[Comparative analysis of clustered regularly interspaced short palindromic repeats (CRISPRs) loci in the genomes of halophilic archaea].

PubMed

Zhang, Fan; Zhang, Bing; Xiang, Hua; Hu, Songnian

2009-11-01

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a widespread system that provides acquired resistance against phages in bacteria and archaea. Here we aim to genome-widely analyze the CRISPR in extreme halophilic archaea, of which the whole genome sequences are available at present time. We used bioinformatics methods including alignment, conservation analysis, GC content and RNA structure prediction to analyze the CRISPR structures of 7 haloarchaeal genomes. We identified the CRISPR structures in 5 halophilic archaea and revealed a conserved palindromic motif in the flanking regions of these CRISPR structures. In addition, we found that the repeat sequences of large CRISPR structures in halophilic archaea were greatly conserved, and two types of predicted RNA secondary structures derived from the repeat sequences were likely determined by the fourth base of the repeat sequence. Our results support the proposal that the leader sequence may function as recognition site by having palindromic structures in flanking regions, and the stem-loop secondary structure formed by repeat sequences may function in mediating the interaction between foreign genetic elements and CAS-encoded proteins.

Conservation of coevolving protein interfaces bridges prokaryote–eukaryote homologies in the twilight zone

PubMed Central

Rodriguez-Rivas, Juan; Marsili, Simone; Juan, David; Valencia, Alfonso

2016-01-01

Protein–protein interactions are fundamental for the proper functioning of the cell. As a result, protein interaction surfaces are subject to strong evolutionary constraints. Recent developments have shown that residue coevolution provides accurate predictions of heterodimeric protein interfaces from sequence information. So far these approaches have been limited to the analysis of families of prokaryotic complexes for which large multiple sequence alignments of homologous sequences can be compiled. We explore the hypothesis that coevolution points to structurally conserved contacts at protein–protein interfaces, which can be reliably projected to homologous complexes with distantly related sequences. We introduce a domain-centered protocol to study the interplay between residue coevolution and structural conservation of protein–protein interfaces. We show that sequence-based coevolutionary analysis systematically identifies residue contacts at prokaryotic interfaces that are structurally conserved at the interface of their eukaryotic counterparts. In turn, this allows the prediction of conserved contacts at eukaryotic protein–protein interfaces with high confidence using solely mutational patterns extracted from prokaryotic genomes. Even in the context of high divergence in sequence (the twilight zone), where standard homology modeling of protein complexes is unreliable, our approach provides sequence-based accurate information about specific details of protein interactions at the residue level. Selected examples of the application of prokaryotic coevolutionary analysis to the prediction of eukaryotic interfaces further illustrate the potential of this approach. PMID:27965389

Conservation of coevolving protein interfaces bridges prokaryote-eukaryote homologies in the twilight zone.

PubMed

Rodriguez-Rivas, Juan; Marsili, Simone; Juan, David; Valencia, Alfonso

2016-12-27

Protein-protein interactions are fundamental for the proper functioning of the cell. As a result, protein interaction surfaces are subject to strong evolutionary constraints. Recent developments have shown that residue coevolution provides accurate predictions of heterodimeric protein interfaces from sequence information. So far these approaches have been limited to the analysis of families of prokaryotic complexes for which large multiple sequence alignments of homologous sequences can be compiled. We explore the hypothesis that coevolution points to structurally conserved contacts at protein-protein interfaces, which can be reliably projected to homologous complexes with distantly related sequences. We introduce a domain-centered protocol to study the interplay between residue coevolution and structural conservation of protein-protein interfaces. We show that sequence-based coevolutionary analysis systematically identifies residue contacts at prokaryotic interfaces that are structurally conserved at the interface of their eukaryotic counterparts. In turn, this allows the prediction of conserved contacts at eukaryotic protein-protein interfaces with high confidence using solely mutational patterns extracted from prokaryotic genomes. Even in the context of high divergence in sequence (the twilight zone), where standard homology modeling of protein complexes is unreliable, our approach provides sequence-based accurate information about specific details of protein interactions at the residue level. Selected examples of the application of prokaryotic coevolutionary analysis to the prediction of eukaryotic interfaces further illustrate the potential of this approach.

Predicting Gene Structure Changes Resulting from Genetic Variants via Exon Definition Features.

PubMed

Majoros, William H; Holt, Carson; Campbell, Michael S; Ware, Doreen; Yandell, Mark; Reddy, Timothy E

2018-04-25

Genetic variation that disrupts gene function by altering gene splicing between individuals can substantially influence traits and disease. In those cases, accurately predicting the effects of genetic variation on splicing can be highly valuable for investigating the mechanisms underlying those traits and diseases. While methods have been developed to generate high quality computational predictions of gene structures in reference genomes, the same methods perform poorly when used to predict the potentially deleterious effects of genetic changes that alter gene splicing between individuals. Underlying that discrepancy in predictive ability are the common assumptions by reference gene finding algorithms that genes are conserved, well-formed, and produce functional proteins. We describe a probabilistic approach for predicting recent changes to gene structure that may or may not conserve function. The model is applicable to both coding and noncoding genes, and can be trained on existing gene annotations without requiring curated examples of aberrant splicing. We apply this model to the problem of predicting altered splicing patterns in the genomes of individual humans, and we demonstrate that performing gene-structure prediction without relying on conserved coding features is feasible. The model predicts an unexpected abundance of variants that create de novo splice sites, an observation supported by both simulations and empirical data from RNA-seq experiments. While these de novo splice variants are commonly misinterpreted by other tools as coding or noncoding variants of little or no effect, we find that in some cases they can have large effects on splicing activity and protein products, and we propose that they may commonly act as cryptic factors in disease. The software is available from geneprediction.org/SGRF. bmajoros@duke.edu. Supplementary information is available at Bioinformatics online.

Probing binding hot spots at protein-RNA recognition sites.

PubMed

Barik, Amita; Nithin, Chandran; Karampudi, Naga Bhushana Rao; Mukherjee, Sunandan; Bahadur, Ranjit Prasad

2016-01-29

We use evolutionary conservation derived from structure alignment of polypeptide sequences along with structural and physicochemical attributes of protein-RNA interfaces to probe the binding hot spots at protein-RNA recognition sites. We find that the degree of conservation varies across the RNA binding proteins; some evolve rapidly compared to others. Additionally, irrespective of the structural class of the complexes, residues at the RNA binding sites are evolutionary better conserved than those at the solvent exposed surfaces. For recognitions involving duplex RNA, residues interacting with the major groove are better conserved than those interacting with the minor groove. We identify multi-interface residues participating simultaneously in protein-protein and protein-RNA interfaces in complexes where more than one polypeptide is involved in RNA recognition, and show that they are better conserved compared to any other RNA binding residues. We find that the residues at water preservation site are better conserved than those at hydrated or at dehydrated sites. Finally, we develop a Random Forests model using structural and physicochemical attributes for predicting binding hot spots. The model accurately predicts 80% of the instances of experimental ΔΔG values in a particular class, and provides a stepping-stone towards the engineering of protein-RNA recognition sites with desired affinity. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein.

PubMed

Agrawal, Neeraj J; Helk, Bernhard; Trout, Bernhardt L

2014-01-21

Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

A strategy for detecting the conservation of folding-nucleus residues in protein superfamilies.

PubMed

Michnick, S W; Shakhnovich, E

1998-01-01

Nucleation-growth theory predicts that fast-folding peptide sequences fold to their native structure via structures in a transition-state ensemble that share a small number of native contacts (the folding nucleus). Experimental and theoretical studies of proteins suggest that residues participating in folding nuclei are conserved among homologs. We attempted to determine if this is true in proteins with highly diverged sequences but identical folds (superfamilies). We describe a strategy based on comparisons of residue conservation in natural superfamily sequences with simulated sequences (generated with a Monte-Carlo sequence design strategy) for the same proteins. The basic assumptions of the strategy were that natural sequences will conserve residues needed for folding and stability plus function, the simulated sequences contain no functional conservation, and nucleus residues make native contacts with each other. Based on these assumptions, we identified seven potential nucleus residues in ubiquitin superfamily members. Non-nucleus conserved residues were also identified; these are proposed to be involved in stabilizing native interactions. We found that all superfamily members conserved the same potential nucleus residue positions, except those for which the structural topology is significantly different. Our results suggest that the conservation of the nucleus of a specific fold can be predicted by comparing designed simulated sequences with natural highly diverged sequences that fold to the same structure. We suggest that such a strategy could be used to help plan protein folding and design experiments, to identify new superfamily members, and to subdivide superfamilies further into classes having a similar folding mechanism.

The sequence, structure and evolutionary features of HOTAIR in mammals

PubMed Central

2011-01-01

Background An increasing number of long noncoding RNAs (lncRNAs) have been identified recently. Different from all the others that function in cis to regulate local gene expression, the newly identified HOTAIR is located between HoxC11 and HoxC12 in the human genome and regulates HoxD expression in multiple tissues. Like the well-characterised lncRNA Xist, HOTAIR binds to polycomb proteins to methylate histones at multiple HoxD loci, but unlike Xist, many details of its structure and function, as well as the trans regulation, remain unclear. Moreover, HOTAIR is involved in the aberrant regulation of gene expression in cancer. Results To identify conserved domains in HOTAIR and study the phylogenetic distribution of this lncRNA, we searched the genomes of 10 mammalian and 3 non-mammalian vertebrates for matches to its 6 exons and the two conserved domains within the 1800 bp exon6 using Infernal. There was just one high-scoring hit for each mammal, but many low-scoring hits were found in both mammals and non-mammalian vertebrates. These hits and their flanking genes in four placental mammals and platypus were examined to determine whether HOTAIR contained elements shared by other lncRNAs. Several of the hits were within unknown transcripts or ncRNAs, many were within introns of, or antisense to, protein-coding genes, and conservation of the flanking genes was observed only between human and chimpanzee. Phylogenetic analysis revealed discrete evolutionary dynamics for orthologous sequences of HOTAIR exons. Exon1 at the 5' end and a domain in exon6 near the 3' end, which contain domains that bind to multiple proteins, have evolved faster in primates than in other mammals. Structures were predicted for exon1, two domains of exon6 and the full HOTAIR sequence. The sequence and structure of two fragments, in exon1 and the domain B of exon6 respectively, were identified to robustly occur in predicted structures of exon1, domain B of exon6 and the full HOTAIR in mammals. Conclusions HOTAIR exists in mammals, has poorly conserved sequences and considerably conserved structures, and has evolved faster than nearby HoxC genes. Exons of HOTAIR show distinct evolutionary features, and a 239 bp domain in the 1804 bp exon6 is especially conserved. These features, together with the absence of some exons and sequences in mouse, rat and kangaroo, suggest ab initio generation of HOTAIR in marsupials. Structure prediction identifies two fragments in the 5' end exon1 and the 3' end domain B of exon6, with sequence and structure invariably occurring in various predicted structures of exon1, the domain B of exon6 and the full HOTAIR. PMID:21496275

Unravelling the structure of species extinction risk for predictive conservation science.

PubMed

Lee, Tien Ming; Jetz, Walter

2011-05-07

Extinction risk varies across species and space owing to the combined and interactive effects of ecology/life history and geography. For predictive conservation science to be effective, large datasets and integrative models that quantify the relative importance of potential factors and separate rapidly changing from relatively static threat drivers are urgently required. Here, we integrate and map in space the relative and joint effects of key correlates of The International Union for Conservation of Nature-assessed extinction risk for 8700 living birds. Extinction risk varies significantly with species' broad-scale environmental niche, geographical range size, and life-history and ecological traits such as body size, developmental mode, primary diet and foraging height. Even at this broad scale, simple quantifications of past human encroachment across species' ranges emerge as key in predicting extinction risk, supporting the use of land-cover change projections for estimating future threat in an integrative setting. A final joint model explains much of the interspecific variation in extinction risk and provides a remarkably strong prediction of its observed global geography. Our approach unravels the species-level structure underlying geographical gradients in extinction risk and offers a means of disentangling static from changing components of current and future threat. This reconciliation of intrinsic and extrinsic, and of past and future extinction risk factors may offer a critical step towards a more continuous, forward-looking assessment of species' threat status based on geographically explicit environmental change projections, potentially advancing global predictive conservation science.

Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation

PubMed Central

Kuan, Lisa; Schaffer, Jessica N.; Zouzias, Christos D.

2014-01-01

Proteus mirabilis is a Gram-negative enteric bacterium that causes complicated urinary tract infections, particularly in patients with indwelling catheters. Sequencing of clinical isolate P. mirabilis HI4320 revealed the presence of 17 predicted chaperone-usher fimbrial operons. We classified these fimbriae into three groups by their genetic relationship to other chaperone-usher fimbriae. Sixteen of these fimbriae are encoded by all seven currently sequenced P. mirabilis genomes. The predicted protein sequence of the major structural subunit for 14 of these fimbriae was highly conserved (≥95 % identity), whereas three other structural subunits (Fim3A, UcaA and Fim6A) were variable. Further examination of 58 clinical isolates showed that 14 of the 17 predicted major structural subunit genes of the fimbriae were present in most strains (>85 %). Transcription of the predicted major structural subunit genes for all 17 fimbriae was measured under different culture conditions designed to mimic conditions in the urinary tract. The majority of the fimbrial genes were induced during stationary phase, static culture or colony growth when compared to exponential-phase aerated culture. Major structural subunit proteins for six of these fimbriae were detected using MS of proteins sheared from the surface of broth-cultured P. mirabilis, demonstrating that this organism may produce multiple fimbriae within a single culture. The high degree of conservation of P. mirabilis fimbriae stands in contrast to uropathogenic Escherichia coli and Salmonella enterica, which exhibit greater variability in their fimbrial repertoires. These findings suggest there may be evolutionary pressure for P. mirabilis to maintain a large fimbrial arsenal. PMID:24809384

Prediction of Breakthrough Curves for Conservative and Reactive Transport from the Structural Parameters of Highly Heterogeneous Media

NASA Astrophysics Data System (ADS)

Hansen, S. K.; Haslauer, C. P.; Cirpka, O. A.; Vesselinov, V. V.

2016-12-01

It is desirable to predict the shape of breakthrough curves downgradient of a solute source from subsurface structural parameters (as in the small-perturbation macrodispersion theory) both for realistically heterogeneous fields, and at early time, before any sort of Fickian model is applicable. Using a combination of a priori knowledge, large-scale Monte Carlo simulation, and regression techniques, we have developed closed-form predictive expressions for pre- and post-Fickian flux-weighted solute breakthrough curves as a function of distance from the source (in integral scales) and variance of the log hydraulic conductivity field. Using the ensemble of Monte Carlo realizations, we have simultaneously computed error envelopes for the estimated flux-weighted breakthrough, and for the divergence of point breakthrough curves from the flux-weighted average, as functions of the predictive parameters. We have also obtained implied late-time macrodispersion coefficients for highly heterogeneous environments from the breakthrough statistics. This analysis is relevant for the modelling of reactive as well as conservative transport, since for many kinetic sorption and decay reactions, Laplace-domain modification of the breakthrough curve for conservative solute produces the correct curve for the reactive system.

Conserved thioredoxin fold is present in Pisum sativum L. sieve element occlusion-1 protein

PubMed Central

Umate, Pavan; Tuteja, Renu

2010-01-01

Homology-based three-dimensional model for Pisum sativum sieve element occlusion 1 (Ps.SEO1) (forisomes) protein was constructed. A stretch of amino acids (residues 320 to 456) which is well conserved in all known members of forisomes proteins was used to model the 3D structure of Ps.SEO1. The structural prediction was done using Protein Homology/analogY Recognition Engine (PHYRE) web server. Based on studies of local sequence alignment, the thioredoxin-fold containing protein [Structural Classification of Proteins (SCOP) code d1o73a_], a member of the glutathione peroxidase family was selected as a template for modeling the spatial structure of Ps.SEO1. Selection was based on comparison of primary sequence, higher match quality and alignment accuracy. Motif 1 (EVF) is conserved in Ps.SEO1, Vicia faba (Vf.For1) and Medicago truncatula (MT.SEO3); motif 2 (KKED) is well conserved across all forisomes proteins and motif 3 (IGYIGNP) is conserved in Ps.SEO1 and Vf.For1. PMID:20404566

CORECLUST: identification of the conserved CRM grammar together with prediction of gene regulation.

PubMed

Nikulova, Anna A; Favorov, Alexander V; Sutormin, Roman A; Makeev, Vsevolod J; Mironov, Andrey A

2012-07-01

Identification of transcriptional regulatory regions and tracing their internal organization are important for understanding the eukaryotic cell machinery. Cis-regulatory modules (CRMs) of higher eukaryotes are believed to possess a regulatory 'grammar', or preferred arrangement of binding sites, that is crucial for proper regulation and thus tends to be evolutionarily conserved. Here, we present a method CORECLUST (COnservative REgulatory CLUster STructure) that predicts CRMs based on a set of positional weight matrices. Given regulatory regions of orthologous and/or co-regulated genes, CORECLUST constructs a CRM model by revealing the conserved rules that describe the relative location of binding sites. The constructed model may be consequently used for the genome-wide prediction of similar CRMs, and thus detection of co-regulated genes, and for the investigation of the regulatory grammar of the system. Compared with related methods, CORECLUST shows better performance at identification of CRMs conferring muscle-specific gene expression in vertebrates and early-developmental CRMs in Drosophila.

A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting

PubMed Central

Firth, Andrew E; Atkins, John F

2009-01-01

Japanese encephalitis, West Nile, Usutu and Murray Valley encephalitis viruses form a tight subgroup within the larger Flavivirus genus. These viruses utilize a single-polyprotein expression strategy, resulting in ~10 mature proteins. Plotting the conservation at synonymous sites along the polyprotein coding sequence reveals strong conservation peaks at the very 5' end of the coding sequence, and also at the 5' end of the sequence encoding the NS2A protein. Such peaks are generally indicative of functionally important non-coding sequence elements. The second peak corresponds to a predicted stable pseudoknot structure whose biological importance is supported by compensatory mutations that preserve the structure. The pseudoknot is preceded by a conserved slippery heptanucleotide (Y CCU UUU), thus forming a classical stimulatory motif for -1 ribosomal frameshifting. We hypothesize, therefore, that the functional importance of the pseudoknot is to stimulate a portion of ribosomes to shift -1 nt into a short (45 codon), conserved, overlapping open reading frame, termed foo. Since cleavage at the NS1-NS2A boundary is known to require synthesis of NS2A in cis, the resulting transframe fusion protein is predicted to be NS1-NS2AN-term-FOO. We hypothesize that this may explain the origin of the previously identified NS1 'extension' protein in JEV-group flaviviruses, known as NS1'. PMID:19196463

Structural Analysis of PTM Hotspots (SAPH-ire) – A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families*

PubMed Central

Dewhurst, Henry M.; Choudhury, Shilpa; Torres, Matthew P.

2015-01-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)—a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits—conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit–N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. PMID:26070665

Evidence of pervasive biologically functional secondary structures within the genomes of eukaryotic single-stranded DNA viruses.

PubMed

Muhire, Brejnev Muhizi; Golden, Michael; Murrell, Ben; Lefeuvre, Pierre; Lett, Jean-Michel; Gray, Alistair; Poon, Art Y F; Ngandu, Nobubelo Kwanele; Semegni, Yves; Tanov, Emil Pavlov; Monjane, Adérito Luis; Harkins, Gordon William; Varsani, Arvind; Shepherd, Dionne Natalie; Martin, Darren Patrick

2014-02-01

Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here.

Evidence of Pervasive Biologically Functional Secondary Structures within the Genomes of Eukaryotic Single-Stranded DNA Viruses

PubMed Central

Muhire, Brejnev Muhizi; Golden, Michael; Murrell, Ben; Lefeuvre, Pierre; Lett, Jean-Michel; Gray, Alistair; Poon, Art Y. F.; Ngandu, Nobubelo Kwanele; Semegni, Yves; Tanov, Emil Pavlov; Monjane, Adérito Luis; Harkins, Gordon William; Varsani, Arvind; Shepherd, Dionne Natalie

2014-01-01

Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here. PMID:24284329

Protein structure based prediction of catalytic residues.

PubMed

Fajardo, J Eduardo; Fiser, Andras

2013-02-22

Worldwide structural genomics projects continue to release new protein structures at an unprecedented pace, so far nearly 6000, but only about 60% of these proteins have any sort of functional annotation. We explored a range of features that can be used for the prediction of functional residues given a known three-dimensional structure. These features include various centrality measures of nodes in graphs of interacting residues: closeness, betweenness and page-rank centrality. We also analyzed the distance of functional amino acids to the general center of mass (GCM) of the structure, relative solvent accessibility (RSA), and the use of relative entropy as a measure of sequence conservation. From the selected features, neural networks were trained to identify catalytic residues. We found that using distance to the GCM together with amino acid type provide a good discriminant function, when combined independently with sequence conservation. Using an independent test set of 29 annotated protein structures, the method returned 411 of the initial 9262 residues as the most likely to be involved in function. The output 411 residues contain 70 of the annotated 111 catalytic residues. This represents an approximately 14-fold enrichment of catalytic residues on the entire input set (corresponding to a sensitivity of 63% and a precision of 17%), a performance competitive with that of other state-of-the-art methods. We found that several of the graph based measures utilize the same underlying feature of protein structures, which can be simply and more effectively captured with the distance to GCM definition. This also has the added the advantage of simplicity and easy implementation. Meanwhile sequence conservation remains by far the most influential feature in identifying functional residues. We also found that due the rapid changes in size and composition of sequence databases, conservation calculations must be recalibrated for specific reference databases.

Structure prediction of Fe(II) 2-oxoglutarate dioxygenase from a psychrophilic yeast Glaciozyma antarctica PI12

NASA Astrophysics Data System (ADS)

Yusof, Nik Yusnoraini; Bakar, Farah Diba Abu; Mahadi, Nor Muhammad; Raih, Mohd Firdaus; Murad, Abdul Munir Abdul

2015-09-01

A cDNA encoding Fe(II) 2-oxoglutarate (2OG) dependent dioxygenases was isolated from psychrophilic yeast, Glaciozyma antarctica PI12. We have successfully amplified 1,029 bp cDNA sequence that encodes 342 amino acid with predicted molecular weight 38 kDa. The prediction protein was analysed using various bioinformatics tools to explore the properties of the protein. Based on a BLAST search analysis, the Fe2OX amino acid sequence showed 61% identity to the sequence of oxoglutarate/iron-dependent oxygenase from Rhodosporidium toruloides NP11. SignalP prediction showed that the Fe2OX protein contains no putative signal peptide, which suggests that this enzyme most probably localised intracellularly.The structure of Fe2OX was predicted by homology modelling using MODELLER9v11. The model with the lowest objective function was selected from hundred models generated using MODELLER9v11. Analysis of the structure revealed the longer loop at Fe2OX from G.antarctica that might be responsible for the flexibility of the structure, which contributes to its adaptation to low temperatures. Fe2OX hold a highly conserved Fe(II) binding HXD/E…H triad motif. The binding site for 2-oxoglutarate was found conserved for Arg280 among reported studies, however the Phe268 was found to be different in Fe2OX.

Predicting protein-protein interactions on a proteome scale by matching evolutionary and structural similarities at interfaces using PRISM.

PubMed

Tuncbag, Nurcan; Gursoy, Attila; Nussinov, Ruth; Keskin, Ozlem

2011-08-11

Prediction of protein-protein interactions at the structural level on the proteome scale is important because it allows prediction of protein function, helps drug discovery and takes steps toward genome-wide structural systems biology. We provide a protocol (termed PRISM, protein interactions by structural matching) for large-scale prediction of protein-protein interactions and assembly of protein complex structures. The method consists of two components: rigid-body structural comparisons of target proteins to known template protein-protein interfaces and flexible refinement using a docking energy function. The PRISM rationale follows our observation that globally different protein structures can interact via similar architectural motifs. PRISM predicts binding residues by using structural similarity and evolutionary conservation of putative binding residue 'hot spots'. Ultimately, PRISM could help to construct cellular pathways and functional, proteome-scale annotation. PRISM is implemented in Python and runs in a UNIX environment. The program accepts Protein Data Bank-formatted protein structures and is available at http://prism.ccbb.ku.edu.tr/prism_protocol/.

A Conserved Steroid Binding Site in Cytochrome c Oxidase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Ling; Mills, Denise A.; Buhrow, Leann

2010-09-02

Micromolar concentrations of the bile salt deoxycholate are shown to rescue the activity of an inactive mutant, E101A, in the K proton pathway of Rhodobacter sphaeroides cytochrome c oxidase. A crystal structure of the wild-type enzyme reveals, as predicted, deoxycholate bound with its carboxyl group at the entrance of the K path. Since cholate is a known potent inhibitor of bovine oxidase and is seen in a similar position in the bovine structure, the crystallographically defined, conserved steroid binding site could reveal a regulatory site for steroids or structurally related molecules that act on the essential K proton path.

Laminar flamelets, conserved scalars, and non-unity Lewis numbers: What does this have to do with chemistry?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, H.J.; Marro, M.A.T.; Smooke, M.

1994-12-31

In general, computation of laminar flame structure involves the simultaneous solution of the conservation equations for mass, energy, momentum, and chemical species. It has been proposed and confirmed in numerous experiments that flame species concentrations can be considered as functions of a conserved scalar (a quantity such as elemental mass fraction, that has no chemical source term). One such conserved scalar is the mixture fraction which is normalized to be zero in the air stream and one in the fuel stream. This allows the species conservation equations to be rewritten as a function of the mixture fraction (itself a conservedmore » scalar) which significantly simplifies the calculation of flame structure. Despite the widespread acceptance that the conserved scalar description of diffusion flame structure has found in the combustion community, there has been surprisingly little effort expended in the development of a detailed evaluation of how well it actually works. In this presentation we compare the results of a {open_quotes}full{close_quotes} transport and chemical calculation performed by Smooke with the predictions of the conserved scalar approach. Our results show that the conserved scalar approach works because some species` concentrations are not dependent only on mixture fraction.« less

HMMerThread: detecting remote, functional conserved domains in entire genomes by combining relaxed sequence-database searches with fold recognition.

PubMed

Bradshaw, Charles Richard; Surendranath, Vineeth; Henschel, Robert; Mueller, Matthias Stefan; Habermann, Bianca Hermine

2011-03-10

Conserved domains in proteins are one of the major sources of functional information for experimental design and genome-level annotation. Though search tools for conserved domain databases such as Hidden Markov Models (HMMs) are sensitive in detecting conserved domains in proteins when they share sufficient sequence similarity, they tend to miss more divergent family members, as they lack a reliable statistical framework for the detection of low sequence similarity. We have developed a greatly improved HMMerThread algorithm that can detect remotely conserved domains in highly divergent sequences. HMMerThread combines relaxed conserved domain searches with fold recognition to eliminate false positive, sequence-based identifications. With an accuracy of 90%, our software is able to automatically predict highly divergent members of conserved domain families with an associated 3-dimensional structure. We give additional confidence to our predictions by validation across species. We have run HMMerThread searches on eight proteomes including human and present a rich resource of remotely conserved domains, which adds significantly to the functional annotation of entire proteomes. We find ∼4500 cross-species validated, remotely conserved domain predictions in the human proteome alone. As an example, we find a DNA-binding domain in the C-terminal part of the A-kinase anchor protein 10 (AKAP10), a PKA adaptor that has been implicated in cardiac arrhythmias and premature cardiac death, which upon stress likely translocates from mitochondria to the nucleus/nucleolus. Based on our prediction, we propose that with this HLH-domain, AKAP10 is involved in the transcriptional control of stress response. Further remotely conserved domains we discuss are examples from areas such as sporulation, chromosome segregation and signalling during immune response. The HMMerThread algorithm is able to automatically detect the presence of remotely conserved domains in proteins based on weak sequence similarity. Our predictions open up new avenues for biological and medical studies. Genome-wide HMMerThread domains are available at http://vm1-hmmerthread.age.mpg.de.

HMMerThread: Detecting Remote, Functional Conserved Domains in Entire Genomes by Combining Relaxed Sequence-Database Searches with Fold Recognition

PubMed Central

Bradshaw, Charles Richard; Surendranath, Vineeth; Henschel, Robert; Mueller, Matthias Stefan; Habermann, Bianca Hermine

2011-01-01

Conserved domains in proteins are one of the major sources of functional information for experimental design and genome-level annotation. Though search tools for conserved domain databases such as Hidden Markov Models (HMMs) are sensitive in detecting conserved domains in proteins when they share sufficient sequence similarity, they tend to miss more divergent family members, as they lack a reliable statistical framework for the detection of low sequence similarity. We have developed a greatly improved HMMerThread algorithm that can detect remotely conserved domains in highly divergent sequences. HMMerThread combines relaxed conserved domain searches with fold recognition to eliminate false positive, sequence-based identifications. With an accuracy of 90%, our software is able to automatically predict highly divergent members of conserved domain families with an associated 3-dimensional structure. We give additional confidence to our predictions by validation across species. We have run HMMerThread searches on eight proteomes including human and present a rich resource of remotely conserved domains, which adds significantly to the functional annotation of entire proteomes. We find ∼4500 cross-species validated, remotely conserved domain predictions in the human proteome alone. As an example, we find a DNA-binding domain in the C-terminal part of the A-kinase anchor protein 10 (AKAP10), a PKA adaptor that has been implicated in cardiac arrhythmias and premature cardiac death, which upon stress likely translocates from mitochondria to the nucleus/nucleolus. Based on our prediction, we propose that with this HLH-domain, AKAP10 is involved in the transcriptional control of stress response. Further remotely conserved domains we discuss are examples from areas such as sporulation, chromosome segregation and signalling during immune response. The HMMerThread algorithm is able to automatically detect the presence of remotely conserved domains in proteins based on weak sequence similarity. Our predictions open up new avenues for biological and medical studies. Genome-wide HMMerThread domains are available at http://vm1-hmmerthread.age.mpg.de. PMID:21423752

Using landscape limnology to classify freshwater ecosystems for multi-ecosystem management and conservation

USGS Publications Warehouse

Soranno, Patricia A.; Cheruvelil, Kendra Spence; Webster, Katherine E.; Bremigan, Mary T.; Wagner, Tyler; Stow, Craig A.

2010-01-01

Governmental entities are responsible for managing and conserving large numbers of lake, river, and wetland ecosystems that can be addressed only rarely on a case-by-case basis. We present a system for predictive classification modeling, grounded in the theoretical foundation of landscape limnology, that creates a tractable number of ecosystem classes to which management actions may be tailored. We demonstrate our system by applying two types of predictive classification modeling approaches to develop nutrient criteria for eutrophication management in 1998 north temperate lakes. Our predictive classification system promotes the effective management of multiple ecosystems across broad geographic scales by explicitly connecting management and conservation goals to the classification modeling approach, considering multiple spatial scales as drivers of ecosystem dynamics, and acknowledging the hierarchical structure of freshwater ecosystems. Such a system is critical for adaptive management of complex mosaics of freshwater ecosystems and for balancing competing needs for ecosystem services in a changing world.

Analysis of conserved noncoding DNA in Drosophila reveals similar constraints in intergenic and intronic sequences.

PubMed

Bergman, C M; Kreitman, M

2001-08-01

Comparative genomic approaches to gene and cis-regulatory prediction are based on the principle that differential DNA sequence conservation reflects variation in functional constraint. Using this principle, we analyze noncoding sequence conservation in Drosophila for 40 loci with known or suspected cis-regulatory function encompassing >100 kb of DNA. We estimate the fraction of noncoding DNA conserved in both intergenic and intronic regions and describe the length distribution of ungapped conserved noncoding blocks. On average, 22%-26% of noncoding sequences surveyed are conserved in Drosophila, with median block length approximately 19 bp. We show that point substitution in conserved noncoding blocks exhibits transition bias as well as lineage effects in base composition, and occurs more than an order of magnitude more frequently than insertion/deletion (indel) substitution. Overall, patterns of noncoding DNA structure and evolution differ remarkably little between intergenic and intronic conserved blocks, suggesting that the effects of transcription per se contribute minimally to the constraints operating on these sequences. The results of this study have implications for the development of alignment and prediction algorithms specific to noncoding DNA, as well as for models of cis-regulatory DNA sequence evolution.

Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs

PubMed Central

2017-01-01

Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package. PMID:29107980

Modular prediction of protein structural classes from sequences of twilight-zone identity with predicting sequences.

PubMed

Mizianty, Marcin J; Kurgan, Lukasz

2009-12-13

Knowledge of structural class is used by numerous methods for identification of structural/functional characteristics of proteins and could be used for the detection of remote homologues, particularly for chains that share twilight-zone similarity. In contrast to existing sequence-based structural class predictors, which target four major classes and which are designed for high identity sequences, we predict seven classes from sequences that share twilight-zone identity with the training sequences. The proposed MODular Approach to Structural class prediction (MODAS) method is unique as it allows for selection of any subset of the classes. MODAS is also the first to utilize a novel, custom-built feature-based sequence representation that combines evolutionary profiles and predicted secondary structure. The features quantify information relevant to the definition of the classes including conservation of residues and arrangement and number of helix/strand segments. Our comprehensive design considers 8 feature selection methods and 4 classifiers to develop Support Vector Machine-based classifiers that are tailored for each of the seven classes. Tests on 5 twilight-zone and 1 high-similarity benchmark datasets and comparison with over two dozens of modern competing predictors show that MODAS provides the best overall accuracy that ranges between 80% and 96.7% (83.5% for the twilight-zone datasets), depending on the dataset. This translates into 19% and 8% error rate reduction when compared against the best performing competing method on two largest datasets. The proposed predictor provides accurate predictions at 58% accuracy for membrane proteins class, which is not considered by majority of existing methods, in spite that this class accounts for only 2% of the data. Our predictive model is analyzed to demonstrate how and why the input features are associated with the corresponding classes. The improved predictions stem from the novel features that express collocation of the secondary structure segments in the protein sequence and that combine evolutionary and secondary structure information. Our work demonstrates that conservation and arrangement of the secondary structure segments predicted along the protein chain can successfully predict structural classes which are defined based on the spatial arrangement of the secondary structures. A web server is available at http://biomine.ece.ualberta.ca/MODAS/.

Modular prediction of protein structural classes from sequences of twilight-zone identity with predicting sequences

PubMed Central

2009-01-01

Background Knowledge of structural class is used by numerous methods for identification of structural/functional characteristics of proteins and could be used for the detection of remote homologues, particularly for chains that share twilight-zone similarity. In contrast to existing sequence-based structural class predictors, which target four major classes and which are designed for high identity sequences, we predict seven classes from sequences that share twilight-zone identity with the training sequences. Results The proposed MODular Approach to Structural class prediction (MODAS) method is unique as it allows for selection of any subset of the classes. MODAS is also the first to utilize a novel, custom-built feature-based sequence representation that combines evolutionary profiles and predicted secondary structure. The features quantify information relevant to the definition of the classes including conservation of residues and arrangement and number of helix/strand segments. Our comprehensive design considers 8 feature selection methods and 4 classifiers to develop Support Vector Machine-based classifiers that are tailored for each of the seven classes. Tests on 5 twilight-zone and 1 high-similarity benchmark datasets and comparison with over two dozens of modern competing predictors show that MODAS provides the best overall accuracy that ranges between 80% and 96.7% (83.5% for the twilight-zone datasets), depending on the dataset. This translates into 19% and 8% error rate reduction when compared against the best performing competing method on two largest datasets. The proposed predictor provides accurate predictions at 58% accuracy for membrane proteins class, which is not considered by majority of existing methods, in spite that this class accounts for only 2% of the data. Our predictive model is analyzed to demonstrate how and why the input features are associated with the corresponding classes. Conclusions The improved predictions stem from the novel features that express collocation of the secondary structure segments in the protein sequence and that combine evolutionary and secondary structure information. Our work demonstrates that conservation and arrangement of the secondary structure segments predicted along the protein chain can successfully predict structural classes which are defined based on the spatial arrangement of the secondary structures. A web server is available at http://biomine.ece.ualberta.ca/MODAS/. PMID:20003388

Practical theories for service life prediction of critical aerospace structural components

NASA Technical Reports Server (NTRS)

Ko, William L.; Monaghan, Richard C.; Jackson, Raymond H.

1992-01-01

A new second-order theory was developed for predicting the service lives of aerospace structural components. The predictions based on this new theory were compared with those based on the Ko first-order theory and the classical theory of service life predictions. The new theory gives very accurate service life predictions. An equivalent constant-amplitude stress cycle method was proposed for representing the random load spectrum for crack growth calculations. This method predicts the most conservative service life. The proposed use of minimum detectable crack size, instead of proof load established crack size as an initial crack size for crack growth calculations, could give a more realistic service life.

Conservation of Matrix Attachment Region-Binding Filament-Like Protein 1 among Higher Plants1

PubMed Central

Harder, Patricia A.; Silverstein, Rebecca A.; Meier, Iris

2000-01-01

The interaction of chromatin with the nuclear matrix via matrix attachment regions (MARs) on the DNA is considered to be of fundamental importance for higher-order chromatin organization and the regulation of gene expression. We have previously isolated a novel nuclear matrix-localized protein (MFP1) from tomato (Lycopersicon esculentum) that preferentially binds to MAR DNA. Tomato MFP1 has a predicted filament-protein-like structure and is associated with the nuclear envelope via an N-terminal targeting domain. Based on the antigenic relationship, we report here that MFP1 is conserved in a large number of dicot and monocot species. Several cDNAs were cloned from tobacco (Nicotiana tabacum) and shown to correspond to two tobacco MFP1 genes. Comparison of the primary and predicted secondary structures of MFP1 from tomato, tobacco, and Arabidopsis indicates a high degree of conservation of the N-terminal targeting domain, the overall putative coiled-coil structure of the protein, and the C-terminal DNA-binding domain. In addition, we show that tobacco MFP1 is regulated in an organ-specific and developmental fashion, and that this regulation occurs at the level of transcription or RNA stability. PMID:10631266

Interolog interfaces in protein–protein docking

PubMed Central

Alsop, James D.

2015-01-01

ABSTRACT Proteins are essential elements of biological systems, and their function typically relies on their ability to successfully bind to specific partners. Recently, an emphasis of study into protein interactions has been on hot spots, or residues in the binding interface that make a significant contribution to the binding energetics. In this study, we investigate how conservation of hot spots can be used to guide docking prediction. We show that the use of evolutionary data combined with hot spot prediction highlights near‐native structures across a range of benchmark examples. Our approach explores various strategies for using hot spots and evolutionary data to score protein complexes, using both absolute and chemical definitions of conservation along with refinements to these strategies that look at windowed conservation and filtering to ensure a minimum number of hot spots in each binding partner. Finally, structure‐based models of orthologs were generated for comparison with sequence‐based scoring. Using two data sets of 22 and 85 examples, a high rate of top 10 and top 1 predictions are observed, with up to 82% of examples returning a top 10 hit and 35% returning top 1 hit depending on the data set and strategy applied; upon inclusion of the native structure among the decoys, up to 55% of examples yielded a top 1 hit. The 20 common examples between data sets show that more carefully curated interolog data yields better predictions, particularly in achieving top 1 hits. Proteins 2015; 83:1940–1946. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. PMID:25740680

Mass Conservation in Modeling Moisture Diffusion in Multi-Layer Carbon Composite Structures

NASA Technical Reports Server (NTRS)

Nurge, Mark A.; Youngquist, Robert C.; Starr, Stanley O.

2009-01-01

Moisture diffusion in multi-layer carbon composite structures is difficult to model using finite difference methods due to the discontinuity in concentrations between adjacent layers of differing materials. Applying a mass conserving approach at these boundaries proved to be effective at accurately predicting moisture uptake for a sample exposed to a fixed temperature and relative humidity. Details of the model developed are presented and compared with actual moisture uptake data gathered over 130 days from a graphite epoxy composite sandwich coupon with a Rohacell foam core.

Comparative analysis of the L, M, and S RNA segments of Crimean-Congo haemorrhagic fever virus isolates from southern Africa.

PubMed

Goedhals, Dominique; Bester, Phillip A; Paweska, Janusz T; Swanepoel, Robert; Burt, Felicity J

2015-05-01

Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family with a tripartite, negative sense RNA genome. This study used predictive software to analyse the L (large), M (medium), and S (small) segments of 14 southern African CCHFV isolates. The OTU-like cysteine protease domain and the RdRp domain of the L segment are highly conserved among southern African CCHFV isolates. The M segment encodes the structural glycoproteins, GN and GC, and the non-structural glycoproteins which are post-translationally cleaved at highly conserved furin and subtilase SKI-1 cleavage sites. All of the sites previously identified were shown to be conserved among southern African CCHFV isolates. The heavily O-glycosylated N-terminal variable mucin-like domain of the M segment shows the highest sequence variability of the CCHFV proteins. Five transmembrane domains are predicted in the M segment polyprotein resulting in three regions internal to and three regions external to the membrane across the G(N), NS(M) and G(C) glycoproteins. The corroboration of conserved genome domains and sequence identity among geographically diverse isolates may assist in the identification of protein function and pathogenic mechanisms, as well as the identification of potential targets for antiviral therapy and vaccine design. As detailed functional studies are lacking for many of the CCHFV proteins, identification of functional domains by prediction of protein structure, and identification of amino acid level similarity to functionally characterised proteins of related viruses or viruses with similar pathogenic mechanisms are a necessary step for selection of areas for further study. © 2015 Wiley Periodicals, Inc.

The structure of a conserved Piezo channel domain reveals a novel beta sandwich fold

PubMed Central

Kamajaya, Aron; Kaiser, Jens; Lee, Jonas; Reid, Michelle; Rees, Douglas C.

2014-01-01

Summary Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a novel beta sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in Dehydrated Hereditary Stomatocytosis (DHS) patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. PMID:25242456

The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold.

PubMed

Kamajaya, Aron; Kaiser, Jens T; Lee, Jonas; Reid, Michelle; Rees, Douglas C

2014-10-07

Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2,000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a topologically distinct β sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in dehydrated hereditary stomatocytosis patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be-identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure Prediction and Analysis of DNA Transposon and LINE Retrotransposon Proteins*

PubMed Central

Abrusán, György; Zhang, Yang; Szilágyi, András

2013-01-01

Despite the considerable amount of research on transposable elements, no large-scale structural analyses of the TE proteome have been performed so far. We predicted the structures of hundreds of proteins from a representative set of DNA and LINE transposable elements and used the obtained structural data to provide the first general structural characterization of TE proteins and to estimate the frequency of TE domestication and horizontal transfer events. We show that 1) ORF1 and Gag proteins of retrotransposons contain high amounts of structural disorder; thus, despite their very low conservation, the presence of disordered regions and probably their chaperone function is conserved. 2) The distribution of SCOP classes in DNA transposons and LINEs indicates that the proteins of DNA transposons are more ancient, containing folds that already existed when the first cellular organisms appeared. 3) DNA transposon proteins have lower contact order than randomly selected reference proteins, indicating rapid folding, most likely to avoid protein aggregation. 4) Structure-based searches for TE homologs indicate that the overall frequency of TE domestication events is low, whereas we found a relatively high number of cases where horizontal transfer, frequently involving parasites, is the most likely explanation for the observed homology. PMID:23530042

Shark class II invariant chain reveals ancient conserved relationships with cathepsins and MHC class II.

PubMed

Criscitiello, Michael F; Ohta, Yuko; Graham, Matthew D; Eubanks, Jeannine O; Chen, Patricia L; Flajnik, Martin F

2012-03-01

The invariant chain (Ii) is the critical third chain required for the MHC class II heterodimer to be properly guided through the cell, loaded with peptide, and expressed on the surface of antigen presenting cells. Here, we report the isolation of the nurse shark Ii gene, and the comparative analysis of Ii splice variants, expression, genomic organization, predicted structure, and function throughout vertebrate evolution. Alternative splicing to yield Ii with and without the putative protease-protective, thyroglobulin-like domain is as ancient as the MHC-based adaptive immune system, as our analyses in shark and lizard further show conservation of this mechanism in all vertebrate classes except bony fish. Remarkable coordinate expression of Ii and class II was found in shark tissues. Conserved Ii residues and cathepsin L orthologs suggest their long co-evolution in the antigen presentation pathway, and genomic analyses suggest 450 million years of conserved Ii exon/intron structure. Other than an extended linker preceding the thyroglobulin-like domain in cartilaginous fish, the Ii gene and protein are predicted to have largely similar physiology from shark to man. Duplicated Ii genes found only in teleosts appear to have become sub-functionalized, as one form is predicted to play the same role as that mediated by Ii mRNA alternative splicing in all other vertebrate classes. No Ii homologs or potential ancestors of any of the functional Ii domains were found in the jawless fish or lower chordates. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prediction of Breakthrough Curves for Conservative and Reactive Transport from the Structural Parameters of Highly Heterogeneous Media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, Scott; Haslauer, Claus P.; Cirpka, Olaf A.

2017-01-05

The key points of this presentation were to approach the problem of linking breakthrough curve shape (RP-CTRW transition distribution) to structural parameters from a Monte Carlo approach and to use the Monte Carlo analysis to determine any empirical error

Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications

PubMed Central

Cvicek, Vaclav; Goddard, William A.; Abrol, Ravinder

2016-01-01

The understanding of G-protein coupled receptors (GPCRs) is undergoing a revolution due to increased information about their signaling and the experimental determination of structures for more than 25 receptors. The availability of at least one receptor structure for each of the GPCR classes, well separated in sequence space, enables an integrated superfamily-wide analysis to identify signatures involving the role of conserved residues, conserved contacts, and downstream signaling in the context of receptor structures. In this study, we align the transmembrane (TM) domains of all experimental GPCR structures to maximize the conserved inter-helical contacts. The resulting superfamily-wide GpcR Sequence-Structure (GRoSS) alignment of the TM domains for all human GPCR sequences is sufficient to generate a phylogenetic tree that correctly distinguishes all different GPCR classes, suggesting that the class-level differences in the GPCR superfamily are encoded at least partly in the TM domains. The inter-helical contacts conserved across all GPCR classes describe the evolutionarily conserved GPCR structural fold. The corresponding structural alignment of the inactive and active conformations, available for a few GPCRs, identifies activation hot-spot residues in the TM domains that get rewired upon activation. Many GPCR mutations, known to alter receptor signaling and cause disease, are located at these conserved contact and activation hot-spot residue positions. The GRoSS alignment places the chemosensory receptor subfamilies for bitter taste (TAS2R) and pheromones (Vomeronasal, VN1R) in the rhodopsin family, known to contain the chemosensory olfactory receptor subfamily. The GRoSS alignment also enables the quantification of the structural variability in the TM regions of experimental structures, useful for homology modeling and structure prediction of receptors. Furthermore, this alignment identifies structurally and functionally important residues in all human GPCRs. These residues can be used to make testable hypotheses about the structural basis of receptor function and about the molecular basis of disease-associated single nucleotide polymorphisms. PMID:27028541

iDBPs: a web server for the identification of DNA binding proteins.

PubMed

Nimrod, Guy; Schushan, Maya; Szilágyi, András; Leslie, Christina; Ben-Tal, Nir

2010-03-01

The iDBPs server uses the three-dimensional (3D) structure of a query protein to predict whether it binds DNA. First, the algorithm predicts the functional region of the protein based on its evolutionary profile; the assumption is that large clusters of conserved residues are good markers of functional regions. Next, various characteristics of the predicted functional region as well as global features of the protein are calculated, such as the average surface electrostatic potential, the dipole moment and cluster-based amino acid conservation patterns. Finally, a random forests classifier is used to predict whether the query protein is likely to bind DNA and to estimate the prediction confidence. We have trained and tested the classifier on various datasets and shown that it outperformed related methods. On a dataset that reflects the fraction of DNA binding proteins (DBPs) in a proteome, the area under the ROC curve was 0.90. The application of the server to an updated version of the N-Func database, which contains proteins of unknown function with solved 3D-structure, suggested new putative DBPs for experimental studies. http://idbps.tau.ac.il/

Virtual Interactomics of Proteins from Biochemical Standpoint

PubMed Central

Kubrycht, Jaroslav; Sigler, Karel; Souček, Pavel

2012-01-01

Virtual interactomics represents a rapidly developing scientific area on the boundary line of bioinformatics and interactomics. Protein-related virtual interactomics then comprises instrumental tools for prediction, simulation, and networking of the majority of interactions important for structural and individual reproduction, differentiation, recognition, signaling, regulation, and metabolic pathways of cells and organisms. Here, we describe the main areas of virtual protein interactomics, that is, structurally based comparative analysis and prediction of functionally important interacting sites, mimotope-assisted and combined epitope prediction, molecular (protein) docking studies, and investigation of protein interaction networks. Detailed information about some interesting methodological approaches and online accessible programs or databases is displayed in our tables. Considerable part of the text deals with the searches for common conserved or functionally convergent protein regions and subgraphs of conserved interaction networks, new outstanding trends and clinically interesting results. In agreement with the presented data and relationships, virtual interactomic tools improve our scientific knowledge, help us to formulate working hypotheses, and they frequently also mediate variously important in silico simulations. PMID:22928109

Structural Analysis of PTM Hotspots (SAPH-ire)--A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families.

PubMed

Dewhurst, Henry M; Choudhury, Shilpa; Torres, Matthew P

2015-08-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)--a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits--conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit-N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Free energy minimization to predict RNA secondary structures and computational RNA design.

PubMed

Churkin, Alexander; Weinbrand, Lina; Barash, Danny

2015-01-01

Determining the RNA secondary structure from sequence data by computational predictions is a long-standing problem. Its solution has been approached in two distinctive ways. If a multiple sequence alignment of a collection of homologous sequences is available, the comparative method uses phylogeny to determine conserved base pairs that are more likely to form as a result of billions of years of evolution than by chance. In the case of single sequences, recursive algorithms that compute free energy structures by using empirically derived energy parameters have been developed. This latter approach of RNA folding prediction by energy minimization is widely used to predict RNA secondary structure from sequence. For a significant number of RNA molecules, the secondary structure of the RNA molecule is indicative of its function and its computational prediction by minimizing its free energy is important for its functional analysis. A general method for free energy minimization to predict RNA secondary structures is dynamic programming, although other optimization methods have been developed as well along with empirically derived energy parameters. In this chapter, we introduce and illustrate by examples the approach of free energy minimization to predict RNA secondary structures.

Protein structure based prediction of catalytic residues

PubMed Central

2013-01-01

Background Worldwide structural genomics projects continue to release new protein structures at an unprecedented pace, so far nearly 6000, but only about 60% of these proteins have any sort of functional annotation. Results We explored a range of features that can be used for the prediction of functional residues given a known three-dimensional structure. These features include various centrality measures of nodes in graphs of interacting residues: closeness, betweenness and page-rank centrality. We also analyzed the distance of functional amino acids to the general center of mass (GCM) of the structure, relative solvent accessibility (RSA), and the use of relative entropy as a measure of sequence conservation. From the selected features, neural networks were trained to identify catalytic residues. We found that using distance to the GCM together with amino acid type provide a good discriminant function, when combined independently with sequence conservation. Using an independent test set of 29 annotated protein structures, the method returned 411 of the initial 9262 residues as the most likely to be involved in function. The output 411 residues contain 70 of the annotated 111 catalytic residues. This represents an approximately 14-fold enrichment of catalytic residues on the entire input set (corresponding to a sensitivity of 63% and a precision of 17%), a performance competitive with that of other state-of-the-art methods. Conclusions We found that several of the graph based measures utilize the same underlying feature of protein structures, which can be simply and more effectively captured with the distance to GCM definition. This also has the added the advantage of simplicity and easy implementation. Meanwhile sequence conservation remains by far the most influential feature in identifying functional residues. We also found that due the rapid changes in size and composition of sequence databases, conservation calculations must be recalibrated for specific reference databases. PMID:23433045

Distribution and cluster analysis of predicted intrinsically disordered protein Pfam domains

PubMed Central

Williams, Robert W; Xue, Bin; Uversky, Vladimir N; Dunker, A Keith

2013-01-01

The Pfam database groups regions of proteins by how well hidden Markov models (HMMs) can be trained to recognize similarities among them. Conservation pressure is probably in play here. The Pfam seed training set includes sequence and structure information, being drawn largely from the PDB. A long standing hypothesis among intrinsically disordered protein (IDP) investigators has held that conservation pressures are also at play in the evolution of different kinds of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not always conserved across Pfam domains. Here we analyze distributions and clusters of PID regions in 193024 members of the version 23.0 Pfam seed database. To include the maximum information available for proteins that remain unfolded in solution, we employ the 10 linearly independent Kidera factors1–3 for the amino acids, combined with PONDR4 predictions of disorder tendency, to transform the sequences of these Pfam members into an 11 column matrix where the number of rows is the length of each Pfam region. Cluster analyses of the set of all regions, including those that are folded, show 6 groupings of domains. Cluster analyses of domains with mean VSL2b scores greater than 0.5 (half predicted disorder or more) show at least 3 separated groups. It is hypothesized that grouping sets into shorter sequences with more uniform length will reveal more information about intrinsic disorder and lead to more finely structured and perhaps more accurate predictions. HMMs could be trained to include this information. PMID:28516017

Structures-of-the-Whole: Is There Any Glue to Hold the Concrete-Operational "Stage" Together?

ERIC Educational Resources Information Center

Brainerd, Charles J.

