ProteinDBS v2.0: a web server for global and local protein structure search

ProteinDBS v2.0 is a web server designed for efficient and accurate comparisons and searches of structurally similar proteins from a large-scale database. It provides two comparison methods, global-to-global and local-to-local, to facilitate the searches of protein structures or substructures. ProteinDBS v2.0 applies advanced feature extraction algorithms and scalable indexing techniques to achieve a high-running speed while preserving reasonably high precision of structural comparison. The experimental results show that our system is able to return results of global comparisons in seconds from a complete Protein Data Bank (PDB) database of 152 959 protein chains and that it takes much less time to complete local comparisons from a non-redundant database of 3276 proteins than other accurate comparison methods. ProteinDBS v2.0 supports query by PDB protein ID and by new structures uploaded by users. To our knowledge, this is the only search engine that can simultaneously support global and local comparisons. ProteinDBS v2.0 is a useful tool to investigate functional or evolutional relationships among proteins. Moreover, the common substructures identified by local comparison can be potentially used to assist the human curation process in discovering new domains or folds from the ever-growing protein structure databases. The system is hosted at http://ProteinDBS.rnet.missouri.edu

Age-appropriate services for people diagnosed with young onset dementia (YOD): a systematic review.

BACKGROUND: Literature agrees that post-diagnostic services for people living with young onset dementia (YOD) need to be age-appropriate, but there is insufficient evidence of 'what works' to inform service design and delivery. OBJECTIVE: To provide an evidence base of age-appropriate services and to review the perceived effectiveness of current interventions. METHODS: We undertook a systematic review including all types of research relating to interventions for YOD. We searched PubMed, CINHAL Plus, SCOPUS, EBSCO Host EJS, Social Care Online and Google Scholar, hand-searched journals and carried out lateral searches (July-October 2016). Included papers were synthesised qualitatively. Primary studies were critically appraised. RESULTS: Twenty articles (peer-reviewed [n = 10], descriptive accounts [n = 10]) discussing 195 participants (persons diagnosed with YOD [n = 94], caregivers [n = 91] and other [n = 10]) were identified for inclusion. Services enabled people with YOD to remain living at home for longer. However, service continuity was compromised by short-term project-based commissioning and ad-hoc service delivery. CONCLUSION: The evidence on the experience of living with YOD is not matched by research and the innovation needed to mitigate the impact of YOD. The inclusion of people with YOD and their caregivers in service design is critical when planning support in order to delay institutional care

Learning pair-wise gene functional similarity by multiplex gene expression maps

Abstract Background The relationships between the gene functional similarity and gene expression profile, and between gene function annotation and gene sequence have been studied extensively. However, not much work has considered the connection between gene functions and location of a gene's expression in the mammalian tissues. On the other hand, although unsupervised learning methods have been commonly used in functional genomics, supervised learning cannot be directly applied to a set of normal genes without having a target (class) attribute. Results Here, we propose a supervised learning methodology to predict pair-wise gene functional similarity from multiplex gene expression maps that provide information about the location of gene expression. The features are extracted from expression maps and the labels denote the functional similarities of pairs of genes. We make use of wavelet features, original expression values, difference and average values of neighboring voxels and other features to perform boosting analysis. The experimental results show that with increasing similarities of gene expression maps, the functional similarities are increased too. The model predicts the functional similarities between genes to a certain degree. The weights of the features in the model indicate the features that are more significant for this prediction. Conclusions By considering pairs of genes, we propose a supervised learning methodology to predict pair-wise gene functional similarity from multiplex gene expression maps. We also explore the relationship between similarities of gene maps and gene functions. By using AdaBoost coupled with our proposed weak classifier we analyze a large-scale gene expression dataset and predict gene functional similarities. We also detect the most significant single voxels and pairs of neighboring voxels and visualize them in the expression map image of a mouse brain. This work is very important for predicting functions of unknown genes. It also has broader applicability since the methodology can be applied to analyze any large-scale dataset without a target attribute and is not restricted to gene expressions

Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation

After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thus, we tested the hypothesis that apical resection either inhibits, delays, or reverses cardiomyocyte centrosome disassembly and binucleation. Our data show that apical resection rather transiently accelerates centrosome disassembly as well as the rate of binucleation. Consistent with the nearly 2-fold increased rate of binucleation there was a nearly 2-fold increase in the number of cardiomyocytes in mitosis indicating that the majority of injury-induced cardiomyocyte cell cycle activity results in binucleation, not proliferation. Concurrently, cardiomyocytes undergoing cytokinesis from embryonic hearts exhibited midbody formation consistent with successful abscission, whereas those from 3 day-old cardiomyocytes after apical resection exhibited midbody formation consistent with abscission failure. Lastly, injured hearts failed to fully regenerate as evidenced by persistent scarring and reduced wall motion. Collectively, these data suggest that should a regenerative program exist in the newborn mammalian heart, it is quickly curtailed by developmental mechanisms that render cardiomyocytes post-mitotic

The biological function of some human transcription factor binding motifs varies with position relative to the transcription start site

