission may reflect submission from a pool of trainees with a higher proportion of women. The authors suggest implementation of strategies that increase invited speakers from minority groups and have been shown to be effective in other disciplines, such as improving minority group representation in organizing committees.</jats:sec