Studies concerned with the synchronous emergence prediction of Piaget's structures-of-the-whole principle are discussed in conjunction with three groups of concrete-operational skills: (1) transitivity/conservation/class inclusion; (2) double classification/double seriation; and (3) ordinal, cardinal, and natural number concepts. Findings show…

Conservation of transcription factor binding events predicts gene expression across species

PubMed Central

Hemberg, Martin; Kreiman, Gabriel

2011-01-01

Recent technological advances have made it possible to determine the genome-wide binding sites of transcription factors (TFs). Comparisons across species have suggested a relatively low degree of evolutionary conservation of experimentally defined TF binding events (TFBEs). Using binding data for six different TFs in hepatocytes and embryonic stem cells from human and mouse, we demonstrate that evolutionary conservation of TFBEs within orthologous proximal promoters is closely linked to function, defined as expression of the target genes. We show that (i) there is a significantly higher degree of conservation of TFBEs when the target gene is expressed in both species; (ii) there is increased conservation of binding events for groups of TFs compared to individual TFs; and (iii) conserved TFBEs have a greater impact on the expression of their target genes than non-conserved ones. These results link conservation of structural elements (TFBEs) to conservation of function (gene expression) and suggest a higher degree of functional conservation than implied by previous studies. PMID:21622661

Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets.

PubMed

Ashford, Paul; Moss, David S; Alex, Alexander; Yeap, Siew K; Povia, Alice; Nobeli, Irene; Williams, Mark A

2012-03-14

Protein structures provide a valuable resource for rational drug design. For a protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate a complementary small-molecule drug. However, pocket prediction against single static structures may miss features of pockets that arise from proteins' dynamic behaviour. In particular, ligand-binding conformations can be observed as transiently populated states of the apo protein, so it is possible to gain insight into ligand-bound forms by considering conformational variation in apo proteins. This variation can be explored by considering sets of related structures: computationally generated conformers, solution NMR ensembles, multiple crystal structures, homologues or homology models. It is non-trivial to compare pockets, either from different programs or across sets of structures. For a single structure, difficulties arise in defining particular pocket's boundaries. For a set of conformationally distinct structures the challenge is how to make reasonable comparisons between them given that a perfect structural alignment is not possible. We have developed a computational method, Provar, that provides a consistent representation of predicted binding pockets across sets of related protein structures. The outputs are probabilities that each atom or residue of the protein borders a predicted pocket. These probabilities can be readily visualised on a protein using existing molecular graphics software. We show how Provar simplifies comparison of the outputs of different pocket prediction algorithms, of pockets across multiple simulated conformations and between homologous structures. We demonstrate the benefits of use of multiple structures for protein-ligand and protein-protein interface analysis on a set of complexes and consider three case studies in detail: i) analysis of a kinase superfamily highlights the conserved occurrence of surface pockets at the active and regulatory sites; ii) a simulated ensemble of unliganded Bcl2 structures reveals extensions of a known ligand-binding pocket not apparent in the apo crystal structure; iii) visualisations of interleukin-2 and its homologues highlight conserved pockets at the known receptor interfaces and regions whose conformation is known to change on inhibitor binding. Through post-processing of the output of a variety of pocket prediction software, Provar provides a flexible approach to the analysis and visualization of the persistence or variability of pockets in sets of related protein structures.

A TALE-inspired computational screen for proteins that contain approximate tandem repeats.

PubMed

Perycz, Malgorzata; Krwawicz, Joanna; Bochtler, Matthias

2017-01-01

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen.

A TALE-inspired computational screen for proteins that contain approximate tandem repeats

PubMed Central

Krwawicz, Joanna

2017-01-01

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen. PMID:28617832

Automated prediction of protein function and detection of functional sites from structure.

PubMed

Pazos, Florencio; Sternberg, Michael J E

2004-10-12

Current structural genomics projects are yielding structures for proteins whose functions are unknown. Accordingly, there is a pressing requirement for computational methods for function prediction. Here we present PHUNCTIONER, an automatic method for structure-based function prediction using automatically extracted functional sites (residues associated to functions). The method relates proteins with the same function through structural alignments and extracts 3D profiles of conserved residues. Functional features to train the method are extracted from the Gene Ontology (GO) database. The method extracts these features from the entire GO hierarchy and hence is applicable across the whole range of function specificity. 3D profiles associated with 121 GO annotations were extracted. We tested the power of the method both for the prediction of function and for the extraction of functional sites. The success of function prediction by our method was compared with the standard homology-based method. In the zone of low sequence similarity (approximately 15%), our method assigns the correct GO annotation in 90% of the protein structures considered, approximately 20% higher than inheritance of function from the closest homologue.

The identification and functional annotation of RNA structures conserved in vertebrates

PubMed Central

Seemann, Stefan E.; Mirza, Aashiq H.; Hansen, Claus; Bang-Berthelsen, Claus H.; Garde, Christian; Christensen-Dalsgaard, Mikkel; Torarinsson, Elfar; Yao, Zizhen; Workman, Christopher T.; Pociot, Flemming; Nielsen, Henrik; Tommerup, Niels; Ruzzo, Walter L.; Gorodkin, Jan

2017-01-01

Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human–mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3′ ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality. PMID:28487280

iDBPs: a web server for the identification of DNA binding proteins

PubMed Central

Nimrod, Guy; Schushan, Maya; Szilágyi, András; Leslie, Christina; Ben-Tal, Nir

2010-01-01

Summary: The iDBPs server uses the three-dimensional (3D) structure of a query protein to predict whether it binds DNA. First, the algorithm predicts the functional region of the protein based on its evolutionary profile; the assumption is that large clusters of conserved residues are good markers of functional regions. Next, various characteristics of the predicted functional region as well as global features of the protein are calculated, such as the average surface electrostatic potential, the dipole moment and cluster-based amino acid conservation patterns. Finally, a random forests classifier is used to predict whether the query protein is likely to bind DNA and to estimate the prediction confidence. We have trained and tested the classifier on various datasets and shown that it outperformed related methods. On a dataset that reflects the fraction of DNA binding proteins (DBPs) in a proteome, the area under the ROC curve was 0.90. The application of the server to an updated version of the N-Func database, which contains proteins of unknown function with solved 3D-structure, suggested new putative DBPs for experimental studies. Availability: http://idbps.tau.ac.il/ Contact: NirB@tauex.tau.ac.il Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20089514

Evolutionary and Functional Relationships in the Truncated Hemoglobin Family.

PubMed

Bustamante, Juan P; Radusky, Leandro; Boechi, Leonardo; Estrin, Darío A; Ten Have, Arjen; Martí, Marcelo A

2016-01-01

Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2 affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends.

Evolutionary and Functional Relationships in the Truncated Hemoglobin Family

PubMed Central

Bustamante, Juan P.; Radusky, Leandro; Boechi, Leonardo; Estrin, Darío A.; ten Have, Arjen; Martí, Marcelo A.

2016-01-01

Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2 affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends. PMID:26788940

Structural habitat predicts functional dispersal habitat of a large carnivore: how leopards change spots.

PubMed

Fattebert, Julien; Robinson, Hugh S; Balme, Guy; Slotow, Rob; Hunter, Luke

2015-10-01

Natal dispersal promotes inter-population linkage, and is key to spatial distribution of populations. Degradation of suitable landscape structures beyond the specific threshold of an individual's ability to disperse can therefore lead to disruption of functional landscape connectivity and impact metapopulation function. Because it ignores behavioral responses of individuals, structural connectivity is easier to assess than functional connectivity and is often used as a surrogate for landscape connectivity modeling. However using structural resource selection models as surrogate for modeling functional connectivity through dispersal could be erroneous. We tested how well a second-order resource selection function (RSF) models (structural connectivity), based on GPS telemetry data from resident adult leopard (Panthera pardus L.), could predict subadult habitat use during dispersal (functional connectivity). We created eight non-exclusive subsets of the subadult data based on differing definitions of dispersal to assess the predictive ability of our adult-based RSF model extrapolated over a broader landscape. Dispersing leopards used habitats in accordance with adult selection patterns, regardless of the definition of dispersal considered. We demonstrate that, for a wide-ranging apex carnivore, functional connectivity through natal dispersal corresponds to structural connectivity as modeled by a second-order RSF. Mapping of the adult-based habitat classes provides direct visualization of the potential linkages between populations, without the need to model paths between a priori starting and destination points. The use of such landscape scale RSFs may provide insight into predicting suitable dispersal habitat peninsulas in human-dominated landscapes where mitigation of human-wildlife conflict should be focused. We recommend the use of second-order RSFs for landscape conservation planning and propose a similar approach to the conservation of other wide-ranging large carnivore species where landscape-scale resource selection data already exist.

Local Geometry and Evolutionary Conservation of Protein Surfaces Reveal the Multiple Recognition Patches in Protein-Protein Interactions

PubMed Central

Laine, Elodie; Carbone, Alessandra

2015-01-01

Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins and binding to multiple partners. Contrary to machine learning approaches, our method combines in a rational and very straightforward way three sequence- and structure-based descriptors of protein residues: evolutionary conservation, physico-chemical properties and local geometry. The implemented strategy yields very precise predictions for a wide range of protein-protein interfaces and discriminates them from small-molecule binding sites. Beyond its predictive power, the approach permits to dissect interaction surfaces and unravel their complexity. We show how the analysis of the predicted patches can foster new strategies for PPIs modulation and interaction surface redesign. The approach is implemented in JET2, an automated tool based on the Joint Evolutionary Trees (JET) method for sequence-based protein interface prediction. JET2 is freely available at www.lcqb.upmc.fr/JET2. PMID:26690684

Structure Predictions of Two Bauhinia variegata Lectins Reveal Patterns of C-Terminal Properties in Single Chain Legume Lectins

PubMed Central

Moreira, Gustavo M. S. G.; Conceição, Fabricio R.; McBride, Alan J. A.; Pinto, Luciano da S.

2013-01-01

Bauhinia variegata lectins (BVL-I and BVL-II) are single chain lectins isolated from the plant Bauhinia variegata. Single chain lectins undergo post-translational processing on its N-terminal and C-terminal regions, which determines their physiological targeting, carbohydrate binding activity and pattern of quaternary association. These two lectins are isoforms, BVL-I being highly glycosylated, and thus far, it has not been possible to determine their structures. The present study used prediction and validation algorithms to elucidate the likely structures of BVL-I and -II. The program Bhageerath-H was chosen from among three different structure prediction programs due to its better overall reliability. In order to predict the C-terminal region cleavage sites, other lectins known to have this modification were analysed and three rules were created: (1) the first amino acid of the excised peptide is small or hydrophobic; (2) the cleavage occurs after an acid, polar, or hydrophobic residue, but not after a basic one; and (3) the cleavage spot is located 5-8 residues after a conserved Leu amino acid. These rules predicted that BVL-I and –II would have fifteen C-terminal residues cleaved, and this was confirmed experimentally by Edman degradation sequencing of BVL-I. Furthermore, the C-terminal analyses predicted that only BVL-II underwent α-helical folding in this region, similar to that seen in SBA and DBL. Conversely, BVL-I and -II contained four conserved regions of a GS-I association, providing evidence of a previously undescribed X4+unusual oligomerisation between the truncated BVL-I and the intact BVL-II. This is the first report on the structural analysis of lectins from Bauhinia spp. and therefore is important for the characterisation C-terminal cleavage and patterns of quaternary association of single chain lectins. PMID:24260572

Structure predictions of two Bauhinia variegata lectins reveal patterns of C-terminal properties in single chain legume lectins.

PubMed

Moreira, Gustavo M S G; Conceição, Fabricio R; McBride, Alan J A; Pinto, Luciano da S

2013-01-01

Bauhinia variegata lectins (BVL-I and BVL-II) are single chain lectins isolated from the plant Bauhinia variegata. Single chain lectins undergo post-translational processing on its N-terminal and C-terminal regions, which determines their physiological targeting, carbohydrate binding activity and pattern of quaternary association. These two lectins are isoforms, BVL-I being highly glycosylated, and thus far, it has not been possible to determine their structures. The present study used prediction and validation algorithms to elucidate the likely structures of BVL-I and -II. The program Bhageerath-H was chosen from among three different structure prediction programs due to its better overall reliability. In order to predict the C-terminal region cleavage sites, other lectins known to have this modification were analysed and three rules were created: (1) the first amino acid of the excised peptide is small or hydrophobic; (2) the cleavage occurs after an acid, polar, or hydrophobic residue, but not after a basic one; and (3) the cleavage spot is located 5-8 residues after a conserved Leu amino acid. These rules predicted that BVL-I and -II would have fifteen C-terminal residues cleaved, and this was confirmed experimentally by Edman degradation sequencing of BVL-I. Furthermore, the C-terminal analyses predicted that only BVL-II underwent α-helical folding in this region, similar to that seen in SBA and DBL. Conversely, BVL-I and -II contained four conserved regions of a GS-I association, providing evidence of a previously undescribed X4+unusual oligomerisation between the truncated BVL-I and the intact BVL-II. This is the first report on the structural analysis of lectins from Bauhinia spp. and therefore is important for the characterisation C-terminal cleavage and patterns of quaternary association of single chain lectins.

Disease-Associated Mutations Disrupt Functionally Important Regions of Intrinsic Protein Disorder

PubMed Central

Vacic, Vladimir; Markwick, Phineus R. L.; Oldfield, Christopher J.; Zhao, Xiaoyue; Haynes, Chad; Uversky, Vladimir N.; Iakoucheva, Lilia M.

2012-01-01

The effects of disease mutations on protein structure and function have been extensively investigated, and many predictors of the functional impact of single amino acid substitutions are publicly available. The majority of these predictors are based on protein structure and evolutionary conservation, following the assumption that disease mutations predominantly affect folded and conserved protein regions. However, the prevalence of the intrinsically disordered proteins (IDPs) and regions (IDRs) in the human proteome together with their lack of fixed structure and low sequence conservation raise a question about the impact of disease mutations in IDRs. Here, we investigate annotated missense disease mutations and show that 21.7% of them are located within such intrinsically disordered regions. We further demonstrate that 20% of disease mutations in IDRs cause local disorder-to-order transitions, which represents a 1.7–2.7 fold increase compared to annotated polymorphisms and neutral evolutionary substitutions, respectively. Secondary structure predictions show elevated rates of transition from helices and strands into loops and vice versa in the disease mutations dataset. Disease disorder-to-order mutations also influence predicted molecular recognition features (MoRFs) more often than the control mutations. The repertoire of disorder-to-order transition mutations is limited, with five most frequent mutations (R→W, R→C, E→K, R→H, R→Q) collectively accounting for 44% of all deleterious disorder-to-order transitions. As a proof of concept, we performed accelerated molecular dynamics simulations on a deleterious disorder-to-order transition mutation of tumor protein p63 and, in agreement with our predictions, observed an increased α-helical propensity of the region harboring the mutation. Our findings highlight the importance of mutations in IDRs and refine the traditional structure-centric view of disease mutations. The results of this study offer a new perspective on the role of mutations in disease, with implications for improving predictors of the functional impact of missense mutations. PMID:23055912

Conserved intergenic sequences revealed by CTAG-profiling in Salmonella: thermodynamic modeling for function prediction

NASA Astrophysics Data System (ADS)

Tang, Le; Zhu, Songling; Mastriani, Emilio; Fang, Xin; Zhou, Yu-Jie; Li, Yong-Guo; Johnston, Randal N.; Guo, Zheng; Liu, Gui-Rong; Liu, Shu-Lin

2017-03-01

Highly conserved short sequences help identify functional genomic regions and facilitate genomic annotation. We used Salmonella as the model to search the genome for evolutionarily conserved regions and focused on the tetranucleotide sequence CTAG for its potentially important functions. In Salmonella, CTAG is highly conserved across the lineages and large numbers of CTAG-containing short sequences fall in intergenic regions, strongly indicating their biological importance. Computer modeling demonstrated stable stem-loop structures in some of the CTAG-containing intergenic regions, and substitution of a nucleotide of the CTAG sequence would radically rearrange the free energy and disrupt the structure. The postulated degeneration of CTAG takes distinct patterns among Salmonella lineages and provides novel information about genomic divergence and evolution of these bacterial pathogens. Comparison of the vertically and horizontally transmitted genomic segments showed different CTAG distribution landscapes, with the genome amelioration process to remove CTAG taking place inward from both terminals of the horizontally acquired segment.

Relative Packing Groups in Template-Based Structure Prediction: Cooperative Effects of True Positive Constraints

PubMed Central

Day, Ryan; Qu, Xiaotao; Swanson, Rosemarie; Bohannan, Zach; Bliss, Robert

2011-01-01

Abstract Most current template-based structure prediction methods concentrate on finding the correct backbone conformation and then packing sidechains within that backbone. Our packing-based method derives distance constraints from conserved relative packing groups (RPGs). In our refinement approach, the RPGs provide a level of resolution that restrains global topology while allowing conformational sampling. In this study, we test our template-based structure prediction method using 51 prediction units from CASP7 experiments. RPG-based constraints are able to substantially improve approximately two-thirds of starting templates. Upon deeper investigation, we find that true positive spatial constraints, especially those non-local in sequence, derived from the RPGs were important to building nearer native models. Surprisingly, the fraction of incorrect or false positive constraints does not strongly influence the quality of the final candidate. This result indicates that our RPG-based true positive constraints sample the self-consistent, cooperative interactions of the native structure. The lack of such reinforcing cooperativity explains the weaker effect of false positive constraints. Generally, these findings are encouraging indications that RPGs will improve template-based structure prediction. PMID:21210729

Coevolutionary modeling of protein sequences: Predicting structure, function, and mutational landscapes

NASA Astrophysics Data System (ADS)

Weigt, Martin

Over the last years, biological research has been revolutionized by experimental high-throughput techniques, in particular by next-generation sequencing technology. Unprecedented amounts of data are accumulating, and there is a growing request for computational methods unveiling the information hidden in raw data, thereby increasing our understanding of complex biological systems. Statistical-physics models based on the maximum-entropy principle have, in the last few years, played an important role in this context. To give a specific example, proteins and many non-coding RNA show a remarkable degree of structural and functional conservation in the course of evolution, despite a large variability in amino acid sequences. We have developed a statistical-mechanics inspired inference approach - called Direct-Coupling Analysis - to link this sequence variability (easy to observe in sequence alignments, which are available in public sequence databases) to bio-molecular structure and function. In my presentation I will show, how this methodology can be used (i) to infer contacts between residues and thus to guide tertiary and quaternary protein structure prediction and RNA structure prediction, (ii) to discriminate interacting from non-interacting protein families, and thus to infer conserved protein-protein interaction networks, and (iii) to reconstruct mutational landscapes and thus to predict the phenotypic effect of mutations. References [1] M. Figliuzzi, H. Jacquier, A. Schug, O. Tenaillon and M. Weigt ''Coevolutionary landscape inference and the context-dependence of mutations in beta-lactamase TEM-1'', Mol. Biol. Evol. (2015), doi: 10.1093/molbev/msv211 [2] E. De Leonardis, B. Lutz, S. Ratz, S. Cocco, R. Monasson, A. Schug, M. Weigt ''Direct-Coupling Analysis of nucleotide coevolution facilitates RNA secondary and tertiary structure prediction'', Nucleic Acids Research (2015), doi: 10.1093/nar/gkv932 [3] F. Morcos, A. Pagnani, B. Lunt, A. Bertolino, D. Marks, C. Sander, R. Zecchina, J.N. Onuchic, T. Hwa, M. Weigt, ''Direct-coupling analysis of residue co-evolution captures native contacts across many protein families'', Proc. Natl. Acad. Sci. 108, E1293-E1301 (2011).

The Druggable Pocketome of Corynebacterium diphtheriae: A New Approach for in silico Putative Druggable Targets

PubMed Central

Hassan, Syed S.; Jamal, Syed B.; Radusky, Leandro G.; Tiwari, Sandeep; Ullah, Asad; Ali, Javed; Behramand; de Carvalho, Paulo V. S. D.; Shams, Rida; Khan, Sabir; Figueiredo, Henrique C. P.; Barh, Debmalya; Ghosh, Preetam; Silva, Artur; Baumbach, Jan; Röttger, Richard; Turjanski, Adrián G.; Azevedo, Vasco A. C.

2018-01-01

Diphtheria is an acute and highly infectious disease, previously regarded as endemic in nature but vaccine-preventable, is caused by Corynebacterium diphtheriae (Cd). In this work, we used an in silico approach along the 13 complete genome sequences of C. diphtheriae followed by a computational assessment of structural information of the binding sites to characterize the “pocketome druggability.” To this end, we first computed the “modelome” (3D structures of a complete genome) of a randomly selected reference strain Cd NCTC13129; that had 13,763 open reading frames (ORFs) and resulted in 1,253 (∼9%) structure models. The amino acid sequences of these modeled structures were compared with the remaining 12 genomes and consequently, 438 conserved protein sequences were obtained. The RCSB-PDB database was consulted to check the template structures for these conserved proteins and as a result, 401 adequate 3D models were obtained. We subsequently predicted the protein pockets for the obtained set of models and kept only the conserved pockets that had highly druggable (HD) values (137 across all strains). Later, an off-target host homology analyses was performed considering the human proteome using NCBI database. Furthermore, the gene essentiality analysis was carried out that gave a final set of 10-conserved targets possessing highly druggable protein pockets. To check the target identification robustness of the pipeline used in this work, we crosschecked the final target list with another in-house target identification approach for C. diphtheriae thereby obtaining three common targets, these were; hisE-phosphoribosyl-ATP pyrophosphatase, glpX-fructose 1,6-bisphosphatase II, and rpsH-30S ribosomal protein S8. Our predicted results suggest that the in silico approach used could potentially aid in experimental polypharmacological target determination in C. diphtheriae and other pathogens, thereby, might complement the existing and new drug-discovery pipelines. PMID:29487617

Octupole correlations in the 144Ba nucleus described with symmetry-conserving configuration-mixing calculations

NASA Astrophysics Data System (ADS)

Bernard, Rémi N.; Robledo, Luis M.; Rodríguez, Tomás R.

2016-06-01

We study the interplay of quadrupole and octupole degrees of freedom in the structure of the isotope 144Ba. A symmetry-conserving configuration-mixing method (SCCM) based on a Gogny energy density functional (EDF) has been used. The method includes particle number, parity, and angular momentum restoration as well as axial quadrupole and octupole shape mixing within the generator coordinate method. Predictions both for excitation energies and electromagnetic transition probabilities are in good agreement with the most recent experimental data.

Ligand Binding Site Detection by Local Structure Alignment and Its Performance Complementarity

PubMed Central

Lee, Hui Sun; Im, Wonpil

2013-01-01

Accurate determination of potential ligand binding sites (BS) is a key step for protein function characterization and structure-based drug design. Despite promising results of template-based BS prediction methods using global structure alignment (GSA), there is a room to improve the performance by properly incorporating local structure alignment (LSA) because BS are local structures and often similar for proteins with dissimilar global folds. We present a template-based ligand BS prediction method using G-LoSA, our LSA tool. A large benchmark set validation shows that G-LoSA predicts drug-like ligands’ positions in single-chain protein targets more precisely than TM-align, a GSA-based method, while the overall success rate of TM-align is better. G-LoSA is particularly efficient for accurate detection of local structures conserved across proteins with diverse global topologies. Recognizing the performance complementarity of G-LoSA to TM-align and a non-template geometry-based method, fpocket, a robust consensus scoring method, CMCS-BSP (Complementary Methods and Consensus Scoring for ligand Binding Site Prediction), is developed and shows improvement on prediction accuracy. The G-LoSA source code is freely available at http://im.bioinformatics.ku.edu/GLoSA. PMID:23957286

Scaling local species-habitat relations to the larger landscape with a hierarchical spatial count model

USGS Publications Warehouse

Thogmartin, W.E.; Knutson, M.G.

2007-01-01

Much of what is known about avian species-habitat relations has been derived from studies of birds at local scales. It is entirely unclear whether the relations observed at these scales translate to the larger landscape in a predictable linear fashion. We derived habitat models and mapped predicted abundances for three forest bird species of eastern North America using bird counts, environmental variables, and hierarchical models applied at three spatial scales. Our purpose was to understand habitat associations at multiple spatial scales and create predictive abundance maps for purposes of conservation planning at a landscape scale given the constraint that the variables used in this exercise were derived from local-level studies. Our models indicated a substantial influence of landscape context for all species, many of which were counter to reported associations at finer spatial extents. We found land cover composition provided the greatest contribution to the relative explained variance in counts for all three species; spatial structure was second in importance. No single spatial scale dominated any model, indicating that these species are responding to factors at multiple spatial scales. For purposes of conservation planning, areas of predicted high abundance should be investigated to evaluate the conservation potential of the landscape in their general vicinity. In addition, the models and spatial patterns of abundance among species suggest locations where conservation actions may benefit more than one species. ?? 2006 Springer Science+Business Media B.V.

The identification and functional annotation of RNA structures conserved in vertebrates.

PubMed

Seemann, Stefan E; Mirza, Aashiq H; Hansen, Claus; Bang-Berthelsen, Claus H; Garde, Christian; Christensen-Dalsgaard, Mikkel; Torarinsson, Elfar; Yao, Zizhen; Workman, Christopher T; Pociot, Flemming; Nielsen, Henrik; Tommerup, Niels; Ruzzo, Walter L; Gorodkin, Jan

2017-08-01

Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human-mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3' ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality. © 2017 Seemann et al.; Published by Cold Spring Harbor Laboratory Press.

Rapid Characterisation of Vegetation Structure to Predict Refugia and Climate Change Impacts across a Global Biodiversity Hotspot

PubMed Central

Schut, Antonius G. T.; Wardell-Johnson, Grant W.; Yates, Colin J.; Keppel, Gunnar; Baran, Ireneusz; Franklin, Steven E.; Hopper, Stephen D.; Van Niel, Kimberley P.; Mucina, Ladislav; Byrne, Margaret

2014-01-01

Identification of refugia is an increasingly important adaptation strategy in conservation planning under rapid anthropogenic climate change. Granite outcrops (GOs) provide extraordinary diversity, including a wide range of taxa, vegetation types and habitats in the Southwest Australian Floristic Region (SWAFR). However, poor characterization of GOs limits the capacity of conservation planning for refugia under climate change. A novel means for the rapid identification of potential refugia is presented, based on the assessment of local-scale environment and vegetation structure in a wider region. This approach was tested on GOs across the SWAFR. Airborne discrete return Light Detection And Ranging (LiDAR) data and Red Green and Blue (RGB) imagery were acquired. Vertical vegetation profiles were used to derive 54 structural classes. Structural vegetation types were described in three areas for supervised classification of a further 13 GOs across the region. Habitat descriptions based on 494 vegetation plots on and around these GOs were used to quantify relationships between environmental variables, ground cover and canopy height. The vegetation surrounding GOs is strongly related to structural vegetation types (Kappa = 0.8) and to its spatial context. Water gaining sites around GOs are characterized by taller and denser vegetation in all areas. The strong relationship between rainfall, soil-depth, and vegetation structure (R2 of 0.8–0.9) allowed comparisons of vegetation structure between current and future climate. Significant shifts in vegetation structural types were predicted and mapped for future climates. Water gaining areas below granite outcrops were identified as important putative refugia. A reduction in rainfall may be offset by the occurrence of deeper soil elsewhere on the outcrop. However, climate change interactions with fire and water table declines may render our conclusions conservative. The LiDAR-based mapping approach presented enables the integration of site-based biotic assessment with structural vegetation types for the rapid delineation and prioritization of key refugia. PMID:24416149

Rapid characterisation of vegetation structure to predict refugia and climate change impacts across a global biodiversity hotspot.

PubMed

Schut, Antonius G T; Wardell-Johnson, Grant W; Yates, Colin J; Keppel, Gunnar; Baran, Ireneusz; Franklin, Steven E; Hopper, Stephen D; Van Niel, Kimberley P; Mucina, Ladislav; Byrne, Margaret

2014-01-01

Identification of refugia is an increasingly important adaptation strategy in conservation planning under rapid anthropogenic climate change. Granite outcrops (GOs) provide extraordinary diversity, including a wide range of taxa, vegetation types and habitats in the Southwest Australian Floristic Region (SWAFR). However, poor characterization of GOs limits the capacity of conservation planning for refugia under climate change. A novel means for the rapid identification of potential refugia is presented, based on the assessment of local-scale environment and vegetation structure in a wider region. This approach was tested on GOs across the SWAFR. Airborne discrete return Light Detection And Ranging (LiDAR) data and Red Green and Blue (RGB) imagery were acquired. Vertical vegetation profiles were used to derive 54 structural classes. Structural vegetation types were described in three areas for supervised classification of a further 13 GOs across the region. Habitat descriptions based on 494 vegetation plots on and around these GOs were used to quantify relationships between environmental variables, ground cover and canopy height. The vegetation surrounding GOs is strongly related to structural vegetation types (Kappa = 0.8) and to its spatial context. Water gaining sites around GOs are characterized by taller and denser vegetation in all areas. The strong relationship between rainfall, soil-depth, and vegetation structure (R(2) of 0.8-0.9) allowed comparisons of vegetation structure between current and future climate. Significant shifts in vegetation structural types were predicted and mapped for future climates. Water gaining areas below granite outcrops were identified as important putative refugia. A reduction in rainfall may be offset by the occurrence of deeper soil elsewhere on the outcrop. However, climate change interactions with fire and water table declines may render our conclusions conservative. The LiDAR-based mapping approach presented enables the integration of site-based biotic assessment with structural vegetation types for the rapid delineation and prioritization of key refugia.

The crystal structure of the regulatory domain of the human sodium-driven chloride/bicarbonate exchanger.

PubMed

Alvadia, Carolina M; Sommer, Theis; Bjerregaard-Andersen, Kaare; Damkier, Helle Hasager; Montrasio, Michele; Aalkjaer, Christian; Morth, J Preben

2017-09-21

The sodium-driven chloride/bicarbonate exchanger (NDCBE) is essential for maintaining homeostatic pH in neurons. The crystal structure at 2.8 Å resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. The VTVLP motif is highly conserved and likely to be the physiologically relevant interface for all other members of the SLC4 family. A novel conserved Zn 2+ -binding motif present in the N-terminal domain of NDCBE is identified and characterized in vitro. Cellular studies confirm the Zn 2+ dependent transport of two electroneutral bicarbonate transporters, NCBE and NBCn1. The Zn 2+ site is mapped to a cluster of histidines close to the conserved ETARWLKFEE motif and likely plays a role in the regulation of this important motif. The combined structural and bioinformatics analysis provides a model that predicts with additional confidence the physiologically relevant interface between the cytoplasmic domain and the transmembrane domain.

Some difficulties and inconsistencies when using habit strength and reasoned action variables in models of metered household water conservation.

PubMed

Jorgensen, Bradley S; Martin, John F; Pearce, Meryl; Willis, Eileen

2013-01-30

Research employing household water consumption data has sought to test models of water demand and conservation using variables from attitude theory. A significant, albeit unrecognised, challenge has been that attitude models describe individual-level motivations while consumption data is recorded at the household level thereby creating inconsistency between units of theory and measurement. This study employs structural equation modelling and moderated regression techniques to addresses the level of analysis problem, and tests hypotheses by isolating effects on water conservation in single-person households. Furthermore, the results question the explanatory utility of habit strength, perceived behavioural control, and intentions for understanding metered water conservation in single-person households. For example, evidence that intentions predict water conservation or that they interact with habit strength in single-person households was contrary to theoretical expectations. On the other hand, habit strength, self-reports of past water conservation, and perceived behavioural control were good predictors of intentions to conserve water. Copyright © 2012 Elsevier Ltd. All rights reserved.

Application of the Collision-Imparted Velocity Method for Analyzing the Responses of Containment and Deflector Structures to Engine Rotor Fragment Impact

NASA Technical Reports Server (NTRS)

Collins, T. P.; Witmer, E. A.

1973-01-01

An approximate analysis, termed the Collision Imparted Velocity Method (CIVM), was employed for predicting the transient structural responses of containment rings or deflector rings which are subjected to impact from turbojet-engine rotor burst fragments. These 2-d structural rings may be initially circular or arbitrarily curved and may have either uniform or variable thickness; elastic, strain hardening, and strain rate material properties are accommodated. This approximate analysis utilizes kinetic energy and momentum conservation relations in order to predict the after-impact velocities of the fragment and the impacted ring segment. This information is then used in conjunction with a finite element structural response computation code to predict the transient, large deflection responses of the ring. Similarly, the equations of motion for each fragment are solved in small steps in time. Also, some comparisons of predictions with experimental data for fragment-impacted free containment rings are presented.

Accurate predictions of population-level changes in sequence and structural properties of HIV-1 Env using a volatility-controlled diffusion model

PubMed Central

DeLeon, Orlando; Hodis, Hagit; O’Malley, Yunxia; Johnson, Jacklyn; Salimi, Hamid; Zhai, Yinjie; Winter, Elizabeth; Remec, Claire; Eichelberger, Noah; Van Cleave, Brandon; Puliadi, Ramya; Harrington, Robert D.; Stapleton, Jack T.; Haim, Hillel

2017-01-01

The envelope glycoproteins (Envs) of HIV-1 continuously evolve in the host by random mutations and recombination events. The resulting diversity of Env variants circulating in the population and their continuing diversification process limit the efficacy of AIDS vaccines. We examined the historic changes in Env sequence and structural features (measured by integrity of epitopes on the Env trimer) in a geographically defined population in the United States. As expected, many Env features were relatively conserved during the 1980s. From this state, some features diversified whereas others remained conserved across the years. We sought to identify “clues” to predict the observed historic diversification patterns. Comparison of viruses that cocirculate in patients at any given time revealed that each feature of Env (sequence or structural) exists at a defined level of variance. The in-host variance of each feature is highly conserved among individuals but can vary between different HIV-1 clades. We designate this property “volatility” and apply it to model evolution of features as a linear diffusion process that progresses with increasing genetic distance. Volatilities of different features are highly correlated with their divergence in longitudinally monitored patients. Volatilities of features also correlate highly with their population-level diversification. Using volatility indices measured from a small number of patient samples, we accurately predict the population diversity that developed for each feature over the course of 30 years. Amino acid variants that evolved at key antigenic sites are also predicted well. Therefore, small “fluctuations” in feature values measured in isolated patient samples accurately describe their potential for population-level diversification. These tools will likely contribute to the design of population-targeted AIDS vaccines by effectively capturing the diversity of currently circulating strains and addressing properties of variants expected to appear in the future. PMID:28384158

G-quadruplex prediction in E. coli genome reveals a conserved putative G-quadruplex-Hairpin-Duplex switch.

PubMed

Kaplan, Oktay I; Berber, Burak; Hekim, Nezih; Doluca, Osman

2016-11-02

Many studies show that short non-coding sequences are widely conserved among regulatory elements. More and more conserved sequences are being discovered since the development of next generation sequencing technology. A common approach to identify conserved sequences with regulatory roles relies on topological changes such as hairpin formation at the DNA or RNA level. G-quadruplexes, non-canonical nucleic acid topologies with little established biological roles, are increasingly considered for conserved regulatory element discovery. Since the tertiary structure of G-quadruplexes is strongly dependent on the loop sequence which is disregarded by the generally accepted algorithm, we hypothesized that G-quadruplexes with similar topology and, indirectly, similar interaction patterns, can be determined using phylogenetic clustering based on differences in the loop sequences. Phylogenetic analysis of 52 G-quadruplex forming sequences in the Escherichia coli genome revealed two conserved G-quadruplex motifs with a potential regulatory role. Further analysis revealed that both motifs tend to form hairpins and G quadruplexes, as supported by circular dichroism studies. The phylogenetic analysis as described in this work can greatly improve the discovery of functional G-quadruplex structures and may explain unknown regulatory patterns. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genomic cloning and promoter functional analysis of myostatin-2 in shi drum, Umbrina cirrosa: conservation of muscle-specific promoter activity.

PubMed

Nadjar-Boger, Elisabeth; Maccatrozzo, Lisa; Radaelli, Giuseppe; Funkenstein, Bruria

2013-02-01

Myostatin (MSTN) is a member of the transforming growth factor-ß superfamily, known as a negative regulator of skeletal muscle development and growth in mammals. In contrast to mammals, fish possess at least two paralogs of MSTN: MSTN-1 and MSTN-2. Here we describe the cloning and sequence analysis of spliced and precursor (unspliced) transcripts as well as the 5' flanking region of MSTN-2 from the marine fish Umbrina cirrosa (ucMSTN-2). In silico analysis revealed numerous putative cis regulatory elements including several E-boxes known as binding sites to myogenic transcription factors. Transient transfection experiments using non-muscle and muscle cell lines showed high transcriptional activity in muscle cells and in differentiated neural cells, in accordance with our previous findings in MSTN-2 promoter from Sparus aurata. Comparative informatics analysis of MSTN-2 from several fish species revealed high conservation of the predicted amino acid sequence as well as the gene structure (exon length) although intron length varied between species. The proximal promoter of MSTN-2 gene was found to be conserved among Perciforms. In conclusion, this study reinforces our conclusion that MSTN-2 promoter is a very strong promoter, especially in muscle cells. In addition, we show that the MSTN-2 gene structure is highly conserved among fishes as is the predicted amino acid sequence of the peptide. Copyright © 2012 Elsevier Inc. All rights reserved.

Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tong, Junsen; Yang, Huiseon; Eom, Soo Hyun

2014-09-12

Graphical abstract: - Highlights: • The crystal structure of GKAP homology domain 1 (GH1) was determined. • GKAP GH1 is a three-helix bundle connected by short flexible loops. • The predicted helix α4 associates weakly with the helix α3, suggesting dynamic nature of the GH1 domain. - Abstract: Guanylate-kinase-associated protein (GKAP) is a scaffolding protein that links NMDA receptor-PSD-95 to Shank–Homer complexes by protein–protein interactions at the synaptic junction. GKAP family proteins are characterized by the presence of a C-terminal conserved GKAP homology domain 1 (GH1) of unknown structure and function. In this study, crystal structure of the GH1 domainmore » of GKAP from Rattus norvegicus was determined in fusion with an N-terminal maltose-binding protein at 2.0 Å resolution. The structure of GKAP GH1 displays a three-helix bundle connected by short flexible loops. The predicted helix α4 which was not visible in the crystal structure associates weakly with the helix α3 suggesting dynamic nature of the GH1 domain. The strict conservation of GH1 domain across GKAP family members and the lack of a catalytic active site required for enzyme activity imply that the GH1 domain might serve as a protein–protein interaction module for the synaptic protein clustering.« less

Filling the gaps: Predicting the distribution of temperate reef biota using high resolution biological and acoustic data

NASA Astrophysics Data System (ADS)

Hill, Nicole A.; Lucieer, Vanessa; Barrett, Neville S.; Anderson, Tara J.; Williams, Stefan B.

2014-06-01

Management of the marine environment is often hampered by a lack of comprehensive spatial information on the distribution of diversity and the bio-physical processes structuring regional ecosystems. This is particularly true in temperate reef systems beyond depths easily accessible to divers. Yet these systems harbor a diversity of sessile life that provide essential ecosystem services, sustain fisheries and, as with shallower ecosystems, are also increasingly vulnerable to anthropogenic impacts and environmental change. Here we use cutting-edge tools (Autonomous Underwater Vehicles and ship-borne acoustics) and analytical approaches (predictive modelling) to quantify and map these highly productive ecosystems. We find the occurrence of key temperate-reef biota can be explained and predicted using standard (depth) and novel (texture) surrogates derived from multibeam acoustic data, and geographic surrogates. This suggests that combinations of fine-scale processes, such as light limitation and habitat complexity, and broad-scale processes, such as regional currents and exposure regimes, are important in structuring these diverse deep-reef communities. While some dominant habitat forming biota, including canopy algae, were widely distributed, others, including gorgonians and sea whips, exhibited patchy and restricted distributions across the reef system. In addition to providing the first quantitative and full coverage maps of reef diversity for this area, our modelling revealed that offshore reefs represented a regional diversity hotspot that is of high ecological and conservation value. Regional reef systems should not, therefore, be considered homogenous units in conservation planning and management. Full-coverage maps of the predicted distribution of biota (and associated uncertainty) are likely to be increasingly valuable, not only for conservation planning, but in the ongoing management and monitoring of these less-accessible ecosystems.

Predicting Greater Prairie-Chicken Lek Site Suitability to Inform Conservation Actions

PubMed Central

Hovick, Torre J.; Dahlgren, David K.; Papeş, Monica; Elmore, R. Dwayne; Pitman, James C.

2015-01-01

The demands of a growing human population dictates that expansion of energy infrastructure, roads, and other development frequently takes place in native rangelands. Particularly, transmission lines and roads commonly divide rural landscapes and increase fragmentation. This has direct and indirect consequences on native wildlife that can be mitigated through thoughtful planning and proactive approaches to identifying areas of high conservation priority. We used nine years (2003–2011) of Greater Prairie-Chicken (Tympanuchus cupido) lek locations totaling 870 unique leks sites in Kansas and seven geographic information system (GIS) layers describing land cover, topography, and anthropogenic structures to model habitat suitability across the state. The models obtained had low omission rates (<0.18) and high area under the curve scores (AUC >0.81), indicating high model performance and reliability of predicted habitat suitability for Greater Prairie-Chickens. We found that elevation was the most influential in predicting lek locations, contributing three times more predictive power than any other variable. However, models were improved by the addition of land cover and anthropogenic features (transmission lines, roads, and oil and gas structures). Overall, our analysis provides a hierarchal understanding of Greater Prairie-Chicken habitat suitability that is broadly based on geomorphological features followed by land cover suitability. We found that when land features and vegetation cover are suitable for Greater Prairie-Chickens, fragmentation by anthropogenic sources such as roadways and transmission lines are a concern. Therefore, it is our recommendation that future human development in Kansas avoid areas that our models identified as highly suitable for Greater Prairie-Chickens and focus development on land cover types that are of lower conservation concern. PMID:26317349

Predicting Greater Prairie-Chicken Lek Site Suitability to Inform Conservation Actions.

PubMed

Hovick, Torre J; Dahlgren, David K; Papeş, Monica; Elmore, R Dwayne; Pitman, James C

2015-01-01

The demands of a growing human population dictates that expansion of energy infrastructure, roads, and other development frequently takes place in native rangelands. Particularly, transmission lines and roads commonly divide rural landscapes and increase fragmentation. This has direct and indirect consequences on native wildlife that can be mitigated through thoughtful planning and proactive approaches to identifying areas of high conservation priority. We used nine years (2003-2011) of Greater Prairie-Chicken (Tympanuchus cupido) lek locations totaling 870 unique leks sites in Kansas and seven geographic information system (GIS) layers describing land cover, topography, and anthropogenic structures to model habitat suitability across the state. The models obtained had low omission rates (<0.18) and high area under the curve scores (AUC >0.81), indicating high model performance and reliability of predicted habitat suitability for Greater Prairie-Chickens. We found that elevation was the most influential in predicting lek locations, contributing three times more predictive power than any other variable. However, models were improved by the addition of land cover and anthropogenic features (transmission lines, roads, and oil and gas structures). Overall, our analysis provides a hierarchal understanding of Greater Prairie-Chicken habitat suitability that is broadly based on geomorphological features followed by land cover suitability. We found that when land features and vegetation cover are suitable for Greater Prairie-Chickens, fragmentation by anthropogenic sources such as roadways and transmission lines are a concern. Therefore, it is our recommendation that future human development in Kansas avoid areas that our models identified as highly suitable for Greater Prairie-Chickens and focus development on land cover types that are of lower conservation concern.

TargetSpy: a supervised machine learning approach for microRNA target prediction.

PubMed

Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

2010-05-28

Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila, suggesting that it may be applicable to a broad range of species. Moreover, we have demonstrated that the application of machine learning techniques in combination with upcoming deep sequencing data results in a powerful microRNA target site prediction tool http://www.targetspy.org.

TargetSpy: a supervised machine learning approach for microRNA target prediction

PubMed Central

2010-01-01

Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila, suggesting that it may be applicable to a broad range of species. Moreover, we have demonstrated that the application of machine learning techniques in combination with upcoming deep sequencing data results in a powerful microRNA target site prediction tool http://www.targetspy.org. PMID:20509939

Scale-Invariant Forms of Conservation Equations in Reactive Fields and a Modified Hydro-Thermo-Diffusive Theory of Laminar Flames

NASA Technical Reports Server (NTRS)

Sohrab, Siavash H.; Piltch, Nancy (Technical Monitor)

2000-01-01

A scale-invariant model of statistical mechanics is applied to present invariant forms of mass, energy, linear, and angular momentum conservation equations in reactive fields. The resulting conservation equations at molecular-dynamic scale are solved by the method of large activation energy asymptotics to describe the hydro-thermo-diffusive structure of laminar premixed flames. The predicted temperature and velocity profiles are in agreement with the observations. Also, with realistic physico-chemical properties and chemical-kinetic parameters for a single-step overall combustion of stoichiometric methane-air premixed flame, the laminar flame propagation velocity of 42.1 cm/s is calculated in agreement with the experimental value.

Towards Long-Range RNA Structure Prediction in Eukaryotic Genes.

PubMed

Pervouchine, Dmitri D

2018-06-15

The ability to form an intramolecular structure plays a fundamental role in eukaryotic RNA biogenesis. Proximate regions in the primary transcripts fold into a local secondary structure, which is then hierarchically assembled into a tertiary structure that is stabilized by RNA-binding proteins and long-range intramolecular base pairings. While the local RNA structure can be predicted reasonably well for short sequences, long-range structure at the scale of eukaryotic genes remains problematic from the computational standpoint. The aim of this review is to list functional examples of long-range RNA structures, to summarize current comparative methods of structure prediction, and to highlight their advances and limitations in the context of long-range RNA structures. Most comparative methods implement the “first-align-then-fold” principle, i.e., they operate on multiple sequence alignments, while functional RNA structures often reside in non-conserved parts of the primary transcripts. The opposite “first-fold-then-align” approach is currently explored to a much lesser extent. Developing novel methods in both directions will improve the performance of comparative RNA structure analysis and help discover novel long-range structures, their higher-order organization, and RNA⁻RNA interactions across the transcriptome.

Hop stunt viroid: molecular cloning and nucleotide sequence of the complete cDNA copy.

PubMed Central

Ohno, T; Takamatsu, N; Meshi, T; Okada, Y

1983-01-01

The complete cDNA of hop stunt viroid (HSV) has been cloned by the method of Okayama and Berg (Mol.Cell.Biol.2,161-170. (1982] and the complete nucleotide sequence has been established. The covalently closed circular single-stranded HSV RNA consists of 297 nucleotides. The secondary structure predicted for HSV contains 67% of its residues base-paired. The native HSV can possess an extended rod-like structure characteristic of viroids previously established. The central region of the native HSV has a similar structure to the conserved region found in all viroids sequenced so far except for avocado sunblotch viroid. The sequence homologous to the 5'-end of U1a RNA is also found in the sequence of HSV but not in the central conserved region. Images PMID:6312412

How does vegetation structure influence woodpeckers and secondary cavity nesting birds in African cork oak forest?

NASA Astrophysics Data System (ADS)

Segura, Amalia

2017-08-01

The Great Spotted Woodpecker provides important information about the status of a forest in terms of structure and age. As a primary cavity creator, it provides small-medium size cavities for passerines. However, despite its interest as an ecosystem engineer, studies of this species in Africa are scarce. Here, spatially explicit predictive models were used to investigate how forest structural variables are related to both the Great Spotted Woodpecker and secondary cavity nesting birds in Maamora cork oak forest (northwest Morocco). A positive association between Great Spotted Woodpecker and both dead-tree density and large mature trees (>60 cm dbh) was found. This study area, Maamora, has an old-growth forest structure incorporating a broad range of size and condition of live and dead trees, favouring Great Spotted Woodpecker by providing high availability of foraging and excavating sites. Secondary cavity nesting birds, represented by Great Tit, African Blue Tit, and Hoopoe, were predicted by Great Spotted Woodpecker detections. The findings suggest that the conservation of the Maamora cork oak forest could be key to maintaining these hole-nesting birds. However, this forest is threatened by forestry practises and livestock overgrazing and the challenge is therefore to find sustainable management strategies that ensure conservation while allowing its exploitation.

GalaxyGPCRloop: Template-Based and Ab Initio Structure Sampling of the Extracellular Loops of G-Protein-Coupled Receptors.

PubMed

Won, Jonghun; Lee, Gyu Rie; Park, Hahnbeom; Seok, Chaok

2018-06-07

The second extracellular loops (ECL2s) of G-protein-coupled receptors (GPCRs) are often involved in GPCR functions, and their structures have important implications in drug discovery. However, structure prediction of ECL2 is difficult because of its long length and the structural diversity among different GPCRs. In this study, a new ECL2 conformational sampling method involving both template-based and ab initio sampling was developed. Inspired by the observation of similar ECL2 structures of closely related GPCRs, a template-based sampling method employing loop structure templates selected from the structure database was developed. A new metric for evaluating similarity of the target loop to templates was introduced for template selection. An ab initio loop sampling method was also developed to treat cases without highly similar templates. The ab initio method is based on the previously developed fragment assembly and loop closure method. A new sampling component that takes advantage of secondary structure prediction was added. In addition, a conserved disulfide bridge restraining ECL2 conformation was predicted and analytically incorporated into sampling, reducing the effective dimension of the conformational search space. The sampling method was combined with an existing energy function for comparison with previously reported loop structure prediction methods, and the benchmark test demonstrated outstanding performance.

Improving predictions of protein-protein interfaces by combining amino acid-specific classifiers based on structural and physicochemical descriptors with their weighted neighbor averages.

PubMed

de Moraes, Fábio R; Neshich, Izabella A P; Mazoni, Ivan; Yano, Inácio H; Pereira, José G C; Salim, José A; Jardine, José G; Neshich, Goran

2014-01-01

Protein-protein interactions are involved in nearly all regulatory processes in the cell and are considered one of the most important issues in molecular biology and pharmaceutical sciences but are still not fully understood. Structural and computational biology contributed greatly to the elucidation of the mechanism of protein interactions. In this paper, we present a collection of the physicochemical and structural characteristics that distinguish interface-forming residues (IFR) from free surface residues (FSR). We formulated a linear discriminative analysis (LDA) classifier to assess whether chosen descriptors from the BlueStar STING database (http://www.cbi.cnptia.embrapa.br/SMS/) are suitable for such a task. Receiver operating characteristic (ROC) analysis indicates that the particular physicochemical and structural descriptors used for building the linear classifier perform much better than a random classifier and in fact, successfully outperform some of the previously published procedures, whose performance indicators were recently compared by other research groups. The results presented here show that the selected set of descriptors can be utilized to predict IFRs, even when homologue proteins are missing (particularly important for orphan proteins where no homologue is available for comparative analysis/indication) or, when certain conformational changes accompany interface formation. The development of amino acid type specific classifiers is shown to increase IFR classification performance. Also, we found that the addition of an amino acid conservation attribute did not improve the classification prediction. This result indicates that the increase in predictive power associated with amino acid conservation is exhausted by adequate use of an extensive list of independent physicochemical and structural parameters that, by themselves, fully describe the nano-environment at protein-protein interfaces. The IFR classifier developed in this study is now integrated into the BlueStar STING suite of programs. Consequently, the prediction of protein-protein interfaces for all proteins available in the PDB is possible through STING_interfaces module, accessible at the following website: (http://www.cbi.cnptia.embrapa.br/SMS/predictions/index.html).

Improving Predictions of Protein-Protein Interfaces by Combining Amino Acid-Specific Classifiers Based on Structural and Physicochemical Descriptors with Their Weighted Neighbor Averages

PubMed Central

de Moraes, Fábio R.; Neshich, Izabella A. P.; Mazoni, Ivan; Yano, Inácio H.; Pereira, José G. C.; Salim, José A.; Jardine, José G.; Neshich, Goran

2014-01-01

Protein-protein interactions are involved in nearly all regulatory processes in the cell and are considered one of the most important issues in molecular biology and pharmaceutical sciences but are still not fully understood. Structural and computational biology contributed greatly to the elucidation of the mechanism of protein interactions. In this paper, we present a collection of the physicochemical and structural characteristics that distinguish interface-forming residues (IFR) from free surface residues (FSR). We formulated a linear discriminative analysis (LDA) classifier to assess whether chosen descriptors from the BlueStar STING database (http://www.cbi.cnptia.embrapa.br/SMS/) are suitable for such a task. Receiver operating characteristic (ROC) analysis indicates that the particular physicochemical and structural descriptors used for building the linear classifier perform much better than a random classifier and in fact, successfully outperform some of the previously published procedures, whose performance indicators were recently compared by other research groups. The results presented here show that the selected set of descriptors can be utilized to predict IFRs, even when homologue proteins are missing (particularly important for orphan proteins where no homologue is available for comparative analysis/indication) or, when certain conformational changes accompany interface formation. The development of amino acid type specific classifiers is shown to increase IFR classification performance. Also, we found that the addition of an amino acid conservation attribute did not improve the classification prediction. This result indicates that the increase in predictive power associated with amino acid conservation is exhausted by adequate use of an extensive list of independent physicochemical and structural parameters that, by themselves, fully describe the nano-environment at protein-protein interfaces. The IFR classifier developed in this study is now integrated into the BlueStar STING suite of programs. Consequently, the prediction of protein-protein interfaces for all proteins available in the PDB is possible through STING_interfaces module, accessible at the following website: (http://www.cbi.cnptia.embrapa.br/SMS/predictions/index.html). PMID:24489849

Novel proteases from the genome of the carnivorous plant Drosera capensis: structural prediction and comparative analysis

PubMed Central

Butts, Carter T.; Bierma, Jan C.; Martin, Rachel W.