A number of previous studies have predicted transcription factor binding sites (TFBSs) by exploiting the position of genomic landmarks like the transcriptional start site (TSS). The studies’ methods are generally too computationally intensive for genome-scale investigation, so the full potential of ‘positional regulomics’ to discover TFBSs and determine their function remains unknown. Because databases often annotate the genomic landmarks in DNA sequences, the methodical exploitation of positional regulomics has become increasingly urgent. Accordingly, we examined a set of 7914 human putative promoter regions (PPRs) with a known TSS. Our methods identified 1226 eight-letter DNA words with significant positional preferences with respect to the TSS, of which only 608 of the 1226 words matched known TFBSs. Many groups of genes whose PPRs contained a common word displayed similar expression profiles and related biological functions, however. Most interestingly, our results included 78 words, each of which clustered significantly in two or three different positions relative to the TSS. Often, the gene groups corresponding to different positional clusters of the same word corresponded to diverse functions, e.g. activation or repression in different tissues. Thus, different clusters of the same word likely reflect the phenomenon of ‘positional regulation’, i.e. a word's regulatory function can vary with its position relative to a genomic landmark, a conclusion inaccessible to methods based purely on sequence. Further integrative analysis of words co-occurring in PPRs also yielded 24 different groups of genes, likely identifying cis-regulatory modules de novo. Whereas comparative genomics requires precise sequence alignments, positional regulomics exploits genomic landmarks to provide a ‘poor man's alignment’. By exploiting the phenomenon of positional regulation, it uses position to differentiate the biological functions of subsets of TFBSs sharing a common sequence motif

Semantic integration to identify overlapping functional modules in protein interaction networks

<p>Abstract</p> <p>Background</p> <p>The systematic analysis of protein-protein interactions can enable a better understanding of cellular organization, processes and functions. Functional modules can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of functional module detection algorithms.</p> <p>Results</p> <p>We have developed novel metrics, called semantic similarity and semantic interactivity, which use Gene Ontology (GO) annotations to measure the reliability of protein-protein interactions. The protein interaction networks can be converted into a weighted graph representation by assigning the reliability values to each interaction as a weight. We presented a flow-based modularization algorithm to efficiently identify overlapping modules in the weighted interaction networks. The experimental results show that the semantic similarity and semantic interactivity of interacting pairs were positively correlated with functional co-occurrence. The effectiveness of the algorithm for identifying modules was evaluated using functional categories from the MIPS database. We demonstrated that our algorithm had higher accuracy compared to other competing approaches.</p> <p>Conclusion</p> <p>The integration of protein interaction networks with GO annotation data and the capability of detecting overlapping modules substantially improve the accuracy of module identification.</p

Recent Salmon Declines: A Result of Lost Feeding Opportunities Due to Bad Timing?

As the timing of spring productivity blooms in near-shore areas advances due to warming trends in global climate, the selection pressures on out-migrating salmon smolts are shifting. Species and stocks that leave natal streams earlier may be favoured over later-migrating fish. The low post-release survival of hatchery fish during recent years may be in part due to static release times that do not take the timing of plankton blooms into account. This study examined the effects of release time on the migratory behaviour and survival of wild and hatchery-reared coho salmon (Oncorhynchus kisutch) using acoustic and coded-wire telemetry. Plankton monitoring and near-shore seining were also conducted to determine which habitat and food sources were favoured. Acoustic tags (n = 140) and coded-wire tags (n = 266,692) were implanted into coho salmon smolts at the Seymour and Quinsam Rivers, in British Columbia, Canada. Differences between wild and hatchery fish, and early and late releases were examined during the entire lifecycle. Physiological sampling was also carried out on 30 fish from each release group. The smolt-to-adult survival of coho salmon released during periods of high marine productivity was 1.5- to 3-fold greater than those released both before and after, and the fish's degree of smoltification affected their downstream migration time and duration of stay in the estuary. Therefore, hatchery managers should consider having smolts fully developed and ready for release during the peak of the near-shore plankton blooms. Monitoring chlorophyll a levels and water temperature early in the spring could provide a forecast of the timing of these blooms, giving hatcheries time to adjust their release schedule

A Synthesis of Tagging Studies Examining the Behaviour and Survival of Anadromous Salmonids in Marine Environments

This paper synthesizes tagging studies to highlight the current state of knowledge concerning the behaviour and survival of anadromous salmonids in the marine environment. Scientific literature was reviewed to quantify the number and type of studies that have investigated behaviour and survival of anadromous forms of Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), brown trout (Salmo trutta), steelhead (Oncorhynchus mykiss), and cutthroat trout (Oncorhynchus clarkii). We examined three categories of tags including electronic (e.g. acoustic, radio, archival), passive (e.g. external marks, Carlin, coded wire, passive integrated transponder [PIT]), and biological (e.g. otolith, genetic, scale, parasites). Based on 207 papers, survival rates and behaviour in marine environments were found to be extremely variable spatially and temporally, with some of the most influential factors being temperature, population, physiological state, and fish size. Salmonids at all life stages were consistently found to swim at an average speed of approximately one body length per second, which likely corresponds with the speed at which transport costs are minimal. We found that there is relatively little research conducted on open-ocean migrating salmonids, and some species (e.g. masu [O. masou] and amago [O. rhodurus]) are underrepresented in the literature. The most common forms of tagging used across life stages were various forms of external tags, coded wire tags, and acoustic tags, however, the majority of studies did not measure tagging/handling effects on the fish, tag loss/failure, or tag detection probabilities when estimating survival. Through the interdisciplinary application of existing and novel technologies, future research examining the behaviour and survival of anadromous salmonids could incorporate important drivers such as oceanography, tagging/handling effects, predation, and physiology