2016-01-01

In his 1875 monograph on insectivorous plants, Darwin described the feeding reactions of Drosera flypaper traps and predicted that their secretions contained a “ferment” similar to mammalian pepsin, an aspartic protease. Here we report a high-quality draft genome sequence for the cape sundew, Drosera capensis, the first genome of a carnivorous plant from order Caryophyllales, which also includes the Venus flytrap (Dionaea) and the tropical pitcher plants (Nepenthes). This species was selected in part for its hardiness and ease of cultivation, making it an excellent model organism for further investigations of plant carnivory. Analysis of predicted protein sequences yields genes encoding proteases homologous to those found in other plants, some of which display sequence and structural features that suggest novel functionalities. Because the sequence similarity to proteins of known structure is in most cases too low for traditional homology modeling, 3D structures of representative proteases are predicted using comparative modeling with all-atom refinement. Although the overall folds and active residues for these proteins are conserved, we find structural and sequence differences consistent with a diversity of substrate recognition patterns. Finally, we predict differences in substrate specificities using in silico experiments, providing targets for structure/function studies of novel enzymes with biological and technological significance. PMID:27353064

Three-Dimensional Molecular Modeling of a Diverse Range of SC Clan Serine Proteases

PubMed Central

Laskar, Aparna; Chatterjee, Aniruddha; Chatterjee, Somnath; Rodger, Euan J.

2012-01-01

Serine proteases are involved in a variety of biological processes and are classified into clans sharing structural homology. Although various three-dimensional structures of SC clan proteases have been experimentally determined, they are mostly bacterial and animal proteases, with some from archaea, plants, and fungi, and as yet no structures have been determined for protozoa. To bridge this gap, we have used molecular modeling techniques to investigate the structural properties of different SC clan serine proteases from a diverse range of taxa. Either SWISS-MODEL was used for homology-based structure prediction or the LOOPP server was used for threading-based structure prediction. The predicted models were refined using Insight II and SCRWL and validated against experimental structures. Investigation of secondary structures and electrostatic surface potential was performed using MOLMOL. The structural geometry of the catalytic core shows clear deviations between taxa, but the relative positions of the catalytic triad residues were conserved. Evolutionary divergence was also exhibited by large variation in secondary structure features outside the core, differences in overall amino acid distribution, and unique surface electrostatic potential patterns between species. Encompassing a wide range of taxa, our structural analysis provides an evolutionary perspective on SC clan serine proteases. PMID:23213528

Networks of high mutual information define the structural proximity of catalytic sites: implications for catalytic residue identification.

PubMed

Marino Buslje, Cristina; Teppa, Elin; Di Doménico, Tomas; Delfino, José María; Nielsen, Morten

2010-11-04

Identification of catalytic residues (CR) is essential for the characterization of enzyme function. CR are, in general, conserved and located in the functional site of a protein in order to attain their function. However, many non-catalytic residues are highly conserved and not all CR are conserved throughout a given protein family making identification of CR a challenging task. Here, we put forward the hypothesis that CR carry a particular signature defined by networks of close proximity residues with high mutual information (MI), and that this signature can be applied to distinguish functional from other non-functional conserved residues. Using a data set of 434 Pfam families included in the catalytic site atlas (CSA) database, we tested this hypothesis and demonstrated that MI can complement amino acid conservation scores to detect CR. The Kullback-Leibler (KL) conservation measurement was shown to significantly outperform both the Shannon entropy and maximal frequency measurements. Residues in the proximity of catalytic sites were shown to be rich in shared MI. A structural proximity MI average score (termed pMI) was demonstrated to be a strong predictor for CR, thus confirming the proposed hypothesis. A structural proximity conservation average score (termed pC) was also calculated and demonstrated to carry distinct information from pMI. A catalytic likeliness score (Cls), combining the KL, pC and pMI measures, was shown to lead to significantly improved prediction accuracy. At a specificity of 0.90, the Cls method was found to have a sensitivity of 0.816. In summary, we demonstrate that networks of residues with high MI provide a distinct signature on CR and propose that such a signature should be present in other classes of functional residues where the requirement to maintain a particular function places limitations on the diversification of the structural environment along the course of evolution.

Trichodesmium genome maintains abundant, widespread noncoding DNA in situ, despite oligotrophic lifestyle

DOE PAGES

Walworth, Nathan; Pfreundt, Ulrike; Nelson, William C.; ...

2015-03-23

Understanding the evolution of the free-living, cyanobacterial, diazotroph Trichodesmium is of great importance because of its critical role in oceanic biogeochemistry and primary production. Unlike the other >150 available genomes of free-living cyanobacteria, only 63.8% of the Trichodesmium erythraeum (strain IMS101) genome is predicted to encode protein, which is 20–25% less than the average for other cyanobacteria and nonpathogenic, free-living bacteria. In this paper, we use distinctive isolates and metagenomic data to show that low coding density observed in IMS101 is a common feature of the Trichodesmium genus, both in culture and in situ. Transcriptome analysis indicates that 86% ofmore » the noncoding space is expressed, although the function of these transcripts is unclear. The density of noncoding, possible regulatory elements predicted in Trichodesmium, when normalized per intergenic kilobase, was comparable and twofold higher than that found in the gene-dense genomes of the sympatric cyanobacterial genera Synechococcus and Prochlorococcus, respectively. Conserved Trichodesmium noncoding RNA secondary structures were predicted between most culture and metagenomic sequences, lending support to the structural conservation. Conservation of these intergenic regions in spatiotemporally separated Trichodesmium populations suggests possible genus-wide selection for their maintenance. These large intergenic spacers may have developed during intervals of strong genetic drift caused by periodic blooms of a subset of genotypes, which may have reduced effective population size. Finally, our data suggest that transposition of selfish DNA, low effective population size, and high-fidelity replication allowed the unusual “inflation” of noncoding sequence observed in Trichodesmium despite its oligotrophic lifestyle.« less

Trichodesmium genome maintains abundant, widespread noncoding DNA in situ, despite oligotrophic lifestyle

DOE PAGES

Walworth, Nathan G.; Pfreundt, Ulrike; Nelson, William C.; ...

2015-04-07

Understanding the evolution of the free-living, cyanobacterial, diazotroph Trichodesmium is of great importance due to its critical role in oceanic biogeochemistry and primary production. Unlike the other >150 available genomes of free-living cyanobacteria, only 63.8% of the Trichodesmium erythraeum (strain IMS101) genome is predicted to encode protein, which is 20-25% less than the average for other cyanobacteria and non-pathogenic, free-living bacteria. We use distinctive isolates and metagenomic data to show that low coding density observed in IMS101 is a common feature of the Trichodesmium genus both in culture and in situ. Transcriptome analysis indicates that 86% of the non-coding spacemore » is expressed, although the function of these transcripts is unclear. The density of noncoding, possible regulatory elements predicted in Trichodesmium, when normalized per intergenic kilobase, was comparable and two fold higher than that found in the gene dense genomes of the sympatric cyanobacterial genera Synechococcus and Prochlorococcus, respectively. Conserved Trichodesmium ncRNA secondary structures were predicted between most culture and metagenomic sequences lending support to the structural conservation. Conservation of these intergenic regions in spatiotemporally separated Trichodesmium populations suggests possible genus-wide selection for their maintenance. These large intergenic spacers may have developed during intervals of strong genetic drift caused by periodic blooms of a subset of genotypes, which may have reduced effective population size. Our data suggest that transposition of selfish DNA, low effective population size, and high fidelity replication allowed the unusual ‘inflation’ of noncoding sequence observed in Trichodesmium despite its oligotrophic lifestyle.« less

Use of conserved key amino acid positions to morph protein folds.

PubMed

Reddy, Boojala V B; Li, Wilfred W; Bourne, Philip E

2002-07-15

By using three-dimensional (3D) structure alignments and a previously published method to determine Conserved Key Amino Acid Positions (CKAAPs) we propose a theoretical method to design mutations that can be used to morph the protein folds. The original Paracelsus challenge, met by several groups, called for the engineering of a stable but different structure by modifying less than 50% of the amino acid residues. We have used the sequences from the Protein Data Bank (PDB) identifiers 1ROP, and 2CRO, which were previously used in the Paracelsus challenge by those groups, and suggest mutation to CKAAPs to morph the protein fold. The total number of mutations suggested is less than 40% of the starting sequence theoretically improving the challenge results. From secondary structure prediction experiments of the proposed mutant sequence structures, we observe that each of the suggested mutant protein sequences likely folds to a different, non-native potentially stable target structure. These results are an early indicator that analyses using structure alignments leading to CKAAPs of a given structure are of value in protein engineering experiments. Copyright 2002 Wiley Periodicals, Inc.

From Structure to Function: A Comprehensive Compendium of Tools to Unveil Protein Domains and Understand Their Role in Cytokinesis.

PubMed

Rincon, Sergio A; Paoletti, Anne

2016-01-01

Unveiling the function of a novel protein is a challenging task that requires careful experimental design. Yeast cytokinesis is a conserved process that involves modular structural and regulatory proteins. For such proteins, an important step is to identify their domains and structural organization. Here we briefly discuss a collection of methods commonly used for sequence alignment and prediction of protein structure that represent powerful tools for the identification homologous domains and design of structure-function approaches to test experimentally the function of multi-domain proteins such as those implicated in yeast cytokinesis.

PIGSPro: prediction of immunoGlobulin structures v2.

PubMed

Lepore, Rosalba; Olimpieri, Pier P; Messih, Mario A; Tramontano, Anna

2017-07-03

PIGSpro is a significant upgrade of the popular PIGS server for the prediction of the structure of immunoglobulins. The software has been completely rewritten in python following a similar pipeline as in the original method, but including, at various steps, relevant modifications found to improve its prediction accuracy, as demonstrated here. The steps of the pipeline include the selection of the appropriate framework for predicting the conserved regions of the molecule by homology; the target template alignment for this portion of the molecule; the selection of the main chain conformation of the hypervariable loops according to the canonical structure model, the prediction of the third loop of the heavy chain (H3) for which complete canonical structures are not available and the packing of the light and heavy chain if derived from different templates. Each of these steps has been improved including updated methods developed along the years. Last but not least, the user interface has been completely redesigned and an automatic monthly update of the underlying database has been implemented. The method is available as a web server at http://biocomputing.it/pigspro. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Successful conservation of a threatened Maculinea butterfly.

PubMed

Thomas, J A; Simcox, D J; Clarke, R T

2009-07-03

Globally threatened butterflies have prompted research-based approaches to insect conservation. Here, we describe the reversal of the decline of Maculinea arion (Large Blue), a charismatic specialist whose larvae parasitize Myrmica ant societies. M. arion larvae were more specialized than had previously been recognized, being adapted to a single host-ant species that inhabits a narrow niche in grassland. Inconspicuous changes in grazing and vegetation structure caused host ants to be replaced by similar but unsuitable congeners, explaining the extinction of European Maculinea populations. Once this problem was identified, UK ecosystems were perturbed appropriately, validating models predicting the recovery and subsequent dynamics of the butterfly and ants at 78 sites. The successful identification and reversal of the problem provides a paradigm for other insect conservation projects.

Animal Social Network Theory Can Help Wildlife Conservation.

PubMed

Snijders, Lysanne; Blumstein, Daniel T; Stanley, Christina R; Franks, Daniel W

2017-08-01

Many animals preferentially associate with certain other individuals. This social structuring can influence how populations respond to changes to their environment, thus making network analysis a promising technique for understanding, predicting, and potentially manipulating population dynamics. Various network statistics can correlate with individual fitness components and key population-level processes, yet the logical role and formal application of animal social network theory for conservation and management have not been well articulated. We outline how understanding of direct and indirect relationships between animals can be profitably applied by wildlife managers and conservationists. By doing so, we aim to stimulate the development and implementation of practical tools for wildlife conservation and management and to inspire novel behavioral research in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Computational RNomics of Drosophilids

PubMed Central

Rose, Dominic; Hackermüller, Jörg; Washietl, Stefan; Reiche, Kristin; Hertel, Jana; Findeiß, Sven; Stadler, Peter F; Prohaska, Sonja J

2007-01-01

Background Recent experimental and computational studies have provided overwhelming evidence for a plethora of diverse transcripts that are unrelated to protein-coding genes. One subclass consists of those RNAs that require distinctive secondary structure motifs to exert their biological function and hence exhibit distinctive patterns of sequence conservation characteristic for positive selection on RNA secondary structure. The deep-sequencing of 12 drosophilid species coordinated by the NHGRI provides an ideal data set of comparative computational approaches to determine those genomic loci that code for evolutionarily conserved RNA motifs. This class of loci includes the majority of the known small ncRNAs as well as structured RNA motifs in mRNAs. We report here on a genome-wide survey using RNAz. Results We obtain 16 000 high quality predictions among which we recover the majority of the known ncRNAs. Taking a pessimistically estimated false discovery rate of 40% into account, this implies that at least some ten thousand loci in the Drosophila genome show the hallmarks of stabilizing selection action of RNA structure, and hence are most likely functional at the RNA level. A subset of RNAz predictions overlapping with TRF1 and BRF binding sites [Isogai et al., EMBO J. 26: 79–89 (2007)], which are plausible candidates of Pol III transcripts, have been studied in more detail. Among these sequences we identify several "clusters" of ncRNA candidates with striking structural similarities. Conclusion The statistical evaluation of the RNAz predictions in comparison with a similar analysis of vertebrate genomes [Washietl et al., Nat. Biotech. 23: 1383–1390 (2005)] shows that qualitatively similar fractions of structured RNAs are found in introns, UTRs, and intergenic regions. The intergenic RNA structures, however, are concentrated much more closely around known protein-coding loci, suggesting that flies have significantly smaller complement of independent structured ncRNAs compared to mammals. PMID:17996037

Effect of local cultural context on the success of community-based conservation interventions.

PubMed

Waylen, Kerry A; Fischer, Anke; McGowan, Philip J K; Thirgood, Simon J; Milner-Gulland, E J

2010-08-01

Conservation interventions require evaluation to understand what factors predict success or failure. To date, there has been little systematic investigation of the effect of social and cultural context on conservation success, although a large body of literature argues it is important. We investigated whether local cultural context, particularly local institutions and the efforts of interventions to engage with this culture significantly influence conservation outcomes. We also tested the effects of community participation, conservation education, benefit provision, and market integration. We systematically reviewed the literature on community-based conservation and identified 68 interventions suitable for inclusion. We used a protocol to extract and code information and evaluated a range of measures of outcome success (attitudinal, behavioral, ecological, and economic). We also examined the association of each predictor with each outcome measure and the structure of predictor covariance. Local institutional context influenced intervention outcomes, and interventions that engaged with local institutions were more likely to succeed. Nevertheless, there was limited support for the role of community participation, conservation education, benefit provision, and market integration on intervention success. We recommend that conservation interventions seek to understand the societies they work with and tailor their activities accordingly. Systematic reviews are a valuable approach for assessing conservation evidence, although sensitive to the continuing lack of high-quality reporting on conservation interventions.

Planning for robust reserve networks using uncertainty analysis

USGS Publications Warehouse

Moilanen, A.; Runge, M.C.; Elith, Jane; Tyre, A.; Carmel, Y.; Fegraus, E.; Wintle, B.A.; Burgman, M.; Ben-Haim, Y.

2006-01-01

Planning land-use for biodiversity conservation frequently involves computer-assisted reserve selection algorithms. Typically such algorithms operate on matrices of species presence?absence in sites, or on species-specific distributions of model predicted probabilities of occurrence in grid cells. There are practically always errors in input data?erroneous species presence?absence data, structural and parametric uncertainty in predictive habitat models, and lack of correspondence between temporal presence and long-run persistence. Despite these uncertainties, typical reserve selection methods proceed as if there is no uncertainty in the data or models. Having two conservation options of apparently equal biological value, one would prefer the option whose value is relatively insensitive to errors in planning inputs. In this work we show how uncertainty analysis for reserve planning can be implemented within a framework of information-gap decision theory, generating reserve designs that are robust to uncertainty. Consideration of uncertainty involves modifications to the typical objective functions used in reserve selection. Search for robust-optimal reserve structures can still be implemented via typical reserve selection optimization techniques, including stepwise heuristics, integer-programming and stochastic global search.

Identification and characterization of the autophagy-related genes Atg12 and Atg5 in hydra.

PubMed

Dixit, Nishikant S; Shravage, Bhupendra V; Ghaskadbi, Surendra

2017-01-01

Autophagy is an evolutionarily conserved process in eukaryotic cells that is involved in the degradation of cytoplasmic contents including organelles via the lysosome. Hydra is an early metazoan which exhibits simple tissue grade organization, a primitive nervous system, and is one of the classical non-bilaterian models extensively used in evo-devo research. Here, we describe the characterization of two core autophagy genes, Atg12 and Atg5, from hydra. In silico analyses including sequence similarity, domain analysis, and phylogenetic analysis demonstrate the conservation of these genes across eukaryotes. The predicted 3D structure of hydra Atg12 showed very little variance when compared to human Atg12 and yeast Atg12, whereas the hydra Atg5 predicted 3D structure was found to be variable, when compared with its human and yeast homologs. Strikingly, whole mount in situ hybridization showed high expression of Atg12 transcripts specifically in nematoblasts, whereas Atg5 transcripts were found to be expressed strongly in budding region and growing buds. This study may provide a framework to understand the evolution of autophagy networks in higher eukaryotes.

Assessing conservation relevance of organism-environment relations using predicted changes in response variables

USGS Publications Warehouse

Gutzwiller, Kevin J.; Barrow, Wylie C.; White, Joseph D.; Johnson-Randall, Lori; Cade, Brian S.; Zygo, Lisa M.

2010-01-01

1. Organism–environment models are used widely in conservation. The degree to which they are useful for informing conservation decisions – the conservation relevance of these relations – is important because lack of relevance may lead to misapplication of scarce conservation resources or failure to resolve important conservation dilemmas. Even when models perform well based on model fit and predictive ability, conservation relevance of associations may not be clear without also knowing the magnitude and variability of predicted changes in response variables. 2. We introduce a method for evaluating the conservation relevance of organism–environment relations that employs confidence intervals for predicted changes in response variables. The confidence intervals are compared to a preselected magnitude of change that marks a threshold (trigger) for conservation action. To demonstrate the approach, we used a case study from the Chihuahuan Desert involving relations between avian richness and broad-scale patterns of shrubland. We considered relations for three winters and two spatial extents (1- and 2-km-radius areas) and compared predicted changes in richness to three thresholds (10%, 20% and 30% change). For each threshold, we examined 48 relations. 3. The method identified seven, four and zero conservation-relevant changes in mean richness for the 10%, 20% and 30% thresholds respectively. These changes were associated with major (20%) changes in shrubland cover, mean patch size, the coefficient of variation for patch size, or edge density but not with major changes in shrubland patch density. The relative rarity of conservation-relevant changes indicated that, overall, the relations had little practical value for informing conservation decisions about avian richness. 4. The approach we illustrate is appropriate for various response and predictor variables measured at any temporal or spatial scale. The method is broadly applicable across ecological environments, conservation objectives, types of statistical predictive models and levels of biological organization. By focusing on magnitudes of change that have practical significance, and by using the span of confidence intervals to incorporate uncertainty of predicted changes, the method can be used to help improve the effectiveness of conservation efforts.

A conserved RNA structural element within the hepatitis B virus post-transcriptional regulatory element enhance nuclear export of intronless transcripts and repress the splicing mechanism.

PubMed

Visootsat, Akasit; Payungporn, Sunchai; T-Thienprasert, Nattanan P

2015-12-01

Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma and liver cirrhosis worldwide. To develop novel antiviral drugs, a better understanding of HBV gene expression regulation is vital. One important aspect is to understand how HBV hijacks the cellular machinery to export unspliced RNA from the nucleus. The HBV post-transcriptional regulatory element (HBV PRE) has been proposed to be the HBV RNA nuclear export element. However, the function remains controversial, and the core element is unclear. This study, therefore, aimed to identify functional regulatory elements within the HBV PRE and investigate their functions. Using bioinformatics programs based on sequence conservation and conserved RNA secondary structures, three regulatory elements were predicted, namely PRE 1151-1410, PRE 1520-1620 and PRE 1650-1684. PRE 1151-1410 significantly increased intronless and unspliced luciferase activity in both HepG2 and COS-7 cells. Likewise, PRE 1151-1410 significantly elevated intronless and unspliced HBV surface transcripts in liver cancer cells. Moreover, motif analysis predicted that PRE 1151-1410 contains several regulatory motifs. This study reported the roles of PRE 1151-1410 in intronless transcript nuclear export and the splicing mechanism. Additionally, these results provide knowledge in the field of HBV RNA regulation. Moreover, PRE 1151-1410 may be used to enhance the expression of other mRNAs in intronless reporter plasmids.

Evolutionary conserved mechanisms pervade structure and transcriptional modulation of allograft inflammatory factor-1 from sea anemone Anemonia viridis.

PubMed

Cuttitta, Angela; Ragusa, Maria Antonietta; Costa, Salvatore; Bennici, Carmelo; Colombo, Paolo; Mazzola, Salvatore; Gianguzza, Fabrizio; Nicosia, Aldo

2017-08-01

Gene family encoding allograft inflammatory factor-1 (AIF-1) is well conserved among organisms; however, there is limited knowledge in lower organisms. In this study, the first AIF-1 homologue from cnidarians was identified and characterised in the sea anemone Anemonia viridis. The full-length cDNA of AvAIF-1 was of 913 bp with a 5' -untranslated region (UTR) of 148 bp, a 3'-UTR of 315 and an open reading frame (ORF) of 450 bp encoding a polypeptide with149 amino acid residues and predicted molecular weight of about 17 kDa. The predicted protein possesses evolutionary conserved EF hand Ca 2+ binding motifs, post-transcriptional modification sites and a 3D structure which can be superimposed with human members of AIF-1 family. The AvAIF-1 transcript was constitutively expressed in all tested tissues of unchallenged sea anemone, suggesting that AvAIF-1 could serve as a general protective factor under normal physiological conditions. Moreover, we profiled the transcriptional activation of AvAIF-1 after challenges with different abiotic/biotic stresses showing induction by warming conditions, heavy metals exposure and immune stimulation. Thus, mechanisms associated to inflammation and immune challenges up-regulated AvAIF-1 mRNA levels. Our results suggest its involvement in the inflammatory processes and immune response of A. viridis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structure of Soot-Containing Laminar Jet Diffusion Flames

NASA Technical Reports Server (NTRS)

Mortazavi, S.; Sunderland, P. B.; Jurng, J.; Koylu, U. O.; Faeth, G. M.

1993-01-01

The structure and soot properties of nonbuoyant and weakly-buoyant round jet diffusion flames were studied, considering ethylene, propane and acetylene burning in air at pressures of 0.125-2.0 atm. Measurements of flame structure included radiative heat loss fractions, flame shape and temperature distributions in the fuel-lean (overfire) region. These measurements were used to evaluate flame structure predictions based on the conserved-scalar formalism in conjunction with the laminar flamelet concept, finding good agreement betweem predictions and measurements. Soot property measurements included laminar smoke points, soot volume function distributions using laser extinction, and soot structure using thermophoretic sampling and analysis by transmission electron microscopy. Nonbuoyant flames were found to exhibit laminar smoke points like buoyant flames but their properties are very different; in particular, nonbuoyant flames have laminar smoke point flame lengths and residence times that are shorter and longer, respectively, than buoyant flames.

A cut-cell finite volume – finite element coupling approach for fluid–structure interaction in compressible flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pasquariello, Vito, E-mail: vito.pasquariello@tum.de; Hammerl, Georg; Örley, Felix

2016-02-15

We present a loosely coupled approach for the solution of fluid–structure interaction problems between a compressible flow and a deformable structure. The method is based on staggered Dirichlet–Neumann partitioning. The interface motion in the Eulerian frame is accounted for by a conservative cut-cell Immersed Boundary method. The present approach enables sub-cell resolution by considering individual cut-elements within a single fluid cell, which guarantees an accurate representation of the time-varying solid interface. The cut-cell procedure inevitably leads to non-matching interfaces, demanding for a special treatment. A Mortar method is chosen in order to obtain a conservative and consistent load transfer. Wemore » validate our method by investigating two-dimensional test cases comprising a shock-loaded rigid cylinder and a deformable panel. Moreover, the aeroelastic instability of a thin plate structure is studied with a focus on the prediction of flutter onset. Finally, we propose a three-dimensional fluid–structure interaction test case of a flexible inflated thin shell interacting with a shock wave involving large and complex structural deformations.« less

Developing Uncertainty Models for Robust Flutter Analysis Using Ground Vibration Test Data

NASA Technical Reports Server (NTRS)

Potter, Starr; Lind, Rick; Kehoe, Michael W. (Technical Monitor)

2001-01-01

A ground vibration test can be used to obtain information about structural dynamics that is important for flutter analysis. Traditionally, this information#such as natural frequencies of modes#is used to update analytical models used to predict flutter speeds. The ground vibration test can also be used to obtain uncertainty models, such as natural frequencies and their associated variations, that can update analytical models for the purpose of predicting robust flutter speeds. Analyzing test data using the -norm, rather than the traditional 2-norm, is shown to lead to a minimum-size uncertainty description and, consequently, a least-conservative robust flutter speed. This approach is demonstrated using ground vibration test data for the Aerostructures Test Wing. Different norms are used to formulate uncertainty models and their associated robust flutter speeds to evaluate which norm is least conservative.

Anthropogenic Influences on Conservation Values of White Rhinoceros

PubMed Central

Ferreira, Sam M.; Botha, Judith M.; Emmett, Megan C.

2012-01-01

White rhinoceros (rhinos) is a keystone conservation species and also provides revenue for protection agencies. Restoring or mimicking the outcomes of impeded ecological processes allows reconciliation of biodiversity and financial objectives. We evaluate the consequences of white rhino management removal, and in recent times, poaching, on population persistence, regional conservation outcomes and opportunities for revenue generation. In Kruger National Park, white rhinos increased from 1998 to 2008. Since then the population may vary non-directionally. In 2010, we estimated 10,621 (95% CI: 8,767–12,682) white rhinos using three different population estimation methods. The desired management effect of a varying population was detectable after 2008. Age and sex structures in sink areas (focal rhino capture areas) were different from elsewhere. This comes from relatively more sub-adults being removed by managers than what the standing age distribution defined. Poachers in turn focused on more adults in 2011. Although the effect of poaching was not detectable at the population level given the confidence intervals of estimates, managers accommodated expected poaching annually and adapted management removals. The present poaching trend predicts that 432 white rhinos may be poached in Kruger during 2012. The white rhino management model mimicking outcomes of impeded ecological processes predicts 397 rhino management removals are required. At present poachers may be doing “management removals,” but conservationists have no opportunity left to contribute to regional rhino conservation strategies or generate revenue through white rhino sales. In addition, continued trends in poaching predict detectable white rhino declines in Kruger National Park by 2016. Our results suggest that conservationists need innovative approaches that reduce financial incentives to curb the threats that poaching poses to several conservation values of natural resources such as white rhinos. PMID:23029354

Distantly related lipocalins share two conserved clusters of hydrophobic residues: use in homology modeling

PubMed Central

Adam, Benoit; Charloteaux, Benoit; Beaufays, Jerome; Vanhamme, Luc; Godfroid, Edmond; Brasseur, Robert; Lins, Laurence

2008-01-01

Background Lipocalins are widely distributed in nature and are found in bacteria, plants, arthropoda and vertebra. In hematophagous arthropods, they are implicated in the successful accomplishment of the blood meal, interfering with platelet aggregation, blood coagulation and inflammation and in the transmission of disease parasites such as Trypanosoma cruzi and Borrelia burgdorferi. The pairwise sequence identity is low among this family, often below 30%, despite a well conserved tertiary structure. Under the 30% identity threshold, alignment methods do not correctly assign and align proteins. The only safe way to assign a sequence to that family is by experimental determination. However, these procedures are long and costly and cannot always be applied. A way to circumvent the experimental approach is sequence and structure analyze. To further help in that task, the residues implicated in the stabilisation of the lipocalin fold were determined. This was done by analyzing the conserved interactions for ten lipocalins having a maximum pairwise identity of 28% and various functions. Results It was determined that two hydrophobic clusters of residues are conserved by analysing the ten lipocalin structures and sequences. One cluster is internal to the barrel, involving all strands and the 310 helix. The other is external, involving four strands and the helix lying parallel to the barrel surface. These clusters are also present in RaHBP2, a unusual "outlier" lipocalin from tick Rhipicephalus appendiculatus. This information was used to assess assignment of LIR2 a protein from Ixodes ricinus and to build a 3D model that helps to predict function. FTIR data support the lipocalin fold for this protein. Conclusion By sequence and structural analyzes, two conserved clusters of hydrophobic residues in interactions have been identified in lipocalins. Since the residues implicated are not conserved for function, they should provide the minimal subset necessary to confer the lipocalin fold. This information has been used to assign LIR2 to lipocalins and to investigate its structure/function relationship. This study could be applied to other protein families with low pairwise similarity, such as the structurally related fatty acid binding proteins or avidins. PMID:18190694

Higher temporal variability of forest breeding bird communities in fragmented landscapes

USGS Publications Warehouse

Boulinier, T.; Nichols, J.D.; Hines, J.E.; Sauer, J.R.; Flather, C.H.; Pollock, K.H.

1998-01-01

Understanding the relationship between animal community dynamics and landscape structure has become a priority for biodiversity conservation. In particular, predicting the effects of habitat destruction that confine species to networks of small patches is an important prerequisite to conservation plan development. Theoretical models that predict the occurrence of species in fragmented landscapes, and relationships between stability and diversity do exist. However, reliable empirical investigations of the dynamics of biodiversity have been prevented by differences in species detection probabilities among landscapes. Using long-term data sampled at a large spatial scale in conjunction with a capture-recapture approach, we developed estimates of parameters of community changes over a 22-year period for forest breeding birds in selected areas of the eastern United States. We show that forest fragmentation was associated not only with a reduced number of forest bird species, but also with increased temporal variability in the number of species. This higher temporal variability was associated with higher local extinction and turnover rates. These results have major conservation implications. Moreover, the approach used provides a practical tool for the study of the dynamics of biodiversity.

Collapse of a pollination web in small conservation areas.

PubMed

Pauw, Anton

2007-07-01

A suspected global decline in pollinators has heightened interest in their ecological significance. In a worst-case scenario, the decline of generalist pollinators is predicted to trigger cascades of linked declines among the multiple specialist plant species to which they are linked, but this has not been documented. I studied a portion of a pollination web involving a generalist pollinator, the oil-collecting bee Rediviva peringueyi, and a community of oil-secreting plants. Across 27 established conservation areas located in the Cape Floral Region, I found substantial variation in the bees' occurrence in relation to soil type and the successional stage of the vegetation. Anthropogenic declines were detectable against this background of naturally occurring variation: R. peringueyi was absent from small conservation areas (< 385 ha) in an urban matrix. In the absence of the bee, seed set failed in six specialist plant species that are pollinated only by R. peringueyi but remained high in a pollination generalist, which had replacement pollinators. The findings are consistent with theoretical predictions of the importance of generalist pollinators in maintaining the structure of pollination webs.

Characteristics of the nuclear (18S, 5.8S, 28S and 5S) and mitochondrial (12S and 16S) rRNA genes of Apis mellifera (Insecta: Hymenoptera): structure, organization, and retrotransposable elements

PubMed Central

Gillespie, J J; Johnston, J S; Cannone, J J; Gutell, R R

2006-01-01

As an accompanying manuscript to the release of the honey bee genome, we report the entire sequence of the nuclear (18S, 5.8S, 28S and 5S) and mitochondrial (12S and 16S) ribosomal RNA (rRNA)-encoding gene sequences (rDNA) and related internally and externally transcribed spacer regions of Apis mellifera (Insecta: Hymenoptera: Apocrita). Additionally, we predict secondary structures for the mature rRNA molecules based on comparative sequence analyses with other arthropod taxa and reference to recently published crystal structures of the ribosome. In general, the structures of honey bee rRNAs are in agreement with previously predicted rRNA models from other arthropods in core regions of the rRNA, with little additional expansion in non-conserved regions. Our multiple sequence alignments are made available on several public databases and provide a preliminary establishment of a global structural model of all rRNAs from the insects. Additionally, we provide conserved stretches of sequences flanking the rDNA cistrons that comprise the externally transcribed spacer regions (ETS) and part of the intergenic spacer region (IGS), including several repetitive motifs. Finally, we report the occurrence of retrotransposition in the nuclear large subunit rDNA, as R2 elements are present in the usual insertion points found in other arthropods. Interestingly, functional R1 elements usually present in the genomes of insects were not detected in the honey bee rRNA genes. The reverse transcriptase products of the R2 elements are deduced from their putative open reading frames and structurally aligned with those from another hymenopteran insect, the jewel wasp Nasonia (Pteromalidae). Stretches of conserved amino acids shared between Apis and Nasonia are illustrated and serve as potential sites for primer design, as target amplicons within these R2 elements may serve as novel phylogenetic markers for Hymenoptera. Given the impending completion of the sequencing of the Nasonia genome, we expect our report eventually to shed light on the evolution of the hymenopteran genome within higher insects, particularly regarding the relative maintenance of conserved rDNA genes, related variable spacer regions and retrotransposable elements. PMID:17069639

ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules

PubMed Central

Ashkenazy, Haim; Abadi, Shiran; Martz, Eric; Chay, Ofer; Mayrose, Itay; Pupko, Tal; Ben-Tal, Nir

2016-01-01

The degree of evolutionary conservation of an amino acid in a protein or a nucleic acid in DNA/RNA reflects a balance between its natural tendency to mutate and the overall need to retain the structural integrity and function of the macromolecule. The ConSurf web server (http://consurf.tau.ac.il), established over 15 years ago, analyses the evolutionary pattern of the amino/nucleic acids of the macromolecule to reveal regions that are important for structure and/or function. Starting from a query sequence or structure, the server automatically collects homologues, infers their multiple sequence alignment and reconstructs a phylogenetic tree that reflects their evolutionary relations. These data are then used, within a probabilistic framework, to estimate the evolutionary rates of each sequence position. Here we introduce several new features into ConSurf, including automatic selection of the best evolutionary model used to infer the rates, the ability to homology-model query proteins, prediction of the secondary structure of query RNA molecules from sequence, the ability to view the biological assembly of a query (in addition to the single chain), mapping of the conservation grades onto 2D RNA models and an advanced view of the phylogenetic tree that enables interactively rerunning ConSurf with the taxa of a sub-tree. PMID:27166375

Novel cis-acting element within the capsid-coding region enhances flavivirus viral-RNA replication by regulating genome cyclization.

PubMed

Liu, Zhong-Yu; Li, Xiao-Feng; Jiang, Tao; Deng, Yong-Qiang; Zhao, Hui; Wang, Hong-Jiang; Ye, Qing; Zhu, Shun-Ya; Qiu, Yang; Zhou, Xi; Qin, E-De; Qin, Cheng-Feng

2013-06-01

cis-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved cis-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The downstream of 5' cyclization sequence (5'CS) pseudoknot (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5'CS, and the presence of DCS-PK facilitates the formation of 5'-3' RNA complexes. Taken together, our results reveal that the cis-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other cis-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution.

Novel cis-Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization

PubMed Central

Liu, Zhong-Yu; Li, Xiao-Feng; Jiang, Tao; Deng, Yong-Qiang; Zhao, Hui; Wang, Hong-Jiang; Ye, Qing; Zhu, Shun-Ya; Qiu, Yang; Zhou, Xi; Qin, E-De

2013-01-01

cis-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved cis-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The downstream of 5′ cyclization sequence (5′CS) pseudoknot (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5′CS, and the presence of DCS-PK facilitates the formation of 5′-3′ RNA complexes. Taken together, our results reveal that the cis-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other cis-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution. PMID:23576500

Closed coronal structures. V - Gasdynamic models of flaring loops and comparison with SMM observations

NASA Technical Reports Server (NTRS)

Peres, G.; Serio, S.; Vaiana, G.; Acton, L.; Leibacher, J.; Rosner, R.; Pallavicini, R.

1983-01-01

A time-dependent one-dimensional code incorporating energy, momentum and mass conservation equations, and taking the entire solar atmospheric structure into account, is used to investigate the hydrodynamic response of confined magnetic structures to strong heating perturbations. Model calculation results are compared with flare observations which include the light curves of spectral lines formed over a wide range of coronal flare temperatures, as well as determinations of Doppler shifts for the high temperature plasma. It is shown that the numerical simulation predictions are in good overall agreement with the observed flare coronal plasma evolution, correctly reproducing the temporal profile of X-ray spectral lines and their relative intensities. The predicted upflow velocities support the interpretation of the blueshifts as due to evaporation of chromospheric material.

A maximum entropy model for chromatin structure

NASA Astrophysics Data System (ADS)

Farre, Pau; Emberly, Eldon; Emberly Group Team

The DNA inside the nucleus of eukaryotic cells shows a variety of conserved structures at different length scales These structures are formed by interactions between protein complexes that bind to the DNA and regulate gene activity. Recent high throughput sequencing techniques allow for the measurement both of the genome wide contact map of the folded DNA within a cell (HiC) and where various proteins are bound to the DNA (ChIP-seq). In this talk I will present a maximum-entropy method capable of both predicting HiC contact maps from binding data, and binding data from HiC contact maps. This method results in an intuitive Ising-type model that is able to predict how altering the presence of binding factors can modify chromosome conformation, without the need of polymer simulations.

Remarkable sequence conservation of the last intron in the PKD1 gene.

PubMed

Rodova, Marianna; Islam, M Rafiq; Peterson, Kenneth R; Calvet, James P

2003-10-01

The last intron of the PKD1 gene (intron 45) was found to have exceptionally high sequence conservation across four mammalian species: human, mouse, rat, and dog. This conservation did not extend to the comparable intron in pufferfish. Pairwise comparisons for intron 45 showed 91% identity (human vs. dog) to 100% identity (mouse vs. rat) for an average for all four species of 94% identity. In contrast, introns 43 and 44 of the PKD1 gene had average pairwise identities of 57% and 54%, and exons 43, 44, and 45 and the coding region of exon 46 had average pairwise identities of 80%, 84%, 82%, and 80%. Intron 45 is 90 to 95 bp in length, with the major region of sequence divergence being in a central 4-bp to 9-bp variable region. RNA secondary structure analysis of intron 45 predicts a branching stem-loop structure in which the central variable region lies in one loop and the putative branch point sequence lies in another loop, suggesting that the intron adopts a specific stem-loop structure that may be important for its removal. Although intron 45 appears to conform to the class of small, G-triplet-containing introns that are spliced by a mechanism utilizing intron definition, its high sequence conservation may be a reflection of constraints imposed by a unique mechanism that coordinates splicing of this last PKD1 intron with polyadenylation.

Determining the drivers of population structure in a highly urbanized landscape to inform conservation planning.

PubMed

Thomassen, Henri A; Harrigan, Ryan J; Semple Delaney, Kathleen; Riley, Seth P D; Serieys, Laurel E K; Pease, Katherine; Wayne, Robert K; Smith, Thomas B

2018-02-01

Understanding the environmental contributors to population structure is of paramount importance for conservation in urbanized environments. We used spatially explicit models to determine genetic population structure under current and future environmental conditions across a highly fragmented, human-dominated environment in Southern California to assess the effects of natural ecological variation and urbanization. We focused on 7 common species with diverse habitat requirements, home-range sizes, and dispersal abilities. We quantified the relative roles of potential barriers, including natural environmental characteristics and an anthropogenic barrier created by a major highway, in shaping genetic variation. The ability to predict genetic variation in our models differed among species: 11-81% of intraspecific genetic variation was explained by environmental variables. Although an anthropogenically induced barrier (a major highway) severely restricted gene flow and movement at broad scales for some species, genetic variation seemed to be primarily driven by natural environmental heterogeneity at a local level. Our results show how assessing environmentally associated variation for multiple species under current and future climate conditions can help identify priority regions for maximizing population persistence under environmental change in urbanized regions. © 2017 Society for Conservation Biology.

Improving protein-protein interaction prediction using evolutionary information from low-quality MSAs.

PubMed

Várnai, Csilla; Burkoff, Nikolas S; Wild, David L

2017-01-01

Evolutionary information stored in multiple sequence alignments (MSAs) has been used to identify the interaction interface of protein complexes, by measuring either co-conservation or co-mutation of amino acid residues across the interface. Recently, maximum entropy related correlated mutation measures (CMMs) such as direct information, decoupling direct from indirect interactions, have been developed to identify residue pairs interacting across the protein complex interface. These studies have focussed on carefully selected protein complexes with large, good-quality MSAs. In this work, we study protein complexes with a more typical MSA consisting of fewer than 400 sequences, using a set of 79 intramolecular protein complexes. Using a maximum entropy based CMM at the residue level, we develop an interface level CMM score to be used in re-ranking docking decoys. We demonstrate that our interface level CMM score compares favourably to the complementarity trace score, an evolutionary information-based score measuring co-conservation, when combined with the number of interface residues, a knowledge-based potential and the variability score of individual amino acid sites. We also demonstrate, that, since co-mutation and co-complementarity in the MSA contain orthogonal information, the best prediction performance using evolutionary information can be achieved by combining the co-mutation information of the CMM with co-conservation information of a complementarity trace score, predicting a near-native structure as the top prediction for 41% of the dataset. The method presented is not restricted to small MSAs, and will likely improve interface prediction also for complexes with large and good-quality MSAs.

Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (η) in pathogenic yeast Candida albicans

NASA Astrophysics Data System (ADS)

Satpati, Suresh; Manohar, Kodavati; Acharya, Narottam; Dixit, Anshuman

2017-01-01

Genomic instability in Candida albicans is believed to play a crucial role in fungal pathogenesis. DNA polymerases contribute significantly to stability of any genome. Although Candida Genome database predicts presence of S. cerevisiae DNA polymerase orthologs; functional and structural characterizations of Candida DNA polymerases are still unexplored. DNA polymerase eta (Polη) is unique as it promotes efficient bypass of cyclobutane pyrimidine dimers. Interestingly, C. albicans is heterozygous in carrying two Polη genes and the nucleotide substitutions were found only in the ORFs. As allelic differences often result in functional differences of the encoded proteins, comparative analyses of structural models and molecular dynamic simulations were performed to characterize these orthologs of DNA Polη. Overall structures of both the ORFs remain conserved except subtle differences in the palm and PAD domains. The complementation analysis showed that both the ORFs equally suppressed UV sensitivity of yeast rad30 deletion strain. Our study has predicted two novel molecular interactions, a highly conserved molecular tetrad of salt bridges and a series of π-π interactions spanning from thumb to PAD. This study suggests these ORFs as the homologues of yeast Polη, and due to its heterogeneity in C. albicans they may play a significant role in pathogenicity.

Low-Resolution Structure of the Full-Length Barley (Hordeum vulgare) SGT1 Protein in Solution, Obtained Using Small-Angle X-Ray Scattering

PubMed Central

Taube, Michał; Pieńkowska, Joanna R.; Jarmołowski, Artur; Kozak, Maciej

2014-01-01

SGT1 is an evolutionarily conserved eukaryotic protein involved in many important cellular processes. In plants, SGT1 is involved in resistance to disease. In a low ionic strength environment, the SGT1 protein tends to form dimers. The protein consists of three structurally independent domains (the tetratricopeptide repeats domain (TPR), the CHORD- and SGT1-containing domain (CS), and the SGT1-specific domain (SGS)), and two less conserved variable regions (VR1 and VR2). In the present study, we provide the low-resolution structure of the barley (Hordeum vulgare) SGT1 protein in solution and its dimer/monomer equilibrium using small-angle scattering of synchrotron radiation, ab-initio modeling and circular dichroism spectroscopy. The multivariate curve resolution least-square method (MCR-ALS) was applied to separate the scattering data of the monomeric and dimeric species from a complex mixture. The models of the barley SGT1 dimer and monomer were formulated using rigid body modeling with ab-initio structure prediction. Both oligomeric forms of barley SGT1 have elongated shapes with unfolded inter-domain regions. Circular dichroism spectroscopy confirmed that the barley SGT1 protein had a modular architecture, with an α-helical TPR domain, a β-sheet sandwich CS domain, and a disordered SGS domain separated by VR1 and VR2 regions. Using molecular docking and ab-initio protein structure prediction, a model of dimerization of the TPR domains was proposed. PMID:24714665

Comparison of SWAT and GeoWEPP model in predicting the impact of stone bunds on runoff and erosion processes in the Northern Ethiopian Highlands

NASA Astrophysics Data System (ADS)

Demelash, Nigus; Flagler, Jared; Renschler, Chris; Strohmeier, Stefan; Holzmann, Hubert; Feras, Ziadat; Addis, Hailu; Zucca, Claudio; Bayu, Wondimu; Klik, Andreas

2017-04-01

Soil degradation is a major issue in the Ethiopian highlands which are most suitable for agriculture and, therefore, support a major part of human population and livestock. Heavy rainstorms during the rainy season in summer create soil erosion and runoff processes which affect soil fertility and food security. In the last years programs for soil conservation and afforestation were initiated by the Ethiopian government to reduce erosion risk, retain water in the landscape and improve crop yields. The study was done in two adjacent watersheds in the Northwestern highlands of Ethiopia. One of the watersheds is developed by soil and water conservation structures (stone bunds) in 2011 and the other one is without soil and water conservation structures. Spatial distribution of soil textures and other soil properties were determined in the field and in the laboratory and a soil map was derived. A land use map was evaluated based on satellite images and ground truth data. A Digital Elevation Model of the watershed was developed based on conventional terrestrial surveying using a total station. At the outlet of the watersheds weirs with cameras were installed to measure surface runoff. During each event runoff samples were collected and sediment concentration was analyzed. The objective of this study is 1) to assess the impact of stone bunds on runoff and erosion processes by using simulation models, and 2) to compare the performance of two soil erosion models in predicting the measurements. The selected erosion models were the Soil and Water Assessment Tool (SWAT) and the Geospatial Interface to the Water Erosion Prediction Project (GeoWEPP). The simulation models were calibrated/verified for the 2011-2013 periods and validated with 2014-2015 data. Results of this comparison will be presented.

Evaluating the intersection of a regional wildlife connectivity network with highways.

PubMed

Cushman, Samuel A; Lewis, Jesse S; Landguth, Erin L

2013-01-01

Reliable predictions of regional-scale population connectivity are needed to prioritize conservation actions. However, there have been few examples of regional connectivity models that are empirically derived and validated. The central goals of this paper were to (1) evaluate the effectiveness of factorial least cost path corridor mapping on an empirical resistance surface in reflecting the frequency of highway crossings by American black bear, (2) predict the location and predicted intensity of use of movement corridors for American black bear, and (3) identify where these corridors cross major highways and rank the intensity of these crossings. We used factorial least cost path modeling coupled with resistant kernel analysis to predict a network of movement corridors across a 30.2 million hectare analysis area in Montana and Idaho, USA. Factorial least cost path corridor mapping was associated with the locations of actual bear highway crossings. We identified corridor-highway intersections and ranked these based on corridor strength. We found that a major wildlife crossing overpass structure was located close to one of the most intense predicted corridors, and that the vast majority of the predicted corridor network was "protected" under federal management. However, narrow, linear corridors connecting the Greater Yellowstone Ecosystem to the rest of the analysis area had limited protection by federal ownership, making these additionally vulnerable to habitat loss and fragmentation. Factorial least cost path modeling coupled with resistant kernel analysis provides detailed, synoptic information about connectivity across populations that vary in distribution and density in complex landscapes. Specifically, our results could be used to quantify the structure of the connectivity network, identify critical linkage nodes and core areas, map potential barriers and fracture zones, and prioritize locations for mitigation, restoration and conservation actions.

From conservative to reactive transport under diffusion-controlled conditions

NASA Astrophysics Data System (ADS)

Babey, Tristan; de Dreuzy, Jean-Raynald; Ginn, Timothy R.

2016-05-01

We assess the possibility to use conservative transport information, such as that contained in transit time distributions, breakthrough curves and tracer tests, to predict nonlinear fluid-rock interactions in fracture/matrix or mobile/immobile conditions. Reference simulated data are given by conservative and reactive transport simulations in several diffusive porosity structures differing by their topological organization. Reactions includes nonlinear kinetically controlled dissolution and desorption. Effective Multi-Rate Mass Transfer models (MRMT) are calibrated solely on conservative transport information without pore topology information and provide concentration distributions on which effective reaction rates are estimated. Reference simulated reaction rates and effective reaction rates evaluated by MRMT are compared, as well as characteristic desorption and dissolution times. Although not exactly equal, these indicators remain very close whatever the porous structure, differing at most by 0.6% and 10% for desorption and dissolution. At early times, this close agreement arises from the fine characterization of the diffusive porosity close to the mobile zone that controls fast mobile-diffusive exchanges. At intermediate to late times, concentration gradients are strongly reduced by diffusion, and reactivity can be captured by a very limited number of rates. We conclude that effective models calibrated solely on conservative transport information like MRMT can accurately estimate monocomponent kinetically controlled nonlinear fluid-rock interactions. Their relevance might extend to more advanced biogeochemical reactions because of the good characterization of conservative concentration distributions, even by parsimonious models (e.g., MRMT with 3-5 rates). We propose a methodology to estimate reactive transport from conservative transport in mobile-immobile conditions.

Terrain and vegetation structural influences on local avian species richness in two mixed-conifer forests

Treesearch

Jody C. Vogeler; Andrew T. Hudak; Lee A. Vierling; Jeffrey Evans; Patricia Green; Kerri T. Vierling

2014-01-01

Using remotely-sensed metrics to identify regions containing high animal diversity and/or specific animal species or guilds can help prioritize forest management and conservation objectives across actively managed landscapes. We predicted avian species richness in two mixed conifer forests, Moscow Mountain and Slate Creek, containing different management contexts and...

A comparison of individual-based genetic distance metrics for landscape genetics

Treesearch

A. J. Shirk; E. L. Landguth; S. A. Cushman

2017-01-01

A major aim of landscape genetics is to understand how landscapes resist gene flow and thereby influence population genetic structure. An empirical understanding of this process provides a wealth of information that can be used to guide conservation and management of species in fragmented landscapes and also to predict how landscape change may affect population...

Sequence conservation from human to prokaryotes of Surf1, a protein involved in cytochrome c oxidase assembly, deficient in Leigh syndrome.

PubMed

Poyau, A; Buchet, K; Godinot, C

1999-12-03

The human SURF1 gene encoding a protein involved in cytochrome c oxidase (COX) assembly, is mutated in most patients presenting Leigh syndrome associated with COX deficiency. Proteins homologous to the human Surf1 have been identified in nine eukaryotes and six prokaryotes using database alignment tools, structure prediction and/or cDNA sequencing. Their sequence comparison revealed a remarkable Surf1 conservation during evolution and put forward at least four highly conserved domains that should be essential for Surf1 function. In Paracoccus denitrificans, the Surf1 homologue is found in the quinol oxidase operon, suggesting that Surf1 is associated with a primitive quinol oxidase which belongs to the same superfamily as cytochrome oxidase.

Identification of a conserved 8 aa insert in the PIP5K protein in the Saccharomycetaceae family of fungi and the molecular dynamics simulations and structural analysis to investigate its potential functional role.

PubMed

Khadka, Bijendra; Gupta, Radhey S

2017-08-01

Homologs of the phosphatidylinositol-4-phosphate-5-kinase (PIP5K), which controls a multitude of essential cellular functions, contain a 8 aa insert in a conserved region that is specific for the Saccharomycetaceae family of fungi. Using structures of human PIP4K proteins as templates, structural models were generated of the Saccharomyces cerevisiae and human PIP5K proteins. In the modeled S. cerevisiae PIP5K, the 8 aa insert forms a surface exposed loop, present on the same face of the protein as the activation loop of the kinase domain. Electrostatic potential analysis indicates that the residues from 8 aa conserved loop form a highly positively charged surface patch, which through electrostatic interaction with the anionic portions of phospholipid head groups, is expected to play a role in the membrane interaction of the yeast PIP5K. To unravel this prediction, molecular dynamics (MD) simulations were carried out to examine the binding interaction of PIP5K, either containing or lacking the conserved signature insert, with two different membrane lipid bilayers. The results from MD studies provide insights concerning the mechanistic of interaction of PIP5K with lipid bilayer, and support the contention that the identified 8 aa conserved insert in fungal PIP5K plays an important role in the binding of this protein with membrane surface. Proteins 2017; 85:1454-1467. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Geography of Genetic Structure in Barley Wild Relative Hordeum vulgare subsp. spontaneum in Jordan.

PubMed

Thormann, Imke; Reeves, Patrick; Reilley, Ann; Engels, Johannes M M; Lohwasser, Ulrike; Börner, Andreas; Pillen, Klaus; Richards, Christopher M

2016-01-01

Informed collecting, conservation, monitoring and utilization of genetic diversity requires knowledge of the distribution and structure of the variation occurring in a species. Hordeum vulgare subsp. spontaneum (K. Koch) Thell., a primary wild relative of barley, is an important source of genetic diversity for barley improvement and co-occurs with the domesticate within the center of origin. We studied the current distribution of genetic diversity and population structure in H. vulgare subsp. spontaneum in Jordan and investigated whether it is correlated with either spatial or climatic variation inferred from publically available climate layers commonly used in conservation and ecogeographical studies. The genetic structure of 32 populations collected in 2012 was analyzed with 37 SSRs. Three distinct genetic clusters were identified. Populations were characterized by admixture and high allelic richness, and genetic diversity was concentrated in the northern part of the study area. Genetic structure, spatial location and climate were not correlated. This may point out a limitation in using large scale climatic data layers to predict genetic diversity, especially as it is applied to regional genetic resources collections in H. vulgare subsp. spontaneum.

Geography of Genetic Structure in Barley Wild Relative Hordeum vulgare subsp. spontaneum in Jordan

PubMed Central

Reeves, Patrick; Reilley, Ann; Engels, Johannes M. M.; Lohwasser, Ulrike; Börner, Andreas; Pillen, Klaus; Richards, Christopher M.

2016-01-01

Informed collecting, conservation, monitoring and utilization of genetic diversity requires knowledge of the distribution and structure of the variation occurring in a species. Hordeum vulgare subsp. spontaneum (K. Koch) Thell., a primary wild relative of barley, is an important source of genetic diversity for barley improvement and co-occurs with the domesticate within the center of origin. We studied the current distribution of genetic diversity and population structure in H. vulgare subsp. spontaneum in Jordan and investigated whether it is correlated with either spatial or climatic variation inferred from publically available climate layers commonly used in conservation and ecogeographical studies. The genetic structure of 32 populations collected in 2012 was analyzed with 37 SSRs. Three distinct genetic clusters were identified. Populations were characterized by admixture and high allelic richness, and genetic diversity was concentrated in the northern part of the study area. Genetic structure, spatial location and climate were not correlated. This may point out a limitation in using large scale climatic data layers to predict genetic diversity, especially as it is applied to regional genetic resources collections in H. vulgare subsp. spontaneum. PMID:27513459

Evidence for the Concerted Evolution between Short Linear Protein Motifs and Their Flanking Regions

PubMed Central

Chica, Claudia; Diella, Francesca; Gibson, Toby J.

2009-01-01

Background Linear motifs are short modules of protein sequences that play a crucial role in mediating and regulating many protein–protein interactions. The function of linear motifs strongly depends on the context, e.g. functional instances mainly occur inside flexible regions that are accessible for interaction. Sometimes linear motifs appear as isolated islands of conservation in multiple sequence alignments. However, they also occur in larger blocks of sequence conservation, suggesting an active role for the neighbouring amino acids. Results The evolution of regions flanking 116 functional linear motif instances was studied. The conservation of the amino acid sequence and order/disorder tendency of those regions was related to presence/absence of the instance. For the majority of the analysed instances, the pairs of sequences conserving the linear motif were also observed to maintain a similar local structural tendency and/or to have higher local sequence conservation when compared to pairs of sequences where one is missing the linear motif. Furthermore, those instances have a higher chance to co–evolve with the neighbouring residues in comparison to the distant ones. Those findings are supported by examples where the regulation of the linear motif–mediated interaction has been shown to depend on the modifications (e.g. phosphorylation) at neighbouring positions or is thought to benefit from the binding versatility of disordered regions. Conclusion The results suggest that flanking regions are relevant for linear motif–mediated interactions, both at the structural and sequence level. More interestingly, they indicate that the prediction of linear motif instances can be enriched with contextual information by performing a sequence analysis similar to the one presented here. This can facilitate the understanding of the role of these predicted instances in determining the protein function inside the broader context of the cellular network where they arise. PMID:19584925

A Conserved Structural Module Regulates Transcriptional Responses to Diverse Stress Signals in Bacteria

PubMed Central

Campbell, Elizabeth A.; Greenwell, Roger; Anthony, Jennifer R.; Wang, Sheng; Lim, Lionel; Das, Kalyan; Sofia, Heidi J.; Donohue, Timothy J.; Darst, Seth A.

2008-01-01

SUMMARY A transcriptional response to singlet oxygen in Rhodobacter sphaeroides is controlled by the group IV σ factor σE and its cognate anti-σ ChrR. Crystal structures of the σE/ChrR complex reveal a modular, two-domain architecture for ChrR. The ChrR N-terminal anti-σ domain (ASD) binds a Zn2+ ion, contacts σE, and is sufficient to inhibit σE-dependent transcription. The ChrR C-terminal domain adopts a cupin fold, can coordinate an additional Zn2+, and is required for the transcriptional response to singlet oxygen. Structure-based sequence analyses predict that the ASD defines a common structural fold among predicted group IV antiσs. These ASDs are fused to diverse C-terminal domains that are likely involved in responding to specific environmental signals that control the activity of their cognate σ factor. PMID:17803943

FuncPatch: a web server for the fast Bayesian inference of conserved functional patches in protein 3D structures.

PubMed

Huang, Yi-Fei; Golding, G Brian

2015-02-15

A number of statistical phylogenetic methods have been developed to infer conserved functional sites or regions in proteins. Many methods, e.g. Rate4Site, apply the standard phylogenetic models to infer site-specific substitution rates and totally ignore the spatial correlation of substitution rates in protein tertiary structures, which may reduce their power to identify conserved functional patches in protein tertiary structures when the sequences used in the analysis are highly similar. The 3D sliding window method has been proposed to infer conserved functional patches in protein tertiary structures, but the window size, which reflects the strength of the spatial correlation, must be predefined and is not inferred from data. We recently developed GP4Rate to solve these problems under the Bayesian framework. Unfortunately, GP4Rate is computationally slow. Here, we present an intuitive web server, FuncPatch, to perform a fast approximate Bayesian inference of conserved functional patches in protein tertiary structures. Both simulations and four case studies based on empirical data suggest that FuncPatch is a good approximation to GP4Rate. However, FuncPatch is orders of magnitudes faster than GP4Rate. In addition, simulations suggest that FuncPatch is potentially a useful tool complementary to Rate4Site, but the 3D sliding window method is less powerful than FuncPatch and Rate4Site. The functional patches predicted by FuncPatch in the four case studies are supported by experimental evidence, which corroborates the usefulness of FuncPatch. The software FuncPatch is freely available at the web site, http://info.mcmaster.ca/yifei/FuncPatch golding@mcmaster.ca Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors.

PubMed

Zafra Ruano, Ana; Cilia, Elisa; Couceiro, José R; Ruiz Sanz, Javier; Schymkowitz, Joost; Rousseau, Frederic; Luque, Irene; Lenaerts, Tom

2016-05-01

Src Homology 3 domains are ubiquitous small interaction modules known to act as docking sites and regulatory elements in a wide range of proteins. Prior experimental NMR work on the SH3 domain of Src showed that ligand binding induces long-range dynamic changes consistent with an induced fit mechanism. The identification of the residues that participate in this mechanism produces a chart that allows for the exploration of the regulatory role of such domains in the activity of the encompassing protein. Here we show that a computational approach focusing on the changes in side chain dynamics through ligand binding identifies equivalent long-range effects in the Src SH3 domain. Mutation of a subset of the predicted residues elicits long-range effects on the binding energetics, emphasizing the relevance of these positions in the definition of intramolecular cooperative networks of signal transduction in this domain. We find further support for this mechanism through the analysis of seven other publically available SH3 domain structures of which the sequences represent diverse SH3 classes. By comparing the eight predictions, we find that, in addition to a dynamic pathway that is relatively conserved throughout all SH3 domains, there are dynamic aspects specific to each domain and homologous subgroups. Our work shows for the first time from a structural perspective, which transduction mechanisms are common between a subset of closely related and distal SH3 domains, while at the same time highlighting the differences in signal transduction that make each family member unique. These results resolve the missing link between structural predictions of dynamic changes and the domain sectors recently identified for SH3 domains through sequence analysis.

From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors

PubMed Central

Ruiz Sanz, Javier; Schymkowitz, Joost; Rousseau, Frederic

2016-01-01

Src Homology 3 domains are ubiquitous small interaction modules known to act as docking sites and regulatory elements in a wide range of proteins. Prior experimental NMR work on the SH3 domain of Src showed that ligand binding induces long-range dynamic changes consistent with an induced fit mechanism. The identification of the residues that participate in this mechanism produces a chart that allows for the exploration of the regulatory role of such domains in the activity of the encompassing protein. Here we show that a computational approach focusing on the changes in side chain dynamics through ligand binding identifies equivalent long-range effects in the Src SH3 domain. Mutation of a subset of the predicted residues elicits long-range effects on the binding energetics, emphasizing the relevance of these positions in the definition of intramolecular cooperative networks of signal transduction in this domain. We find further support for this mechanism through the analysis of seven other publically available SH3 domain structures of which the sequences represent diverse SH3 classes. By comparing the eight predictions, we find that, in addition to a dynamic pathway that is relatively conserved throughout all SH3 domains, there are dynamic aspects specific to each domain and homologous subgroups. Our work shows for the first time from a structural perspective, which transduction mechanisms are common between a subset of closely related and distal SH3 domains, while at the same time highlighting the differences in signal transduction that make each family member unique. These results resolve the missing link between structural predictions of dynamic changes and the domain sectors recently identified for SH3 domains through sequence analysis. PMID:27213566

Structural and functional features of lysine acetylation of plant and animal tubulins.

PubMed

Rayevsky, Alexey V; Sharifi, Mohsen; Samofalova, Dariya A; Karpov, Pavel A; Blume, Yaroslav B

2017-10-10

The study of the genome and the proteome of different species and representatives of distinct kingdoms, especially detection of proteome via wide-scaled analyses has various challenges and pitfalls. Attempts to combine all available information together and isolate some common features for determination of the pathway and their mechanism of action generally have a highly complicated nature. However, microtubule (MT) monomers are highly conserved protein structures, and microtubules are structurally conserved from Homo sapiens to Arabidopsis thaliana. The interaction of MT elements with microtubule-associated proteins and post-translational modifiers is fully dependent on protein interfaces, and almost all MT modifications are well described except acetylation. Crystallography and interactome data using different approaches were combined to identify conserved proteins important in acetylation of microtubules. Application of computational methods and comparative analysis of binding modes generated a robust predictive model of acetylation of the ϵ-amino group of Lys40 in α-tubulins. In turn, the model discarded some probable mechanisms of interaction between elements of interest. Reconstruction of unresolved protein structures was carried out with modeling by homology to the existing crystal structure (PDBID: 1Z2B) from B. taurus using Swiss-model server, followed by a molecular dynamics simulation. Docking of the human tubulin fragment with Lys40 into the active site of α-tubulin acetyltransferase, reproduces the binding mode of peptidomimetic from X-ray structure (PDBID: 4PK3). © 2017 International Federation for Cell Biology.

Insights into Structural and Mechanistic Features of Viral IRES Elements

PubMed Central

Martinez-Salas, Encarnacion; Francisco-Velilla, Rosario; Fernandez-Chamorro, Javier; Embarek, Azman M.

2018-01-01

Internal ribosome entry site (IRES) elements are cis-acting RNA regions that promote internal initiation of protein synthesis using cap-independent mechanisms. However, distinct types of IRES elements present in the genome of various RNA viruses perform the same function despite lacking conservation of sequence and secondary RNA structure. Likewise, IRES elements differ in host factor requirement to recruit the ribosomal subunits. In spite of this diversity, evolutionarily conserved motifs in each family of RNA viruses preserve sequences impacting on RNA structure and RNA–protein interactions important for IRES activity. Indeed, IRES elements adopting remarkable different structural organizations contain RNA structural motifs that play an essential role in recruiting ribosomes, initiation factors and/or RNA-binding proteins using different mechanisms. Therefore, given that a universal IRES motif remains elusive, it is critical to understand how diverse structural motifs deliver functions relevant for IRES activity. This will be useful for understanding the molecular mechanisms beyond cap-independent translation, as well as the evolutionary history of these regulatory elements. Moreover, it could improve the accuracy to predict IRES-like motifs hidden in genome sequences. This review summarizes recent advances on the diversity and biological relevance of RNA structural motifs for viral IRES elements. PMID:29354113

Fatigue crack growth and life prediction under mixed-mode loading

NASA Astrophysics Data System (ADS)

Sajith, S.; Murthy, K. S. R. K.; Robi, P. S.

2018-04-01

Fatigue crack growth life as a function of crack length is essential for the prevention of catastrophic failures from damage tolerance perspective. In damage tolerance design approach, principles of fracture mechanics are usually applied to predict the fatigue life of structural components. Numerical prediction of crack growth versus number of cycles is essential in damage tolerance design. For cracks under mixed mode I/II loading, modified Paris law (d/a d N =C (ΔKe q ) m ) along with different equivalent stress intensity factor (ΔKeq) model is used for fatigue crack growth rate prediction. There are a large number of ΔKeq models available for the mixed mode I/II loading, the selection of proper ΔKeq model has significant impact on fatigue life prediction. In the present investigation, the performance of ΔKeq models in fatigue life prediction is compared with respect to the experimental findings as there are no guidelines/suggestions available on the selection of these models for accurate and/or conservative predictions of fatigue life. Within the limitations of availability of experimental data and currently available numerical simulation techniques, the results of present study attempt to outline models that would provide accurate and conservative life predictions. Such a study aid the numerical analysts or engineers in the proper selection of the model for numerical simulation of the fatigue life. Moreover, the present investigation also suggests a procedure to enhance the accuracy of life prediction using Paris law.

Topology of membrane proteins-predictions, limitations and variations.

PubMed

Tsirigos, Konstantinos D; Govindarajan, Sudha; Bassot, Claudio; Västermark, Åke; Lamb, John; Shu, Nanjiang; Elofsson, Arne

2017-10-26

Transmembrane proteins perform a variety of important biological functions necessary for the survival and growth of the cells. Membrane proteins are built up by transmembrane segments that span the lipid bilayer. The segments can either be in the form of hydrophobic alpha-helices or beta-sheets which create a barrel. A fundamental aspect of the structure of transmembrane proteins is the membrane topology, that is, the number of transmembrane segments, their position in the protein sequence and their orientation in the membrane. Along these lines, many predictive algorithms for the prediction of the topology of alpha-helical and beta-barrel transmembrane proteins exist. The newest algorithms obtain an accuracy close to 80% both for alpha-helical and beta-barrel transmembrane proteins. However, lately it has been shown that the simplified picture presented when describing a protein family by its topology is limited. To demonstrate this, we highlight examples where the topology is either not conserved in a protein superfamily or where the structure cannot be described solely by the topology of a protein. The prediction of these non-standard features from sequence alone was not successful until the recent revolutionary progress in 3D-structure prediction of proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES)

PubMed Central

Kolekar, Pandurang; Pataskar, Abhijeet; Kulkarni-Kale, Urmila; Pal, Jayanta; Kulkarni, Abhijeet

2016-01-01

Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5′ untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/. PMID:27264539

Online interactive analysis of protein structure ensembles with Bio3D-web.

PubMed

Skjærven, Lars; Jariwala, Shashank; Yao, Xin-Qiu; Grant, Barry J

2016-11-15

Bio3D-web is an online application for analyzing the sequence, structure and conformational heterogeneity of protein families. Major functionality is provided for identifying protein structure sets for analysis, their alignment and refined structure superposition, sequence and structure conservation analysis, mapping and clustering of conformations and the quantitative comparison of their predicted structural dynamics. Bio3D-web is based on the Bio3D and Shiny R packages. All major browsers are supported and full source code is available under a GPL2 license from http://thegrantlab.org/bio3d-web CONTACT: bjgrant@umich.edu or lars.skjarven@uib.no. © The Author 2016. Published by Oxford University Press.

Comparison of statistical and theoretical habitat models for conservation planning: the benefit of ensemble prediction

USGS Publications Warehouse

Jones-Farrand, D. Todd; Fearer, Todd M.; Thogmartin, Wayne E.; Thompson, Frank R.; Nelson, Mark D.; Tirpak, John M.

2011-01-01

Selection of a modeling approach is an important step in the conservation planning process, but little guidance is available. We compared two statistical and three theoretical habitat modeling approaches representing those currently being used for avian conservation planning at landscape and regional scales: hierarchical spatial count (HSC), classification and regression tree (CRT), habitat suitability index (HSI), forest structure database (FS), and habitat association database (HA). We focused our comparison on models for five priority forest-breeding species in the Central Hardwoods Bird Conservation Region: Acadian Flycatcher, Cerulean Warbler, Prairie Warbler, Red-headed Woodpecker, and Worm-eating Warbler. Lacking complete knowledge on the distribution and abundance of each species with which we could illuminate differences between approaches and provide strong grounds for recommending one approach over another, we used two approaches to compare models: rank correlations among model outputs and comparison of spatial correspondence. In general, rank correlations were significantly positive among models for each species, indicating general agreement among the models. Worm-eating Warblers had the highest pairwise correlations, all of which were significant (P , 0.05). Red-headed Woodpeckers had the lowest agreement among models, suggesting greater uncertainty in the relative conservation value of areas within the region. We assessed model uncertainty by mapping the spatial congruence in priorities (i.e., top ranks) resulting from each model for each species and calculating the coefficient of variation across model ranks for each location. This allowed identification of areas more likely to be good targets of conservation effort for a species, those areas that were least likely, and those in between where uncertainty is higher and thus conservation action incorporates more risk. Based on our results, models developed independently for the same purpose (conservation planning for a particular species in a particular geography) yield different answers and thus different conservation strategies. We assert that using only one habitat model (even if validated) as the foundation of a conservation plan is risky. Using multiple models (i.e., ensemble prediction) can reduce uncertainty and increase efficacy of conservation action when models corroborate one another and increase understanding of the system when they do not.

Coevolution at protein complex interfaces can be detected by the complementarity trace with important impact for predictive docking

PubMed Central

Madaoui, Hocine; Guerois, Raphaël

2008-01-01

Protein surfaces are under significant selection pressure to maintain interactions with their partners throughout evolution. Capturing how selection pressure acts at the interfaces of protein–protein complexes is a fundamental issue with high interest for the structural prediction of macromolecular assemblies. We tackled this issue under the assumption that, throughout evolution, mutations should minimally disrupt the physicochemical compatibility between specific clusters of interacting residues. This constraint drove the development of the so-called Surface COmplementarity Trace in Complex History score (SCOTCH), which was found to discriminate with high efficiency the structure of biological complexes. SCOTCH performances were assessed not only with respect to other evolution-based approaches, such as conservation and coevolution analyses, but also with respect to statistically based scoring methods. Validated on a set of 129 complexes of known structure exhibiting both permanent and transient intermolecular interactions, SCOTCH appears as a robust strategy to guide the prediction of protein–protein complex structures. Of particular interest, it also provides a basic framework to efficiently track how protein surfaces could evolve while keeping their partners in contact. PMID:18511568

An evolutionary conserved pattern of 18S rRNA sequence complementarity to mRNA 5′ UTRs and its implications for eukaryotic gene translation regulation

PubMed Central

Pánek, Josef; Kolář, Michal; Vohradský, Jiří; Shivaya Valášek, Leoš

2013-01-01

There are several key mechanisms regulating eukaryotic gene expression at the level of protein synthesis. Interestingly, the least explored mechanisms of translational control are those that involve the translating ribosome per se, mediated for example via predicted interactions between the ribosomal RNAs (rRNAs) and mRNAs. Here, we took advantage of robustly growing large-scale data sets of mRNA sequences for numerous organisms, solved ribosomal structures and computational power to computationally explore the mRNA–rRNA complementarity that is statistically significant across the species. Our predictions reveal highly specific sequence complementarity of 18S rRNA sequences with mRNA 5′ untranslated regions (UTRs) forming a well-defined 3D pattern on the rRNA sequence of the 40S subunit. Broader evolutionary conservation of this pattern may imply that 5′ UTRs of eukaryotic mRNAs, which have already emerged from the mRNA-binding channel, may contact several complementary spots on 18S rRNA situated near the exit of the mRNA binding channel and on the middle-to-lower body of the solvent-exposed 40S ribosome including its left foot. We discuss physiological significance of this structurally conserved pattern and, in the context of previously published experimental results, propose that it modulates scanning of the 40S subunit through 5′ UTRs of mRNAs. PMID:23804757

Nuclear Graphite - Fracture Behavior and Modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burchell, Timothy D; Battiste, Rick; Strizak, Joe P

2011-01-01

Evidence for the graphite fracture mechanism is reviewed and discussed. The roles of certain microstructural features in the graphite fracture process are reported. The Burchell fracture model is described and its derivation reported. The successful application of the fracture model to uniaxial tensile data from several graphites with widely ranging structure and texture is reported. The extension of the model to multiaxial loading scenarios using two criteria is discussed. Initially, multiaxial strength data for H-451 graphite were modeled using the fracture model and the Principle of Independent Action. The predicted 4th stress quadrant failure envelope was satisfactory but the 1stmore » quadrant predictions were not conservative and thus were unsatisfactory. Multiaxial strength data from the 1st and 4th stress quadrant for NBG-18 graphite are reported. To improve the conservatism of the predicted 1st quadrant failure envelope for NBG-18 the Shetty criterion has been applied to obtain the equivalent critical stress intensity factor, KIc (Equi), for each applied biaxial stress ratio. The equivalent KIc value is used in the Burchell fracture model to predict the failure envelope. The predicted 1st stress quadrant failure envelope is conservative and thus more satisfactory than achieved previously using the fracture model combined with the Principle of Independent Action.« less

Prediction of Protein Modification Sites of Pyrrolidone Carboxylic Acid Using mRMR Feature Selection and Analysis

PubMed Central

Zheng, Lu-Lu; Niu, Shen; Hao, Pei; Feng, KaiYan; Cai, Yu-Dong; Li, Yixue

2011-01-01

Pyrrolidone carboxylic acid (PCA) is formed during a common post-translational modification (PTM) of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR) and incremental feature selection (IFS). We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations. PMID:22174779

Gardenia jasminoides Encodes an Inhibitor-2 Protein for Protein Phosphatase Type 1

NASA Astrophysics Data System (ADS)

Gao, Lan; Li, Hao-Ming

2017-08-01

Protein phosphatase-1 (PP1) regulates diverse, essential cellular processes such as cell cycle progression, protein synthesis, muscle contraction, carbohydrate metabolism, transcription and neuronal signaling. Inhibitor-2 (I-2) can inhibit the activity of PP1 and has been found in diverse organisms. In this work, a Gardenia jasminoides fruit cDNA library was constructed, and the GjI-2 cDNA was isolated from the cDNA library by sequencing method. The GjI-2 cDNA contains a predicted 543 bp open reading frame that encodes 180 amino acids. The bioinformatics analysis suggested that the GjI-2 has conserved PP1c binding motif, and contains a conserved phosphorylation site, which is important in regulation of its activity. The three-dimensional model structure of GjI-2 was buite, its similar with the structure of I-2 from mouse. The results suggest that GjI-2 has relatively conserved RVxF, FxxR/KxR/K and HYNE motif, and these motifs are involved in interaction with PP1.

OST-HTH: a novel predicted RNA-binding domain

PubMed Central

2010-01-01

Background The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria. Results Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Conclusions Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs. Reviewers This article was reviewed by Sandor Pongor and Arcady Mushegian. PMID:20302647

Secondary structural analyses of ITS1 in Paramecium.

PubMed

Hoshina, Ryo

2010-01-01

The nuclear ribosomal RNA gene operon is interrupted by internal transcribed spacer (ITS) 1 and ITS2. Although the secondary structure of ITS2 has been widely investigated, less is known about ITS1 and its structure. In this study, the secondary structure of ITS1 sequences for Paramecium and other ciliates was predicted. Each Paramecium ITS1 forms an open loop with three helices, A through C. Helix B was highly conserved among Paramecium, and similar helices were found in other ciliates. A phylogenetic analysis using the ITS1 sequences showed high-resolution, implying that ITS1 is a good tool for species-level analyses.

Experimental evidence that simplified forest structure interacts with snow cover to influence functional connectivity for Pacific martens

Treesearch

Katie M. Moriarty; Clinton W. Epps; Matthew G. Betts; Dalton J. Hance; J. D. Bailey; William J. Zielinski

2015-01-01

Context Functional connectivity—the facilitation of individual movements among habitat patches—is essential for species’ persistence in fragmented landscapes. Evaluating functional connectivity is critical for predicting range shifts, developing conservation plans, and anticipating effects of disturbance, especially for species affected by climate change. Objectives We...

APPRIS: annotation of principal and alternative splice isoforms

PubMed Central

Rodriguez, Jose Manuel; Maietta, Paolo; Ezkurdia, Iakes; Pietrelli, Alessandro; Wesselink, Jan-Jaap; Lopez, Gonzalo; Valencia, Alfonso; Tress, Michael L.

2013-01-01

Here, we present APPRIS (http://appris.bioinfo.cnio.es), a database that houses annotations of human splice isoforms. APPRIS has been designed to provide value to manual annotations of the human genome by adding reliable protein structural and functional data and information from cross-species conservation. The visual representation of the annotations provided by APPRIS for each gene allows annotators and researchers alike to easily identify functional changes brought about by splicing events. In addition to collecting, integrating and analyzing reliable predictions of the effect of splicing events, APPRIS also selects a single reference sequence for each gene, here termed the principal isoform, based on the annotations of structure, function and conservation for each transcript. APPRIS identifies a principal isoform for 85% of the protein-coding genes in the GENCODE 7 release for ENSEMBL. Analysis of the APPRIS data shows that at least 70% of the alternative (non-principal) variants would lose important functional or structural information relative to the principal isoform. PMID:23161672

Improving effectiveness of systematic conservation planning with density data.

PubMed

Veloz, Samuel; Salas, Leonardo; Altman, Bob; Alexander, John; Jongsomjit, Dennis; Elliott, Nathan; Ballard, Grant

2015-08-01

Systematic conservation planning aims to design networks of protected areas that meet conservation goals across large landscapes. The optimal design of these conservation networks is most frequently based on the modeled habitat suitability or probability of occurrence of species, despite evidence that model predictions may not be highly correlated with species density. We hypothesized that conservation networks designed using species density distributions more efficiently conserve populations of all species considered than networks designed using probability of occurrence models. To test this hypothesis, we used the Zonation conservation prioritization algorithm to evaluate conservation network designs based on probability of occurrence versus density models for 26 land bird species in the U.S. Pacific Northwest. We assessed the efficacy of each conservation network based on predicted species densities and predicted species diversity. High-density model Zonation rankings protected more individuals per species when networks protected the highest priority 10-40% of the landscape. Compared with density-based models, the occurrence-based models protected more individuals in the lowest 50% priority areas of the landscape. The 2 approaches conserved species diversity in similar ways: predicted diversity was higher in higher priority locations in both conservation networks. We conclude that both density and probability of occurrence models can be useful for setting conservation priorities but that density-based models are best suited for identifying the highest priority areas. Developing methods to aggregate species count data from unrelated monitoring efforts and making these data widely available through ecoinformatics portals such as the Avian Knowledge Network will enable species count data to be more widely incorporated into systematic conservation planning efforts. © 2015, Society for Conservation Biology.

Modeling approaches in avian conservation and the role of field biologists

USGS Publications Warehouse

Beissinger, Steven R.; Walters, J.R.; Catanzaro, D.G.; Smith, Kimberly G.; Dunning, J.B.; Haig, Susan M.; Noon, Barry; Stith, Bradley M.

2006-01-01

This review grew out of our realization that models play an increasingly important role in conservation but are rarely used in the research of most avian biologists. Modelers are creating models that are more complex and mechanistic and that can incorporate more of the knowledge acquired by field biologists. Such models require field biologists to provide more specific information, larger sample sizes, and sometimes new kinds of data, such as habitat-specific demography and dispersal information. Field biologists need to support model development by testing key model assumptions and validating models. The best conservation decisions will occur where cooperative interaction enables field biologists, modelers, statisticians, and managers to contribute effectively. We begin by discussing the general form of ecological models—heuristic or mechanistic, "scientific" or statistical—and then highlight the structure, strengths, weaknesses, and applications of six types of models commonly used in avian conservation: (1) deterministic single-population matrix models, (2) stochastic population viability analysis (PVA) models for single populations, (3) metapopulation models, (4) spatially explicit models, (5) genetic models, and (6) species distribution models. We end by considering their unique attributes, determining whether the assumptions that underlie the structure are valid, and testing the ability of the model to predict the future correctly.

Mobile Element Evolution Playing Jigsaw—SINEs in Gastropod and Bivalve Mollusks

PubMed Central

Matetovici, Irina; Sajgo, Szilard; Ianc, Bianca; Ochis, Cornelia; Bulzu, Paul; Popescu, Octavian; Damert, Annette

2016-01-01

SINEs (Short INterspersed Elements) are widely distributed among eukaryotes. Some SINE families are organized in superfamilies characterized by a shared central domain. These central domains are conserved across species, classes, and even phyla. Here we report the identification of two novel such superfamilies in the genomes of gastropod and bivalve mollusks. The central conserved domain of the first superfamily is present in SINEs in Caenogastropoda and Vetigastropoda as well as in all four subclasses of Bivalvia. We designated the domain MESC (Romanian for MElc—snail and SCoica—mussel) because it appears to be restricted to snails and mussels. The second superfamily is restricted to Caenogastropoda. Its central conserved domain—Snail—is related to the Nin-DC domain. Furthermore, we provide evidence that a 40-bp subdomain of the SINE V-domain is conserved in SINEs in mollusks and arthropods. It is predicted to form a stable stem-loop structure that is preserved in the context of the overall SINE RNA secondary structure in invertebrates. Our analysis also recovered short retrotransposons with a Long INterspersed Element (LINE)-derived 5′ end. These share the body and/or the tail with transfer RNA (tRNA)-derived SINEs within and across species. Finally, we identified CORE SINEs in gastropods and bivalves—extending the distribution range of this superfamily. PMID:26739168

Noncanoncial signal recognition particle RNAs in a major eukaryotic phylum revealed by purification of SRP from the human pathogen Cryptococcus neoformans

PubMed Central

Dumesic, Phillip A.; Rosenblad, Magnus A.; Samuelsson, Tore; Nguyen, Tiffany; Moresco, James J.; Yates, John R.; Madhani, Hiten D.

2015-01-01

Despite conservation of the signal recognition particle (SRP) from bacteria to man, computational approaches have failed to identify SRP components from genomes of many lower eukaryotes, raising the possibility that they have been lost or altered in those lineages. We report purification and analysis of SRP in the human pathogen Cryptococcus neoformans, providing the first description of SRP in basidiomycetous yeast. The C. neoformans SRP RNA displays a predicted structure in which the universally conserved helix 8 contains an unprecedented stem-loop insertion. Guided by this sequence, we computationally identified 152 SRP RNAs throughout the phylum Basidiomycota. This analysis revealed additional helix 8 alterations including single and double stem-loop insertions as well as loop diminutions affecting RNA structural elements that are otherwise conserved from bacteria to man. Strikingly, these SRP RNA features in Basidiomycota are accompanied by phylum-specific alterations in the RNA-binding domain of Srp54, the SRP protein subunit that directly interacts with helix 8. Our findings reveal unexpected fungal SRP diversity and suggest coevolution of the two most conserved SRP features—SRP RNA helix 8 and Srp54—in basidiomycetes. Because members of this phylum include important human and plant pathogens, these noncanonical features provide new targets for antifungal compound development. PMID:26275773

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madu, Ikenna G.; Belouzard, Sandrine; Whittaker, Gary R., E-mail: grw7@cornell.ed

The S2 domain of the coronavirus spike (S) protein is known to be responsible for mediating membrane fusion. In addition to a well-recognized cleavage site at the S1-S2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (SARS-CoV) S2 domain (R797). C-terminal to this S2 cleavage site is a conserved region flanked by cysteine residues C822 and C833. Here, we investigated the importance of this well conserved region for SARS-CoV S-mediated fusion activation. We show that the residues between C822-C833 are well conserved across all coronaviruses. Mutagenic analysis of SARS-CoV S, combined withmore » cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for the core-conserved residues C822, D830, L831, and C833. Based on available predictive models, we propose that the conserved domain flanked by cysteines 822 and 833 forms a loop structure that interacts with components of the SARS-CoV S trimer to control the activation of membrane fusion.« less

Flexibility Correlation between Active Site Regions Is Conserved across Four AmpC β-Lactamase Enzymes.

PubMed

Brown, Jenna R; Livesay, Dennis R

2015-01-01

β-lactamases are bacterial enzymes that confer resistance to β-lactam antibiotics, such as penicillins and cephalosporins. There are four classes of β-lactamase enzymes, each with characteristic sequence and structure properties. Enzymes from class A are the most common and have been well characterized across the family; however, less is known about how physicochemical properties vary across the C and D families. In this report, we compare the dynamical properties of four AmpC (class C) β-lactamases using our distance constraint model (DCM). The DCM reliably predicts thermodynamic and mechanical properties in an integrated way. As a consequence, quantitative stability/flexibility relationships (QSFR) can be determined and compared across the whole family. The DCM calculates a large number of QSFR metrics. Perhaps the most useful is the flexibility index (FI), which quantifies flexibility along the enzyme backbone. As typically observed in other systems, FI is well conserved across the four AmpC enzymes. Cooperativity correlation (CC), which quantifies intramolecular couplings within structure, is rarely conserved across protein families; however, it is in AmpC. In particular, the bulk of each structure is composed of a large rigid cluster, punctuated by three flexibly correlated regions located at the active site. These regions include several catalytic residues and the Ω-loop. This evolutionary conservation combined with active their site location strongly suggests that these coupled dynamical modes are important for proper functioning of the enzyme.

Flexibility Correlation between Active Site Regions Is Conserved across Four AmpC β-Lactamase Enzymes

PubMed Central

Brown, Jenna R.; Livesay, Dennis R.

2015-01-01

β-lactamases are bacterial enzymes that confer resistance to β-lactam antibiotics, such as penicillins and cephalosporins. There are four classes of β-lactamase enzymes, each with characteristic sequence and structure properties. Enzymes from class A are the most common and have been well characterized across the family; however, less is known about how physicochemical properties vary across the C and D families. In this report, we compare the dynamical properties of four AmpC (class C) β-lactamases using our distance constraint model (DCM). The DCM reliably predicts thermodynamic and mechanical properties in an integrated way. As a consequence, quantitative stability/flexibility relationships (QSFR) can be determined and compared across the whole family. The DCM calculates a large number of QSFR metrics. Perhaps the most useful is the flexibility index (FI), which quantifies flexibility along the enzyme backbone. As typically observed in other systems, FI is well conserved across the four AmpC enzymes. Cooperativity correlation (CC), which quantifies intramolecular couplings within structure, is rarely conserved across protein families; however, it is in AmpC. In particular, the bulk of each structure is composed of a large rigid cluster, punctuated by three flexibly correlated regions located at the active site. These regions include several catalytic residues and the Ω-loop. This evolutionary conservation combined with active their site location strongly suggests that these coupled dynamical modes are important for proper functioning of the enzyme. PMID:26018804

Megabrasion: a conservative strategy for the anterior dentition.

PubMed

Magne, P

1997-05-01

Continuous developments in adhesive restorative techniques, tooth whitening procedures, and restorative materials have significantly broadened the initially defined spectrum of indications for composite restorations. These developments have thereby contributed to the achievement of one of the major objectives of conservative restorative dentistry--the maximum preservation of sound tooth structure. In order to optimize the application of modern composite resin technology, mastering the basic principles of natural aesthetics is an essential prerequisite. The learning objective of this article is to discuss the etiology of enamel discoloration and conservative treatment strategies, including microabrasion and masking procedures. Emphasis is placed on a simple procedure--the megabrasion technique--which does not depend extensively on the artistic skills of the operator. It represents a useful and predictable approach for the elimination of white opaque stains on the enamel and yellow-brown enamel discolorations.

Predicting species distributions for conservation decisions

PubMed Central

Guisan, Antoine; Tingley, Reid; Baumgartner, John B; Naujokaitis-Lewis, Ilona; Sutcliffe, Patricia R; Tulloch, Ayesha I T; Regan, Tracey J; Brotons, Lluis; McDonald-Madden, Eve; Mantyka-Pringle, Chrystal; Martin, Tara G; Rhodes, Jonathan R; Maggini, Ramona; Setterfield, Samantha A; Elith, Jane; Schwartz, Mark W; Wintle, Brendan A; Broennimann, Olivier; Austin, Mike; Ferrier, Simon; Kearney, Michael R; Possingham, Hugh P; Buckley, Yvonne M

2013-01-01

Species distribution models (SDMs) are increasingly proposed to support conservation decision making. However, evidence of SDMs supporting solutions for on-ground conservation problems is still scarce in the scientific literature. Here, we show that successful examples exist but are still largely hidden in the grey literature, and thus less accessible for analysis and learning. Furthermore, the decision framework within which SDMs are used is rarely made explicit. Using case studies from biological invasions, identification of critical habitats, reserve selection and translocation of endangered species, we propose that SDMs may be tailored to suit a range of decision-making contexts when used within a structured and transparent decision-making process. To construct appropriate SDMs to more effectively guide conservation actions, modellers need to better understand the decision process, and decision makers need to provide feedback to modellers regarding the actual use of SDMs to support conservation decisions. This could be facilitated by individuals or institutions playing the role of ‘translators’ between modellers and decision makers. We encourage species distribution modellers to get involved in real decision-making processes that will benefit from their technical input; this strategy has the potential to better bridge theory and practice, and contribute to improve both scientific knowledge and conservation outcomes. PMID:24134332

Combining Structural Modeling with Ensemble Machine Learning to Accurately Predict Protein Fold Stability and Binding Affinity Effects upon Mutation

PubMed Central

Garcia Lopez, Sebastian; Kim, Philip M.

2014-01-01

Advances in sequencing have led to a rapid accumulation of mutations, some of which are associated with diseases. However, to draw mechanistic conclusions, a biochemical understanding of these mutations is necessary. For coding mutations, accurate prediction of significant changes in either the stability of proteins or their affinity to their binding partners is required. Traditional methods have used semi-empirical force fields, while newer methods employ machine learning of sequence and structural features. Here, we show how combining both of these approaches leads to a marked boost in accuracy. We introduce ELASPIC, a novel ensemble machine learning approach that is able to predict stability effects upon mutation in both, domain cores and domain-domain interfaces. We combine semi-empirical energy terms, sequence conservation, and a wide variety of molecular details with a Stochastic Gradient Boosting of Decision Trees (SGB-DT) algorithm. The accuracy of our predictions surpasses existing methods by a considerable margin, achieving correlation coefficients of 0.77 for stability, and 0.75 for affinity predictions. Notably, we integrated homology modeling to enable proteome-wide prediction and show that accurate prediction on modeled structures is possible. Lastly, ELASPIC showed significant differences between various types of disease-associated mutations, as well as between disease and common neutral mutations. Unlike pure sequence-based prediction methods that try to predict phenotypic effects of mutations, our predictions unravel the molecular details governing the protein instability, and help us better understand the molecular causes of diseases. PMID:25243403

The Measurement, Nomological Net, and Theory of Perceived Self-Esteem Instability: Applying the Conservation of Resources Theory to Understand the Construct.

PubMed

Howard, Matt C

2018-01-01

The current article performs the first focused investigation into the construct of perceived self-esteem instability (P-SEI). Four studies investigate the construct's measurement, nomological net, and theoretical dynamics. Study 1 confirms the factor structure of a P-SEI Measure, supporting that P-SEI can be adequately measured. Study 2 identifies an initial nomological net surrounding P-SEI, showing that the construct is strongly related to stable aspects of the self (i.e., neuroticism and core self-evaluations). In Studies 3 and 4, the Conservation of Resources Theory is applied to develop and test five hypotheses. These studies show that P-SEI is predicted by self-esteem level and stressors, and the relationship of certain stressors is moderated by self-esteem contingencies. P-SEI also predicts stress, depression, anxiety, and certain defensive postures. From these studies and the integration of Conservation of Resources Theory, we suggest that P-SEI emerges through an interaction between environmental influences and personal resources, and we provide a theoretical model to better understand the construct of P-SEI. We suggest that this theory-driven model can prompt the initial field of study on P-SEI.

Black and white and read all over: the past, present and future of giant panda genetics.

PubMed

Wei, Fuwen; Hu, Yibo; Zhu, Lifeng; Bruford, Michael W; Zhan, Xiangjiang; Zhang, Lei

2012-12-01

Few species attract much more attention from the public and scientists than the giant panda (Ailuropoda melanoleuca), a popular, enigmatic but highly endangered species. The application of molecular genetics to its biology and conservation has facilitated surprising insights into the biology of giant pandas as well as the effectiveness of conservation efforts during the past decades. Here, we review the history of genetic advances in this species, from phylogeny, demographical history, genetic variation, population structure, noninvasive population census and adaptive evolution to reveal to what extent the current status of the giant panda is a reflection of its evolutionary legacy, as opposed to the influence of anthropogenic factors that have negatively impacted this species. In addition, we summarize the conservation implications of these genetic findings applied for the management of this high-profile species. Finally, on the basis of these advances and predictable future changes in genetic technology, we discuss future research directions that seem promising for giant panda biology and conservation. © 2012 Blackwell Publishing Ltd.

Evolutionary conservation of Ebola virus proteins predicts important functions at residue level.

PubMed

Arslan, Ahmed; van Noort, Vera

2017-01-15

The recent outbreak of Ebola virus disease (EVD) resulted in a large number of human deaths. Due to this devastation, the Ebola virus has attracted renewed interest as model for virus evolution. Recent literature on Ebola virus (EBOV) has contributed substantially to our understanding of the underlying genetics and its scope with reference to the 2014 outbreak. But no study yet, has focused on the conservation patterns of EBOV proteins. We analyzed the evolution of functional regions of EBOV and highlight the function of conserved residues in protein activities. We apply an array of computational tools to dissect the functions of EBOV proteins in detail: (i) protein sequence conservation, (ii) protein-protein interactome analysis, (iii) structural modeling and (iv) kinase prediction. Our results suggest the presence of novel post-translational modifications in EBOV proteins and their role in the modulation of protein functions and protein interactions. Moreover, on the basis of the presence of ATM recognition motifs in all EBOV proteins we postulate a role of DNA damage response pathways and ATM kinase in EVD. The ATM kinase is put forward, for further evaluation, as novel potential therapeutic target. http://www.biw.kuleuven.be/CSB/EBOV-PTMs CONTACT: vera.vannoort@biw.kuleuven.beSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Human attitudes towards herpetofauna: The influence of folklore and negative values on the conservation of amphibians and reptiles in Portugal

PubMed Central

2012-01-01

Background Human values and folklore of wildlife strongly influence the effectiveness of conservation efforts. These values and folklore may also vary with certain demographic characteristics such as gender, age, or education. Reptiles and amphibians are among the least appreciated of vertebrates and are victims of many negative values and wrong ideas resulting from the direct interpretation of folklore. We try to demonstrate how these values and folklore can affect the way people relate to them and also the possible conservation impacts on these animals. Methods A questionnaire survey distributed to 514 people in the district of Évora, Portugal, was used to obtain data regarding the hypothesis that the existence of wrong ideas and negative values contributes to the phenomenon of human-associated persecution of these animals. A structural equation model was specified in order to confirm the hypothesis about the possible relationships between the presence of perceptions and negative values about amphibians and reptiles and persecution and anti-conservation attitudes. Sociodemographic variables were also added. Results The results of the model suggest that the presence of folklore and negative values clearly predicts persecution and anti-conservation attitudes towards amphibians and reptiles. Also, the existence of folklore varies sociodemographically, but negative values concerning these animals are widespread in the population. Conclusions With the use of structural equation models, this work is a contribution to the study of how certain ideas and values can directly influence human attitudes towards herpetofauna and how they can be a serious conservation issue. PMID:22316318

Human attitudes towards herpetofauna: the influence of folklore and negative values on the conservation of amphibians and reptiles in Portugal.

PubMed

Ceríaco, Luis Mp

2012-02-08

Human values and folklore of wildlife strongly influence the effectiveness of conservation efforts. These values and folklore may also vary with certain demographic characteristics such as gender, age, or education. Reptiles and amphibians are among the least appreciated of vertebrates and are victims of many negative values and wrong ideas resulting from the direct interpretation of folklore. We try to demonstrate how these values and folklore can affect the way people relate to them and also the possible conservation impacts on these animals. A questionnaire survey distributed to 514 people in the district of Évora, Portugal, was used to obtain data regarding the hypothesis that the existence of wrong ideas and negative values contributes to the phenomenon of human-associated persecution of these animals. A structural equation model was specified in order to confirm the hypothesis about the possible relationships between the presence of perceptions and negative values about amphibians and reptiles and persecution and anti-conservation attitudes. Sociodemographic variables were also added. The results of the model suggest that the presence of folklore and negative values clearly predicts persecution and anti-conservation attitudes towards amphibians and reptiles. Also, the existence of folklore varies sociodemographically, but negative values concerning these animals are widespread in the population. With the use of structural equation models, this work is a contribution to the study of how certain ideas and values can directly influence human attitudes towards herpetofauna and how they can be a serious conservation issue.

G-LoSA: An efficient computational tool for local structure-centric biological studies and drug design.

PubMed

Lee, Hui Sun; Im, Wonpil

2016-04-01

Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G-LoSA. G-LoSA aligns protein local structures in a sequence order independent way and provides a GA-score, a chemical feature-based and size-independent structure similarity score. Our benchmark validation shows the robust performance of G-LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure-centric comparative biology studies. In particular, G-LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G-LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer-aided drug design. We hope that G-LoSA can be a useful computational method for exploring interesting biological problems through large-scale comparison of protein local structures and facilitating drug discovery research and development. G-LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. © 2016 The Protein Society.

Conserved antigenic sites between MERS-CoV and Bat-coronavirus are revealed through sequence analysis.

PubMed

Sharmin, Refat; Islam, Abul B M M K

2016-01-01

MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein's antigenic sites are found to be conserved with those in HKU4 and HKU5. This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity.

In silico assessment of phosphorylation and O-β-GlcNAcylation sites in human NPC1 protein critical for Ebola virus entry.

PubMed

Basharat, Zarrin; Yasmin, Azra

2015-08-01

Ebola is a highly pathogenic enveloped virus responsible for deadly outbreaks of severe hemorrhagic fever. It enters human cells by binding a multifunctional cholesterol transporter Niemann-Pick C1 (NPC1) protein. Post translational modification (PTM) information for NPC1 is crucial to understand Ebola virus (EBOV) entry and action due to changes in phosphorylation or glycosylation at the binding site. It is difficult and costly to experimentally assess this type of interaction, so in silico strategy was employed. Identification of phosphorylation sites, including conserved residues that could be possible targets for 21 predicted kinases was followed by interplay study between phosphorylation and O-β-GlcNAc modification of NPC1. Results revealed that only 4 out of 48 predicted phosphosites exhibited O-β-GlcNAc activity. Predicted outcomes were integrated with residue conservation and 3D structural information. Three Yin Yang sites were located in the α-helix regions and were conserved in studied vertebrate and mammalian species. Only one modification site S425 was found in β-turn region located near the N-terminus of NPC1 and was found to differ in pig, mouse, cobra and humans. The predictions suggest that Yin Yang sites may not be important for virus attachment to NPC1, whereas phosphosite 473 may be important for binding and hence entry of Ebola virus. This information could be useful in addressing further experimental studies and therapeutic strategies targeting PTM events in EBOV entry. Copyright © 2015 Elsevier B.V. All rights reserved.

7 CFR 610.13 - Equations for predicting soil loss due to wind erosion.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 6 2014-01-01 2014-01-01 false Equations for predicting soil loss due to wind erosion... RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.13 Equations for predicting soil loss due to wind erosion. (a) The...

7 CFR 610.13 - Equations for predicting soil loss due to wind erosion.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Equations for predicting soil loss due to wind erosion... RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.13 Equations for predicting soil loss due to wind erosion. (a) The...

7 CFR 610.13 - Equations for predicting soil loss due to wind erosion.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 6 2012-01-01 2012-01-01 false Equations for predicting soil loss due to wind erosion... RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.13 Equations for predicting soil loss due to wind erosion. (a) The...

7 CFR 610.13 - Equations for predicting soil loss due to wind erosion.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 6 2011-01-01 2011-01-01 false Equations for predicting soil loss due to wind erosion... RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.13 Equations for predicting soil loss due to wind erosion. (a) The...

7 CFR 610.13 - Equations for predicting soil loss due to wind erosion.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 6 2013-01-01 2013-01-01 false Equations for predicting soil loss due to wind erosion... RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.13 Equations for predicting soil loss due to wind erosion. (a) The...

Tibrogargan and Coastal Plains rhabdoviruses: genomic characterization, evolution of novel genes and seroprevalence in Australian livestock.

PubMed

Gubala, Aneta; Davis, Steven; Weir, Richard; Melville, Lorna; Cowled, Chris; Boyle, David

2011-09-01

Tibrogargan virus (TIBV) and Coastal Plains virus (CPV) were isolated from cattle in Australia and TIBV has also been isolated from the biting midge Culicoides brevitarsis. Complete genomic sequencing revealed that the viruses share a novel genome structure within the family Rhabdoviridae, each virus containing two additional putative genes between the matrix protein (M) and glycoprotein (G) genes and one between the G and viral RNA polymerase (L) genes. The predicted novel protein products are highly diverged at the sequence level but demonstrate clear conservation of secondary structure elements, suggesting conservation of biological functions. Phylogenetic analyses showed that TIBV and CPV form an independent group within the 'dimarhabdovirus supergroup'. Although no disease has been observed in association with these viruses, antibodies were detected at high prevalence in cattle and buffalo in northern Australia, indicating the need for disease monitoring and further study of this distinctive group of viruses.

Vulnerability of a killer whale social network to disease outbreaks

NASA Astrophysics Data System (ADS)

Guimarães, Paulo R., Jr.; de Menezes, Márcio Argollo; Baird, Robin W.; Lusseau, David; Guimarães, Paulo; Dos Reis, Sérgio F.

2007-10-01

Emerging infectious diseases are among the main threats to conservation of biological diversity. A crucial task facing epidemiologists is to predict the vulnerability of populations of endangered animals to disease outbreaks. In this context, the network structure of social interactions within animal populations may affect disease spreading. However, endangered animal populations are often small and to investigate the dynamics of small networks is a difficult task. Using network theory, we show that the social structure of an endangered population of mammal-eating killer whales is vulnerable to disease outbreaks. This feature was found to be a consequence of the combined effects of the topology and strength of social links among individuals. Our results uncover a serious challenge for conservation of the species and its ecosystem. In addition, this study shows that the network approach can be useful to study dynamical processes in very small networks.

Explicit Not Implicit Preferences Predict Conservation Intentions for Endangered Species and Biomes.

PubMed

Echeverri, Alejandra; Callahan, Megan M; Chan, Kai M A; Satterfield, Terre; Zhao, Jiaying

2017-01-01

Conservation of biodiversity is determined in part by human preferences. Preferences relevant to conservation have been examined largely via explicit measures (e.g., a self-reported degree of liking), with implicit measures (e.g., preconscious, automatic evaluations) receiving relatively less attention. This is the case despite psychological evidence from other contexts that implicit preferences are more informative of behavior. Thus, the type of measure that predicts conservation intentions for biodiversity is unknown. We conducted three studies to examine conservation intentions in light of people's explicit and implicit preferences toward four endangered species (sea otter, American badger, caribou, yellow-breasted chat) and four biomes (forest, ocean, grassland, tundra). In Study 1 (n = 55), we found that people implicitly preferred caribou most, but explicitly preferred sea otter most, with a significant multiple regression where participants' explicit preferences dictated their stated intended donations for conservation of each species. In Study 2 (n = 57) we found that people implicitly and explicitly preferred forest and ocean over grassland and tundra. Explicit rather than implicit preferences predicted the intended donation for conservation of the ocean biome. Study 3 involved a broader online sample of participants (n = 463) and also found that explicit preferences dictated the intended donations for conservation of biomes and species. Our findings reveal discrepancies between implicit and explicit preferences toward species, but not toward biomes. Importantly, the results demonstrate that explicit rather than implicit preferences predict conservation intentions for biodiversity. The current findings have several implications for conservation and the communication of biodiversity initiatives.

Structural mapping of the coiled-coil domain of a bacterial condensin and comparative analyses across all domains of life suggest conserved features of SMC proteins.

PubMed

Waldman, Vincent M; Stanage, Tyler H; Mims, Alexandra; Norden, Ian S; Oakley, Martha G

2015-06-01

The structural maintenance of chromosomes (SMC) proteins form the cores of multisubunit complexes that are required for the segregation and global organization of chromosomes in all domains of life. These proteins share a common domain structure in which N- and C- terminal regions pack against one another to form a globular ATPase domain. This "head" domain is connected to a central, globular, "hinge" or dimerization domain by a long, antiparallel coiled coil. To date, most efforts for structural characterization of SMC proteins have focused on the globular domains. Recently, however, we developed a method to map interstrand interactions in the 50-nm coiled-coil domain of MukB, the divergent SMC protein found in γ-proteobacteria. Here, we apply that technique to map the structure of the Bacillus subtilis SMC (BsSMC) coiled-coil domain. We find that, in contrast to the relatively complicated coiled-coil domain of MukB, the BsSMC domain is nearly continuous, with only two detectable coiled-coil interruptions. Near the middle of the domain is a break in coiled-coil structure in which there are three more residues on the C-terminal strand than on the N-terminal strand. Close to the head domain, there is a second break with a significantly longer insertion on the same strand. These results provide an experience base that allows an informed interpretation of the output of coiled-coil prediction algorithms for this family of proteins. A comparison of such predictions suggests that these coiled-coil deviations are highly conserved across SMC types in a wide variety of organisms, including humans. © 2015 Wiley Periodicals, Inc.

Importance of dispersal routes that minimize open-ocean movement to the genetic structure of island populations.

PubMed

Harradine, E L; Andrew, M E; Thomas, J W; How, R A; Schmitt, L H; Spencer, P B S

2015-12-01

Islands present a unique scenario in conservation biology, offering refuge yet imposing limitations on insular populations. The Kimberley region of northwestern Australia has more than 2500 islands that have recently come into focus as substantial conservation resources. It is therefore of great interest for managers to understand the driving forces of genetic structure of species within these island archipelagos. We used the ubiquitous bar-shouldered skink (Ctenotus inornatus) as a model species to represent the influence of landscape factors on genetic structure across the Kimberley islands. On 41 islands and 4 mainland locations in a remote area of Australia, we genotyped individuals across 18 nuclear (microsatellite) markers. Measures of genetic differentiation and diversity were used in two complementary analyses. We used circuit theory and Mantel tests to examine the influence of the landscape matrix on population connectivity and linear regression and model selection based on Akaike's information criterion to investigate landscape controls on genetic diversity. Genetic differentiation between islands was best predicted with circuit-theory models that accounted for the large difference in resistance to dispersal between land and ocean. In contrast, straight-line distances were unrelated to either resistance distances or genetic differentiation. Instead, connectivity was determined by island-hopping routes that allow organisms to minimize the distance of difficult ocean passages. Island populations of C. inornatus retained varying degrees of genetic diversity (NA = 1.83 - 7.39), but it was greatest on islands closer to the mainland, in terms of resistance-distance units. In contrast, genetic diversity was unrelated to island size. Our results highlight the potential for islands to contribute to both theoretical and applied conservation, provide strong evidence of the driving forces of population structure within undisturbed landscapes, and identify the islands most valuable for conservation based on their contributions to gene flow and genetic diversity. © 2015 Society for Conservation Biology.

Trait-based prediction of extinction risk of small-bodied freshwater fishes.

PubMed

Kopf, R Keller; Shaw, Casey; Humphries, Paul

2017-06-01

Small body size is generally correlated with r-selected life-history traits, including early maturation, short-generation times, and rapid growth rates, that result in high population turnover and a reduced risk of extinction. Unlike other classes of vertebrates, however, small freshwater fishes appear to have an equal or greater risk of extinction than large fishes. We explored whether particular traits explain the International Union for Conservation of Nature (IUCN) Red List conservation status of small-bodied freshwater fishes from 4 temperate river basins: Murray-Darling, Australia; Danube, Europe; Mississippi-Missouri, North America; and the Rio Grande, North America. Twenty-three ecological and life-history traits were collated for all 171 freshwater fishes of ≤120 mm total length. We used generalized linear mixed-effects models to assess which combination of the 23 traits best explained whether a species was threatened or not threatened. We used the best models to predict the probability of 29 unclassified species being listed as threatened. With and without controlling for phylogeny at the family level, small body size-among small-bodied species-was the most influential trait correlated with threatened species listings. The k-folds cross-validation demonstrated that body size and a random effect structure that included family predicted the threat status with an accuracy of 78% (SE 0.5). We identified 10 species likely to be threatened that are not listed as such on the IUCN Red List. Small body size is not a trait that provides universal resistance to extinction, particularly for vertebrates inhabiting environments affected by extreme habitat loss and fragmentation. We hypothesize that this is because small-bodied species have smaller home ranges, lower dispersal capabilities, and heightened ecological specialization relative to larger vertebrates. Trait data and further model development are needed to predict the IUCN conservation status of the over 11,000 unclassified freshwater fishes, especially those under threat from proposed dam construction in the world's most biodiverse river basins. © 2016 Society for Conservation Biology.

Effect of Ecological Restoration on Body Condition of a Predator

PubMed Central

González-Tokman, Daniel; Martínez-Garza, Cristina

2015-01-01

Ecological restoration attempts to recover the structure and function of ecosystems that have been degraded by human activities. A crucial test of ecosystem recovery would be to determine whether individuals in restored environments are as healthy as those in conserved environments. However, the impact of restoration on physiology of terrestrial animals has never been tested. Here, we evaluated the effect of two restoration methods on body condition measured as body size, body mass, lipid and muscle content of the spider Nephila clavipes in a tropical dry forest that has suffered chronic disturbance due to cattle grazing. We used experimental plots that had been excluded from disturbance by cattle grazing during eight years. Plots were either planted with native trees (i. e. maximal intervention), or only excluded from disturbance (i. e. minimal intervention), and were compared with control conserved (remnants of original forest) and disturbed plots (where cattle is allowed to graze). We predicted (1) better body condition in spiders of conserved and restored sites, compared to disturbed sites, and (2) better body condition in plots with maximal intervention than in plots with minimal intervention. The first prediction was not supported in males or females, and the second prediction was only supported in females: body dry mass was higher in planted than in conserved plots for spiders of both sexes and also higher that in disturbed plots for males, suggesting that plantings are providing more resources. We discuss how different life histories and environmental pressures, such as food availability, parasitism, and competition for resources can explain our contrasting findings in male and female spiders. By studying animal physiology in restoration experiments it is possible to understand the mechanistic basis of ecological and evolutionary processes that determine success of ecological restoration. PMID:26226363

Effect of Ecological Restoration on Body Condition of a Predator.

PubMed

González-Tokman, Daniel; Martínez-Garza, Cristina

2015-01-01

Ecological restoration attempts to recover the structure and function of ecosystems that have been degraded by human activities. A crucial test of ecosystem recovery would be to determine whether individuals in restored environments are as healthy as those in conserved environments. However, the impact of restoration on physiology of terrestrial animals has never been tested. Here, we evaluated the effect of two restoration methods on body condition measured as body size, body mass, lipid and muscle content of the spider Nephila clavipes in a tropical dry forest that has suffered chronic disturbance due to cattle grazing. We used experimental plots that had been excluded from disturbance by cattle grazing during eight years. Plots were either planted with native trees (i. e. maximal intervention), or only excluded from disturbance (i. e. minimal intervention), and were compared with control conserved (remnants of original forest) and disturbed plots (where cattle is allowed to graze). We predicted (1) better body condition in spiders of conserved and restored sites, compared to disturbed sites, and (2) better body condition in plots with maximal intervention than in plots with minimal intervention. The first prediction was not supported in males or females, and the second prediction was only supported in females: body dry mass was higher in planted than in conserved plots for spiders of both sexes and also higher that in disturbed plots for males, suggesting that plantings are providing more resources. We discuss how different life histories and environmental pressures, such as food availability, parasitism, and competition for resources can explain our contrasting findings in male and female spiders. By studying animal physiology in restoration experiments it is possible to understand the mechanistic basis of ecological and evolutionary processes that determine success of ecological restoration.

The 5S rRNA loop E: chemical probing and phylogenetic data versus crystal structure.

PubMed

Leontis, N B; Westhof, E

1998-09-01

A significant fraction of the bases in a folded, structured RNA molecule participate in noncanonical base pairing interactions, often in the context of internal loops or multi-helix junction loops. The appearance of each new high-resolution RNA structure provides welcome data to guide efforts to understand and predict RNA 3D structure, especially when the RNA in question is a functionally conserved molecule. The recent publication of the crystal structure of the "Loop E" region of bacterial 5S ribosomal RNA is such an event [Correll CC, Freeborn B, Moore PB, Steitz TA, 1997, Cell 91:705-712]. In addition to providing more examples of already established noncanonical base pairs, such as purine-purine sheared pairings, trans-Hoogsteen UA, and GU wobble pairs, the structure provides the first high-resolution views of two new purine-purine pairings and a new GU pairing. The goal of the present analysis is to expand the capabilities of both chemical probing and phylogenetic analysis to predict with greater accuracy the structures of RNA molecules. First, in light of existing chemical probing data, we investigate what lessons could be learned regarding the interpretation of this widely used method of RNA structure probing. Then we analyze the 3D structure with reference to molecular phylogeny data (assuming conservation of function) to discover what alternative base pairings are geometrically compatible with the structure. The comparisons between previous modeling efforts and crystal structures show that the intricate involvements of ions and water molecules in the maintenance of non-Watson-Crick pairs render the process of correctly identifying the interacting sites in such pairs treacherous, except in cases of trans-Hoogsteen A/U or sheared A/G pairs for the adenine N1 site. The phylogenetic analysis identifies A/A, A/C, A/U and C/A, C/C, and C/U pairings isosteric with sheared A/G, as well as A/A and A/C pairings isosteric with both G/U and G/G bifurcated pairings. Thus, each non-Watson-Crick pair could be characterized by a phylogenetic signature of variations between isosteric-like pairings. In addition to the conservative changes, which form a dictionary of pairings isosterically compatible with those observed in the crystal structure, concerted changes involving several base pairs also occur. The latter covariations may indicate transitions between related but distinctive motifs within the loop E of 5S ribosomal RNA.

Identification and Characterization of MicroRNAs in Small Brown Planthopper (Laodephax striatellus) by Next-Generation Sequencing

PubMed Central

Lou, Yonggen; Cheng, Jia'an; Zhang, Hengmu; Xu, Jian-Hong

2014-01-01

MicroRNAs (miRNAs) are endogenous non-coding small RNAs that regulate gene expression at the post-transcriptional level and are thought to play critical roles in many metabolic activities in eukaryotes. The small brown planthopper (Laodephax striatellus Fallén), one of the most destructive agricultural pests, causes great damage to crops including rice, wheat, and maize. However, information about the genome of L. striatellus is limited. In this study, a small RNA library was constructed from a mixed L. striatellus population and sequenced by Solexa sequencing technology. A total of 501 mature miRNAs were identified, including 227 conserved and 274 novel miRNAs belonging to 125 and 250 families, respectively. Sixty-nine conserved miRNAs that are included in 38 families are predicted to have an RNA secondary structure typically found in miRNAs. Many miRNAs were validated by stem-loop RT-PCR. Comparison with the miRNAs in 84 animal species from miRBase showed that the conserved miRNA families we identified are highly conserved in the Arthropoda phylum. Furthermore, miRanda predicted 2701 target genes for 378 miRNAs, which could be categorized into 52 functional groups annotated by gene ontology. The function of miRNA target genes was found to be very similar between conserved and novel miRNAs. This study of miRNAs in L. striatellus will provide new information and enhance the understanding of the role of miRNAs in the regulation of L. striatellus metabolism and development. PMID:25057821

Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets

PubMed Central

2012-01-01

Background To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. Results We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. Conclusions SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery. PMID:23281852

Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets.

PubMed

Chiu, Yi-Yuan; Lin, Chun-Yu; Lin, Chih-Ta; Hsu, Kai-Cheng; Chang, Li-Zen; Yang, Jinn-Moon

2012-01-01

To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery.

Early Prediction of Lupus Nephritis Using Advanced Proteomics

DTIC Science & Technology

2008-06-01

Structure of the Conserved Hypothetical Protein Rv2302 from Mycobacterium tuberculosis ” 188, 5993-6001, J. Bacteriology, 2006. 11. T.A. Ramelot, A. Yee...currently elusive renal biomarkers crucial for the prognosis of SLE. A well-defined cohort of patients with SLE (n=150), disease and healthy...enhanced various TOF- MS, we discovered a set urinary lupus nephritis candidate biomarkers ; namely transferrin, ceruloplasmin, alpha1-acid

Implications of Mycobacterium Major Facilitator Superfamily for Novel Measures against Tuberculosis.

PubMed

Wang, Rui; Zhang, Zhen; Xie, Longxiang; Xie, Jianping

2015-01-01

Major facilitator superfamily (MFS) is an important secondary membrane transport protein superfamily conserved from prokaryotes to eukaryotes. The MFS proteins are widespread among bacteria and are responsible for the transfer of substrates. Pathogenic Mycobacterium MFS transporters, their distribution, function, phylogeny, and predicted crystal structures were studied to better understand the function of MFS and to discover specific inhibitors of MFS for better tuberculosis control.

Antibody-protein interactions: benchmark datasets and prediction tools evaluation

PubMed Central

Ponomarenko, Julia V; Bourne, Philip E

2007-01-01

Background The ability to predict antibody binding sites (aka antigenic determinants or B-cell epitopes) for a given protein is a precursor to new vaccine design and diagnostics. Among the various methods of B-cell epitope identification X-ray crystallography is one of the most reliable methods. Using these experimental data computational methods exist for B-cell epitope prediction. As the number of structures of antibody-protein complexes grows, further interest in prediction methods using 3D structure is anticipated. This work aims to establish a benchmark for 3D structure-based epitope prediction methods. Results Two B-cell epitope benchmark datasets inferred from the 3D structures of antibody-protein complexes were defined. The first is a dataset of 62 representative 3D structures of protein antigens with inferred structural epitopes. The second is a dataset of 82 structures of antibody-protein complexes containing different structural epitopes. Using these datasets, eight web-servers developed for antibody and protein binding sites prediction have been evaluated. In no method did performance exceed a 40% precision and 46% recall. The values of the area under the receiver operating characteristic curve for the evaluated methods were about 0.6 for ConSurf, DiscoTope, and PPI-PRED methods and above 0.65 but not exceeding 0.70 for protein-protein docking methods when the best of the top ten models for the bound docking were considered; the remaining methods performed close to random. The benchmark datasets are included as a supplement to this paper. Conclusion It may be possible to improve epitope prediction methods through training on datasets which include only immune epitopes and through utilizing more features characterizing epitopes, for example, the evolutionary conservation score. Notwithstanding, overall poor performance may reflect the generality of antigenicity and hence the inability to decipher B-cell epitopes as an intrinsic feature of the protein. It is an open question as to whether ultimately discriminatory features can be found. PMID:17910770

Identification and cloning of four riboswitches from Burkholderia pseudomallei strain K96243

NASA Astrophysics Data System (ADS)

Munyati-Othman, Noor; Fatah, Ahmad Luqman Abdul; Piji, Mohd Al Akmarul Fizree Bin Md; Ramlan, Effirul Ikhwan; Raih, Mohd Firdaus

2015-09-01

Structured RNAs referred as riboswitches have been predicted to be present in the genome sequence of Burkholderia pseudomallei strain K96243. Four of the riboswitches were identified and analyzed through BLASTN, Rfam search and multiple sequence alignment. The RNA aptamers belong to the following riboswitch classifications: glycine riboswitch, cobalamin riboswitch, S-adenosyl-(L)-homocysteine (SAH) riboswitch and flavin mononucleotide (FMN) riboswitch. The conserved nucleotides for each aptamer were identified and were marked on the secondary structure generated by RNAfold. These riboswitches were successfully amplified and cloned for further study.

Inference of Expanded Lrp-Like Feast/Famine Transcription Factor Targets in a Non-Model Organism Using Protein Structure-Based Prediction

PubMed Central

Ashworth, Justin; Plaisier, Christopher L.; Lo, Fang Yin; Reiss, David J.; Baliga, Nitin S.

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer. PMID:25255272

Inference of expanded Lrp-like feast/famine transcription factor targets in a non-model organism using protein structure-based prediction.

PubMed

Ashworth, Justin; Plaisier, Christopher L; Lo, Fang Yin; Reiss, David J; Baliga, Nitin S

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer.

Motif discovery with data mining in 3D protein structure databases: discovery, validation and prediction of the U-shape zinc binding ("Huf-Zinc") motif.

PubMed

Maurer-Stroh, Sebastian; Gao, He; Han, Hao; Baeten, Lies; Schymkowitz, Joost; Rousseau, Frederic; Zhang, Louxin; Eisenhaber, Frank

2013-02-01

Data mining in protein databases, derivatives from more fundamental protein 3D structure and sequence databases, has considerable unearthed potential for the discovery of sequence motif--structural motif--function relationships as the finding of the U-shape (Huf-Zinc) motif, originally a small student's project, exemplifies. The metal ion zinc is critically involved in universal biological processes, ranging from protein-DNA complexes and transcription regulation to enzymatic catalysis and metabolic pathways. Proteins have evolved a series of motifs to specifically recognize and bind zinc ions. Many of these, so called zinc fingers, are structurally independent globular domains with discontinuous binding motifs made up of residues mostly far apart in sequence. Through a systematic approach starting from the BRIX structure fragment database, we discovered that there exists another predictable subset of zinc-binding motifs that not only have a conserved continuous sequence pattern but also share a characteristic local conformation, despite being included in totally different overall folds. While this does not allow general prediction of all Zn binding motifs, a HMM-based web server, Huf-Zinc, is available for prediction of these novel, as well as conventional, zinc finger motifs in protein sequences. The Huf-Zinc webserver can be freely accessed through this URL (http://mendel.bii.a-star.edu.sg/METHODS/hufzinc/).

Prediction of Protein-Protein Interaction Sites by Random Forest Algorithm with mRMR and IFS

PubMed Central

Li, Bi-Qing; Feng, Kai-Yan; Chen, Lei; Huang, Tao; Cai, Yu-Dong

2012-01-01

Prediction of protein-protein interaction (PPI) sites is one of the most challenging problems in computational biology. Although great progress has been made by employing various machine learning approaches with numerous characteristic features, the problem is still far from being solved. In this study, we developed a novel predictor based on Random Forest (RF) algorithm with the Minimum Redundancy Maximal Relevance (mRMR) method followed by incremental feature selection (IFS). We incorporated features of physicochemical/biochemical properties, sequence conservation, residual disorder, secondary structure and solvent accessibility. We also included five 3D structural features to predict protein-protein interaction sites and achieved an overall accuracy of 0.672997 and MCC of 0.347977. Feature analysis showed that 3D structural features such as Depth Index (DPX) and surface curvature (SC) contributed most to the prediction of protein-protein interaction sites. It was also shown via site-specific feature analysis that the features of individual residues from PPI sites contribute most to the determination of protein-protein interaction sites. It is anticipated that our prediction method will become a useful tool for identifying PPI sites, and that the feature analysis described in this paper will provide useful insights into the mechanisms of interaction. PMID:22937126

Optimizing multiple sequence alignments using a genetic algorithm based on three objectives: structural information, non-gaps percentage and totally conserved columns.

PubMed

Ortuño, Francisco M; Valenzuela, Olga; Rojas, Fernando; Pomares, Hector; Florido, Javier P; Urquiza, Jose M; Rojas, Ignacio

2013-09-01

Multiple sequence alignments (MSAs) are widely used approaches in bioinformatics to carry out other tasks such as structure predictions, biological function analyses or phylogenetic modeling. However, current tools usually provide partially optimal alignments, as each one is focused on specific biological features. Thus, the same set of sequences can produce different alignments, above all when sequences are less similar. Consequently, researchers and biologists do not agree about which is the most suitable way to evaluate MSAs. Recent evaluations tend to use more complex scores including further biological features. Among them, 3D structures are increasingly being used to evaluate alignments. Because structures are more conserved in proteins than sequences, scores with structural information are better suited to evaluate more distant relationships between sequences. The proposed multiobjective algorithm, based on the non-dominated sorting genetic algorithm, aims to jointly optimize three objectives: STRIKE score, non-gaps percentage and totally conserved columns. It was significantly assessed on the BAliBASE benchmark according to the Kruskal-Wallis test (P < 0.01). This algorithm also outperforms other aligners, such as ClustalW, Multiple Sequence Alignment Genetic Algorithm (MSA-GA), PRRP, DIALIGN, Hidden Markov Model Training (HMMT), Pattern-Induced Multi-sequence Alignment (PIMA), MULTIALIGN, Sequence Alignment Genetic Algorithm (SAGA), PILEUP, Rubber Band Technique Genetic Algorithm (RBT-GA) and Vertical Decomposition Genetic Algorithm (VDGA), according to the Wilcoxon signed-rank test (P < 0.05), whereas it shows results not significantly different to 3D-COFFEE (P > 0.05) with the advantage of being able to use less structures. Structural information is included within the objective function to evaluate more accurately the obtained alignments. The source code is available at http://www.ugr.es/~fortuno/MOSAStrE/MO-SAStrE.zip.

Predicting the process of extinction in experimental microcosms and accounting for interspecific interactions in single-species time series

PubMed Central

Ferguson, Jake M; Ponciano, José M

2014-01-01

Predicting population extinction risk is a fundamental application of ecological theory to the practice of conservation biology. Here, we compared the prediction performance of a wide array of stochastic, population dynamics models against direct observations of the extinction process from an extensive experimental data set. By varying a series of biological and statistical assumptions in the proposed models, we were able to identify the assumptions that affected predictions about population extinction. We also show how certain autocorrelation structures can emerge due to interspecific interactions, and that accounting for the stochastic effect of these interactions can improve predictions of the extinction process. We conclude that it is possible to account for the stochastic effects of community interactions on extinction when using single-species time series. PMID:24304946

Mutations that Cause Human Disease: A Computational/Experimental Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beernink, P; Barsky, D; Pesavento, B

International genome sequencing projects have produced billions of nucleotides (letters) of DNA sequence data, including the complete genome sequences of 74 organisms. These genome sequences have created many new scientific opportunities, including the ability to identify sequence variations among individuals within a species. These genetic differences, which are known as single nucleotide polymorphisms (SNPs), are particularly important in understanding the genetic basis for disease susceptibility. Since the report of the complete human genome sequence, over two million human SNPs have been identified, including a large-scale comparison of an entire chromosome from twenty individuals. Of the protein coding SNPs (cSNPs), approximatelymore » half leads to a single amino acid change in the encoded protein (non-synonymous coding SNPs). Most of these changes are functionally silent, while the remainder negatively impact the protein and sometimes cause human disease. To date, over 550 SNPs have been found to cause single locus (monogenic) diseases and many others have been associated with polygenic diseases. SNPs have been linked to specific human diseases, including late-onset Parkinson disease, autism, rheumatoid arthritis and cancer. The ability to predict accurately the effects of these SNPs on protein function would represent a major advance toward understanding these diseases. To date several attempts have been made toward predicting the effects of such mutations. The most successful of these is a computational approach called ''Sorting Intolerant From Tolerant'' (SIFT). This method uses sequence conservation among many similar proteins to predict which residues in a protein are functionally important. However, this method suffers from several limitations. First, a query sequence must have a sufficient number of relatives to infer sequence conservation. Second, this method does not make use of or provide any information on protein structure, which can be used to understand how an amino acid change affects the protein. The experimental methods that provide the most detailed structural information on proteins are X-ray crystallography and NMR spectroscopy. However, these methods are labor intensive and currently cannot be carried out on a genomic scale. Nonetheless, Structural Genomics projects are being pursued by more than a dozen groups and consortia worldwide and as a result the number of experimentally determined structures is rising exponentially. Based on the expectation that protein structures will continue to be determined at an ever-increasing rate, reliable structure prediction schemes will become increasingly valuable, leading to information on protein function and disease for many different proteins. Given known genetic variability and experimentally determined protein structures, can we accurately predict the effects of single amino acid substitutions? An objective assessment of this question would involve comparing predicted and experimentally determined structures, which thus far has not been rigorously performed. The completed research leveraged existing expertise at LLNL in computational and structural biology, as well as significant computing resources, to address this question.« less

Quantum coupled mutation finder: predicting functionally or structurally important sites in proteins using quantum Jensen-Shannon divergence and CUDA programming.

PubMed

Gültas, Mehmet; Düzgün, Güncel; Herzog, Sebastian; Jäger, Sven Joachim; Meckbach, Cornelia; Wingender, Edgar; Waack, Stephan

2014-04-03

The identification of functionally or structurally important non-conserved residue sites in protein MSAs is an important challenge for understanding the structural basis and molecular mechanism of protein functions. Despite the rich literature on compensatory mutations as well as sequence conservation analysis for the detection of those important residues, previous methods often rely on classical information-theoretic measures. However, these measures usually do not take into account dis/similarities of amino acids which are likely to be crucial for those residues. In this study, we present a new method, the Quantum Coupled Mutation Finder (QCMF) that incorporates significant dis/similar amino acid pair signals in the prediction of functionally or structurally important sites. The result of this study is twofold. First, using the essential sites of two human proteins, namely epidermal growth factor receptor (EGFR) and glucokinase (GCK), we tested the QCMF-method. The QCMF includes two metrics based on quantum Jensen-Shannon divergence to measure both sequence conservation and compensatory mutations. We found that the QCMF reaches an improved performance in identifying essential sites from MSAs of both proteins with a significantly higher Matthews correlation coefficient (MCC) value in comparison to previous methods. Second, using a data set of 153 proteins, we made a pairwise comparison between QCMF and three conventional methods. This comparison study strongly suggests that QCMF complements the conventional methods for the identification of correlated mutations in MSAs. QCMF utilizes the notion of entanglement, which is a major resource of quantum information, to model significant dissimilar and similar amino acid pair signals in the detection of functionally or structurally important sites. Our results suggest that on the one hand QCMF significantly outperforms the previous method, which mainly focuses on dissimilar amino acid signals, to detect essential sites in proteins. On the other hand, it is complementary to the existing methods for the identification of correlated mutations. The method of QCMF is computationally intensive. To ensure a feasible computation time of the QCMF's algorithm, we leveraged Compute Unified Device Architecture (CUDA).The QCMF server is freely accessible at http://qcmf.informatik.uni-goettingen.de/.

Analysis of evolutionary conservation patterns and their influence on identifying protein functional sites.

PubMed

Fang, Chun; Noguchi, Tamotsu; Yamana, Hayato

2014-10-01

Evolutionary conservation information included in position-specific scoring matrix (PSSM) has been widely adopted by sequence-based methods for identifying protein functional sites, because all functional sites, whether in ordered or disordered proteins, are found to be conserved at some extent. However, different functional sites have different conservation patterns, some of them are linear contextual, some of them are mingled with highly variable residues, and some others seem to be conserved independently. Every value in PSSMs is calculated independently of each other, without carrying the contextual information of residues in the sequence. Therefore, adopting the direct output of PSSM for prediction fails to consider the relationship between conservation patterns of residues and the distribution of conservation scores in PSSMs. In order to demonstrate the importance of combining PSSMs with the specific conservation patterns of functional sites for prediction, three different PSSM-based methods for identifying three kinds of functional sites have been analyzed. Results suggest that, different PSSM-based methods differ in their capability to identify different patterns of functional sites, and better combining PSSMs with the specific conservation patterns of residues would largely facilitate the prediction.

Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients.

PubMed

Poyau, A; Buchet, K; Bouzidi, M F; Zabot, M T; Echenne, B; Yao, J; Shoubridge, E A; Godinot, C

2000-02-01

We have studied the fibroblasts of three patients suffering from Leigh syndrome associated with cytochrome c oxidase deficiency (LS-COX-). Their mitochondrial DNA was functional and all nuclear COX subunits had a normal sequence. The expression of transcripts encoding mitochondrial and nuclear COX subunits was normal or slightly increased. Similarly, the OXA1 transcript coding for a protein involved in COX assembly was increased. However, several COX-protein subunits were severely depressed, indicating deficient COX assembly. Surf1, a factor involved in COX biogenesis, was recently reported as mutated in LS-COX- patients, all mutations predicting a truncated protein. Sequence analysis of SURF1 gene in our three patients revealed seven heterozygous mutations, six of which were new : an insertion, a nonsense mutation, a splicing mutation of intron 7 in addition to three missense mutations. The mutation G385 A (Gly124-->Glu) changes a Gly that is strictly conserved in Surfl homologs of 12 species. The substitution G618 C (Asp202-->His), changing an Asp that is conserved only in mammals, appears to be a polymorphism. The mutation T751 C changes Ile246 to Thr, a position at which a hydrophobic amino acid is conserved in all eukaryotic and some bacterial species. Replacing Ile246 by Thr disrupts a predicted beta sheet structure present in all higher eukaryotes. COX activity could be restored in fibroblasts of the three patients by complementation with a retroviral vector containing normal SURF1 cDNA. These mutations identify domains essential to Surf1 protein structure and/or function.

Molecular Cloning and Characterization of cDNA Encoding a Putative Stress-Induced Heat-Shock Protein from Camelus dromedarius

PubMed Central

Elrobh, Mohamed S.; Alanazi, Mohammad S.; Khan, Wajahatullah; Abduljaleel, Zainularifeen; Al-Amri, Abdullah; Bazzi, Mohammad D.

2011-01-01

Heat shock proteins are ubiquitous, induced under a number of environmental and metabolic stresses, with highly conserved DNA sequences among mammalian species. Camelus dromedaries (the Arabian camel) domesticated under semi-desert environments, is well adapted to tolerate and survive against severe drought and high temperatures for extended periods. This is the first report of molecular cloning and characterization of full length cDNA of encoding a putative stress-induced heat shock HSPA6 protein (also called HSP70B′) from Arabian camel. A full-length cDNA (2417 bp) was obtained by rapid amplification of cDNA ends (RACE) and cloned in pET-b expression vector. The sequence analysis of HSPA6 gene showed 1932 bp-long open reading frame encoding 643 amino acids. The complete cDNA sequence of the Arabian camel HSPA6 gene was submitted to NCBI GeneBank (accession number HQ214118.1). The BLAST analysis indicated that C. dromedaries HSPA6 gene nucleotides shared high similarity (77–91%) with heat shock gene nucleotide of other mammals. The deduced 643 amino acid sequences (accession number ADO12067.1) showed that the predicted protein has an estimated molecular weight of 70.5 kDa with a predicted isoelectric point (pI) of 6.0. The comparative analyses of camel HSPA6 protein sequences with other mammalian heat shock proteins (HSPs) showed high identity (80–94%). Predicted camel HSPA6 protein structure using Protein 3D structural analysis high similarities with human and mouse HSPs. Taken together, this study indicates that the cDNA sequences of HSPA6 gene and its amino acid and protein structure from the Arabian camel are highly conserved and have similarities with other mammalian species. PMID:21845074

Limitations of outsourcing on-the-ground biodiversity conservation.

PubMed

Iacona, Gwenllian D; Bode, Michael; Armsworth, Paul R

2016-12-01

To counteract global species decline, modern biodiversity conservation engages in large projects, spends billions of dollars, and includes many organizations working simultaneously within regions. To add to this complexity, the conservation sector has hierarchical structure, where conservation actions are often outsourced by funders (foundations, government, etc.) to local organizations that work on-the-ground. In contrast, conservation science usually assumes that a single organization makes resource allocation decisions. This discrepancy calls for theory to understand how the expected biodiversity outcomes change when interactions between organizations are accounted for. Here, we used a game theoretic model to explore how biodiversity outcomes are affected by vertical and horizontal interactions between 3 conservation organizations: a funder that outsourced its actions and 2 local conservation organizations that work on-the-ground. Interactions between the organizations changed the spending decisions made by individual organizations, and thereby the magnitude and direction of the conservation benefits. We showed that funders would struggle to incentivize recipient organizations with set priorities to perform desired actions, even when they control substantial amounts of the funding and employ common contracting approaches to enhance outcomes. Instead, biodiversity outcomes depended on priority alignment across the organizations. Conservation outcomes for the funder were improved by strategic interactions when organizational priorities were well aligned, but decreased when priorities were misaligned. Meanwhile, local organizations had improved outcomes regardless of alignment due to additional funding in the system. Given that conservation often involves the aggregate actions of multiple organizations with different objectives, strategic interactions between organizations need to be considered if we are to predict possible outcomes of conservation programs or costs of achieving conservation targets. © 2016 Society for Conservation Biology.

Overlooked habitat of a vulnerable gorgonian revealed in the Mediterranean and Eastern Atlantic by ecological niche modelling

PubMed Central

Boavida, Joana; Assis, Jorge; Silva, Inga; Serrão, Ester A.

2016-01-01

Factors shaping the distribution of mesophotic octocorals (30–200 m depth) remain poorly understood, potentially leaving overlooked coral areas, particularly near their bathymetric and geographic distributional limits. Yet, detailed knowledge about habitat requirements is crucial for conservation of sensitive gorgonians. Here we use Ecological Niche Modelling (ENM) relating thirteen environmental predictors and a highly comprehensive presence dataset, enhanced by SCUBA diving surveys, to investigate the suitable habitat of an important structuring species, Paramuricea clavata, throughout its distribution (Mediterranean and adjacent Atlantic). Models showed that temperature (11.5–25.5 °C) and slope are the most important predictors carving the niche of P. clavata. Prediction throughout the full distribution (TSS 0.9) included known locations of P. clavata alongside with previously unknown or unreported sites along the coast of Portugal and Africa, including seamounts. These predictions increase the understanding of the potential distribution for the northern Mediterranean and indicate suitable hard bottom areas down to >150 m depth. Poorly sampled habitats with predicted presence along Algeria, Alboran Sea and adjacent Atlantic coasts encourage further investigation. We propose that surveys of target areas from the predicted distribution map, together with local expert knowledge, may lead to discoveries of new P. clavata sites and identify priority conservation areas. PMID:27841263

A Novel Method for Accurate Operon Predictions in All SequencedProkaryotes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, Morgan N.; Huang, Katherine H.; Alm, Eric J.

2004-12-01

We combine comparative genomic measures and the distance separating adjacent genes to predict operons in 124 completely sequenced prokaryotic genomes. Our method automatically tailors itself to each genome using sequence information alone, and thus can be applied to any prokaryote. For Escherichia coli K12 and Bacillus subtilis, our method is 85 and 83% accurate, respectively, which is similar to the accuracy of methods that use the same features but are trained on experimentally characterized transcripts. In Halobacterium NRC-1 and in Helicobacterpylori, our method correctly infers that genes in operons are separated by shorter distances than they are in E.coli, andmore » its predictions using distance alone are more accurate than distance-only predictions trained on a database of E.coli transcripts. We use microarray data from sixphylogenetically diverse prokaryotes to show that combining intergenic distance with comparative genomic measures further improves accuracy and that our method is broadly effective. Finally, we survey operon structure across 124 genomes, and find several surprises: H.pylori has many operons, contrary to previous reports; Bacillus anthracis has an unusual number of pseudogenes within conserved operons; and Synechocystis PCC6803 has many operons even though it has unusually wide spacings between conserved adjacent genes.« less

Dynamic Deployment Simulations of Inflatable Space Structures

NASA Technical Reports Server (NTRS)

Wang, John T.

2005-01-01

The feasibility of using Control Volume (CV) method and the Arbitrary Lagrangian Eulerian (ALE) method in LSDYNA to simulate the dynamic deployment of inflatable space structures is investigated. The CV and ALE methods were used to predict the inflation deployments of three folded tube configurations. The CV method was found to be a simple and computationally efficient method that may be adequate for modeling slow inflation deployment sine the inertia of the inflation gas can be neglected. The ALE method was found to be very computationally intensive since it involves the solving of three conservative equations of fluid as well as dealing with complex fluid structure interactions.

Bioinformatics prediction of siRNAs as potential antiviral agents against dengue viruses

PubMed Central

Villegas-Rosales, Paula M; Méndez-Tenorio, Alfonso; Ortega-Soto, Elizabeth; Barrón, Blanca L

2012-01-01

Dengue virus (DENV 1-4) represents the major emerging arthropod-borne viral infection in the world. Currently, there is neither an available vaccine nor a specific treatment. Hence, there is a need of antiviral drugs for these viral infections; we describe the prediction of short interfering RNA (siRNA) as potential therapeutic agents against the four DENV serotypes. Our strategy was to carry out a series of multiple alignments using ClustalX program to find conserved sequences among the four DENV serotype genomes to obtain a consensus sequence for siRNAs design. A highly conserved sequence among the four DENV serotypes, located in the encoding sequence for NS4B and NS5 proteins was found. A total of 2,893 complete DENV genomes were downloaded from the NCBI, and after a depuration procedure to identify identical sequences, 220 complete DENV genomes were left. They were edited to select the NS4B and NS5 sequences, which were aligned to obtain a consensus sequence. Three different servers were used for siRNA design, and the resulting siRNAs were aligned to identify the most prevalent sequences. Three siRNAs were chosen, one targeted the genome region that codifies for NS4B protein and the other two; the region for NS5 protein. Predicted secondary structure for DENV genomes was used to demonstrate that the siRNAs were able to target the viral genome forming double stranded structures, necessary to activate the RNA silencing machinery. PMID:22829722

Conservation of hot regions in protein-protein interaction in evolution.

PubMed

Hu, Jing; Li, Jiarui; Chen, Nansheng; Zhang, Xiaolong

2016-11-01

The hot regions of protein-protein interactions refer to the active area which formed by those most important residues to protein combination process. With the research development on protein interactions, lots of predicted hot regions can be discovered efficiently by intelligent computing methods, while performing biology experiments to verify each every prediction is hardly to be done due to the time-cost and the complexity of the experiment. This study based on the research of hot spot residue conservations, the proposed method is used to verify authenticity of predicted hot regions that using machine learning algorithm combined with protein's biological features and sequence conservation, though multiple sequence alignment, module substitute matrix and sequence similarity to create conservation scoring algorithm, and then using threshold module to verify the conservation tendency of hot regions in evolution. This research work gives an effective method to verify predicted hot regions in protein-protein interactions, which also provides a useful way to deeply investigate the functional activities of protein hot regions. Copyright © 2016. Published by Elsevier Inc.

Optimal packaging of FIV genomic RNA depends upon a conserved long-range interaction and a palindromic sequence within gag.

PubMed

Rizvi, Tahir A; Kenyon, Julia C; Ali, Jahabar; Aktar, Suriya J; Phillip, Pretty S; Ghazawi, Akela; Mustafa, Farah; Lever, Andrew M L

2010-10-15

The feline immunodeficiency virus (FIV) is a lentivirus that is related to human immunodeficiency virus (HIV), causing a similar pathology in cats. It is a potential small animal model for AIDS and the FIV-based vectors are also being pursued for human gene therapy. Previous studies have mapped the FIV packaging signal (ψ) to two or more discontinuous regions within the 5' 511 nt of the genomic RNA and structural analyses have determined its secondary structure. The 5' and 3' sequences within ψ region interact through extensive long-range interactions (LRIs), including a conserved heptanucleotide interaction between R/U5 and gag. Other secondary structural elements identified include a conserved 150 nt stem-loop (SL2) and a small palindromic stem-loop within gag open reading frame that might act as a viral dimerization initiation site. We have performed extensive mutational analysis of these sequences and structures and ascertained their importance in FIV packaging using a trans-complementation assay. Disrupting the conserved heptanucleotide LRI to prevent base pairing between R/U5 and gag reduced packaging by 2.8-5.5 fold. Restoration of pairing using an alternative, non-wild type (wt) LRI sequence restored RNA packaging and propagation to wt levels, suggesting that it is the structure of the LRI, rather than its sequence, that is important for FIV packaging. Disrupting the palindrome within gag reduced packaging by 1.5-3-fold, but substitution with a different palindromic sequence did not restore packaging completely, suggesting that the sequence of this region as well as its palindromic nature is important. Mutation of individual regions of SL2 did not have a pronounced effect on FIV packaging, suggesting that either it is the structure of SL2 as a whole that is necessary for optimal packaging, or that there is redundancy within this structure. The mutational analysis presented here has further validated the previously predicted RNA secondary structure of FIV ψ. Copyright © 2010 Elsevier Ltd. All rights reserved.

Discriminative motif discovery via simulated evolution and random under-sampling.

PubMed

Song, Tao; Gu, Hong

2014-01-01

Conserved motifs in biological sequences are closely related to their structure and functions. Recently, discriminative motif discovery methods have attracted more and more attention. However, little attention has been devoted to the data imbalance problem, which is one of the main reasons affecting the performance of the discriminative models. In this article, a simulated evolution method is applied to solve the multi-class imbalance problem at the stage of data preprocessing, and at the stage of Hidden Markov Models (HMMs) training, a random under-sampling method is introduced for the imbalance between the positive and negative datasets. It is shown that, in the task of discovering targeting motifs of nine subcellular compartments, the motifs found by our method are more conserved than the methods without considering data imbalance problem and recover the most known targeting motifs from Minimotif Miner and InterPro. Meanwhile, we use the found motifs to predict protein subcellular localization and achieve higher prediction precision and recall for the minority classes.

R-chie: a web server and R package for visualizing RNA secondary structures

PubMed Central

Lai, Daniel; Proctor, Jeff R.; Zhu, Jing Yun A.; Meyer, Irmtraud M.

2012-01-01

Visually examining RNA structures can greatly aid in understanding their potential functional roles and in evaluating the performance of structure prediction algorithms. As many functional roles of RNA structures can already be studied given the secondary structure of the RNA, various methods have been devised for visualizing RNA secondary structures. Most of these methods depict a given RNA secondary structure as a planar graph consisting of base-paired stems interconnected by roundish loops. In this article, we present an alternative method of depicting RNA secondary structure as arc diagrams. This is well suited for structures that are difficult or impossible to represent as planar stem-loop diagrams. Arc diagrams can intuitively display pseudo-knotted structures, as well as transient and alternative structural features. In addition, they facilitate the comparison of known and predicted RNA secondary structures. An added benefit is that structure information can be displayed in conjunction with a corresponding multiple sequence alignments, thereby highlighting structure and primary sequence conservation and variation. We have implemented the visualization algorithm as a web server R-chie as well as a corresponding R package called R4RNA, which allows users to run the software locally and across a range of common operating systems. PMID:22434875

Designing synthetic RNAs to determine the relevance of structural motifs in picornavirus IRES elements

NASA Astrophysics Data System (ADS)

Fernandez-Chamorro, Javier; Lozano, Gloria; Garcia-Martin, Juan Antonio; Ramajo, Jorge; Dotu, Ivan; Clote, Peter; Martinez-Salas, Encarnacion

2016-04-01

The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES elements are organized in modular domains consisting of one or more stem-loops that harbor conserved RNA motifs critical for internal initiation of translation. A conserved motif is the pyrimidine-tract located upstream of the functional initiation codon in type I and II picornavirus IRES. By computationally designing synthetic RNAs to fold into a structure that sequesters the polypyrimidine tract in a hairpin, we establish a correlation between predicted inaccessibility of the pyrimidine tract and IRES activity, as determined in both in vitro and in vivo systems. Our data supports the hypothesis that structural sequestration of the pyrimidine-tract within a stable hairpin inactivates IRES activity, since the stronger the stability of the hairpin the higher the inhibition of protein synthesis. Destabilization of the stem-loop immediately upstream of the pyrimidine-tract also decreases IRES activity. Our work introduces a hybrid computational/experimental method to determine the importance of structural motifs for biological function. Specifically, we show the feasibility of using the software RNAiFold to design synthetic RNAs with particular sequence and structural motifs that permit subsequent experimental determination of the importance of such motifs for biological function.

G‐LoSA: An efficient computational tool for local structure‐centric biological studies and drug design

PubMed Central

2016-01-01

Abstract Molecular recognition by protein mostly occurs in a local region on the protein surface. Thus, an efficient computational method for accurate characterization of protein local structural conservation is necessary to better understand biology and drug design. We present a novel local structure alignment tool, G‐LoSA. G‐LoSA aligns protein local structures in a sequence order independent way and provides a GA‐score, a chemical feature‐based and size‐independent structure similarity score. Our benchmark validation shows the robust performance of G‐LoSA to the local structures of diverse sizes and characteristics, demonstrating its universal applicability to local structure‐centric comparative biology studies. In particular, G‐LoSA is highly effective in detecting conserved local regions on the entire surface of a given protein. In addition, the applications of G‐LoSA to identifying template ligands and predicting ligand and protein binding sites illustrate its strong potential for computer‐aided drug design. We hope that G‐LoSA can be a useful computational method for exploring interesting biological problems through large‐scale comparison of protein local structures and facilitating drug discovery research and development. G‐LoSA is freely available to academic users at http://im.compbio.ku.edu/GLoSA/. PMID:26813336

Mobile Element Evolution Playing Jigsaw - SINEs in Gastropod and Bivalve Mollusks.

PubMed

Matetovici, Irina; Sajgo, Szilard; Ianc, Bianca; Ochis, Cornelia; Bulzu, Paul; Popescu, Octavian; Damert, Annette

2016-01-06

SINEs (Short INterspersed Elements) are widely distributed among eukaryotes. Some SINE families are organized in superfamilies characterized by a shared central domain. These central domains are conserved across species, classes, and even phyla. Here we report the identification of two novel such superfamilies in the genomes of gastropod and bivalve mollusks. The central conserved domain of the first superfamily is present in SINEs in Caenogastropoda and Vetigastropoda as well as in all four subclasses of Bivalvia. We designated the domain MESC (Romanian for MElc-snail and SCoica-mussel) because it appears to be restricted to snails and mussels. The second superfamily is restricted to Caenogastropoda. Its central conserved domain-Snail-is related to the Nin-DC domain. Furthermore, we provide evidence that a 40-bp subdomain of the SINE V-domain is conserved in SINEs in mollusks and arthropods. It is predicted to form a stable stem-loop structure that is preserved in the context of the overall SINE RNA secondary structure in invertebrates. Our analysis also recovered short retrotransposons with a Long INterspersed Element (LINE)-derived 5' end. These share the body and/or the tail with transfer RNA (tRNA)-derived SINEs within and across species. Finally, we identified CORE SINEs in gastropods and bivalves-extending the distribution range of this superfamily. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis

PubMed Central

Du, Yushen; Wu, Nicholas C.; Jiang, Lin; Zhang, Tianhao; Gong, Danyang; Shu, Sara; Wu, Ting-Ting

2016-01-01

ABSTRACT Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available. PMID:27803181

The homologue of mannose-binding lectin in the carp family Cyprinidae is expressed at high level in spleen, and the deduced primary structure predicts affinity for galactose.

PubMed

Vitved, L; Holmskov, U; Koch, C; Teisner, B; Hansen, S; Salomonsen, J; Skjødt, K

2000-09-01

Mannose-binding lectin (MBL) participates in the innate immune system as an activator of the complement system and as an opsonin after binding to certain carbohydrate structures on microorganisms. We isolated and characterized cDNA transcripts encoding an MBL homologue from three members of the carp family Cyprinidae, the zebrafish Danio rerio, the goldfish Carassius auratus, and the carp Cyprinus carpio. The carp and zebrafish transcripts contain two polyadenylation sites and RT-PCR on mRNA from carp tissues revealed the carp transcript to be most prominently expressed in the spleen. The deduced mature proteins contain 228 or 233 amino acids with a short N-terminal segment containing a single conserved cysteine expected to form interchain disulfide bridges, a collagen domain interrupted by four amino acids between two glycine residues, a neck region predicted to form an alpha-helical coiled-coil structure, and a C-terminal carbohydrate recognition domain (CRD). Several of the structurally important residues in the CRD are conserved, but the residues known to interact with the calcium ion and hydroxyl groups of the carbohydrate ligand are different. The amino acid motif EPN, important for mannose specificity, was QPD in the Cyprinidae homologue, suggesting specificity for galactose instead. The identity between the deduced amino acid sequences is more than 90% between the carp and the goldfish and 68% and 65% between these two species, respectively, and the zebrafish. The identity with bird and mammalian MBLs ranges from 28 to 33%.

Wildfires alter rodent community structure across four vegetation types in southern California, USA

USGS Publications Warehouse

Brehme, Cheryl S.; Clark, Denise R.; Rochester, Carlton J.; Fisher, Robert N.

2011-01-01

We surveyed burned and unburned plots across four habitat reserves in San Diego County, California, USA, in 2005 and 2006, to assess the effects of the 2003 wildfires on the community structure and relative abundance of rodent species. The reserves each contained multiple vegetation types (coastal sage scrub, chaparral, woodland, and grassland) and spanned from 250 m to 1078 m in elevation. Multivariate analyses revealed a more simplified rodent community structure in all burned habitats in comparison to unburned habitats. Reduction in shrub and tree cover was highly predictive of changes in post-fire rodent community structure in the burned coastal sage scrub and chaparral habitats. Reduction in cover was not predictive for the less substantially burned woodlands and grasslands, for which we hypothesized that interspecific competition played a greater role in post-fire community structure. Across vegetation types, generalists and open habitat specialists typically increased in relative abundance, whereas closed habitat specialists decreased. We documented significant increases in relative abundance of the deer mouse (Peromyscus maniculatus Wagner) and Dulzura kangaroo rat (Dipodomys simulans Merriam). In contrast, we found significant decreases in relative abundance for the California mouse (Peromyscus californicus Gambel), San Diego pocket mouse (Chaetodipus fallax Merriam), desert woodrat (Neotoma lepida Thomas), and brush mouse (Peromyscus boylii Baird). Currently, our research program involves assessment of whether habitat conservation plans (HCPs) in southern California provide long-term protection to HCP covered species, as well as preserve ecosystem function. The scenario of increased wildfires needs to be incorporated into this assessment. We discuss our results in relation to management and conservation planning under a future scenario of larger and more frequent wildfires in southern California.

Subjective analysis of energy-management projects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, R.

The most successful energy conservation projects always reflect human effort to fine-tune engineering and technological improvements. Subjective analysis is a technique for predicting and measuring human interaction before a project begins. The examples of a subjective analysis for office buildings incorporate evaluative questions that are structured to produce numeric values for computer scoring. Each project would need to develop its own pertinent questions and determine appropriate values for the answers.

Identification and Classification of Conserved RNA Secondary Structures in the Human Genome

PubMed Central

Pedersen, Jakob Skou; Bejerano, Gill; Siepel, Adam; Rosenbloom, Kate; Lindblad-Toh, Kerstin; Lander, Eric S; Kent, Jim; Miller, Webb; Haussler, David

2006-01-01

The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars for identifying functional RNAs encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose threshold for acceptance, this search resulted in a set of 48,479 candidate RNA structures. This screen finds a large number of known functional RNAs, including 195 miRNAs, 62 histone 3′UTR stem loops, and various types of known genetic recoding elements. Among the highest-scoring new predictions are 169 new miRNA candidates, as well as new candidate selenocysteine insertion sites, RNA editing hairpins, RNAs involved in transcript auto regulation, and many folds that form singletons or small functional RNA families of completely unknown function. While the rate of false positives in the overall set is difficult to estimate and is likely to be substantial, the results nevertheless provide evidence for many new human functional RNAs and present specific predictions to facilitate their further characterization. PMID:16628248

Predicting chromatin architecture from models of polymer physics.

PubMed

Bianco, Simona; Chiariello, Andrea M; Annunziatella, Carlo; Esposito, Andrea; Nicodemi, Mario

2017-03-01

We review the picture of chromatin large-scale 3D organization emerging from the analysis of Hi-C data and polymer modeling. In higher mammals, Hi-C contact maps reveal a complex higher-order organization, extending from the sub-Mb to chromosomal scales, hierarchically folded in a structure of domains-within-domains (metaTADs). The domain folding hierarchy is partially conserved throughout differentiation, and deeply correlated to epigenomic features. Rearrangements in the metaTAD topology relate to gene expression modifications: in particular, in neuronal differentiation models, topologically associated domains (TADs) tend to have coherent expression changes within architecturally conserved metaTAD niches. To identify the nature of architectural domains and their molecular determinants within a principled approach, we discuss models based on polymer physics. We show that basic concepts of interacting polymer physics explain chromatin spatial organization across chromosomal scales and cell types. The 3D structure of genomic loci can be derived with high accuracy and its molecular determinants identified by crossing information with epigenomic databases. In particular, we illustrate the case of the Sox9 locus, linked to human congenital disorders. The model in-silico predictions on the effects of genomic rearrangements are confirmed by available 5C data. That can help establishing new diagnostic tools for diseases linked to chromatin mis-folding, such as congenital disorders and cancer.

Different types of employee well-being across time and their relationships with job crafting.

PubMed

Hakanen, Jari J; Peeters, Maria C W; Schaufeli, Wilmar B

2018-04-01

We used and integrated the circumplex model of affect (Russell, 1980) and the conservation of resources theory (Hobfoll, 1998) to hypothesize how various types of employee well-being, which can be differentiated on theoretical grounds (i.e., work engagement, job satisfaction, burnout, and workaholism), may differently predict various job crafting behaviors (i.e., increasing structural and social resources and challenging demands, and decreasing hindering demands) and each other over time. At Time 1, we measured employee well-being, and 4 years later at Time 2, job crafting and well-being, using a large sample of Finnish dentists (N = 1,877). The results of structural equation modeling showed that (a) work engagement positively predicted both types of increasing resources and challenging demands and negatively predicted decreasing hindering demands; (b) workaholism positively predicted increasing structural resources and challenging demands; (c) burnout positively predicted decreasing hindering demands and negatively predicted increasing structural resources, whereas (d) job satisfaction did not relate to job crafting over time; and (e) work engagement positively influenced job satisfaction and negatively influenced burnout, whereas (f) workaholism predicted burnout after controlling for baseline levels. Thus, work engagement was a stronger predictor of future job crafting and other types of employee well-being than job satisfaction. Although workaholism was positively associated with job crafting, it also predicted burnout. We conclude that the relationship between job crafting and employee well-being may be more complex than assumed, because the way in which employees will craft their jobs in the future seems to depend on how they currently feel. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

In silico identification of functional regions in proteins.

PubMed

Nimrod, Guy; Glaser, Fabian; Steinberg, David; Ben-Tal, Nir; Pupko, Tal

2005-06-01

In silico prediction of functional regions on protein surfaces, i.e. sites of interaction with DNA, ligands, substrates and other proteins, is of utmost importance in various applications in the emerging fields of proteomics and structural genomics. When a sufficient number of homologs is found, powerful prediction schemes can be based on the observation that evolutionarily conserved regions are often functionally important, typically, only the principal functionally important region of the protein is detected, while secondary functional regions with weaker conservation signals are overlooked. Moreover, it is challenging to unambiguously identify the boundaries of the functional regions. We present a new methodology, called PatchFinder, that automatically identifies patches of conserved residues that are located in close proximity to each other on the protein surface. PatchFinder is based on the following steps: (1) Assignment of conservation scores to each amino acid position on the protein surface. (2) Assignment of a score to each putative patch, based on its likelihood to be functionally important. The patch of maximum likelihood is considered to be the main functionally important region, and the search is continued for non-overlapping patches of secondary importance. We examined the accuracy of the method using the IGPS enzyme, the SH2 domain and a benchmark set of 112 proteins. These examples demonstrated that PatchFinder is capable of identifying both the main and secondary functional patches. The PatchFinder program is available at: http://ashtoret.tau.ac.il/~nimrodg/

Protein structure and evolution: are they constrained globally by a principle derived from information theory?

PubMed

Hatton, Leslie; Warr, Gregory

2015-01-01

That the physicochemical properties of amino acids constrain the structure, function and evolution of proteins is not in doubt. However, principles derived from information theory may also set bounds on the structure (and thus also the evolution) of proteins. Here we analyze the global properties of the full set of proteins in release 13-11 of the SwissProt database, showing by experimental test of predictions from information theory that their collective structure exhibits properties that are consistent with their being guided by a conservation principle. This principle (Conservation of Information) defines the global properties of systems composed of discrete components each of which is in turn assembled from discrete smaller pieces. In the system of proteins, each protein is a component, and each protein is assembled from amino acids. Central to this principle is the inter-relationship of the unique amino acid count and total length of a protein and its implications for both average protein length and occurrence of proteins with specific unique amino acid counts. The unique amino acid count is simply the number of distinct amino acids (including those that are post-translationally modified) that occur in a protein, and is independent of the number of times that the particular amino acid occurs in the sequence. Conservation of Information does not operate at the local level (it is independent of the physicochemical properties of the amino acids) where the influences of natural selection are manifest in the variety of protein structure and function that is well understood. Rather, this analysis implies that Conservation of Information would define the global bounds within which the whole system of proteins is constrained; thus it appears to be acting to constrain evolution at a level different from natural selection, a conclusion that appears counter-intuitive but is supported by the studies described herein.

Recent advances in computational structural reliability analysis methods

NASA Astrophysics Data System (ADS)

Thacker, Ben H.; Wu, Y.-T.; Millwater, Harry R.; Torng, Tony Y.; Riha, David S.

1993-10-01

The goal of structural reliability analysis is to determine the probability that the structure will adequately perform its intended function when operating under the given environmental conditions. Thus, the notion of reliability admits the possibility of failure. Given the fact that many different modes of failure are usually possible, achievement of this goal is a formidable task, especially for large, complex structural systems. The traditional (deterministic) design methodology attempts to assure reliability by the application of safety factors and conservative assumptions. However, the safety factor approach lacks a quantitative basis in that the level of reliability is never known and usually results in overly conservative designs because of compounding conservatisms. Furthermore, problem parameters that control the reliability are not identified, nor their importance evaluated. A summary of recent advances in computational structural reliability assessment is presented. A significant level of activity in the research and development community was seen recently, much of which was directed towards the prediction of failure probabilities for single mode failures. The focus is to present some early results and demonstrations of advanced reliability methods applied to structural system problems. This includes structures that can fail as a result of multiple component failures (e.g., a redundant truss), or structural components that may fail due to multiple interacting failure modes (e.g., excessive deflection, resonate vibration, or creep rupture). From these results, some observations and recommendations are made with regard to future research needs.

Recent advances in computational structural reliability analysis methods

NASA Technical Reports Server (NTRS)

Thacker, Ben H.; Wu, Y.-T.; Millwater, Harry R.; Torng, Tony Y.; Riha, David S.

1993-01-01

The goal of structural reliability analysis is to determine the probability that the structure will adequately perform its intended function when operating under the given environmental conditions. Thus, the notion of reliability admits the possibility of failure. Given the fact that many different modes of failure are usually possible, achievement of this goal is a formidable task, especially for large, complex structural systems. The traditional (deterministic) design methodology attempts to assure reliability by the application of safety factors and conservative assumptions. However, the safety factor approach lacks a quantitative basis in that the level of reliability is never known and usually results in overly conservative designs because of compounding conservatisms. Furthermore, problem parameters that control the reliability are not identified, nor their importance evaluated. A summary of recent advances in computational structural reliability assessment is presented. A significant level of activity in the research and development community was seen recently, much of which was directed towards the prediction of failure probabilities for single mode failures. The focus is to present some early results and demonstrations of advanced reliability methods applied to structural system problems. This includes structures that can fail as a result of multiple component failures (e.g., a redundant truss), or structural components that may fail due to multiple interacting failure modes (e.g., excessive deflection, resonate vibration, or creep rupture). From these results, some observations and recommendations are made with regard to future research needs.

Conservation of the sequence of the Alzheimer's disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis.

PubMed

Johnstone, E M; Chaney, M O; Norris, F H; Pascual, R; Little, S P

1991-07-01

Neuritic plaque and cerebrovascular amyloid deposits have been detected in the aged monkey, dog, and polar bear and have rarely been found in aged rodents (Biochem. Biophy. Res. Commun., 12 (1984) 885-890; Proc. Natl. Acad. Sci. U.S.A., 82 (1985) 4245-4249). To determine if the primary structure of the 42-43 residue amyloid peptide is conserved in species that accumulate plaques, the region of the amyloid precursor protein (APP) cDNA that encodes the peptide region was amplified by the polymerase chain reaction and sequenced. The deduced amino acid sequence was compared to those species where amyloid accumulation has not been detected. The DNA sequences of dog, polar bear, rabbit, cow, sheep, pig and guinea pig were compared and a phylogenetic tree was generated. We conclude that the amino acid sequence of dog and polar bear and other mammals which may form amyloid plaques is conserved and the species where amyloid has not been detected (mouse, rat) may be evolutionarily a distinct group. In addition, the predicted secondary structure of mouse and rat amyloid that differs from that of amyloid bearing species is its lack of propensity to form a beta sheeted structure. Thus, a cross-species examination of the amyloid peptide may suggest what is essential for amyloid deposition.

Rice Cellulose SynthaseA8 Plant-Conserved Region Is a Coiled-Coil at the Catalytic Core Entrance1[OPEN

PubMed Central

Rushton, Phillip S.; Olek, Anna T.; Makowski, Lee; Badger, John

2017-01-01

The crystallographic structure of a rice (Oryza sativa) cellulose synthase, OsCesA8, plant-conserved region (P-CR), one of two unique domains in the catalytic domain of plant CesAs, was solved to 2.4 Å resolution. Two antiparallel α-helices form a coiled-coil domain linked by a large extended connector loop containing a conserved trio of aromatic residues. The P-CR structure was fit into a molecular envelope for the P-CR domain derived from small-angle X-ray scattering data. The P-CR structure and molecular envelope, combined with a homology-based chain trace of the CesA8 catalytic core, were modeled into a previously determined CesA8 small-angle X-ray scattering molecular envelope to produce a detailed topological model of the CesA8 catalytic domain. The predicted position for the P-CR domain from the molecular docking models places the P-CR connector loop into a hydrophobic pocket of the catalytic core, with the coiled-coil aligned near the entrance of the substrate UDP-glucose into the active site. In this configuration, the P-CR coiled-coil alone is unlikely to regulate substrate access to the active site, but it could interact with other domains of CesA, accessory proteins, or other CesA catalytic domains to control substrate delivery. PMID:27879387

Search for 5'-leader regulatory RNA structures based on gene annotation aided by the RiboGap database.

PubMed

Naghdi, Mohammad Reza; Smail, Katia; Wang, Joy X; Wade, Fallou; Breaker, Ronald R; Perreault, Jonathan

2017-03-15

The discovery of noncoding RNAs (ncRNAs) and their importance for gene regulation led us to develop bioinformatics tools to pursue the discovery of novel ncRNAs. Finding ncRNAs de novo is challenging, first due to the difficulty of retrieving large numbers of sequences for given gene activities, and second due to exponential demands on calculation needed for comparative genomics on a large scale. Recently, several tools for the prediction of conserved RNA secondary structure were developed, but many of them are not designed to uncover new ncRNAs, or are too slow for conducting analyses on a large scale. Here we present various approaches using the database RiboGap as a primary tool for finding known ncRNAs and for uncovering simple sequence motifs with regulatory roles. This database also can be used to easily extract intergenic sequences of eubacteria and archaea to find conserved RNA structures upstream of given genes. We also show how to extend analysis further to choose the best candidate ncRNAs for experimental validation. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of S. cerevisiae F-BAR domain structures reveals a conserved inositol phosphate binding site

PubMed Central

Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R.; Kenniston, Jon A.; Mendrola, Jeannine M.; Ferguson, Kathryn M.; Lemmon, Mark A.

2015-01-01

SUMMARY F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the S. cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences, and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip, and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity, and provide a basis for its prediction from sequence. PMID:25620000

Conservation, expression, and knockdown of zebrafish plxnb2a and plxnb2b.

PubMed

Perälä, Nina; Peitsaro, Nina; Sundvik, Maria; Koivula, Henri; Sainio, Kirsi; Sariola, Hannu; Panula, Pertti; Immonen, Tiina

2010-10-01

In mice lacking Plexin B2, a receptor of the axon guidance molecules Semaphorin 4C and Semaphorin 4D, the closure of the neural tube and structural organization of the cerebellum are severely impaired. We cloned two Plexin B2 orthologs, plxnb2a and plxnb2b, in zebrafish, which is a widely used model for the development of the vertebrate central nervous system (CNS). The predicted proteins, Plexin B2a and Plexin B2b, contain all the conserved and functional domains of the plexin B-subfamily. During embryonic development, plxnb2a is expressed, e.g., in pharyngeal arches while plxnb2b expression is more confined to neuronal structures like the cerebellum. However, both plxnb2a and plxnb2b are expressed at the midbrain-hindbrain boundary, in the otic vesicles, facial ganglia, and pectoral fins. Knockdown of both plxnb2a and plxnb2b simultaneously (>95% and 45%, respectively) resulted in normal CNS structure, axon guidance and swimming performance of the morphants.

Genomic characterization and phylogenetic analysis of Zika virus circulating in the Americas.

PubMed

Ye, Qing; Liu, Zhong-Yu; Han, Jian-Feng; Jiang, Tao; Li, Xiao-Feng; Qin, Cheng-Feng

2016-09-01

The rapid spread and potential link with birth defects have made Zika virus (ZIKV) a global public health problem. The virus was discovered 70years ago, yet the knowledge about its genomic structure and the genetic variations associated with current ZIKV explosive epidemics remains not fully understood. In this review, the genome organization, especially conserved terminal structures of ZIKV genome were characterized and compared with other mosquito-borne flaviviruses. It is suggested that major viral proteins of ZIKV share high structural and functional similarity with other known flaviviruses as shown by sequence comparison and prediction of functional motifs in viral proteins. Phylogenetic analysis demonstrated that all ZIKV strains circulating in the America form a unique clade within the Asian lineage. Furthermore, we identified a series of conserved amino acid residues that differentiate the Asian strains including the current circulating American strains from the ancient African strains. Overall, our findings provide an overview of ZIKV genome characterization and evolutionary dynamics in the Americas and point out critical clues for future virological and epidemiological studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Management of chronic low back pain: rationales, principles, and targets of imaging-guided spinal injections.

PubMed

Fritz, Jan; Niemeyer, Thomas; Clasen, Stephan; Wiskirchen, Jakub; Tepe, Gunnar; Kastler, Bruno; Nägele, Thomas; König, Claudius W; Claussen, Claus D; Pereira, Philippe L

2007-01-01

If low back pain does not improve with conservative management, the cause of the pain must be determined before further therapy is initiated. Information obtained from the patient's medical history, physical examination, and imaging may suffice to rule out many common causes of chronic pain (eg, fracture, malignancy, visceral or metabolic abnormality, deformity, inflammation, and infection). However, in most cases, the initial clinical and imaging findings have a low predictive value for the identification of specific pain-producing spinal structures. Diagnostic spinal injections performed in conjunction with imaging may be necessary to test the hypothesis that a particular structure is the source of pain. To ensure a valid test result, diagnostic injection procedures should be monitored with fluoroscopy, computed tomography, or magnetic resonance imaging. The use of controlled and comparative injections helps maximize the reliability of the test results. After a symptomatic structure has been identified, therapeutic spinal injections may be administered as an adjunct to conservative management, especially in patients with inoperable conditions. Therapeutic injections also may help hasten the recovery of patients with persistent or recurrent pain after spinal surgery. RSNA, 2007

Multi-model comparison highlights consistency in predicted effect of warming on a semi-arid shrub

USGS Publications Warehouse

Renwick, Katherine M.; Curtis, Caroline; Kleinhesselink, Andrew R.; Schlaepfer, Daniel R.; Bradley, Bethany A.; Aldridge, Cameron L.; Poulter, Benjamin; Adler, Peter B.

2018-01-01

A number of modeling approaches have been developed to predict the impacts of climate change on species distributions, performance, and abundance. The stronger the agreement from models that represent different processes and are based on distinct and independent sources of information, the greater the confidence we can have in their predictions. Evaluating the level of confidence is particularly important when predictions are used to guide conservation or restoration decisions. We used a multi-model approach to predict climate change impacts on big sagebrush (Artemisia tridentata), the dominant plant species on roughly 43 million hectares in the western United States and a key resource for many endemic wildlife species. To evaluate the climate sensitivity of A. tridentata, we developed four predictive models, two based on empirically derived spatial and temporal relationships, and two that applied mechanistic approaches to simulate sagebrush recruitment and growth. This approach enabled us to produce an aggregate index of climate change vulnerability and uncertainty based on the level of agreement between models. Despite large differences in model structure, predictions of sagebrush response to climate change were largely consistent. Performance, as measured by change in cover, growth, or recruitment, was predicted to decrease at the warmest sites, but increase throughout the cooler portions of sagebrush's range. A sensitivity analysis indicated that sagebrush performance responds more strongly to changes in temperature than precipitation. Most of the uncertainty in model predictions reflected variation among the ecological models, raising questions about the reliability of forecasts based on a single modeling approach. Our results highlight the value of a multi-model approach in forecasting climate change impacts and uncertainties and should help land managers to maximize the value of conservation investments.

Developing a general conceptual framework for avian conservation science

USGS Publications Warehouse

Sauer, J.R.

2003-01-01

Avian conservation science in North America has produced a variety of monitoring programs designed to provide information on population status of birds. Waterfowl surveys provide population estimates for breeding ducks over most of the continent, the North American Breeding Bird Survey (BBS) provides indexes to population change for >400 breeding bird species, and many other surveys exist that index bird populations at a variety of scales and seasons. However, many fundamental questions about bird population change remain unanswered. I suggest that analyses of monitoring data provide limited understanding of causes of population change, and that the declining species paradigm (Caughley 1994) is sometimes an inefficient approach to increasing our understanding of causes of population change. In North America, the North American Bird Conservation Initiative (NABCI) provides an opportunity to implement alternative approaches that use management, modeling of population responses to management, and monitoring in combination to increase our understanding of bird populations. In adaptive resources management, modeling provides predictions about consequences of management, and monitoring data allow us to assess the population consequences of management. In this framework, alternative hypotheses about response of populations to management can be evaluated by formulating a series of models with differing structure, and management and monitoring provide information about which model best predicts population response.

A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26)

PubMed Central

van Wijk, E; Krieger, E; Kemperman, M; De Leenheer, E M R; Huygen, P; Cremers, C; Cremers, F; Kremer, H

2003-01-01

Linkage analysis in a multigenerational family with autosomal dominant hearing loss yielded a chromosomal localisation of the underlying genetic defect in the DFNA20/26 locus at 17q25-qter. The 6-cM critical region harboured the γ-1-actin (ACTG1) gene, which was considered an attractive candidate gene because actins are important structural elements of the inner ear hair cells. In this study, a Thr278Ile mutation was identified in helix 9 of the modelled protein structure. The alteration of residue Thr278 is predicted to have a small but significant effect on the γ 1 actin structure owing to its close proximity to a methionine residue at position 313 in helix 11. Met313 has no space in the structure to move away. Moreover, the Thr278 residue is highly conserved throughout eukaryotic evolution. Using a known actin structure the mutation could be predicted to impair actin polymerisation. These findings strongly suggest that the Thr278Ile mutation in ACTG1 represents the first disease causing germline mutation in a cytoplasmic actin isoform. PMID:14684684

Prediction of a common beta-propeller catalytic domain for fructosyltransferases of different origin and substrate specificity.

PubMed

Pons, T; Hernández, L; Batista, F R; Chinea, G

2000-11-01

The three-dimensional (3D) structure of fructan biosynthetic enzymes is still unknown. Here, we have explored folding similarities between reported microbial and plant enzymes that catalyze transfructosylation reactions. A sequence-structure compatibility search using TOPITS, SDP, 3D-PSSM, and SAM-T98 programs identified a beta-propeller fold with scores above the confidence threshold that indicate a structurally conserved catalytic domain in fructosyltransferases (FTFs) of diverse origin and substrate specificity. The predicted fold appeared related to that of neuraminidase and sialidase, of glycoside hydrolase families 33 and 34, respectively. The most reliable structural model was obtained using the crystal structure of neuraminidase (Protein Data Bank file: 5nn9) as template, and it is consistent with the location of previously identified functional residues of bacterial levansucrases (Batista et al., 1999; Song & Jacques, 1999). The sequence-sequence analysis presented here reinforces the recent inclusion of fungal and plant FTFs into glycoside hydrolase family 32, and suggests a modified sequence pattern H-x (2)-[PTV]-x (4)-[LIVMA]-[NSCAYG]-[DE]-P-[NDSC][GA]3 for this family.

Prediction of a common beta-propeller catalytic domain for fructosyltransferases of different origin and substrate specificity.

PubMed Central

Pons, T.; Hernández, L.; Batista, F. R.; Chinea, G.

2000-01-01

The three-dimensional (3D) structure of fructan biosynthetic enzymes is still unknown. Here, we have explored folding similarities between reported microbial and plant enzymes that catalyze transfructosylation reactions. A sequence-structure compatibility search using TOPITS, SDP, 3D-PSSM, and SAM-T98 programs identified a beta-propeller fold with scores above the confidence threshold that indicate a structurally conserved catalytic domain in fructosyltransferases (FTFs) of diverse origin and substrate specificity. The predicted fold appeared related to that of neuraminidase and sialidase, of glycoside hydrolase families 33 and 34, respectively. The most reliable structural model was obtained using the crystal structure of neuraminidase (Protein Data Bank file: 5nn9) as template, and it is consistent with the location of previously identified functional residues of bacterial levansucrases (Batista et al., 1999; Song & Jacques, 1999). The sequence-sequence analysis presented here reinforces the recent inclusion of fungal and plant FTFs into glycoside hydrolase family 32, and suggests a modified sequence pattern H-x (2)-[PTV]-x (4)-[LIVMA]-[NSCAYG]-[DE]-P-[NDSC][GA]3 for this family. PMID:11305239

Systematic analysis of snake neurotoxins' functional classification using a data warehousing approach.

PubMed

Siew, Joyce Phui Yee; Khan, Asif M; Tan, Paul T J; Koh, Judice L Y; Seah, Seng Hong; Koo, Chuay Yeng; Chai, Siaw Ching; Armugam, Arunmozhiarasi; Brusic, Vladimir; Jeyaseelan, Kandiah

2004-12-12

Sequence annotations, functional and structural data on snake venom neurotoxins (svNTXs) are scattered across multiple databases and literature sources. Sequence annotations and structural data are available in the public molecular databases, while functional data are almost exclusively available in the published articles. There is a need for a specialized svNTXs database that contains NTX entries, which are organized, well annotated and classified in a systematic manner. We have systematically analyzed svNTXs and classified them using structure-function groups based on their structural, functional and phylogenetic properties. Using conserved motifs in each phylogenetic group, we built an intelligent module for the prediction of structural and functional properties of unknown NTXs. We also developed an annotation tool to aid the functional prediction of newly identified NTXs as an additional resource for the venom research community. We created a searchable online database of NTX proteins sequences (http://research.i2r.a-star.edu.sg/Templar/DB/snake_neurotoxin). This database can also be found under Swiss-Prot Toxin Annotation Project website (http://www.expasy.org/sprot/).

Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis

DOE PAGES

Prigozhin, Daniil M.; Krieger, Inna V.; Huizar, John P.; ...

2014-12-31

Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows thatmore » Rv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis.« less

Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prigozhin, Daniil M.; Krieger, Inna V.; Huizar, John P.

Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows thatmore » Rv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis.« less

A multivariate prediction model for Rho-dependent termination of transcription.

PubMed

Nadiras, Cédric; Eveno, Eric; Schwartz, Annie; Figueroa-Bossi, Nara; Boudvillain, Marc

2018-06-21

Bacterial transcription termination proceeds via two main mechanisms triggered either by simple, well-conserved (intrinsic) nucleic acid motifs or by the motor protein Rho. Although bacterial genomes can harbor hundreds of termination signals of either type, only intrinsic terminators are reliably predicted. Computational tools to detect the more complex and diversiform Rho-dependent terminators are lacking. To tackle this issue, we devised a prediction method based on Orthogonal Projections to Latent Structures Discriminant Analysis [OPLS-DA] of a large set of in vitro termination data. Using previously uncharacterized genomic sequences for biochemical evaluation and OPLS-DA, we identified new Rho-dependent signals and quantitative sequence descriptors with significant predictive value. Most relevant descriptors specify features of transcript C>G skewness, secondary structure, and richness in regularly-spaced 5'CC/UC dinucleotides that are consistent with known principles for Rho-RNA interaction. Descriptors collectively warrant OPLS-DA predictions of Rho-dependent termination with a ∼85% success rate. Scanning of the Escherichia coli genome with the OPLS-DA model identifies significantly more termination-competent regions than anticipated from transcriptomics and predicts that regions intrinsically refractory to Rho are primarily located in open reading frames. Altogether, this work delineates features important for Rho activity and describes the first method able to predict Rho-dependent terminators in bacterial genomes.

Discovery of small molecule inhibitors of ubiquitin-like poxvirus proteinase I7L using homology modeling and covalent docking approaches

NASA Astrophysics Data System (ADS)

Katritch, Vsevolod; Byrd, Chelsea M.; Tseitin, Vladimir; Dai, Dongcheng; Raush, Eugene; Totrov, Maxim; Abagyan, Ruben; Jordan, Robert; Hruby, Dennis E.

2007-10-01

Essential for viral replication and highly conserved among poxviridae, the vaccinia virus I7L ubiquitin-like proteinase (ULP) is an attractive target for development of smallpox antiviral drugs. At the same time, the I7L proteinase exemplifies several interesting challenges from the rational drug design perspective. In the absence of a published I7L X-ray structure, we have built a detailed 3D model of the I7L ligand binding site (S2-S2' pocket) based on exceptionally high structural conservation of this site in proteases of the ULP family. The accuracy and limitations of this model were assessed through comparative analysis of available X-ray structures of ULPs, as well as energy based conformational modeling. The 3D model of the I7L ligand binding site was used to perform covalent docking and VLS of a comprehensive library of about 230,000 available ketone and aldehyde compounds. Out of 456 predicted ligands, 97 inhibitors of I7L proteinase activity were confirmed in biochemical assays (˜20% overall hit rate). These experimental results both validate our I7L ligand binding model and provide initial leads for rational optimization of poxvirus I7L proteinase inhibitors. Thus, fragments predicted to bind in the prime portion of the active site can be combined with fragments on non-prime side to yield compounds with improved activity and specificity.

Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hudson, William H.; Pickard, Mark R.; de Vera, Ian Mitchelle S.

2014-12-23

The majority of the eukaryotic genome is transcribed, generating a significant number of long intergenic noncoding RNAs (lincRNAs). Although lincRNAs represent the most poorly understood product of transcription, recent work has shown lincRNAs fulfill important cellular functions. In addition to low sequence conservation, poor understanding of structural mechanisms driving lincRNA biology hinders systematic prediction of their function. Here we report the molecular requirements for the recognition of steroid receptors (SRs) by the lincRNA growth arrest-specific 5 (Gas5), which regulates steroid-mediated transcriptional regulation, growth arrest and apoptosis. We identify the functional Gas5-SR interface and generate point mutations that ablate the SR-Gas5more » lincRNA interaction, altering Gas5-driven apoptosis in cancer cell lines. Further, we find that the Gas5 SR-recognition sequence is conserved among haplorhines, with its evolutionary origin as a splice acceptor site. This study demonstrates that lincRNAs can recognize protein targets in a conserved, sequence-specific manner in order to affect critical cell functions.« less

Structural and functional determinants of conserved lipid interaction domains of inward rectifying Kir6.2 channels.

PubMed

Cukras, Catherine A; Jeliazkova, Iana; Nichols, Colin G

2002-06-01

All members of the inward rectifiier K(+) (Kir) channel family are activated by phosphoinositides and other amphiphilic lipids. To further elucidate the mechanistic basis, we examined the membrane association of Kir6.2 fragments of K(ATP) channels, and the effects of site-directed mutations of these fragments and full-length Kir6.2 on membrane association and K(ATP) channel activity, respectively. GFP-tagged Kir6.2 COOH terminus and GFP-tagged pleckstrin homology domain from phospholipase C delta1 both associate with isolated membranes, and association of each is specifically reduced by muscarinic m1 receptor-mediated phospholipid depletion. Kir COOH termini are predicted to contain multiple beta-strands and a conserved alpha-helix (residues approximately 306-311 in Kir6.2). Systematic mutagenesis of D307-F315 reveals a critical role of E308, I309, W311 and F315, consistent with residues lying on one side of a alpha-helix. Together with systematic mutation of conserved charges, the results define critical determinants of a conserved domain that underlies phospholipid interaction in Kir channels.

Predicting the process of extinction in experimental microcosms and accounting for interspecific interactions in single-species time series.

PubMed

Ferguson, Jake M; Ponciano, José M

2014-02-01

Predicting population extinction risk is a fundamental application of ecological theory to the practice of conservation biology. Here, we compared the prediction performance of a wide array of stochastic, population dynamics models against direct observations of the extinction process from an extensive experimental data set. By varying a series of biological and statistical assumptions in the proposed models, we were able to identify the assumptions that affected predictions about population extinction. We also show how certain autocorrelation structures can emerge due to interspecific interactions, and that accounting for the stochastic effect of these interactions can improve predictions of the extinction process. We conclude that it is possible to account for the stochastic effects of community interactions on extinction when using single-species time series. © 2013 The Authors. Ecology Letters published by John Wiley & Sons Ltd and CNRS.

Analysis of deep learning methods for blind protein contact prediction in CASP12.

PubMed

Wang, Sheng; Sun, Siqi; Xu, Jinbo

2018-03-01

Here we present the results of protein contact prediction achieved in CASP12 by our RaptorX-Contact server, which is an early implementation of our deep learning method for contact prediction. On a set of 38 free-modeling target domains with a median family size of around 58 effective sequences, our server obtained an average top L/5 long- and medium-range contact accuracy of 47% and 44%, respectively (L = length). A complete implementation has an average accuracy of 59% and 57%, respectively. Our deep learning method formulates contact prediction as a pixel-level image labeling problem and simultaneously predicts all residue pairs of a protein using a combination of two deep residual neural networks, taking as input the residue conservation information, predicted secondary structure and solvent accessibility, contact potential, and coevolution information. Our approach differs from existing methods mainly in (1) formulating contact prediction as a pixel-level image labeling problem instead of an image-level classification problem; (2) simultaneously predicting all contacts of an individual protein to make effective use of contact occurrence patterns; and (3) integrating both one-dimensional and two-dimensional deep convolutional neural networks to effectively learn complex sequence-structure relationship including high-order residue correlation. This paper discusses the RaptorX-Contact pipeline, both contact prediction and contact-based folding results, and finally the strength and weakness of our method. © 2017 Wiley Periodicals, Inc.

PARS: a web server for the prediction of Protein Allosteric and Regulatory Sites.

PubMed

Panjkovich, Alejandro; Daura, Xavier

2014-05-01

The regulation of protein activity is a key aspect of life at the molecular level. Unveiling its details is thus crucial to understanding signalling and metabolic pathways. The most common and powerful mechanism of protein-function regulation is allostery, which has been increasingly calling the attention of medicinal chemists due to its potential for the discovery of novel therapeutics. In this context, PARS is a simple and fast method that queries protein dynamics and structural conservation to identify pockets on a protein structure that may exert a regulatory effect on the binding of a small-molecule ligand.

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis.

PubMed

Du, Yushen; Wu, Nicholas C; Jiang, Lin; Zhang, Tianhao; Gong, Danyang; Shu, Sara; Wu, Ting-Ting; Sun, Ren

2016-11-01

Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available. To fully comprehend the diverse functions of a protein, it is essential to understand the functionality of individual residues. Current methods are highly dependent on evolutionary sequence conservation, which is usually limited by sampling size. Sequence conservation-based methods are further confounded by structural constraints and multifunctionality of proteins. Here we present a method that can systematically identify and annotate functional residues of a given protein. We used a high-throughput functional profiling platform to identify essential residues. Coupling it with homologous-structure comparison, we were able to annotate multiple functions of proteins. We demonstrated the method with the PB1 protein of influenza A virus and identified novel functional residues in addition to its canonical function as an RNA-dependent RNA polymerase. Not limited to virology, this method is generally applicable to other proteins that can be functionally selected and about which homologous-structure information is available. Copyright © 2016 Du et al.

Two rapidly evolving genes contribute to male fitness in Drosophila

PubMed Central

Reinhardt, Josephine A; Jones, Corbin D

2013-01-01

Purifying selection often results in conservation of gene sequence and function. The most functionally conserved genes are also thought to be among the most biologically essential. These observations have led to the use of sequence conservation as a proxy for functional conservation. Here we describe two genes that are exceptions to this pattern. We show that lack of sequence conservation among orthologs of CG15460 and CG15323 – herein named jean-baptiste (jb) and karr respectively – does not necessarily predict lack of functional conservation. These two Drosophila melanogaster genes are among the most rapidly evolving protein-coding genes in this species, being nearly as diverged from their D. yakuba orthologs as random sequences are. jb and karr are both expressed at an elevated level in larval males and adult testes, but they are not accessory gland proteins and their loss does not affect male fertility. Instead, knockdown of these genes in D. melanogaster via RNA interference caused male-biased viability defects. These viability effects occur prior to the third instar for jb and during late pupation for karr. We show that putative orthologs to jb and karr are also expressed strongly in the testes of other Drosophila species and have similar gene structure across species despite low levels of sequence conservation. While standard molecular evolution tests could not reject neutrality, other data hint at a role for natural selection. Together these data provide a clear case where a lack of sequence conservation does not imply a lack of conservation of expression or function. PMID:24221639

Influence of Na+ and Mg2+ ions on RNA structures studied with molecular dynamics simulations.

PubMed

Fischer, Nina M; Polêto, Marcelo D; Steuer, Jakob; van der Spoel, David

2018-06-01

The structure of ribonucleic acid (RNA) polymers is strongly dependent on the presence of, in particular Mg2+ cations to stabilize structural features. Only in high-resolution X-ray crystallography structures can ions be identified reliably. Here, we perform molecular dynamics simulations of 24 RNA structures with varying ion concentrations. Twelve of the structures were helical and the others complex folded. The aim of the study is to predict ion positions but also to evaluate the impact of different types of ions (Na+ or Mg2+) and the ionic strength on structural stability and variations of RNA. As a general conclusion Mg2+ is found to conserve the experimental structure better than Na+ and, where experimental ion positions are available, they can be reproduced with reasonable accuracy. If a large surplus of ions is present the added electrostatic screening makes prediction of binding-sites less reproducible. Distinct differences in ion-binding between helical and complex folded structures are found. The strength of binding (ΔG‡ for breaking RNA atom-ion interactions) is found to differ between roughly 10 and 26 kJ/mol for the different RNA atoms. Differences in stability between helical and complex folded structures and of the influence of metal ions on either are discussed.

Towards a Delamination Fatigue Methodology for Composite Materials

NASA Technical Reports Server (NTRS)

OBrien, Thomas K.

2007-01-01

A methodology that accounts for both delaminaton onset and growth in composite structural components is proposed for improved fatigue life prediction to reduce life cycle costs and improve accept/reject criteria for manufacturing flaws. The benefits of using a Delamination Onset Threshold (DOT) approach in combination with a Modified Damage Tolerance (MDT) approach is highlighted. The use of this combined approach to establish accept/reject criteria, requiring less conservative initial manufacturing flaw sizes, is illustrated.

Mapping forest structure and composition from low-density LiDAR for informed forest, fuel, and fire management at Eglin Air Force Base, Florida, USA

Treesearch

Andrew T. Hudak; Benjamin C. Bright; Scott M. Pokswinski; E. Louise Loudermilk; Joseph J. O' Brien; Benjamin S. Hornsby; Carine Klauberg; Carlos A. Silva

2016-01-01

Eglin Air Force Base (AFB) in Florida, in the United States, conserves a large reservoir of native longleaf pine (Pinus palustris Mill.) stands that land managers maintain by using frequent fires. We predicted tree density, basal area, and dominant tree species from 195 forest inventory plots, low-density airborne LiDAR, and Landsat data available across the entirety...

Climatic niche conservatism and biogeographical non-equilibrium in Eschscholzia californica (Papaveraceae), an invasive plant in the Chilean Mediterranean region.

PubMed

Peña-Gómez, Francisco T; Guerrero, Pablo C; Bizama, Gustavo; Duarte, Milén; Bustamante, Ramiro O

2014-01-01

Species climate requirements are useful for predicting their geographic distribution. It is often assumed that the niche requirements for invasive plants are conserved during invasion, especially when the invaded regions share similar climate conditions. California and central Chile have a remarkable degree of convergence in their vegetation structure, and a similar Mediterranean climate. Such similarities make these geographic areas an interesting natural experiment for testing climatic niche dynamics and the equilibrium of invasive species in a new environment. We tested to see if the climatic niche of Eschscholzia californica is conserved in the invaded range (central Chile), and we assessed whether the invasion process has reached a biogeographical equilibrium, i.e., occupy all the suitable geographic locations that have suitable conditions under native niche requirements. We compared the climatic niche in the native and invaded ranges as well as the projected potential geographic distribution in the invaded range. In order to compare climatic niches, we conducted a Principal Component Analysis (PCA) and Species Distribution Models (SDMs), to estimate E. californica's potential geographic distribution. We also used SDMs to predict altitudinal distribution limits in central Chile. Our results indicated that the climatic niche occupied by E. californica in the invaded range is firmly conserved, occupying a subset of the native climatic niche but leaving a substantial fraction of it unfilled. Comparisons of projected SDMs for central Chile indicate a similarity, yet the projection from native range predicted a larger geographic distribution in central Chile compared to the prediction of the model constructed for central Chile. The projected niche occupancy profile from California predicted a higher mean elevation than that projected from central Chile. We concluded that the invasion process of E. californica in central Chile is consistent with climatic niche conservatism but there is potential for further expansion in Chile.

Sequence diversity within the reovirus S2 gene: reovirus genes reassort in nature, and their termini are predicted to form a panhandle motif.

PubMed Central

Chapell, J D; Goral, M I; Rodgers, S E; dePamphilis, C W; Dermody, T S

1994-01-01

To better understand genetic diversity within mammalian reoviruses, we determined S2 nucleotide and deduced sigma 2 amino acid sequences of nine reovirus strains and compared these sequences with those of prototype strains of the three reovirus serotypes. The S2 gene and sigma 2 protein are highly conserved among the four type 1, one type 2, and seven type 3 strains studied. Phylogenetic analyses based on S2 nucleotide sequences of the 12 reovirus strains indicate that diversity within the S2 gene is independent of viral serotype. Additionally, we found marked topological differences between phylogenetic trees generated from S1 and S2 gene nucleotide sequences of the seven type 3 strains. These results demonstrate that reovirus S1 and S2 genes have distinct evolutionary histories, thus providing phylogenetic evidence for lateral transfer of reovirus genes in nature. When variability among the 12 sigma 2-encoding S2 nucleotide sequences was analyzed at synonymous positions, we found that approximately 60 nucleotides at the 5' terminus and 30 nucleotides at the 3' terminus were markedly conserved in comparison with other sigma 2-encoding regions of S2. Predictions of RNA secondary structures indicate that the more conserved S2 sequences participate in the formation of an extended region of duplex RNA interrupted by a pair of stem-loops. Among the 12 deduced sigma 2 amino acid sequences examined, substitutions were observed at only 11% of amino acid positions. This finding suggests that constraints on the structure or function of sigma 2, perhaps in part because of its location in the virion core, have limited sequence diversity within this protein. PMID:8289378

STRUM: structure-based prediction of protein stability changes upon single-point mutation.

PubMed

Quan, Lijun; Lv, Qiang; Zhang, Yang

2016-10-01

Mutations in human genome are mainly through single nucleotide polymorphism, some of which can affect stability and function of proteins, causing human diseases. Several methods have been proposed to predict the effect of mutations on protein stability; but most require features from experimental structure. Given the fast progress in protein structure prediction, this work explores the possibility to improve the mutation-induced stability change prediction using low-resolution structure modeling. We developed a new method (STRUM) for predicting stability change caused by single-point mutations. Starting from wild-type sequences, 3D models are constructed by the iterative threading assembly refinement (I-TASSER) simulations, where physics- and knowledge-based energy functions are derived on the I-TASSER models and used to train STRUM models through gradient boosting regression. STRUM was assessed by 5-fold cross validation on 3421 experimentally determined mutations from 150 proteins. The Pearson correlation coefficient (PCC) between predicted and measured changes of Gibbs free-energy gap, ΔΔG, upon mutation reaches 0.79 with a root-mean-square error 1.2 kcal/mol in the mutation-based cross-validations. The PCC reduces if separating training and test mutations from non-homologous proteins, which reflects inherent correlations in the current mutation sample. Nevertheless, the results significantly outperform other state-of-the-art methods, including those built on experimental protein structures. Detailed analyses show that the most sensitive features in STRUM are the physics-based energy terms on I-TASSER models and the conservation scores from multiple-threading template alignments. However, the ΔΔG prediction accuracy has only a marginal dependence on the accuracy of protein structure models as long as the global fold is correct. These data demonstrate the feasibility to use low-resolution structure modeling for high-accuracy stability change prediction upon point mutations. http://zhanglab.ccmb.med.umich.edu/STRUM/ CONTACT: qiang@suda.edu.cn and zhng@umich.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

STRUM: structure-based prediction of protein stability changes upon single-point mutation

PubMed Central

Quan, Lijun; Lv, Qiang; Zhang, Yang

2016-01-01

Motivation: Mutations in human genome are mainly through single nucleotide polymorphism, some of which can affect stability and function of proteins, causing human diseases. Several methods have been proposed to predict the effect of mutations on protein stability; but most require features from experimental structure. Given the fast progress in protein structure prediction, this work explores the possibility to improve the mutation-induced stability change prediction using low-resolution structure modeling. Results: We developed a new method (STRUM) for predicting stability change caused by single-point mutations. Starting from wild-type sequences, 3D models are constructed by the iterative threading assembly refinement (I-TASSER) simulations, where physics- and knowledge-based energy functions are derived on the I-TASSER models and used to train STRUM models through gradient boosting regression. STRUM was assessed by 5-fold cross validation on 3421 experimentally determined mutations from 150 proteins. The Pearson correlation coefficient (PCC) between predicted and measured changes of Gibbs free-energy gap, ΔΔG, upon mutation reaches 0.79 with a root-mean-square error 1.2 kcal/mol in the mutation-based cross-validations. The PCC reduces if separating training and test mutations from non-homologous proteins, which reflects inherent correlations in the current mutation sample. Nevertheless, the results significantly outperform other state-of-the-art methods, including those built on experimental protein structures. Detailed analyses show that the most sensitive features in STRUM are the physics-based energy terms on I-TASSER models and the conservation scores from multiple-threading template alignments. However, the ΔΔG prediction accuracy has only a marginal dependence on the accuracy of protein structure models as long as the global fold is correct. These data demonstrate the feasibility to use low-resolution structure modeling for high-accuracy stability change prediction upon point mutations. Availability and Implementation: http://zhanglab.ccmb.med.umich.edu/STRUM/ Contact: qiang@suda.edu.cn and zhng@umich.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27318206

Genome-wide analysis of TCP family in tobacco.

PubMed

Chen, L; Chen, Y Q; Ding, A M; Chen, H; Xia, F; Wang, W F; Sun, Y H

2016-05-23

The TCP family is a transcription factor family, members of which are extensively involved in plant growth and development as well as in signal transduction in the response against many physiological and biochemical stimuli. In the present study, 61 TCP genes were identified in tobacco (Nicotiana tabacum) genome. Bioinformatic methods were employed for predicting and analyzing the gene structure, gene expression, phylogenetic analysis, and conserved domains of TCP proteins in tobacco. The 61 NtTCP genes were divided into three diverse groups, based on the division of TCP genes in tomato and Arabidopsis, and the results of the conserved domain and sequence analyses further confirmed the classification of the NtTCP genes. The expression pattern of NtTCP also demonstrated that majority of these genes play important roles in all the tissues, while some special genes exercise their functions only in specific tissues. In brief, the comprehensive and thorough study of the TCP family in other plants provides sufficient resources for studying the structure and functions of TCPs in tobacco.

Accuracy of topographic index models at identifying ephemeral gully trajectories on agricultural fields

NASA Astrophysics Data System (ADS)

Sheshukov, Aleksey Y.; Sekaluvu, Lawrence; Hutchinson, Stacy L.

2018-04-01

Topographic index (TI) models have been widely used to predict trajectories and initiation points of ephemeral gullies (EGs) in agricultural landscapes. Prediction of EGs strongly relies on the selected value of critical TI threshold, and the accuracy depends on topographic features, agricultural management, and datasets of observed EGs. This study statistically evaluated the predictions by TI models in two paired watersheds in Central Kansas that had different levels of structural disturbances due to implemented conservation practices. Four TI models with sole dependency on topographic factors of slope, contributing area, and planform curvature were used in this study. The observed EGs were obtained by field reconnaissance and through the process of hydrological reconditioning of digital elevation models (DEMs). The Kernel Density Estimation analysis was used to evaluate TI distribution within a 10-m buffer of the observed EG trajectories. The EG occurrence within catchments was analyzed using kappa statistics of the error matrix approach, while the lengths of predicted EGs were compared with the observed dataset using the Nash-Sutcliffe Efficiency (NSE) statistics. The TI frequency analysis produced bi-modal distribution of topographic indexes with the pixels within the EG trajectory having a higher peak. The graphs of kappa and NSE versus critical TI threshold showed similar profile for all four TI models and both watersheds with the maximum value representing the best comparison with the observed data. The Compound Topographic Index (CTI) model presented the overall best accuracy with NSE of 0.55 and kappa of 0.32. The statistics for the disturbed watershed showed higher best critical TI threshold values than for the undisturbed watershed. Structural conservation practices implemented in the disturbed watershed reduced ephemeral channels in headwater catchments, thus producing less variability in catchments with EGs. The variation in critical thresholds for all TI models suggested that TI models tend to predict EG occurrence and length over a range of thresholds rather than find a single best value.

Improving supplementary feeding in species conservation.

PubMed

Ewen, John G; Walker, Leila; Canessa, Stefano; Groombridge, Jim J

2015-04-01

Supplementary feeding is often a knee-jerk reaction to population declines, and its application is not critically evaluated, leading to polarized views among managers on its usefulness. Here, we advocate a more strategic approach to supplementary feeding so that the choice to use it is clearly justified over, or in combination with, other management actions and the predicted consequences are then critically assessed following implementation. We propose combining methods from a set of specialist disciplines that will allow critical evaluation of the need, benefit, and risks of food supplementation. Through the use of nutritional ecology, population ecology, and structured decision making, conservation managers can make better choices about what and how to feed by estimating consequences on population recovery across a range of possible actions. This structured approach also informs targeted monitoring and more clearly allows supplementary feeding to be integrated in recovery plans and reduces the risk of inefficient decisions. In New Zealand, managers of the endangered Hihi (Notiomystis cincta) often rely on supplementary feeding to support reintroduced populations. On Kapiti island the reintroduced Hihi population has responded well to food supplementation, but the logistics of providing an increasing demand recently outstretched management capacity. To decide whether and how the feeding regime should be revised, managers used a structured decision making approach informed by population responses to alternative feeding regimes. The decision was made to reduce the spatial distribution of feeders and invest saved time in increasing volume of food delivered into a smaller core area. The approach used allowed a transparent and defendable management decision in regard to supplementary feeding, reflecting the multiple objectives of managers and their priorities. © 2014 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of Society for Conservation Biology.

Genome-Wide Identification of the Alba Gene Family in Plants and Stress-Responsive Expression of the Rice Alba Genes.

PubMed

Verma, Jitendra Kumar; Wardhan, Vijay; Singh, Deepali; Chakraborty, Subhra; Chakraborty, Niranjan

2018-03-28

Architectural proteins play key roles in genome construction and regulate the expression of many genes, albeit the modulation of genome plasticity by these proteins is largely unknown. A critical screening of the architectural proteins in five crop species, viz., Oryza sativa , Zea mays , Sorghum bicolor , Cicer arietinum , and Vitis vinifera , and in the model plant Arabidopsis thaliana along with evolutionary relevant species such as Chlamydomonas reinhardtii , Physcomitrella patens , and Amborella trichopoda , revealed 9, 20, 10, 7, 7, 6, 1, 4, and 4 Alba (acetylation lowers binding affinity) genes, respectively. A phylogenetic analysis of the genes and of their counterparts in other plant species indicated evolutionary conservation and diversification. In each group, the structural components of the genes and motifs showed significant conservation. The chromosomal location of the Alba genes of rice ( OsAlba ), showed an unequal distribution on 8 of its 12 chromosomes. The expression profiles of the OsAlba genes indicated a distinct tissue-specific expression in the seedling, vegetative, and reproductive stages. The quantitative real-time PCR (qRT-PCR) analysis of the OsAlba genes confirmed their stress-inducible expression under multivariate environmental conditions and phytohormone treatments. The evaluation of the regulatory elements in 68 Alba genes from the 9 species studied led to the identification of conserved motifs and overlapping microRNA (miRNA) target sites, suggesting the conservation of their function in related proteins and a divergence in their biological roles across species. The 3D structure and the prediction of putative ligands and their binding sites for OsAlba proteins offered a key insight into the structure-function relationship. These results provide a comprehensive overview of the subtle genetic diversification of the OsAlba genes, which will help in elucidating their functional role in plants.

Effects of model complexity and priors on estimation using sequential importance sampling/resampling for species conservation

USGS Publications Warehouse

Dunham, Kylee; Grand, James B.

2016-01-01

We examined the effects of complexity and priors on the accuracy of models used to estimate ecological and observational processes, and to make predictions regarding population size and structure. State-space models are useful for estimating complex, unobservable population processes and making predictions about future populations based on limited data. To better understand the utility of state space models in evaluating population dynamics, we used them in a Bayesian framework and compared the accuracy of models with differing complexity, with and without informative priors using sequential importance sampling/resampling (SISR). Count data were simulated for 25 years using known parameters and observation process for each model. We used kernel smoothing to reduce the effect of particle depletion, which is common when estimating both states and parameters with SISR. Models using informative priors estimated parameter values and population size with greater accuracy than their non-informative counterparts. While the estimates of population size and trend did not suffer greatly in models using non-informative priors, the algorithm was unable to accurately estimate demographic parameters. This model framework provides reasonable estimates of population size when little to no information is available; however, when information on some vital rates is available, SISR can be used to obtain more precise estimates of population size and process. Incorporating model complexity such as that required by structured populations with stage-specific vital rates affects precision and accuracy when estimating latent population variables and predicting population dynamics. These results are important to consider when designing monitoring programs and conservation efforts requiring management of specific population segments.

Multiple isoforms for the catalytic subunit of PKA in the basal fungal lineage Mucor circinelloides.

PubMed

Fernández Núñez, Lucas; Ocampo, Josefina; Gottlieb, Alexandra M; Rossi, Silvia; Moreno, Silvia

2016-12-01

Protein kinase A (PKA) activity is involved in dimorphism of the basal fungal lineage Mucor. From the recently sequenced genome of Mucor circinelloides we could predict ten catalytic subunits of PKA. From sequence alignment and structural prediction we conclude that the catalytic core of the isoforms is conserved, and the difference between them resides in their amino termini. This high number of isoforms is maintained in the subdivision Mucoromycotina. Each paralogue, when compared to the ones form other fungi is more homologous to one of its orthologs than to its paralogs. All of these fungal isoforms cannot be included in the class I or II in which fungal protein kinases have been classified. mRNA levels for each isoform were measured during aerobic and anaerobic growth. The expression of each isoform is differential and associated to a particular growth stage. We reanalyzed the sequence of PKAC (GI 20218944), the only cloned sequence available until now for a catalytic subunit of M. circinelloides. PKAC cannot be classified as a PKA because of its difference in the conserved C-tail; it shares with PKB a conserved C2 domain in the N-terminus. No catalytic activity could be measured for this protein nor predicted bioinformatically. It can thus be classified as a pseudokinase. Its importance can not be underestimated since it is expressed at the mRNA level in different stages of growth, and its deletion is lethal. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Causes of variation among rice models in yield response to CO2 examined with Free-Air CO2 Enrichment and growth chamber experiments.

PubMed

Hasegawa, Toshihiro; Li, Tao; Yin, Xinyou; Zhu, Yan; Boote, Kenneth; Baker, Jeffrey; Bregaglio, Simone; Buis, Samuel; Confalonieri, Roberto; Fugice, Job; Fumoto, Tamon; Gaydon, Donald; Kumar, Soora Naresh; Lafarge, Tanguy; Marcaida Iii, Manuel; Masutomi, Yuji; Nakagawa, Hiroshi; Oriol, Philippe; Ruget, Françoise; Singh, Upendra; Tang, Liang; Tao, Fulu; Wakatsuki, Hitomi; Wallach, Daniel; Wang, Yulong; Wilson, Lloyd Ted; Yang, Lianxin; Yang, Yubin; Yoshida, Hiroe; Zhang, Zhao; Zhu, Jianguo

2017-11-01

The CO 2 fertilization effect is a major source of uncertainty in crop models for future yield forecasts, but coordinated efforts to determine the mechanisms of this uncertainty have been lacking. Here, we studied causes of uncertainty among 16 crop models in predicting rice yield in response to elevated [CO 2 ] (E-[CO 2 ]) by comparison to free-air CO 2 enrichment (FACE) and chamber experiments. The model ensemble reproduced the experimental results well. However, yield prediction in response to E-[CO 2 ] varied significantly among the rice models. The variation was not random: models that overestimated at one experiment simulated greater yield enhancements at the others. The variation was not associated with model structure or magnitude of photosynthetic response to E-[CO 2 ] but was significantly associated with the predictions of leaf area. This suggests that modelled secondary effects of E-[CO 2 ] on morphological development, primarily leaf area, are the sources of model uncertainty. Rice morphological development is conservative to carbon acquisition. Uncertainty will be reduced by incorporating this conservative nature of the morphological response to E-[CO 2 ] into the models. Nitrogen levels, particularly under limited situations, make the prediction more uncertain. Improving models to account for [CO 2 ] × N interactions is necessary to better evaluate management practices under climate change.

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold

PubMed Central

Huber, Roland G.; Bond, Peter J.

2017-01-01

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners. PMID:29016650

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.

PubMed

Ivanov, Stefan M; Cawley, Andrew; Huber, Roland G; Bond, Peter J; Warwicker, Jim

2017-01-01

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.

Genome-Wide Analysis of Oleosin Gene Family in 22 Tree Species: An Accelerator for Metabolic Engineering of BioFuel Crops and Agrigenomics Industrial Applications?

PubMed Central

2015-01-01

Abstract Trees contribute to enormous plant oil reserves because many trees contain 50%–80% of oil (triacylglycerols, TAGs) in the fruits and kernels. TAGs accumulate in subcellular structures called oil bodies/droplets, in which TAGs are covered by low-molecular-mass hydrophobic proteins called oleosins (OLEs). The OLEs/TAGs ratio determines the size and shape of intracellular oil bodies. There is a lack of comprehensive sequence analysis and structural information of OLEs among diverse trees. The objectives of this study were to identify OLEs from 22 tree species (e.g., tung tree, tea-oil tree, castor bean), perform genome-wide analysis of OLEs, classify OLEs, identify conserved sequence motifs and amino acid residues, and predict secondary and three-dimensional structures in tree OLEs and OLE subfamilies. Data mining identified 65 OLEs with perfect conservation of the “proline knot” motif (PX5SPX3P) from 19 trees. These OLEs contained >40% hydrophobic amino acid residues. They displayed similar properties and amino acid composition. Genome-wide phylogenetic analysis and multiple sequence alignment demonstrated that these proteins could be classified into five OLE subfamilies. There were distinct patterns of sequence conservation among the OLE subfamilies and within individual tree species. Computational modeling indicated that OLEs were composed of at least three α-helixes connected with short coils without any β-strand and that they exhibited distinct 3D structures and ligand binding sites. These analyses provide fundamental information in the similarity and specificity of diverse OLE isoforms within the same subfamily and among the different species, which should facilitate studying the structure-function relationship and identify critical amino acid residues in OLEs for metabolic engineering of tree TAGs. PMID:26258573

Genome-Wide Analysis of Oleosin Gene Family in 22 Tree Species: An Accelerator for Metabolic Engineering of BioFuel Crops and Agrigenomics Industrial Applications?

PubMed

Cao, Heping

2015-09-01

Trees contribute to enormous plant oil reserves because many trees contain 50%-80% of oil (triacylglycerols, TAGs) in the fruits and kernels. TAGs accumulate in subcellular structures called oil bodies/droplets, in which TAGs are covered by low-molecular-mass hydrophobic proteins called oleosins (OLEs). The OLEs/TAGs ratio determines the size and shape of intracellular oil bodies. There is a lack of comprehensive sequence analysis and structural information of OLEs among diverse trees. The objectives of this study were to identify OLEs from 22 tree species (e.g., tung tree, tea-oil tree, castor bean), perform genome-wide analysis of OLEs, classify OLEs, identify conserved sequence motifs and amino acid residues, and predict secondary and three-dimensional structures in tree OLEs and OLE subfamilies. Data mining identified 65 OLEs with perfect conservation of the "proline knot" motif (PX5SPX3P) from 19 trees. These OLEs contained >40% hydrophobic amino acid residues. They displayed similar properties and amino acid composition. Genome-wide phylogenetic analysis and multiple sequence alignment demonstrated that these proteins could be classified into five OLE subfamilies. There were distinct patterns of sequence conservation among the OLE subfamilies and within individual tree species. Computational modeling indicated that OLEs were composed of at least three α-helixes connected with short coils without any β-strand and that they exhibited distinct 3D structures and ligand binding sites. These analyses provide fundamental information in the similarity and specificity of diverse OLE isoforms within the same subfamily and among the different species, which should facilitate studying the structure-function relationship and identify critical amino acid residues in OLEs for metabolic engineering of tree TAGs.

Characterization of the interaction between the small RNA-encoded peptide SR1P and GapA from Bacillus subtilis.

PubMed

Gimpel, Matthias; Maiwald, Caroline; Wiedemann, Christoph; Görlach, Matthias; Brantl, Sabine

2017-08-01

Small regulatory RNAs (sRNAs) are the most prominent post-transcriptional regulators in all kingdoms of life. A few of them, e.g. SR1 from Bacillus subtilis, are dual-function sRNAs. SR1 acts as a base-pairing sRNA in arginine catabolism and as an mRNA encoding the small peptide SR1P in RNA degradation. Both functions of SR1 are highly conserved among 23 species of Bacillales. Here, we investigate the interaction between SR1P and GapA by a combination of in vivo and in vitro methods. De novo prediction of the structure of SR1P yielded five models, one of which was consistent with experimental circular dichroism spectroscopy data of a purified, synthetic peptide. Based on this model structure and a comparison between the 23 SR1P homologues, a series of SR1P mutants was constructed and analysed by Northern blotting and co-elution experiments. The known crystal structure of Geobacillus stearothermophilus GapA was used to model SR1P onto this structure. The hypothetical SR1P binding pocket, composed of two α-helices at both termini of GapA, was investigated by constructing and assaying a number of GapA mutants in the presence and absence of wild-type or mutated SR1P. Almost all residues of SR1P located in the two highly conserved motifs are implicated in the interaction with GapA. A critical lysine residue (K332) in the C-terminal α-helix 14 of GapA corroborated the predicted binding pocket.

Rose spring dwarf-associated virus has RNA structural and gene-expression features like those of Barley yellow dwarf virus

PubMed Central

Salem, Nida’ M.; Miller, W. Allen; Rowhani, Adib; Golino, Deborah A.; Moyne, Anne-Laure; Falk, Bryce W.

2015-01-01

We determined the complete nucleotide sequence of the Rose spring dwarf-associated virus (RSDaV) genomic RNA (GenBank accession no. EU024678) and compared its predicted RNA structural characteristics affecting gene expression. A cDNA library was derived from RSDaV double-stranded RNAs (dsRNAs) purified from infected tissue. Nucleotide sequence analysis of the cloned cDNAs, plus for clones generated by 5′- and 3′-RACE showed the RSDaV genomic RNA to be 5,808 nucleotides. The genomic RNA contains five major open reading frames (ORFs), and three small ORFs in the 3′-terminal 800 nucleotides, typical for viruses of genus Luteovirus in the family Luteoviridae. Northern blot hybridization analysis revealed the genomic RNA and two prominent subgenomic RNAs of approximately 3 kb and 1 kb. Putative 5′ ends of the sgRNAs were predicted by identification of conserved sequences and secondary structures which resembled the Barley yellow dwarf virus (BYDV) genomic RNA 5′ end and subgenomic RNA promoter sequences. Secondary structures of the BYDV-like ribosomal frameshift elements and cap-independent translation elements, including long-distance base pairing spanning four kb were identified. These contain similarities but also informative differences with the BYDV structures, including a strikingly different structure predicted for the 3′ cap-independent translation element. These analyses of the RSDaV genomic RNA show more complexity for the RNA structural elements for members of the Luteoviridae. PMID:18329064

Rose spring dwarf-associated virus has RNA structural and gene-expression features like those of Barley yellow dwarf virus.

PubMed

Salem, Nida' M; Miller, W Allen; Rowhani, Adib; Golino, Deborah A; Moyne, Anne-Laure; Falk, Bryce W

2008-06-05

We determined the complete nucleotide sequence of the Rose spring dwarf-associated virus (RSDaV) genomic RNA (GenBank accession no. EU024678) and compared its predicted RNA structural characteristics affecting gene expression. A cDNA library was derived from RSDaV double-stranded RNAs (dsRNAs) purified from infected tissue. Nucleotide sequence analysis of the cloned cDNAs, plus for clones generated by 5'- and 3'-RACE showed the RSDaV genomic RNA to be 5808 nucleotides. The genomic RNA contains five major open reading frames (ORFs), and three small ORFs in the 3'-terminal 800 nucleotides, typical for viruses of genus Luteovirus in the family Luteoviridae. Northern blot hybridization analysis revealed the genomic RNA and two prominent subgenomic RNAs of approximately 3 kb and 1 kb. Putative 5' ends of the sgRNAs were predicted by identification of conserved sequences and secondary structures which resembled the Barley yellow dwarf virus (BYDV) genomic RNA 5' end and subgenomic RNA promoter sequences. Secondary structures of the BYDV-like ribosomal frameshift elements and cap-independent translation elements, including long-distance base pairing spanning four kb were identified. These contain similarities but also informative differences with the BYDV structures, including a strikingly different structure predicted for the 3' cap-independent translation element. These analyses of the RSDaV genomic RNA show more complexity for the RNA structural elements for members of the Luteoviridae.

Evolutionary conservation analysis increases the colocalization of predicted exonic splicing enhancers in the BRCA1 gene with missense sequence changes and in-frame deletions, but not polymorphisms

PubMed Central

Pettigrew, Christopher; Wayte, Nicola; Lovelock, Paul K; Tavtigian, Sean V; Chenevix-Trench, Georgia; Spurdle, Amanda B; Brown, Melissa A

2005-01-01

Introduction Aberrant pre-mRNA splicing can be more detrimental to the function of a gene than changes in the length or nature of the encoded amino acid sequence. Although predicting the effects of changes in consensus 5' and 3' splice sites near intron:exon boundaries is relatively straightforward, predicting the possible effects of changes in exonic splicing enhancers (ESEs) remains a challenge. Methods As an initial step toward determining which ESEs predicted by the web-based tool ESEfinder in the breast cancer susceptibility gene BRCA1 are likely to be functional, we have determined their evolutionary conservation and compared their location with known BRCA1 sequence variants. Results Using the default settings of ESEfinder, we initially detected 669 potential ESEs in the coding region of the BRCA1 gene. Increasing the threshold score reduced the total number to 464, while taking into consideration the proximity to splice donor and acceptor sites reduced the number to 211. Approximately 11% of these ESEs (23/211) either are identical at the nucleotide level in human, primates, mouse, cow, dog and opossum Brca1 (conserved) or are detectable by ESEfinder in the same position in the Brca1 sequence (shared). The frequency of conserved and shared predicted ESEs between human and mouse is higher in BRCA1 exons (2.8 per 100 nucleotides) than in introns (0.6 per 100 nucleotides). Of conserved or shared putative ESEs, 61% (14/23) were predicted to be affected by sequence variants reported in the Breast Cancer Information Core database. Applying the filters described above increased the colocalization of predicted ESEs with missense changes, in-frame deletions and unclassified variants predicted to be deleterious to protein function, whereas they decreased the colocalization with known polymorphisms or unclassified variants predicted to be neutral. Conclusion In this report we show that evolutionary conservation analysis may be used to improve the specificity of an ESE prediction tool. This is the first report on the prediction of the frequency and distribution of ESEs in the BRCA1 gene, and it is the first reported attempt to predict which ESEs are most likely to be functional and therefore which sequence variants in ESEs are most likely to be pathogenic. PMID:16280041

Structural basis for substrate placement by an archaeal box C/D ribonucleoprotein particle.

PubMed

Xue, Song; Wang, Ruiying; Yang, Fangping; Terns, Rebecca M; Terns, Michael P; Zhang, Xinxin; Maxwell, E Stuart; Li, Hong

2010-09-24

Box C/D small nucleolar and Cajal body ribonucleoprotein particles (sno/scaRNPs) direct site-specific 2'-O-methylation of ribosomal and spliceosomal RNAs and are critical for gene expression. Here we report crystal structures of an archaeal box C/D RNP containing three core proteins (fibrillarin, Nop56/58, and L7Ae) and a half-mer box C/D guide RNA paired with a substrate RNA. The structure reveals a guide-substrate RNA duplex orientation imposed by a composite protein surface and the conserved GAEK motif of Nop56/58. Molecular modeling supports a dual C/D RNP structure that closely mimics that recently visualized by electron microscopy. The substrate-bound dual RNP model predicts an asymmetric protein distribution between the RNP that binds and methylates the substrate RNA. The predicted asymmetric nature of the holoenzyme is consistent with previous biochemical data on RNP assembly and provides a simple solution for accommodating base-pairing between the C/D guide RNA and large ribosomal and spliceosomal substrate RNAs. Copyright © 2010 Elsevier Inc. All rights reserved.

On the relationship between residue structural environment and sequence conservation in proteins.

PubMed

Liu, Jen-Wei; Lin, Jau-Ji; Cheng, Chih-Wen; Lin, Yu-Feng; Hwang, Jenn-Kang; Huang, Tsun-Tsao

2017-09-01

Residues that are crucial to protein function or structure are usually evolutionarily conserved. To identify the important residues in protein, sequence conservation is estimated, and current methods rely upon the unbiased collection of homologous sequences. Surprisingly, our previous studies have shown that the sequence conservation is closely correlated with the weighted contact number (WCN), a measure of packing density for residue's structural environment, calculated only based on the C α positions of a protein structure. Moreover, studies have shown that sequence conservation is correlated with environment-related structural properties calculated based on different protein substructures, such as a protein's all atoms, backbone atoms, side-chain atoms, or side-chain centroid. To know whether the C α atomic positions are adequate to show the relationship between residue environment and sequence conservation or not, here we compared C α atoms with other substructures in their contributions to the sequence conservation. Our results show that C α positions are substantially equivalent to the other substructures in calculations of various measures of residue environment. As a result, the overlapping contributions between C α atoms and the other substructures are high, yielding similar structure-conservation relationship. Take the WCN as an example, the average overlapping contribution to sequence conservation is 87% between C α and all-atom substructures. These results indicate that only C α atoms of a protein structure could reflect sequence conservation at the residue level. © 2017 Wiley Periodicals, Inc.

RAG-3D: A search tool for RNA 3D substructures

DOE PAGES

Zahran, Mai; Sevim Bayrak, Cigdem; Elmetwaly, Shereef; ...

2015-08-24

In this study, to address many challenges in RNA structure/function prediction, the characterization of RNA's modular architectural units is required. Using the RNA-As-Graphs (RAG) database, we have previously explored the existence of secondary structure (2D) submotifs within larger RNA structures. Here we present RAG-3D—a dataset of RNA tertiary (3D) structures and substructures plus a web-based search tool—designed to exploit graph representations of RNAs for the goal of searching for similar 3D structural fragments. The objects in RAG-3D consist of 3D structures translated into 3D graphs, cataloged based on the connectivity between their secondary structure elements. Each graph is additionally describedmore » in terms of its subgraph building blocks. The RAG-3D search tool then compares a query RNA 3D structure to those in the database to obtain structurally similar structures and substructures. This comparison reveals conserved 3D RNA features and thus may suggest functional connections. Though RNA search programs based on similarity in sequence, 2D, and/or 3D structural elements are available, our graph-based search tool may be advantageous for illuminating similarities that are not obvious; using motifs rather than sequence space also reduces search times considerably. Ultimately, such substructuring could be useful for RNA 3D structure prediction, structure/function inference and inverse folding.« less

RAG-3D: a search tool for RNA 3D substructures

PubMed Central

Zahran, Mai; Sevim Bayrak, Cigdem; Elmetwaly, Shereef; Schlick, Tamar

2015-01-01

To address many challenges in RNA structure/function prediction, the characterization of RNA's modular architectural units is required. Using the RNA-As-Graphs (RAG) database, we have previously explored the existence of secondary structure (2D) submotifs within larger RNA structures. Here we present RAG-3D—a dataset of RNA tertiary (3D) structures and substructures plus a web-based search tool—designed to exploit graph representations of RNAs for the goal of searching for similar 3D structural fragments. The objects in RAG-3D consist of 3D structures translated into 3D graphs, cataloged based on the connectivity between their secondary structure elements. Each graph is additionally described in terms of its subgraph building blocks. The RAG-3D search tool then compares a query RNA 3D structure to those in the database to obtain structurally similar structures and substructures. This comparison reveals conserved 3D RNA features and thus may suggest functional connections. Though RNA search programs based on similarity in sequence, 2D, and/or 3D structural elements are available, our graph-based search tool may be advantageous for illuminating similarities that are not obvious; using motifs rather than sequence space also reduces search times considerably. Ultimately, such substructuring could be useful for RNA 3D structure prediction, structure/function inference and inverse folding. PMID:26304547

RAG-3D: A search tool for RNA 3D substructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zahran, Mai; Sevim Bayrak, Cigdem; Elmetwaly, Shereef

In this study, to address many challenges in RNA structure/function prediction, the characterization of RNA's modular architectural units is required. Using the RNA-As-Graphs (RAG) database, we have previously explored the existence of secondary structure (2D) submotifs within larger RNA structures. Here we present RAG-3D—a dataset of RNA tertiary (3D) structures and substructures plus a web-based search tool—designed to exploit graph representations of RNAs for the goal of searching for similar 3D structural fragments. The objects in RAG-3D consist of 3D structures translated into 3D graphs, cataloged based on the connectivity between their secondary structure elements. Each graph is additionally describedmore » in terms of its subgraph building blocks. The RAG-3D search tool then compares a query RNA 3D structure to those in the database to obtain structurally similar structures and substructures. This comparison reveals conserved 3D RNA features and thus may suggest functional connections. Though RNA search programs based on similarity in sequence, 2D, and/or 3D structural elements are available, our graph-based search tool may be advantageous for illuminating similarities that are not obvious; using motifs rather than sequence space also reduces search times considerably. Ultimately, such substructuring could be useful for RNA 3D structure prediction, structure/function inference and inverse folding.« less

RNA 3D Structure Modeling by Combination of Template-Based Method ModeRNA, Template-Free Folding with SimRNA, and Refinement with QRNAS.

PubMed

Piatkowski, Pawel; Kasprzak, Joanna M; Kumar, Deepak; Magnus, Marcin; Chojnowski, Grzegorz; Bujnicki, Janusz M

2016-01-01

RNA encompasses an essential part of all known forms of life. The functions of many RNA molecules are dependent on their ability to form complex three-dimensional (3D) structures. However, experimental determination of RNA 3D structures is laborious and challenging, and therefore, the majority of known RNAs remain structurally uncharacterized. To address this problem, computational structure prediction methods were developed that either utilize information derived from known structures of other RNA molecules (by way of template-based modeling) or attempt to simulate the physical process of RNA structure formation (by way of template-free modeling). All computational methods suffer from various limitations that make theoretical models less reliable than high-resolution experimentally determined structures. This chapter provides a protocol for computational modeling of RNA 3D structure that overcomes major limitations by combining two complementary approaches: template-based modeling that is capable of predicting global architectures based on similarity to other molecules but often fails to predict local unique features, and template-free modeling that can predict the local folding, but is limited to modeling the structure of relatively small molecules. Here, we combine the use of a template-based method ModeRNA with a template-free method SimRNA. ModeRNA requires a sequence alignment of the target RNA sequence to be modeled with a template of the known structure; it generates a model that predicts the structure of a conserved core and provides a starting point for modeling of variable regions. SimRNA can be used to fold small RNAs (<80 nt) without any additional structural information, and to refold parts of models for larger RNAs that have a correctly modeled core. ModeRNA can be either downloaded, compiled and run locally or run through a web interface at http://genesilico.pl/modernaserver/ . SimRNA is currently available to download for local use as a precompiled software package at http://genesilico.pl/software/stand-alone/simrna and as a web server at http://genesilico.pl/SimRNAweb . For model optimization we use QRNAS, available at http://genesilico.pl/qrnas .

Cloning and characterisation of type 4 fimbrial genes from Actinobacillus pleuropneumoniae.

PubMed

Stevenson, Andrew; Macdonald, Julie; Roberts, Mark

2003-03-20

Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumoniae. Little is known about the mechanisms by which A. pleuropneumoniae colonises the respiratory tract. Fimbriae are common mediators of bacterial adherence to mucosal epithelia and have been observed on the surface of A. pleuropneumoniae cells. Here we report the identification and characterisation of the type 4 fimbrial structural gene (apfA) from A. pleuropneumoniae. In addition a number of open reading frames were identified in A. pleuropneumoniae that have significant homology to type 4 fimbrial biogenesis genes from other species, including a putative leader specific peptidase (apfD). A. pleuropneumoniae apfA codes for a predicted polypeptide of approximately 16kDa, removal of the leader sequence at the predicted cleavage site would yield a 14.5kDa polypeptide. The first 30 residues of the mature polypeptide are well conserved with other members of the group A type 4 fimbriae family. The signal sequence of ApfA is 13 amino acids in length and, unusually, the residue that precedes the cleavage site is alanine rather than glycine which is found in most other type 4 fimbriae. The C-terminus of ApfA possesses cysteine residues that are conserved in type 4 fimbriae of many species. In other type 4 fimbriae the distal C-terminal cysteines form a disulphide bond that produces a loop, which is important for the function of fimbriae and also comprises a major antigenic determinant. A motif within the predicted loop in ApfA was found to be highly conserved in type 4 fimbriae of other HAP organisms (Haemophilus, Actinobacillus, Pasteurella). The A. pleuropneumoniae type 4 fimbrial biogenesis genes showed the strongest homology to putative type 4 fimbrial genes of Haemophilus ducreyi. A. pleuropneumoniae apfA gene was shown to be present and highly conserved in different serotypes of A. pleuropneumoniae. Recombinant ApfA was produced and used to raise anti-ApfA antisera.

Versatility and Invariance in the Evolution of Homologous Heteromeric Interfaces

PubMed Central

Andreani, Jessica; Faure, Guilhem; Guerois, Raphaël

2012-01-01

Evolutionary pressures act on protein complex interfaces so that they preserve their complementarity. Nonetheless, the elementary interactions which compose the interface are highly versatile throughout evolution. Understanding and characterizing interface plasticity across evolution is a fundamental issue which could provide new insights into protein-protein interaction prediction. Using a database of 1,024 couples of close and remote heteromeric structural interologs, we studied protein-protein interactions from a structural and evolutionary point of view. We systematically and quantitatively analyzed the conservation of different types of interface contacts. Our study highlights astonishing plasticity regarding polar contacts at complex interfaces. It also reveals that up to a quarter of the residues switch out of the interface when comparing two homologous complexes. Despite such versatility, we identify two important interface descriptors which correlate with an increased conservation in the evolution of interfaces: apolar patches and contacts surrounding anchor residues. These observations hold true even when restricting the dataset to transiently formed complexes. We show that a combination of six features related either to sequence or to geometric properties of interfaces can be used to rank positions likely to share similar contacts between two interologs. Altogether, our analysis provides important tracks for extracting meaningful information from multiple sequence alignments of conserved binding partners and for discriminating near-native interfaces using evolutionary information. PMID:22952442

Genetic population structure of muskellunge in the Great Lakes

USGS Publications Warehouse

Kapuscinski, Kevin L.; Sloss, Brian L.; Farrell, John M.

2013-01-01

We quantified genetic relationships among Muskellunge Esox masquinongy from 15 locations in the Great Lakes to determine the extent and distribution of measurable population structure and to identify appropriate spatial scales for fishery management and genetic conservation. We hypothesized that Muskellunge from each area represented genetically distinct populations, which would be evident from analyses of genotype data. A total of 691 Muskellunge were sampled (n = 10–127/site) and genetic data were collected at 13 microsatellite loci. Results from a suite of analyses (including pairwise genetic differentiation, Bayesian admixture prediction, analysis of molecular variance, and tests of isolation by distance) indicated the presence of nine distinct genetic groups, including two that were approximately 50 km apart. Geographic proximity and low habitat complexity seemed to facilitate genetic similarity among areas, whereas Muskellunge from areas of greater habitat heterogeneity exhibited high differentiation. Muskellunge from most areas contained private alleles, and mean within-area genetic variation was similar to that reported for other freshwater fishes. Management programs aimed at conserving the broader diversity and long-term sustainability of Muskellunge could benefit by considering the genetically distinct groups as independent fisheries, and individual spawning and nursery habitats could subsequently be protected to conserve the evolutionary potential of Muskellunge.

Structural Mechanisms of Inactivation in Scabies Mite Serine Protease Paralogues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fischer, Katja; Langendorf, Christopher G.; Irving, James A.

2009-08-07

The scabies mite (Sarcoptes scabiei) is a parasite responsible for major morbidity in disadvantaged communities and immuno-compromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by Streptococcal species via skin lesions, resulting in a high prevalence of rheumatic fever/heart disease in affected communities. The scabies mite produces 33 proteins that are closely related to those in the dust mite group 3 allergen and belong to the S1-like protease family (chymotrypsin-like). However, all but one of these molecules contain mutations in the conserved active-site catalytic triad that are predicted to render them catalyticallymore » inactive. These molecules are thus termed scabies mite inactivated protease paralogues (SMIPPs). The precise function of SMIPPs is unclear; however, it has been suggested that these proteins might function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge. In order to begin to understand the structural basis for SMIPP function, we solved the crystal structures of SMIPP-S-I1 and SMIPP-S-D1 at 1.85 {angstrom} and 2.0 {angstrom} resolution, respectively. Both structures adopt the characteristic serine protease fold, albeit with large structural variations over much of the molecule. In both structures, mutations in the catalytic triad together with occlusion of the S1 subsite by a conserved Tyr200 residue is predicted to block substrate ingress. Accordingly, we show that both proteases lack catalytic function. Attempts to restore function (via site-directed mutagenesis of catalytic residues as well as Tyr200) were unsuccessful. Taken together, these data suggest that SMIPPs have lost the ability to bind substrates in a classical 'canonical' fashion, and instead have evolved alternative functions in the lifecycle of the scabies mite.« less

Phocid Seal Leptin: Tertiary Structure and Hydrophobic Receptor Binding Site Preservation during Distinct Leptin Gene Evolution

PubMed Central

Hammond, John A.; Hauton, Chris; Bennett, Kimberley A.; Hall, Ailsa J.

2012-01-01

The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus. PMID:22536379

Potential impacts of global warming on the diversity and distribution of stream insects in South Korea.

PubMed

Li, Fengqing; Kwon, Yong-Su; Bae, Mi-Jung; Chung, Namil; Kwon, Tae-Sung; Park, Young-Seuk

2014-04-01

Globally, the East Asian monsoon region is one of the richest environments in terms of biodiversity. The region is undergoing rapid human development, yet its river ecosystems have not been well studied. Global warming represents a major challenge to the survival of species in this region and makes it necessary to assess and reduce the potential consequences of warming on species of conservation concern. We projected the effects of global warming on stream insect (Ephemeroptera, Odonata, Plecoptera, and Trichoptera [EOPT]) diversity and predicted the changes of geographical ranges for 121 species throughout South Korea. Plecoptera was the most sensitive (decrease of 71.4% in number of species from the 2000s through the 2080s) order, whereas Odonata benefited (increase of 66.7% in number of species from the 2000s through the 2080s) from the effects of global warming. The impact of global warming on stream insects was predicted to be minimal prior to the 2060s; however, by the 2080s, species extirpation of up to 20% in the highland areas and 2% in the lowland areas were predicted. The projected responses of stream insects under global warming indicated that species occupying specific habitats could undergo major reductions in habitat. Nevertheless, habitat of 33% of EOPT (including two-thirds of Odonata and one-third of Ephemeroptera, Plecoptera, and Trichoptera) was predicted to increase due to global warming. The community compositions predicted by generalized additive models varied over this century, and a large difference in community structure in the highland areas was predicted between the 2000s and the 2080s. However, stream insect communities, especially Odonata, Plecoptera, and Trichoptera, were predicted to become more homogenous under global warming. © 2013 Society for Conservation Biology.

Image Texture Predicts Avian Density and Species Richness

PubMed Central

Wood, Eric M.; Pidgeon, Anna M.; Radeloff, Volker C.; Keuler, Nicholas S.

2013-01-01

For decades, ecologists have measured habitat attributes in the field to understand and predict patterns of animal distribution and abundance. However, the scale of inference possible from field measured data is typically limited because large-scale data collection is rarely feasible. This is problematic given that conservation and management typical require data that are fine grained yet broad in extent. Recent advances in remote sensing methodology offer alternative tools for efficiently characterizing wildlife habitat across broad areas. We explored the use of remotely sensed image texture, which is a surrogate for vegetation structure, calculated from both an air photo and from a Landsat TM satellite image, compared with field-measured vegetation structure, characterized by foliage-height diversity and horizontal vegetation structure, to predict avian density and species richness within grassland, savanna, and woodland habitats at Fort McCoy Military Installation, Wisconsin, USA. Image texture calculated from the air photo best predicted density of a grassland associated species, grasshopper sparrow (Ammodramus savannarum), within grassland habitat (R2 = 0.52, p-value <0.001), and avian species richness among habitats (R2 = 0.54, p-value <0.001). Density of field sparrow (Spizella pusilla), a savanna associated species, was not particularly well captured by either field-measured or remotely sensed vegetation structure variables, but was best predicted by air photo image texture (R2 = 0.13, p-value = 0.002). Density of ovenbird (Seiurus aurocapillus), a woodland associated species, was best predicted by pixel-level satellite data (mean NDVI, R2 = 0.54, p-value <0.001). Surprisingly and interestingly, remotely sensed vegetation structure measures (i.e., image texture) were often better predictors of avian density and species richness than field-measured vegetation structure, and thus show promise as a valuable tool for mapping habitat quality and characterizing biodiversity across broad areas. PMID:23675463

Structural motif screening reveals a novel, conserved carbohydrate-binding surface in the pathogenesis-related protein PR-5d.

PubMed

Doxey, Andrew C; Cheng, Zhenyu; Moffatt, Barbara A; McConkey, Brendan J

2010-08-03

Aromatic amino acids play a critical role in protein-glycan interactions. Clusters of surface aromatic residues and their features may therefore be useful in distinguishing glycan-binding sites as well as predicting novel glycan-binding proteins. In this work, a structural bioinformatics approach was used to screen the Protein Data Bank (PDB) for coplanar aromatic motifs similar to those found in known glycan-binding proteins. The proteins identified in the screen were significantly associated with carbohydrate-related functions according to gene ontology (GO) enrichment analysis, and predicted motifs were found frequently within novel folds and glycan-binding sites not included in the training set. In addition to numerous binding sites predicted in structural genomics proteins of unknown function, one novel prediction was a surface motif (W34/W36/W192) in the tobacco pathogenesis-related protein, PR-5d. Phylogenetic analysis revealed that the surface motif is exclusive to a subfamily of PR-5 proteins from the Solanaceae family of plants, and is absent completely in more distant homologs. To confirm PR-5d's insoluble-polysaccharide binding activity, a cellulose-pulldown assay of tobacco proteins was performed and PR-5d was identified in the cellulose-binding fraction by mass spectrometry. Based on the combined results, we propose that the putative binding site in PR-5d may be an evolutionary adaptation of Solanaceae plants including potato, tomato, and tobacco, towards defense against cellulose-containing pathogens such as species of the deadly oomycete genus, Phytophthora. More generally, the results demonstrate that coplanar aromatic clusters on protein surfaces are a structural signature of glycan-binding proteins, and can be used to computationally predict novel glycan-binding proteins from 3 D structure.

Prediction of Ras-effector interactions using position energy matrices.

PubMed

Kiel, Christina; Serrano, Luis

2007-09-01

One of the more challenging problems in biology is to determine the cellular protein interaction network. Progress has been made to predict protein-protein interactions based on structural information, assuming that structural similar proteins interact in a similar way. In a previous publication, we have determined a genome-wide Ras-effector interaction network based on homology models, with a high accuracy of predicting binding and non-binding domains. However, for a prediction on a genome-wide scale, homology modelling is a time-consuming process. Therefore, we here successfully developed a faster method using position energy matrices, where based on different Ras-effector X-ray template structures, all amino acids in the effector binding domain are sequentially mutated to all other amino acid residues and the effect on binding energy is calculated. Those pre-calculated matrices can then be used to score for binding any Ras or effector sequences. Based on position energy matrices, the sequences of putative Ras-binding domains can be scanned quickly to calculate an energy sum value. By calibrating energy sum values using quantitative experimental binding data, thresholds can be defined and thus non-binding domains can be excluded quickly. Sequences which have energy sum values above this threshold are considered to be potential binding domains, and could be further analysed using homology modelling. This prediction method could be applied to other protein families sharing conserved interaction types, in order to determine in a fast way large scale cellular protein interaction networks. Thus, it could have an important impact on future in silico structural genomics approaches, in particular with regard to increasing structural proteomics efforts, aiming to determine all possible domain folds and interaction types. All matrices are deposited in the ADAN database (http://adan-embl.ibmc.umh.es/). Supplementary data are available at Bioinformatics online.

Prostate Cell Specific Regulation of Androgen Receptor Phosphorylation in Vivo

DTIC Science & Technology

2009-11-01

includes both Rpb5, a subunit shared by RNA polymerase (Pol) I, II , and III, and the corepressor, Unconventional prefoldin Rpb5-Interactor (URI/C19orf2...complex that contains RNA polymerase II subunit 5, a subunit shared by all three RNA polymerases; unconventional prefoldin RPB5-in- teractor (URI), which...sequence of ART-27 is conserved throughout evolution from worms to humans and its predicted protein structure is homologous to the prefoldin -a family of

Eastern Mediterranean Sea Spatial and Temporal Variability of Thermohaline Structure and Circulation Identified from Observational (T, S) Profiles

DTIC Science & Technology

2015-12-01

effect of Etesian winds between the late May and early October. Although they are generally dry, cool and moderate; they may turn into a windstorm...very significant to provide the realization of ocean modeling and prediction. The Optimal Spectral Decomposition (OSD) method is an effective ...represents the potential density, by differentiating this equation with respect to z and multiplying with the coriolis parameter f, conservation of

Mutations in the Arabidopsis Peroxisomal ABC Transporter COMATOSE Allow Differentiation between Multiple Functions In Planta: Insights from an Allelic Series

PubMed Central

Dietrich, Daniela; Schmuths, Heike; Lousa, Carine De Marcos; Baldwin, Jocelyn M.; Baldwin, Stephen A.; Baker, Alison; Holdsworth, Michael J.

2009-01-01

COMATOSE (CTS), the Arabidopsis homologue of human Adrenoleukodystrophy protein (ALDP), is required for import of substrates for peroxisomal β-oxidation. A new allelic series and a homology model based on the bacterial ABC transporter, Sav1866, provide novel insights into structure-function relations of ABC subfamily D proteins. In contrast to ALDP, where the majority of mutations result in protein absence from the peroxisomal membrane, all CTS mutants produced stable protein. Mutation of conserved residues in the Walker A and B motifs in CTS nucleotide-binding domain (NBD) 1 resulted in a null phenotype but had little effect in NBD2, indicating that the NBDs are functionally distinct in vivo. Two alleles containing mutations in NBD1 outside the Walker motifs (E617K and C631Y) exhibited resistance to auxin precursors 2,4-dichlorophenoxybutyric acid (2,4-DB) and indole butyric acid (IBA) but were wild type in all other tests. The homology model predicted that the transmission interfaces are domain-swapped in CTS, and the differential effects of mutations in the conserved “EAA motif” of coupling helix 2 supported this prediction, consistent with distinct roles for each NBD. Our findings demonstrate that CTS functions can be separated by mutagenesis and the structural model provides a framework for interpretation of phenotypic data. PMID:19019987

Influence of proximal side mutations on the molecular and electronic structure of cyanomet myoglobin: an 1H NMR study.

PubMed

Wu, Y; Chien, E Y; Sligar, S G; La Mar, G N

1998-05-12

A series of proximal side mutants of sperm whale metmyoglobin (metMb) that involves residues which provide hydrogen bonds to the axial His and heme have been prepared, and the CO binding and solution molecular and electronic structure has been investigated by 1H NMR. These include Ser92(F7), whose O gamma serves as a hydrogen-bond acceptor to the axial His ring NdeltaH and whose O gamma H serves as hydrogen-bond donor to the 7-propionate carboxylate, and His97(FG3) whose ring provides the other hydrogen-bond donor to the 7-propionate carboxylate. 2D NMR data on the S92A-metMbCN, S92P-metMbCN and H97F-metMbCN show that the distal structure is completely conserved and that proximal side structural changes are highly localized. For the S92A-metMbCN, altered dipolar contacts to the F-helix backbone show that the axial His imidazole has rotated clockwise by approximately 10 degrees relative to a stationary heme, while in H97F-metMbCN, the altered heme-E helix backbone contacts reveal that the heme has rotated counterclockwise by approximately 3 degrees relative to a conserved axial His. The pattern of axial His rotation was qualitatively predicted by energy minimization calculations. The assignments and conserved structural elements allow the determination of a set of magnetic axes whose major magnetic axis is unchanged with respect to WT and confirms that local distal, and not proximal, interactions control the orientation of the major magnetic axis and, by inference, the degree and direction of tilt of the Fe-CN from the heme normal. The rhombic magnetic axes in S92A-metMbCN are rotated approximately 10 degrees in the opposite direction from the established approximately 10 degrees rotation for the axial His ring as expected. It is shown, moreover, that the pairwise alpha-, gamma-meso vs beta-, delta-meso-H hyperfine shift differences are well predicted by the change in the location of the rhombic magnetic axes. Carbon monoxide ligation rates experience minor but systematic perturbation for the S92A substitutions which confirms an influence (albeit very small) for axial His orientation on ligand affinity.

Sequence harmony: detecting functional specificity from alignments

PubMed Central

Feenstra, K. Anton; Pirovano, Walter; Krab, Klaas; Heringa, Jaap

2007-01-01

Multiple sequence alignments are often used for the identification of key specificity-determining residues within protein families. We present a web server implementation of the Sequence Harmony (SH) method previously introduced. SH accurately detects subfamily specific positions from a multiple alignment by scoring compositional differences between subfamilies, without imposing conservation. The SH web server allows a quick selection of subtype specific sites from a multiple alignment given a subfamily grouping. In addition, it allows the predicted sites to be directly mapped onto a protein structure and displayed. We demonstrate the use of the SH server using the family of plant mitochondrial alternative oxidases (AOX). In addition, we illustrate the usefulness of combining sequence and structural information by showing that the predicted sites are clustered into a few distinct regions in an AOX homology model. The SH web server can be accessed at www.ibi.vu.nl/programs/seqharmwww. PMID:17584793

Identification of human short introns

PubMed Central

Abebrese, Emmanuel L.; Arnold, Zachary R.; Armstrong, Katharine; Burns, Lindsay; Day, R. Thomas; Hsu, Daniel G.; Jarrell, Katherine; Luo, Yi; Mugayo, Daphine

2017-01-01

Canonical pre-mRNA splicing requires snRNPs and associated splicing factors to excise conserved intronic sequences, with a minimum intron length required for efficient splicing. Non-canonical splicing–intron excision without the spliceosome–has been documented; most notably, some tRNAs and the XBP1 mRNA contain short introns that are not removed by the spliceosome. There have been some efforts to identify additional short introns, but little is known about how many short introns are processed from mRNAs. Here, we report an approach to identify RNA short introns from RNA-Seq data, discriminating against small genomic deletions. We identify hundreds of short introns conserved among multiple human cell lines. These short introns are often alternatively spliced and are found in a variety of RNAs–both mRNAs and lncRNAs. Short intron splicing efficiency is increased by secondary structure, and we detect both canonical and non-canonical short introns. In many cases, splicing of these short introns from mRNAs is predicted to alter the reading frame and change protein output. Our findings imply that standard gene prediction models which often assume a lower limit for intron size fail to predict short introns effectively. We conclude that short introns are abundant in the human transcriptome, and short intron splicing represents an added layer to mRNA regulation. PMID:28520720

Conserved Daily Transcriptional Programs in Carica papaya

PubMed Central

Zdepski, Anna; Wang, Wenqin; Priest, Henry D.; Ali, Faraz; Alam, Maqsudul; Mockler, Todd C.

2008-01-01

Most organisms have internal circadian clocks that mediate responses to daily environmental changes in order to synchronize biological functions to the correct times of the day. Previous studies have focused on plants found in temperate and sub-tropical climates, and little is known about the circadian transcriptional networks of plants that typically grow under conditions with relatively constant day lengths and temperatures over the year. In this study we conducted a genomic and computational analysis of the circadian biology of Carica papaya, a tropical tree. We found that predicted papaya circadian clock genes cycle with the same phase as Arabidopsis genes. The patterns of time-of-day overrepresentation of circadian-associated promoter elements were nearly identical across papaya, Arabidopsis, rice, and poplar. Evolution of promoter structure predicts the observed morning- and evening-specific expression profiles of the papaya PRR5 paralogs. The strong conservation of previously identified circadian transcriptional networks in papaya, despite its tropical habitat and distinct life-style, suggest that circadian timing has played a major role in the evolution of plant genomes, consistent with the selective pressure of anticipating daily environmental changes. Further studies could exploit this conservation to elucidate general design principles that will facilitate engineering plant growth pathways for specific environments. Electronic supplementary material The online version of this article (doi:10.1007/s12042-008-9020-3) contains supplementary material, which is available to authorized users. PMID:20671772

7 CFR 610.11 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.11 Purpose... by the Natural Resources Conservation Service (NRCS) to predict soil erosion due to water and wind... Act, as amended, 16 U.S.C. 3801-3813 specified that the Secretary would publish the universal soil...

7 CFR 610.11 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.11 Purpose... by the Natural Resources Conservation Service (NRCS) to predict soil erosion due to water and wind... Act, as amended, 16 U.S.C. 3801-3813 specified that the Secretary would publish the universal soil...

7 CFR 610.11 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.11 Purpose... by the Natural Resources Conservation Service (NRCS) to predict soil erosion due to water and wind... Act, as amended, 16 U.S.C. 3801-3813 specified that the Secretary would publish the universal soil...

7 CFR 610.11 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.11 Purpose... by the Natural Resources Conservation Service (NRCS) to predict soil erosion due to water and wind... Act, as amended, 16 U.S.C. 3801-3813 specified that the Secretary would publish the universal soil...

7 CFR 610.11 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE CONSERVATION OPERATIONS TECHNICAL ASSISTANCE Soil Erosion Prediction Equations § 610.11 Purpose... by the Natural Resources Conservation Service (NRCS) to predict soil erosion due to water and wind... Act, as amended, 16 U.S.C. 3801-3813 specified that the Secretary would publish the universal soil...

Kassiopeia: a database and web application for the analysis of mutually exclusive exomes of eukaryotes

PubMed Central

2014-01-01

Background Alternative splicing is an important process in higher eukaryotes that allows obtaining several transcripts from one gene. A specific case of alternative splicing is mutually exclusive splicing, in which exactly one exon out of a cluster of neighbouring exons is spliced into the mature transcript. Recently, a new algorithm for the prediction of these exons has been developed based on the preconditions that the exons of the cluster have similar lengths, sequence homology, and conserved splice sites, and that they are translated in the same reading frame. Description In this contribution we introduce Kassiopeia, a database and web application for the generation, storage, and presentation of genome-wide analyses of mutually exclusive exomes. Currently, Kassiopeia provides access to the mutually exclusive exomes of twelve Drosophila species, the thale cress Arabidopsis thaliana, the flatworm Caenorhabditis elegans, and human. Mutually exclusive spliced exons (MXEs) were predicted based on gene reconstructions from Scipio. Based on the standard prediction values, with which 83.5% of the annotated MXEs of Drosophila melanogaster were reconstructed, the exomes contain surprisingly more MXEs than previously supposed and identified. The user can search Kassiopeia using BLAST or browse the genes of each species optionally adjusting the parameters used for the prediction to reveal more divergent or only very similar exon candidates. Conclusions We developed a pipeline to predict MXEs in the genomes of several model organisms and a web interface, Kassiopeia, for their visualization. For each gene Kassiopeia provides a comprehensive gene structure scheme, the sequences and predicted secondary structures of the MXEs, and, if available, further evidence for MXE candidates from cDNA/EST data, predictions of MXEs in homologous genes of closely related species, and RNA secondary structure predictions. Kassiopeia can be accessed at http://www.motorprotein.de/kassiopeia. PMID:24507667

Fine-tuning structural RNA alignments in the twilight zone.

PubMed

Bremges, Andreas; Schirmer, Stefanie; Giegerich, Robert

2010-04-30

A widely used method to find conserved secondary structure in RNA is to first construct a multiple sequence alignment, and then fold the alignment, optimizing a score based on thermodynamics and covariance. This method works best around 75% sequence similarity. However, in a "twilight zone" below 55% similarity, the sequence alignment tends to obscure the covariance signal used in the second phase. Therefore, while the overall shape of the consensus structure may still be found, the degree of conservation cannot be estimated reliably. Based on a combination of available methods, we present a method named planACstar for improving structure conservation in structural alignments in the twilight zone. After constructing a consensus structure by alignment folding, planACstar abandons the original sequence alignment, refolds the sequences individually, but consistent with the consensus, aligns the structures, irrespective of sequence, by a pure structure alignment method, and derives an improved sequence alignment from the alignment of structures, to be re-submitted to alignment folding, etc.. This circle may be iterated as long as structural conservation improves, but normally, one step suffices. Employing the tools ClustalW, RNAalifold, and RNAforester, we find that for sequences with 30-55% sequence identity, structural conservation can be improved by 10% on average, with a large variation, measured in terms of RNAalifold's own criterion, the structure conservation index.

Computational-based structural, functional and phylogenetic analysis of Enterobacter phytases.

PubMed

Pramanik, Krishnendu; Kundu, Shreyasi; Banerjee, Sandipan; Ghosh, Pallab Kumar; Maiti, Tushar Kanti

2018-06-01

Myo-inositol hexakisphosphate phosphohydrolases (i.e., phytases) are known to be a very important enzyme responsible for solubilization of insoluble phosphates. In the present study, Enterobacter phytases have characterized by different phylogenetic, structural and functional parameters using some standard bio-computational tools. Results showed that majority of the Enterobacter phytases are acidic in nature as most of the isoelectric points were under 7.0. The aliphatic indices predicted for the selected proteins were below 40 indicating their thermostable nature. The average molecular weight of the proteins was 48 kDa. The lower values of GRAVY of the said proteins implied that they have better interactions with water. Secondary structure prediction revealed that alpha-helical content was highest among the other forms such as sheets, coils, etc. Moreover, the predicted 3D structure of Enterobacter phytases divulged that the proteins consisted of four monomeric polypeptide chains i.e., it was a tetrameric protein. The predicted tertiary model of E. aerogenes (A0A0M3HCJ2) was deposited in Protein Model Database (Acc. No.: PM0080561) for further utilization after a thorough quality check from QMEAN and SAVES server. Functional analysis supported their classification as histidine acid phosphatases. Besides, multiple sequence alignment revealed that "DG-DP-LG" was the most highly conserved residues within the Enterobacter phytases. Thus, the present study will be useful in selecting suitable phytase-producing microbe exclusively for using in the animal food industry as a food additive.

Comparison of Saccharomyces cerevisiae F-BAR domain structures reveals a conserved inositol phosphate binding site.

PubMed

Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R; Kenniston, Jon A; Mendrola, Jeannine M; Ferguson, Kathryn M; Lemmon, Mark A

2015-02-03

F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although they are generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the Saccharomyces cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity and provide a basis for its prediction from sequence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site

DOE PAGES

Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R.; ...

2015-01-22

F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although they are generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here in this paper, we compare membrane-binding properties of the Saccharomyces cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound tomore » an inositol phosphate. The structures explain phospholipid-binding selectivity differences and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip and is partly retained in certain other F-BAR domains. In conclusion, our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity and provide a basis for its prediction from sequence.« less

Maintaining replication origins in the face of genomic change.

PubMed

Di Rienzi, Sara C; Lindstrom, Kimberly C; Mann, Tobias; Noble, William S; Raghuraman, M K; Brewer, Bonita J

2012-10-01

Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L. waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved.

Maintaining replication origins in the face of genomic change

PubMed Central

Di Rienzi, Sara C.; Lindstrom, Kimberly C.; Mann, Tobias; Noble, William S.; Raghuraman, M.K.; Brewer, Bonita J.

2012-01-01

Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L. waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved. PMID:22665441

Controllability of flow-conservation networks

NASA Astrophysics Data System (ADS)

Zhao, Chen; Zeng, An; Jiang, Rui; Yuan, Zhengzhong; Wang, Wen-Xu

2017-07-01

The ultimate goal of exploring complex networks is to control them. As such, controllability of complex networks has been intensively investigated. Despite recent advances in studying the impact of a network's topology on its controllability, a comprehensive understanding of the synergistic impact of network topology and dynamics on controllability is still lacking. Here, we explore the controllability of flow-conservation networks, trying to identify the minimal number of driver nodes that can guide the network to any desirable state. We develop a method to analyze the controllability on flow-conservation networks based on exact controllability theory, transforming the original analysis on adjacency matrix to Laplacian matrix. With this framework, we systematically investigate the impact of some key factors of networks, including link density, link directionality, and link polarity, on the controllability of these networks. We also obtain the analytical equations by investigating the network's structural properties approximatively and design the efficient tools. Finally, we consider some real networks with flow dynamics, finding that their controllability is significantly different from that predicted by only considering the topology. These findings deepen our understanding of network controllability with flow-conservation dynamics and provide a general framework to incorporate real dynamics in the analysis of network controllability.

Modelling and measurement of crack closure and crack growth following overloads and underloads

NASA Technical Reports Server (NTRS)

Dexter, R. J.; Hudak, S. J.; Davidson, D. L.

1989-01-01

Ignoring crack growth retardation following overloads can result in overly conservative life predictions in structures subjected to variable amplitude fatigue loading. Crack closure is believed to contribute to the crack growth retardation, although the specific closure mechanism is dabatable. The delay period and corresponding crack growth rate transients following overload and overload/underload cycles were systematically measured as a function of load ratio and overload magnitude. These responses are correlated in terms of the local 'driving force' for crack growth, i.e. the effective stress intensity factor range. Experimental results are compared with the predictions of a Dugdale-type (1960) crack closure model, and improvements in the model are suggested.

A Worst-Case Approach for On-Line Flutter Prediction

NASA Technical Reports Server (NTRS)

Lind, Rick C.; Brenner, Martin J.

1998-01-01

Worst-case flutter margins may be computed for a linear model with respect to a set of uncertainty operators using the structured singular value. This paper considers an on-line implementation to compute these robust margins in a flight test program. Uncertainty descriptions are updated at test points to account for unmodeled time-varying dynamics of the airplane by ensuring the robust model is not invalidated by measured flight data. Robust margins computed with respect to this uncertainty remain conservative to the changing dynamics throughout the flight. A simulation clearly demonstrates this method can improve the efficiency of flight testing by accurately predicting the flutter margin to improve safety while reducing the necessary flight time.

PACCMIT/PACCMIT-CDS: identifying microRNA targets in 3′ UTRs and coding sequences

PubMed Central

Šulc, Miroslav; Marín, Ray M.; Robins, Harlan S.; Vaníček, Jiří

2015-01-01

The purpose of the proposed web server, publicly available at http://paccmit.epfl.ch, is to provide a user-friendly interface to two algorithms for predicting messenger RNA (mRNA) molecules regulated by microRNAs: (i) PACCMIT (Prediction of ACcessible and/or Conserved MIcroRNA Targets), which identifies primarily mRNA transcripts targeted in their 3′ untranslated regions (3′ UTRs), and (ii) PACCMIT-CDS, designed to find mRNAs targeted within their coding sequences (CDSs). While PACCMIT belongs among the accurate algorithms for predicting conserved microRNA targets in the 3′ UTRs, the main contribution of the web server is 2-fold: PACCMIT provides an accurate tool for predicting targets also of weakly conserved or non-conserved microRNAs, whereas PACCMIT-CDS addresses the lack of similar portals adapted specifically for targets in CDS. The web server asks the user for microRNAs and mRNAs to be analyzed, accesses the precomputed P-values for all microRNA–mRNA pairs from a database for all mRNAs and microRNAs in a given species, ranks the predicted microRNA–mRNA pairs, evaluates their significance according to the false discovery rate and finally displays the predictions in a tabular form. The results are also available for download in several standard formats. PMID:25948580

The relative importance of regional, local, and evolutionary factors structuring cryptobenthic coral-reef assemblages

NASA Astrophysics Data System (ADS)

Ahmadia, Gabby N.; Tornabene, Luke; Smith, David J.; Pezold, Frank L.

2018-03-01

Factors shaping coral-reef fish species assemblages can operate over a wide range of spatial scales (local versus regional) and across both proximate and evolutionary time. Niche theory and neutral theory provide frameworks for testing assumptions and generating insights about the importance of local versus regional processes. Niche theory postulates that species assemblages are an outcome of evolutionary processes at regional scales followed by local-scale interactions, whereas neutral theory presumes that species assemblages are formed by largely random processes drawing from regional species pools. Indo-Pacific cryptobenthic coral-reef fishes are highly evolved, ecologically diverse, temporally responsive, and situated on a natural longitudinal diversity gradient, making them an ideal group for testing predictions from niche and neutral theories and effects of regional and local processes on species assemblages. Using a combination of ecological metrics (fish density, diversity, assemblage composition) and evolutionary analyses (testing for phylogenetic niche conservatism), we demonstrate that the structure of cryptobenthic fish assemblages can be explained by a mixture of regional factors, such as the size of regional species pools and broad-scale barriers to gene flow/drivers of speciation, coupled with local-scale factors, such as the relative abundance of specific microhabitat types. Furthermore, species of cryptobenthic fishes have distinct microhabitat associations that drive significant differences in assemblage community structure between microhabitat types, and these distinct microhabitat associations are phylogenetically conserved over evolutionary timescales. The implied differential fitness of cryptobenthic fishes across varied microhabitats and the conserved nature of their ecology are consistent with predictions from niche theory. Neutral theory predictions may still hold true for early life-history stages, where stochastic factors may be more important in explaining recruitment. Overall, through integration of ecological and evolutionary techniques, and using multiple spatial scales, our study offers a unique perspective on factors determining coral-reef fish assemblages.

Stochastic multifractal forecasts: from theory to applications in radar meteorology

NASA Astrophysics Data System (ADS)

da Silva Rocha Paz, Igor; Tchiguirinskaia, Ioulia; Schertzer, Daniel

2017-04-01

Radar meteorology has been very inspiring for the development of multifractals. It has enabled to work on a 3D+1 field with many challenging applications, including predictability and stochastic forecasts, especially nowcasts that are particularly demanding in computation speed. Multifractals are indeed parsimonious stochastic models that require only a few physically meaningful parameters, e.g. Universal Multifractal (UM) parameters, because they are based on non-trivial symmetries of nonlinear equations. We first recall the physical principles of multifractal predictability and predictions, which are so closely related that the latter correspond to the most optimal predictions in the multifractal framework. Indeed, these predictions are based on the fundamental duality of a relatively slow decay of large scale structures and an injection of new born small scale structures. Overall, this triggers a mulfitractal inverse cascade of unpredictability. With the help of high resolution rainfall radar data (≈ 100 m), we detail and illustrate the corresponding stochastic algorithm in the framework of (causal) UM Fractionally Integrated Flux models (UM-FIF), where the rainfall field is obtained with the help of a fractional integration of a conservative multifractal flux, whose average is strictly scale invariant (like the energy flux in a dynamic cascade). Whereas, the introduction of small structures is rather straightforward, the deconvolution of the past of the field is more subtle, but nevertheless achievable, to obtain the past of the flux. Then, one needs to only fractionally integrate a multiplicative combination of past and future fluxes to obtain a nowcast realisation.

Evolutionarily conserved regions and hydrophobic contacts at the superfamily level: The case of the fold-type I, pyridoxal-5′-phosphate-dependent enzymes

PubMed Central

Paiardini, Alessandro; Bossa, Francesco; Pascarella, Stefano

2004-01-01

The wealth of biological information provided by structural and genomic projects opens new prospects of understanding life and evolution at the molecular level. In this work, it is shown how computational approaches can be exploited to pinpoint protein structural features that remain invariant upon long evolutionary periods in the fold-type I, PLP-dependent enzymes. A nonredundant set of 23 superposed crystallographic structures belonging to this superfamily was built. Members of this family typically display high-structural conservation despite low-sequence identity. For each structure, a multiple-sequence alignment of orthologous sequences was obtained, and the 23 alignments were merged using the structural information to obtain a comprehensive multiple alignment of 921 sequences of fold-type I enzymes. The structurally conserved regions (SCRs), the evolutionarily conserved residues, and the conserved hydrophobic contacts (CHCs) were extracted from this data set, using both sequence and structural information. The results of this study identified a structural pattern of hydrophobic contacts shared by all of the superfamily members of fold-type I enzymes and involved in native interactions. This profile highlights the presence of a nucleus for this fold, in which residues participating in the most conserved native interactions exhibit preferential evolutionary conservation, that correlates significantly (r = 0.70) with the extent of mean hydrophobic contact value of their apolar fraction. PMID:15498941

ACTP: A webserver for predicting potential targets and relevant pathways of autophagy-modulating compounds

PubMed Central

Ouyang, Liang; Cai, Haoyang; Liu, Bo

2016-01-01

Autophagy (macroautophagy) is well known as an evolutionarily conserved lysosomal degradation process for long-lived proteins and damaged organelles. Recently, accumulating evidence has revealed a series of small-molecule compounds that may activate or inhibit autophagy for therapeutic potential on human diseases. However, targeting autophagy for drug discovery still remains in its infancy. In this study, we developed a webserver called Autophagic Compound-Target Prediction (ACTP) (http://actp.liu-lab.com/) that could predict autophagic targets and relevant pathways for a given compound. The flexible docking of submitted small-molecule compound (s) to potential autophagic targets could be performed by backend reverse docking. The webpage would return structure-based scores and relevant pathways for each predicted target. Thus, these results provide a basis for the rapid prediction of potential targets/pathways of possible autophagy-activating or autophagy-inhibiting compounds without labor-intensive experiments. Moreover, ACTP will be helpful to shed light on identifying more novel autophagy-activating or autophagy-inhibiting compounds for future therapeutic implications. PMID:26824420

Structural annotation of Beta-1,4-N-acetyl galactosaminyltransferase 1 (B4GALNT1) causing Hereditary Spastic Paraplegia 26.

PubMed

Dad, Rubina; Malik, Uzma; Javed, Aneela; Minassian, Berge A; Hassan, Muhammad Jawad

2017-08-30

Beta-1,4-N-acetyl galactosaminyltransferase 1, B4GALNT1, is a GM2/GD2 synthase, involved in the expression of glycosphingolipids (GSLs) containing sialic acid. Mutations in the gene B4GALNT1 cause Hereditary Spastic Paraplegia 26 (HSP26). In present study we have made attempt to predict the potential structural of the human B4GALNT1 protein. The results illustrated that the amino acid sequences of B4GALNT1 are not 100% conserved among selected twenty species. One signal peptide and one transmembrane domain predicted in human wild type B4GALNT1 protein with aliphatic index of 92.76 and theoretical (iso-electric point) pI of 8.93. It was a kind of unstable protein with Grand average of hydropathicity (GRAVY) of -0.127. Various post-translational modifications were also predicted to exist in B4GALNT1 and predicted to interact with different proteins including ST8SIA5, SLC33A1, GLB1 and others. In the final round, reported missense mutations have shown the further decrease in stability of the protein. This in-silico analysis of B4GALNT1 protein will provide the basis for the further studies on structural variations and biological pathways involving B4GALNT1 in the HSP26. Copyright © 2017. Published by Elsevier B.V.

[Bioinformatics analysis of mosquito densovirus nostructure protein NS1].

PubMed

Dong, Yun-qiao; Ma, Wen-li; Gu, Jin-bao; Zheng, Wen-ling

2009-12-01

To analyze and predict the structure and function of mosquito densovirus (MDV) nostructual protein1 (NS1). Using different bioinformatics software, the EXPASY pmtparam tool, ClustalX1.83, Bioedit, MEGA3.1, ScanProsite, and Motifscan, respectively to comparatively analyze and predict the physic-chemical parameters, homology, evolutionary relation, secondary structure and main functional motifs of NS1. MDV NS1 protein was a unstable hydrophilic protein and the amino acid sequence was highly conserved which had a relatively closer evolutionary distance with infectious hypodermal and hematopoietic necrosis virus (IHHNV). MDV NS1 has a specific domain of superfamily 3 helicase of small DNA viruses. This domain contains the NTP-binding region with a metal ion-dependent ATPase activity. A virus replication roller rolling-circle replication(RCR) initiation domain was found near the N terminal of this protein. This protien has the biological function of single stranded incision enzyme. The bioinformatics prediction results suggest that MDV NS1 protein plays a key role in viral replication, packaging, and the other stages of viral life.

Prediction of hearing loss among the noise-exposed workers in a steel factory using artificial intelligence approach.

PubMed

Aliabadi, Mohsen; Farhadian, Maryam; Darvishi, Ebrahim

2015-08-01

Prediction of hearing loss in noisy workplaces is considered to be an important aspect of hearing conservation program. Artificial intelligence, as a new approach, can be used to predict the complex phenomenon such as hearing loss. Using artificial neural networks, this study aims to present an empirical model for the prediction of the hearing loss threshold among noise-exposed workers. Two hundred and ten workers employed in a steel factory were chosen, and their occupational exposure histories were collected. To determine the hearing loss threshold, the audiometric test was carried out using a calibrated audiometer. The personal noise exposure was also measured using a noise dosimeter in the workstations of workers. Finally, data obtained five variables, which can influence the hearing loss, were used for the development of the prediction model. Multilayer feed-forward neural networks with different structures were developed using MATLAB software. Neural network structures had one hidden layer with the number of neurons being approximately between 5 and 15 neurons. The best developed neural networks with one hidden layer and ten neurons could accurately predict the hearing loss threshold with RMSE = 2.6 dB and R(2) = 0.89. The results also confirmed that neural networks could provide more accurate predictions than multiple regressions. Since occupational hearing loss is frequently non-curable, results of accurate prediction can be used by occupational health experts to modify and improve noise exposure conditions.

Predicting compliance with an information-based residential outdoor water conservation program

NASA Astrophysics Data System (ADS)

Landon, Adam C.; Kyle, Gerard T.; Kaiser, Ronald A.

2016-05-01

Residential water conservation initiatives often involve some form of education or persuasion intended to change the attitudes and behaviors of residential consumers. However, the ability of these instruments to change attitudes toward conservation and their efficacy in affecting water use remains poorly understood. In this investigation the authors examine consumer attitudes toward complying with a persuasive water conservation program, the extent to which those attitudes predict compliance, and the influence of environmental contextual factors on outdoor water use. Results indicate that the persuasive program was successful in developing positive attitudes toward compliance, and that those attitudes predict water use. However, attitudinal variables explain a relatively small proportion of the variance in objectively measured water use behavior. Recommendations for policy are made stressing the importance of understanding both the effects of attitudes and environmental contextual factors in behavior change initiatives in the municipal water sector.

The bankfull hydraulic geometry of evolving meander bends

NASA Astrophysics Data System (ADS)

Monegaglia, F.; Tubino, M.; Zolezzi, G.

2017-12-01

Changes in the bankfull hydraulic geometry of meandering rivers associated with meander growth from incipient meandering to cutoffs have seldom been analysed in detail. Such information is also needed by meander morphodynamic models, most of which simulate the evolution of bankfull channel geometry by simply accounting for channel slope reduction inversely proportional to elongation, while changes in bankfull channel width are often neglected or, when they are considered, they are not consistent with the few available observations. To address these gaps we first perform an extensive, systematic, bend-scale evolutionary analysis of bankfull channel widths in several large meandering rivers in the Amazon basin, over a three decades time period, from remotely sensed field data. The analysis consistently show a slight decreasing trend of the bankfull channel width during the planform evolution towards cutoff. Furthermore, we develop a physically based model for the evolution of bankfull channel geometry during the planform development of meandering rivers. The model is based on the conservation of sediment discharge. An integrated one-dimensional Exner equation that accounts for meander elongation, sediment supply conservation and sediment income from the channel banks, allows us to predict the evolution of the channel slope. The evolution of the channel width is modeled through a threshold equation. The model correctly predicts the slight variability of channel width during meander development and a gentler reduction of the channel slope, which is mitigated by the conservation of sediment supply. The bankfull geometry of highly dynamic meandering rivers is predicted to be elongation-dominated, while the one related to slowly evolving meandering rivers is sediment supply-dominated. Finally, we discuss the implications of the proposed modeling framework in terms of planform structure, meander shape and morphodynamic influence.

El Grupo Cerúleo: collaboration to assess nonbreeding range of cerulean warbler in South America

USGS Publications Warehouse

Colorado, G.; Hamel, P.; Rodewald, A.; Thogmartin, W.

2008-01-01

Cerulean Warbler (Dendroica cerulea. Parulidae) has been listed as a vulnerable species by the International Union for the Conservation of Nature because of recent population declines. An international, proactive approach to Cerulean Warbler conservation, the Cerulean Warbler Technical Group, was founded in 2001. One of its subcommittees, El Grupo Cerúleo, addresses nonbreeding season issues to promote the protection of this bird through habitat conservation, field research on Cerulean Warbler winter ecology, public awareness, and the development of a predictive model to allow for assessment and monitoring of Cerulean Warbler. Most of the recent efforts of this group have been devoted to studying and understanding the spatial distribution of the Cerulean Warbler in South America through predictive models as a highly necessary strategy to elucidating the bird's occurrence, and thereby to identify and locate important nonbreeding habitats and areas of concentration in the Neotropics. To address this issue, members of EI Grupo Cerúleo developed five hypothetical models of potential distribution of the bird in the northern Andes based on existing historical records and surveys conducted by EI Grupo members. In order to validate the model output, we selected locations to verify the occurrence of the species, based on a stratified-random design, using locations where the Cerulean Warbler was predicted to occur by all five models. We elaborated field protocols to survey these locations. Resulting data will be structured for analysis using the techniques of occupancy modeling. Basic survey designs to carry out the fieldwork as well as preliminary results of the first year's fieldwork are presented. - See more at: http://www.srs.fs.usda.gov/pubs/31535#sthash.Lt3G7a8H.dpuf

A proposed architecture for lecithin cholesterol acyl transferase (LCAT): identification of the catalytic triad and molecular modeling.

PubMed Central

Peelman, F.; Vinaimont, N.; Verhee, A.; Vanloo, B.; Verschelde, J. L.; Labeur, C.; Seguret-Mace, S.; Duverger, N.; Hutchinson, G.; Vandekerckhove, J.; Tavernier, J.; Rosseneu, M.

1998-01-01

The enzyme cholesterol lecithin acyl transferase (LCAT) shares the Ser/Asp-Glu/His triad with lipases, esterases and proteases, but the low level of sequence homology between LCAT and these enzymes did not allow for the LCAT fold to be identified yet. We, therefore, relied upon structural homology calculations using threading methods based on alignment of the sequence against a library of solved three-dimensional protein structures, for prediction of the LCAT fold. We propose that LCAT, like lipases, belongs to the alpha/beta hydrolase fold family, and that the central domain of LCAT consists of seven conserved parallel beta-strands connected by four alpha-helices and separated by loops. We used the conserved features of this protein fold for the prediction of functional domains in LCAT, and carried out site-directed mutagenesis for the localization of the active site residues. The wild-type enzyme and mutants were expressed in Cos-1 cells. LCAT mass was measured by ELISA, and enzymatic activity was measured on recombinant HDL, on LDL and on a monomeric substrate. We identified D345 and H377 as the catalytic residues of LCAT, together with F103 and L182 as the oxyanion hole residues. In analogy with lipases, we further propose that a potential "lid" domain at residues 50-74 of LCAT might be involved in the enzyme-substrate interaction. Molecular modeling of human LCAT was carried out using human pancreatic and Candida antarctica lipases as templates. The three-dimensional model proposed here is compatible with the position of natural mutants for either LCAT deficiency or Fish-eye disease. It enables moreover prediction of the LCAT domains involved in the interaction with the phospholipid and cholesterol substrates. PMID:9541390

Plastoglobules in algae: A comprehensive comparative study of the presence of major structural and functional components in complex plastids.

PubMed

Lohscheider, Jens N; Río Bártulos, Carolina

2016-08-01

Plastoglobules (PG) are lipophilic droplets attached to thylakoid membranes in higher plants and green algae and are implicated in prenyl lipid biosynthesis. They might also represent a central hub for integration of plastid signals under stress and therefore the adaptation of the thylakoid membrane under such conditions. In Arabidopsis thaliana, PG contain around 30 specific proteins of which Fibrillins (FBN) and Activity of bc1 complex kinases (ABC1K) represent the majority with respect to both number and protein mass. However, nothing is known about the presence of PG in most algal species, which are responsible for about 50% of global primary production. Therefore, we searched the genomes of publicly available algal genomes for components of PG and the associated functional network in order to predict their presence and potential evolutionary conservation of physiological functions. We could identify homologous sequences for core components of PG, like FBN and ABC1K, in most investigated algal species. Furthermore, proteins at central and interesting positions within the PG functional coexpression network were identified. Phylogenetic sequence analysis revealed diversity within FBN and ABC1K sequences among algal species with complex plastids of the red lineage and large differences compared with green lineage species. Two types of FBN were detected that differ in their isoelectric point which seems to correlate with subcellular localization. Subgroups of FBN were shared between many investigated species and modeling of their 3D-structure implied a conserved structure. FBN and ABC1K are essential structural and functional components of PG. Their occurrence in investigated algal species suggests presence of PG therein and functions in prenyl lipid metabolism and adaptation of the thylakoid membrane that are conserved during evolution. Copyright © 2016 Elsevier B.V. All rights reserved.

Genome-wide identification of galactinol synthase (GolS) genes in Solanum lycopersicum and Brachypodium distachyon.

PubMed

Filiz, Ertugrul; Ozyigit, Ibrahim Ilker; Vatansever, Recep

2015-10-01

GolS genes stand as potential candidate genes for molecular breeding and/or engineering programs in order for improving abiotic stress tolerance in plant species. In this study, a total of six galactinol synthase (GolS) genes/proteins were retrieved for Solanum lycopersicum and Brachypodium distachyon. GolS protein sequences were identified to include glyco_transf_8 (PF01501) domain structure, and to have a close molecular weight (36.40-39.59kDa) and amino acid length (318-347 aa) with a slightly acidic pI (5.35-6.40). The sub-cellular location was mainly predicted as cytoplasmic. S. lycopersicum genes located on chr 1 and 2, and included one segmental duplication while genes of B. distachyon were only on chr 1 with one tandem duplication. GolS sequences were found to have well conserved motif structures. Cis-acting analysis was performed for three abiotic stress responsive elements, including ABA responsive element (ABRE), dehydration and cold responsive elements (DRE/CRT) and low-temperature responsive element (LTRE). ABRE elements were found in all GolS genes, except for SlGolS4; DRE/CRT was not detected in any GolS genes and LTRE element found in SlGolS1 and BdGolS1 genes. AU analysis in UTR and ORF regions indicated that SlGolS and BdGolS mRNAs may have a short half-life. SlGolS3 and SlGolS4 genes may generate more stable transcripts since they included AATTAAA motif for polyadenylation signal POLASIG2. Seconder structures of SlGolS proteins were well conserved than that of BdGolS. Some structural divergences were detected in 3D structures and predicted binding sites exhibited various patterns in GolS proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

The biological roots of political extremism.

PubMed

Keene, Justin Robert; Shoenberger, Heather; Berke, Collin K; Bolls, Paul D

2017-01-01

Recent research has revealed the complex origins of political identification and the possible effects of this identification on social and political behavior. This article reports the results of a structural equation analysis of national survey data that attempts to replicate the finding that an individual's negativity bias predicts conservative ideology. The analysis employs the Motivational Activation Measure (MAM) as an index of an individual's positivity offset and negativity bias. In addition, information-seeking behavior is assessed in relation to traditional and interactive media sources of political information. Results show that although MAM does not consistently predict political identification, it can be used to predict extremeness of political views. Specifically, high negativity bias was associated with extreme conservatism, whereas low negativity bias was associated with extreme liberalism. In addition, political identification was found to moderate the relationship between motivational traits and information-seeking behavior.

Fine-tuning structural RNA alignments in the twilight zone

PubMed Central

2010-01-01

Background A widely used method to find conserved secondary structure in RNA is to first construct a multiple sequence alignment, and then fold the alignment, optimizing a score based on thermodynamics and covariance. This method works best around 75% sequence similarity. However, in a "twilight zone" below 55% similarity, the sequence alignment tends to obscure the covariance signal used in the second phase. Therefore, while the overall shape of the consensus structure may still be found, the degree of conservation cannot be estimated reliably. Results Based on a combination of available methods, we present a method named planACstar for improving structure conservation in structural alignments in the twilight zone. After constructing a consensus structure by alignment folding, planACstar abandons the original sequence alignment, refolds the sequences individually, but consistent with the consensus, aligns the structures, irrespective of sequence, by a pure structure alignment method, and derives an improved sequence alignment from the alignment of structures, to be re-submitted to alignment folding, etc.. This circle may be iterated as long as structural conservation improves, but normally, one step suffices. Conclusions Employing the tools ClustalW, RNAalifold, and RNAforester, we find that for sequences with 30-55% sequence identity, structural conservation can be improved by 10% on average, with a large variation, measured in terms of RNAalifold's own criterion, the structure conservation index. PMID:20433706

Bridging the Gap Between Global and Local Strategies of Architectural Conservation, Examples of the Current Scenarios in India

NASA Astrophysics Data System (ADS)

Kavuru, M.

2017-05-01

Culture develops from a civilization and progresses through the generations in tangible and intangible forms affecting various aspects of living. It gradually becomes a rulebook that guides the way of life for some people. This holds true in the Indian Society, which is punctuated by constant incorporation of migrating people with the diverse cultures that surround India. Such illustrious past should predict augmented conservation efforts. However, that is not the case. Following the Hindu philosophy of the life cycle, buildings are allowed to be deteriorating over the passage of time. It was only much later that the occidental influence of the British Empire encouraged conservation of built heritage. Yet today these efforts are absent at the most basic levels. On one side are the international organizations such as UNESCO providing guidelines for protection of these buildings and the on the other side are the government and non-government organizations which help maintain the structures. Co-relation between the two levels of conservation are non-existent in a way that initiatives by the government focus on improving infrastructure but neglect the Risk-assessment of the buildings. Such examples will be discussed further in the paper with suggestions to improve the situation with the help of new technologies and simplified methods that include making conservation education easier for even the most rural population. The research explores avenues of diagnosis integrated in the Italian philosophy of conservation to make maintenance more easy and effective.

Model-based conservation planning of the genetic diversity of Phellodendron amurense Rupr due to climate change

PubMed Central

Wan, Jizhong; Wang, Chunjing; Yu, Jinghua; Nie, Siming; Han, Shijie; Zu, Yuangang; Chen, Changmei; Yuan, Shusheng; Wang, Qinggui

2014-01-01

Climate change affects both habitat suitability and the genetic diversity of wild plants. Therefore, predicting and establishing the most effective and coherent conservation areas is essential for the conservation of genetic diversity in response to climate change. This is because genetic variance is a product not only of habitat suitability in conservation areas but also of efficient protection and management. Phellodendron amurense Rupr. is a tree species (family Rutaceae) that is endangered due to excessive and illegal harvesting for use in Chinese medicine. Here, we test a general computational method for the prediction of priority conservation areas (PCAs) by measuring the genetic diversity of P. amurense across the entirety of northeast China using a single strand repeat analysis of twenty microsatellite markers. Using computational modeling, we evaluated the geographical distribution of the species, both now and in different future climate change scenarios. Different populations were analyzed according to genetic diversity, and PCAs were identified using a spatial conservation prioritization framework. These conservation areas were optimized to account for the geographical distribution of P. amurense both now and in the future, to effectively promote gene flow, and to have a long period of validity. In situ and ex situ conservation, strategies for vulnerable populations were proposed. Three populations with low genetic diversity are predicted to be negatively affected by climate change, making conservation of genetic diversity challenging due to decreasing habitat suitability. Habitat suitability was important for the assessment of genetic variability in existing nature reserves, which were found to be much smaller than the proposed PCAs. Finally, a simple set of conservation measures was established through modeling. This combined molecular and computational ecology approach provides a framework for planning the protection of species endangered by climate change. PMID:25165526

Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites.

PubMed

Betel, Doron; Koppal, Anjali; Agius, Phaedra; Sander, Chris; Leslie, Christina

2010-01-01

mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation, miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally determined non-canonical and non-conserved sites.

RNA 3D Structural Motifs: Definition, Identification, Annotation, and Database Searching

NASA Astrophysics Data System (ADS)

Nasalean, Lorena; Stombaugh, Jesse; Zirbel, Craig L.; Leontis, Neocles B.

Structured RNA molecules resemble proteins in the hierarchical organization of their global structures, folding and broad range of functions. Structured RNAs are composed of recurrent modular motifs that play specific functional roles. Some motifs direct the folding of the RNA or stabilize the folded structure through tertiary interactions. Others bind ligands or proteins or catalyze chemical reactions. Therefore, it is desirable, starting from the RNA sequence, to be able to predict the locations of recurrent motifs in RNA molecules. Conversely, the potential occurrence of one or more known 3D RNA motifs may indicate that a genomic sequence codes for a structured RNA molecule. To identify known RNA structural motifs in new RNA sequences, precise structure-based definitions are needed that specify the core nucleotides of each motif and their conserved interactions. By comparing instances of each recurrent motif and applying base pair isosteriCity relations, one can identify neutral mutations that preserve its structure and function in the contexts in which it occurs.

Functional evolution and structural conservation in chimeric cytochromes p450: calibrating a structure-guided approach.

PubMed

Otey, Christopher R; Silberg, Jonathan J; Voigt, Christopher A; Endelman, Jeffrey B; Bandara, Geethani; Arnold, Frances H

2004-03-01

Recombination generates chimeric proteins whose ability to fold depends on minimizing structural perturbations that result when portions of the sequence are inherited from different parents. These chimeric sequences can display functional properties characteristic of the parents or acquire entirely new functions. Seventeen chimeras were generated from two CYP102 members of the functionally diverse cytochrome p450 family. Chimeras predicted to have limited structural disruption, as defined by the SCHEMA algorithm, displayed CO binding spectra characteristic of folded p450s. Even this small population exhibited significant functional diversity: chimeras displayed altered substrate specificities, a wide range in thermostabilities, up to a 40-fold increase in peroxidase activity, and ability to hydroxylate a substrate toward which neither parent heme domain shows detectable activity. These results suggest that SCHEMA-guided recombination can be used to generate diverse p450s for exploring function evolution within the p450 structural framework.

Social traditionalism and economic conservatism: two conservative political ideologies in the United States.

PubMed

Johnson, S D; Tamney, J B

2001-04-01

The authors surveyed by telephone a random sample of voters in the 1996 presidential election from the Standard Metropolitan Statistical Area of Muncie, IN ("Middletown"; R. Lynd & H. Lynd, 1929) to test a model describing the nature of 2 conservative political ideologies--social traditionalism and economic conservatism. The model, based on functions of attitudes theory, predicted (a) that the 2 political ideologies would appeal to 2 rather distinct constituency groups--the former, to conservative Protestants; the latter, to people of higher incomes--and (b) that social traditionalists would be more dogmatic and economic conservatives would be more open-minded in their respective views. The findings were consistent with those predictions.

PACCMIT/PACCMIT-CDS: identifying microRNA targets in 3' UTRs and coding sequences.

PubMed

Šulc, Miroslav; Marín, Ray M; Robins, Harlan S; Vaníček, Jiří

2015-07-01

The purpose of the proposed web server, publicly available at http://paccmit.epfl.ch, is to provide a user-friendly interface to two algorithms for predicting messenger RNA (mRNA) molecules regulated by microRNAs: (i) PACCMIT (Prediction of ACcessible and/or Conserved MIcroRNA Targets), which identifies primarily mRNA transcripts targeted in their 3' untranslated regions (3' UTRs), and (ii) PACCMIT-CDS, designed to find mRNAs targeted within their coding sequences (CDSs). While PACCMIT belongs among the accurate algorithms for predicting conserved microRNA targets in the 3' UTRs, the main contribution of the web server is 2-fold: PACCMIT provides an accurate tool for predicting targets also of weakly conserved or non-conserved microRNAs, whereas PACCMIT-CDS addresses the lack of similar portals adapted specifically for targets in CDS. The web server asks the user for microRNAs and mRNAs to be analyzed, accesses the precomputed P-values for all microRNA-mRNA pairs from a database for all mRNAs and microRNAs in a given species, ranks the predicted microRNA-mRNA pairs, evaluates their significance according to the false discovery rate and finally displays the predictions in a tabular form. The results are also available for download in several standard formats. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Comprehensive inventory of protein complexes in the Protein Data Bank from consistent classification of interfaces

DOE PAGES

Bordner, Andrew J.; Gorin, Andrey A.

2008-05-12

Here, protein-protein interactions are ubiquitous and essential for cellular processes. High-resolution X-ray crystallographic structures of protein complexes can elucidate the details of their function and provide a basis for many computational and experimental approaches. Here we demonstrate that existing annotations of protein complexes, including those provided by the Protein Data Bank (PDB) itself, contain a significant fraction of incorrect annotations. Results: We have developed a method for identifying protein complexes in the PDB X-ray structures by a four step procedure: (1) comprehensively collecting all protein-protein interfaces; (2) clustering similar protein-protein interfaces together; (3) estimating the probability that each cluster ismore » relevant based on a diverse set of properties; and (4) finally combining these scores for each entry in order to predict the complex structure. Unlike previous annotation methods, consistent prediction of complexes with identical or almost identical protein content is insured. The resulting clusters of biologically relevant interfaces provide a reliable catalog of evolutionary conserved protein-protein interactions.« less

Dynamic Structure Factor and Transport Coefficients of a Homogeneously Driven Granular Fluid in Steady State

NASA Astrophysics Data System (ADS)

Vollmayr-Lee, Katharina; Zippelius, Annette; Aspelmeier, Timo

2011-03-01

We study the dynamic structure factor of a granular fluid of hard spheres, driven into a stationary nonequilibrium state by balancing the energy loss due to inelastic collisions with the energy input due to driving. The driving is chosen to conserve momentum, so that fluctuating hydrodynamics predicts the existence of sound modes. We present results of computer simulations which are based on an event driven algorithm. The dynamic structure factor F (q , ω) is determined for volume fractions 0.05, 0.1 and 0.2 and coefficients of normal restitution 0.8 and 0.9. We observe sound waves, and compare our results for F (q , ω) with the predictions of generalized fluctuating hydrodynamics which takes into account that temperature fluctuations decay either diffusively or with a finite relaxation rate, depending on wave number and inelasticity. We determine the speed of sound and the transport coefficients and compare them to the results of kinetic theory. K.V.L. thanks the Institute of Theoretical Physics, University of Goettingen, for financial support and hospitality.

Weak coordination between leaf structure and function among closely related tomato species.

PubMed

Muir, Christopher D; Conesa, Miquel À; Roldán, Emilio J; Molins, Arántzazu; Galmés, Jeroni

2017-03-01

Theory predicts that natural selection should favor coordination between leaf physiology, biochemistry and anatomical structure along a functional trait spectrum from fast, resource-acquisitive syndromes to slow, resource-conservative syndromes. However, the coordination hypothesis has rarely been tested at a phylogenetic scale most relevant for understanding rapid adaptation in the recent past or for the prediction of evolutionary trajectories in response to climate change. We used a common garden to examine genetically based coordination between leaf traits across 19 wild and cultivated tomato taxa. We found weak integration between leaf structure (e.g. leaf mass per area) and physiological function (photosynthetic rate, biochemical capacity and CO 2 diffusion), even though all were arrayed in the predicted direction along a 'fast-slow' spectrum. This suggests considerable scope for unique trait combinations to evolve in response to new environments or in crop breeding. In particular, we found that partially independent variation in stomatal and mesophyll conductance may allow a plant to improve water-use efficiency without necessarily sacrificing maximum photosynthetic rates. Our study does not imply that functional trait spectra, such as the leaf economics spectrum, are unimportant, but that many important axes of variation within a taxonomic group may be unique and not generalizable to other taxa. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Unintended consequences of conservation actions: managing disease in complex ecosystems.

PubMed

Chauvenet, Aliénor L M; Durant, Sarah M; Hilborn, Ray; Pettorelli, Nathalie

2011-01-01

Infectious diseases are increasingly recognised to be a major threat to biodiversity. Disease management tools such as control of animal movements and vaccination can be used to mitigate the impact and spread of diseases in targeted species. They can reduce the risk of epidemics and in turn the risks of population decline and extinction. However, all species are embedded in communities and interactions between species can be complex, hence increasing the chance of survival of one species can have repercussions on the whole community structure. In this study, we use an example from the Serengeti ecosystem in Tanzania to explore how a vaccination campaign against Canine Distemper Virus (CDV) targeted at conserving the African lion (Panthera leo), could affect the viability of a coexisting threatened species, the cheetah (Acinonyx jubatus). Assuming that CDV plays a role in lion regulation, our results suggest that a vaccination programme, if successful, risks destabilising the simple two-species system considered, as simulations show that vaccination interventions could almost double the probability of extinction of an isolated cheetah population over the next 60 years. This work uses a simple example to illustrate how predictive modelling can be a useful tool in examining the consequence of vaccination interventions on non-target species. It also highlights the importance of carefully considering linkages between human-intervention, species viability and community structure when planning species-based conservation actions.

Unintended Consequences of Conservation Actions: Managing Disease in Complex Ecosystems

PubMed Central

Chauvenet, Aliénor L. M.; Durant, Sarah M.; Hilborn, Ray; Pettorelli, Nathalie

2011-01-01

Infectious diseases are increasingly recognised to be a major threat to biodiversity. Disease management tools such as control of animal movements and vaccination can be used to mitigate the impact and spread of diseases in targeted species. They can reduce the risk of epidemics and in turn the risks of population decline and extinction. However, all species are embedded in communities and interactions between species can be complex, hence increasing the chance of survival of one species can have repercussions on the whole community structure. In this study, we use an example from the Serengeti ecosystem in Tanzania to explore how a vaccination campaign against Canine Distemper Virus (CDV) targeted at conserving the African lion (Panthera leo), could affect the viability of a coexisting threatened species, the cheetah (Acinonyx jubatus). Assuming that CDV plays a role in lion regulation, our results suggest that a vaccination programme, if successful, risks destabilising the simple two-species system considered, as simulations show that vaccination interventions could almost double the probability of extinction of an isolated cheetah population over the next 60 years. This work uses a simple example to illustrate how predictive modelling can be a useful tool in examining the consequence of vaccination interventions on non-target species. It also highlights the importance of carefully considering linkages between human-intervention, species viability and community structure when planning species-based conservation actions. PMID:22163323

Evolutionary origins of hepatitis A virus in small mammals.

PubMed

Drexler, Jan Felix; Corman, Victor M; Lukashev, Alexander N; van den Brand, Judith M A; Gmyl, Anatoly P; Brünink, Sebastian; Rasche, Andrea; Seggewiβ, Nicole; Feng, Hui; Leijten, Lonneke M; Vallo, Peter; Kuiken, Thijs; Dotzauer, Andreas; Ulrich, Rainer G; Lemon, Stanley M; Drosten, Christian

2015-12-08

Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3D(pol) sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses.

Evolutionary origins of hepatitis A virus in small mammals

PubMed Central

Drexler, Jan Felix; Corman, Victor M.; Lukashev, Alexander N.; van den Brand, Judith M. A.; Gmyl, Anatoly P.; Brünink, Sebastian; Rasche, Andrea; Seggewiβ, Nicole; Feng, Hui; Leijten, Lonneke M.; Vallo, Peter; Kuiken, Thijs; Dotzauer, Andreas; Ulrich, Rainer G.; Lemon, Stanley M.; Drosten, Christian

2015-01-01

Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3Dpol sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses. PMID:26575627

Protein-Protein Interactions in Clathrin Vesicular Assembly: Radial Distribution of Evolutionary Constraints in Interfaces

PubMed Central

Gadkari, Rupali A.; Srinivasan, Narayanaswamy

2012-01-01

In eukaryotic organisms clathrin-coated vesicles are instrumental in the processes of endocytosis as well as intracellular protein trafficking. Hence, it is important to understand how these vesicles have evolved across eukaryotes, to carry cargo molecules of varied shapes and sizes. The intricate nature and functional diversity of the vesicles are maintained by numerous interacting protein partners of the vesicle system. However, to delineate functionally important residues participating in protein-protein interactions of the assembly is a daunting task as there are no high-resolution structures of the intact assembly available. The two cryoEM structures closely representing intact assembly were determined at very low resolution and provide positions of Cα atoms alone. In the present study, using the method developed by us earlier, we predict the protein-protein interface residues in clathrin assembly, taking guidance from the available low-resolution structures. The conservation status of these interfaces when investigated across eukaryotes, revealed a radial distribution of evolutionary constraints, i.e., if the members of the clathrin vesicular assembly can be imagined to be arranged in spherical manner, the cargo being at the center and clathrins being at the periphery, the detailed phylogenetic analysis of these members of the assembly indicated high-residue variation in the members of the assembly closer to the cargo while high conservation was noted in clathrins and in other proteins at the periphery of the vesicle. This points to the strategy adopted by the nature to package diverse proteins but transport them through a highly conserved mechanism. PMID:22384024

Unusual features of fibrillarin cDNA and gene structure in Euglena gracilis: evolutionary conservation of core proteins and structural predictions for methylation-guide box C/D snoRNPs throughout the domain Eucarya.

PubMed

Russell, Anthony G; Watanabe, Yoh-ichi; Charette, J Michael; Gray, Michael W

2005-01-01

Box C/D ribonucleoprotein (RNP) particles mediate O2'-methylation of rRNA and other cellular RNA species. In higher eukaryotic taxa, these RNPs are more complex than their archaeal counterparts, containing four core protein components (Snu13p, Nop56p, Nop58p and fibrillarin) compared with three in Archaea. This increase in complexity raises questions about the evolutionary emergence of the eukaryote-specific proteins and structural conservation in these RNPs throughout the eukaryotic domain. In protists, the primarily unicellular organisms comprising the bulk of eukaryotic diversity, the protein composition of box C/D RNPs has not yet been extensively explored. This study describes the complete gene, cDNA and protein sequences of the fibrillarin homolog from the protozoon Euglena gracilis, the first such information to be obtained for a nucleolus-localized protein in this organism. The E.gracilis fibrillarin gene contains a mixture of intron types exhibiting markedly different sizes. In contrast to most other E.gracilis mRNAs characterized to date, the fibrillarin mRNA lacks a spliced leader (SL) sequence. The predicted fibrillarin protein sequence itself is unusual in that it contains a glycine-lysine (GK)-rich domain at its N-terminus rather than the glycine-arginine-rich (GAR) domain found in most other eukaryotic fibrillarins. In an evolutionarily diverse collection of protists that includes E.gracilis, we have also identified putative homologs of the other core protein components of box C/D RNPs, thereby providing evidence that the protein composition seen in the higher eukaryotic complexes was established very early in eukaryotic cell evolution.

JABAWS 2.2 distributed web services for Bioinformatics: protein disorder, conservation and RNA secondary structure.

PubMed

Troshin, Peter V; Procter, James B; Sherstnev, Alexander; Barton, Daniel L; Madeira, Fábio; Barton, Geoffrey J

2018-06-01

JABAWS 2.2 is a computational framework that simplifies the deployment of web services for Bioinformatics. In addition to the five multiple sequence alignment (MSA) algorithms in JABAWS 1.0, JABAWS 2.2 includes three additional MSA programs (Clustal Omega, MSAprobs, GLprobs), four protein disorder prediction methods (DisEMBL, IUPred, Ronn, GlobPlot), 18 measures of protein conservation as implemented in AACon, and RNA secondary structure prediction by the RNAalifold program. JABAWS 2.2 can be deployed on a variety of in-house or hosted systems. JABAWS 2.2 web services may be accessed from the Jalview multiple sequence analysis workbench (Version 2.8 and later), as well as directly via the JABAWS command line interface (CLI) client. JABAWS 2.2 can be deployed on a local virtual server as a Virtual Appliance (VA) or simply as a Web Application Archive (WAR) for private use. Improvements in JABAWS 2.2 also include simplified installation and a range of utility tools for usage statistics collection, and web services querying and monitoring. The JABAWS CLI client has been updated to support all the new services and allow integration of JABAWS 2.2 services into conventional scripts. A public JABAWS 2 server has been in production since December 2011 and served over 800 000 analyses for users worldwide. JABAWS 2.2 is made freely available under the Apache 2 license and can be obtained from: http://www.compbio.dundee.ac.uk/jabaws. g.j.barton@dundee.ac.uk.

Quasi-Static Probabilistic Structural Analyses Process and Criteria

NASA Technical Reports Server (NTRS)

Goldberg, B.; Verderaime, V.

1999-01-01

Current deterministic structural methods are easily applied to substructures and components, and analysts have built great design insights and confidence in them over the years. However, deterministic methods cannot support systems risk analyses, and it was recently reported that deterministic treatment of statistical data is inconsistent with error propagation laws that can result in unevenly conservative structural predictions. Assuming non-nal distributions and using statistical data formats throughout prevailing stress deterministic processes lead to a safety factor in statistical format, which integrated into the safety index, provides a safety factor and first order reliability relationship. The embedded safety factor in the safety index expression allows a historically based risk to be determined and verified over a variety of quasi-static metallic substructures consistent with the traditional safety factor methods and NASA Std. 5001 criteria.

New generation of elastic network models.

PubMed

López-Blanco, José Ramón; Chacón, Pablo

2016-04-01

The intrinsic flexibility of proteins and nucleic acids can be grasped from remarkably simple mechanical models of particles connected by springs. In recent decades, Elastic Network Models (ENMs) combined with Normal Model Analysis widely confirmed their ability to predict biologically relevant motions of biomolecules and soon became a popular methodology to reveal large-scale dynamics in multiple structural biology scenarios. The simplicity, robustness, low computational cost, and relatively high accuracy are the reasons behind the success of ENMs. This review focuses on recent advances in the development and application of ENMs, paying particular attention to combinations with experimental data. Successful application scenarios include large macromolecular machines, structural refinement, docking, and evolutionary conservation. Copyright © 2015 Elsevier Ltd. All rights reserved.

CoSMoS: Conserved Sequence Motif Search in the proteome

PubMed Central

Liu, Xiao I; Korde, Neeraj; Jakob, Ursula; Leichert, Lars I

2006-01-01

Background With the ever-increasing number of gene sequences in the public databases, generating and analyzing multiple sequence alignments becomes increasingly time consuming. Nevertheless it is a task performed on a regular basis by researchers in many labs. Results We have now created a database called CoSMoS to find the occurrences and at the same time evaluate the significance of sequence motifs and amino acids encoded in the whole genome of the model organism Escherichia coli K12. We provide a precomputed set of multiple sequence alignments for each individual E. coli protein with all of its homologues in the RefSeq database. The alignments themselves, information about the occurrence of sequence motifs together with information on the conservation of each of the more than 1.3 million amino acids encoded in the E. coli genome can be accessed via the web interface of CoSMoS. Conclusion CoSMoS is a valuable tool to identify highly conserved sequence motifs, to find regions suitable for mutational studies in functional analyses and to predict important structural features in E. coli proteins. PMID:16433915

A novel PTCH1 mutation underlies non-syndromic cleft lip and/or palate in a Han Chinese family.

PubMed

Zhao, Huaxiang; Zhong, Wenjie; Leng, Chuntao; Zhang, Jieni; Zhang, Mengqi; Huang, Wenbin; Zhang, Yunfan; Li, Weiran; Jia, Peizeng; Lin, Jiuxiang; Maimaitili, Gulibaha; Chen, Feng

2018-06-16

Cleft lip and/or palate (CL/P) is the most common craniofacial congenital disease, and it has a complex aetiology. This study aimed to identify the causative gene mutation of a Han Chinese family with CL/P. Whole exome sequencing was conducted on the proband and her mother, who exhibited the same phenotype. A Mendelian dominant inheritance model, allele frequency, mutation regions, functional prediction and literature review were used to screen and filter the variants. The candidate was validated by Sanger sequencing. Conservation analysis and homology modelling were conducted. A heterozygous missense mutation c.1175C>T in the PTCH1 gene predicting p.Ala392Val was identified. This variant has not been reported and was predicted to be deleterious. Sanger sequencing verified the variant and the dominant inheritance model in the family. The missense alteration affects an amino acid that is evolutionarily conserved in the first extracellular loop of the PTCH1 protein. The local structure of the mutant protein was significantly altered according to homology modelling. Our findings suggest that c.1175C>T in PTCH1 (NM_000264) may be the causative mutation of this pedigree. Our results add to the evidence that PTCH1 variants play a role in the pathogenesis of orofacial clefts. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

In Silico Prediction and Validation of Novel RNA Binding Proteins and Residues in the Human Proteome.

PubMed

Chowdhury, Shomeek; Zhang, Jian; Kurgan, Lukasz

2018-05-28

Deciphering a complete landscape of protein-RNA interactions in the human proteome remains an elusive challenge. We computationally elucidate RNA binding proteins (RBPs) using an approach that complements previous efforts. We employ two modern complementary sequence-based methods that provide accurate predictions from the structured and the intrinsically disordered sequences, even in the absence of sequence similarity to the known RBPs. We generate and analyze putative RNA binding residues on the whole proteome scale. Using a conservative setting that ensures low, 5% false positive rate, we identify 1511 putative RBPs that include 281 known RBPs and 166 RBPs that were previously predicted. We empirically demonstrate that these overlaps are statistically significant. We also validate the putative RBPs based on two major hallmarks of their RNA binding residues: high levels of evolutionary conservation and enrichment in charged amino acids. Moreover, we show that the novel RBPs are significantly under-annotated functionally which coincides with the fact that they were not yet found to interact with RNAs. We provide two examples of our novel putative RBPs for which there is recent evidence of their interactions with RNAs. The dataset of novel putative RBPs and RNA binding residues for the future hypothesis generation is provided in the Supporting Information. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Habitat continuity and stepping-stone oceanographic distances explain population genetic connectivity of the brown alga Cystoseira amentacea.

PubMed

Buonomo, Roberto; Assis, Jorge; Fernandes, Francisco; Engelen, Aschwin H; Airoldi, Laura; Serrão, Ester A

2017-02-01

Effective predictive and management approaches for species occurring in a metapopulation structure require good understanding of interpopulation connectivity. In this study, we ask whether population genetic structure of marine species with fragmented distributions can be predicted by stepping-stone oceanographic transport and habitat continuity, using as model an ecosystem-structuring brown alga, Cystoseira amentacea var. stricta. To answer this question, we analysed the genetic structure and estimated the connectivity of populations along discontinuous rocky habitat patches in southern Italy, using microsatellite markers at multiple scales. In addition, we modelled the effect of rocky habitat continuity and ocean circulation on gene flow by simulating Lagrangian particle dispersal based on ocean surface currents allowing multigenerational stepping-stone dynamics. Populations were highly differentiated, at scales from few metres up to thousands of kilometres. The best possible model fit to explain the genetic results combined current direction, rocky habitat extension and distance along the coast among rocky sites. We conclude that a combination of variable suitable habitat and oceanographic transport is a useful predictor of genetic structure. This relationship provides insight into the mechanisms of dispersal and the role of life-history traits. Our results highlight the importance of spatially explicit modelling of stepping-stone dynamics and oceanographic directional transport coupled with habitat suitability, to better describe and predict marine population structure and differentiation. This study also suggests the appropriate spatial scales for the conservation, restoration and management of species that are increasingly affected by habitat modifications. © 2016 John Wiley & Sons Ltd.

Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas

PubMed Central

Petrov, Anton I.; Zirbel, Craig L.; Leontis, Neocles B.

2013-01-01

The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals that many internal and hairpin loops are modular, recurrent, and structured by conserved non-Watson–Crick base pairs. Structurally similar loops define RNA 3D motifs that are conserved in homologous RNA molecules, but can also occur at nonhomologous sites in diverse RNAs, and which often vary in sequence. To further our understanding of RNA motif structure and sequence variability and to provide a useful resource for structure modeling and prediction, we present a new method for automated classification of internal and hairpin loop RNA 3D motifs and a new online database called the RNA 3D Motif Atlas. To classify the motif instances, a representative set of internal and hairpin loops is automatically extracted from a nonredundant list of RNA-containing PDB files. Their structures are compared geometrically, all-against-all, using the FR3D program suite. The loops are clustered into motif groups, taking into account geometric similarity and structural annotations and making allowance for a variable number of bulged bases. The automated procedure that we have implemented identifies all hairpin and internal loop motifs previously described in the literature. All motif instances and motif groups are assigned unique and stable identifiers and are made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is automatically updated every four weeks. The RNA 3D Motif Atlas provides an interactive user interface for exploring motif diversity and tools for programmatic data access. PMID:23970545

Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulkarni, Manjiri R.; Numoto, Nobutaka; Ito, Nobutoshi

Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4-L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile{sup 387} conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is usedmore » as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile{sup 387} confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4-L387I at 2 Å resolution. Ile{sup 387} indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile{sup 387} using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4-L387I and confirmed the modeling. • Side-chain repacking occurring around Ile{sup 387} involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.« less

Function-based classification of carbohydrate-active enzymes by recognition of short, conserved peptide motifs.

PubMed

Busk, Peter Kamp; Lange, Lene

2013-06-01

Functional prediction of carbohydrate-active enzymes is difficult due to low sequence identity. However, similar enzymes often share a few short motifs, e.g., around the active site, even when the overall sequences are very different. To exploit this notion for functional prediction of carbohydrate-active enzymes, we developed a simple algorithm, peptide pattern recognition (PPR), that can divide proteins into groups of sequences that share a set of short conserved sequences. When this method was used on 118 glycoside hydrolase 5 proteins with 9% average pairwise identity and representing four characterized enzymatic functions, 97% of the proteins were sorted into groups correlating with their enzymatic activity. Furthermore, we analyzed 8,138 glycoside hydrolase 13 proteins including 204 experimentally characterized enzymes with 28 different functions. There was a 91% correlation between group and enzyme activity. These results indicate that the function of carbohydrate-active enzymes can be predicted with high precision by finding short, conserved motifs in their sequences. The glycoside hydrolase 61 family is important for fungal biomass conversion, but only a few proteins of this family have been functionally characterized. Interestingly, PPR divided 743 glycoside hydrolase 61 proteins into 16 subfamilies useful for targeted investigation of the function of these proteins and pinpointed three conserved motifs with putative importance for enzyme activity. Furthermore, the conserved sequences were useful for cloning of new, subfamily-specific glycoside hydrolase 61 proteins from 14 fungi. In conclusion, identification of conserved sequence motifs is a new approach to sequence analysis that can predict carbohydrate-active enzyme functions with high precision.

Failure of conservative treatment with Gastrografin® for adhesive small bowel obstruction after colorectal surgery.

PubMed

Miquel, Jordi; Biondo, Sebastiano; Kreisler, Esther; Uribe, Catalina; Trenti, Loris

2017-07-01

The aim of this study was to identify risk factors related with failure of conservative management of adhesive small bowel obstruction (ASBO) in patients with previous colorectal surgery. Patients admitted with the diagnosis of ASBO after previous colorectal resection, were included. All patients underwent administration of Gastrografin®. Abdominal radiography was done after 24 h, to confirm the presence of contrast in colon (incomplete obstruction) or not (complete obstruction). Several factors were investigated to study their relationship with the failure of conservative management. Failure of conservative management was considered when emergency operation was needed to solve ASBO. Incomplete obstruction was observed in 174 episodes (93.0%) while in 13 (7.0%) was complete. One hundred seventy-one ASBO episodes (91.4%) responded successfully to nonoperative treatment and 16 (8.6%) required emergency surgery. Five patients needed bowel resection. Results on the diagnostic test with Gastrografin® showed a sensitivity of 75%, specificity of 99%, positive predictive value 92%, and negative predictive value 98%. Age over 75 years was the only predictive factor for failure of conservative management. The median waiting time from the radiologic confirmation of complete obstruction to surgery was higher in patients requiring bowel resection when compared to those who did not need resection. The use of Gastrografin® in ASBO after colorectal resection is a safe and useful tool for the indication of conservative management. Age over 75 years is a predictive factor for need of surgery. Surgery should be performed no later than the following 24 h of confirmed complete obstruction.

A Novel Predicted Bromodomain-Related Protein Affects Coordination Between Meiosis and Spermiogenesis in Drosophila and Is Required for Male Meiotic Cytokinesis

PubMed Central

Bergner, Laura M.; Hickman, F. Edward; Wood, Kathleen H.; Wakeman, Carolyn M.; Stone, Hunter H.; Campbell, Tessa J.; Lightcap, Samantha B.; Favors, Sheena M.; Aldridge, Amanda C.

2010-01-01

Temporal coordination of meiosis with spermatid morphogenesis is crucial for successful generation of mature sperm cells. We identified a recessive male sterile Drosophila melanogaster mutant, mitoshell, in which events of spermatid morphogenesis are initiated too early, before meiotic onset. Premature mitochondrial aggregation and fusion lead to an aberrant mitochondrial shell around premeiotic nuclei. Despite successful meiotic karyokinesis, improper mitochondrial localization in mitoshell testes is associated with defective astral central spindles and a lack of contractile rings, leading to meiotic cytokinesis failure. We mapped and cloned the mitoshell gene and found that it encodes a novel protein with a bromodomain-related region. It is conserved in some insect lineages. Bromodomains typically bind to histone acetyl-lysine residues and therefore are often associated with chromatin. The Mitoshell bromodomain-related region is predicted to have an alpha helical structure similar to that of bromodomains, but not all the crucial residues in the ligand-binding loops are conserved. We speculate that Mitoshell may participate in transcriptional regulation of spermatogenesis-specific genes, though perhaps with different ligand specificity compared to traditional bromodomains. PMID:20491580

Enhancing the Predictive Power of Mutations in the C-Terminus of the KCNQ1-Encoded Kv7.1 Voltage-Gated Potassium Channel.

PubMed

Kapplinger, Jamie D; Tseng, Andrew S; Salisbury, Benjamin A; Tester, David J; Callis, Thomas E; Alders, Marielle; Wilde, Arthur A M; Ackerman, Michael J

2015-04-01

Despite the overrepresentation of Kv7.1 mutations among patients with a robust diagnosis of long QT syndrome (LQTS), a background rate of innocuous Kv7.1 missense variants observed in healthy controls creates ambiguity in the interpretation of LQTS genetic test results. A recent study showed that the probability of pathogenicity for rare missense mutations depends in part on the topological location of the variant in Kv7.1's various structure-function domains. Since the Kv7.1's C-terminus accounts for nearly 50 % of the overall protein and nearly 50 % of the overall background rate of rare variants falls within the C-terminus, further enhancement in mutation calling may provide guidance in distinguishing pathogenic long QT syndrome type 1 (LQT1)-causing mutations from rare non-disease-causing variants in the Kv7.1's C-terminus. Therefore, we have used conservation analysis and a large case-control study to generate topology-based estimative predictive values to aid in interpretation, identifying three regions of high conservation within the Kv7.1's C-terminus which have a high probability of LQT1 pathogenicity.

Large-Scale Bioinformatics Analysis of Bacillus Genomes Uncovers Conserved Roles of Natural Products in Bacterial Physiology.

PubMed

Grubbs, Kirk J; Bleich, Rachel M; Santa Maria, Kevin C; Allen, Scott E; Farag, Sherif; Shank, Elizabeth A; Bowers, Albert A

2017-01-01

Bacteria possess an amazing capacity to synthesize a diverse range of structurally complex, bioactive natural products known as specialized (or secondary) metabolites. Many of these specialized metabolites are used as clinical therapeutics, while others have important ecological roles in microbial communities. The biosynthetic gene clusters (BGCs) that generate these metabolites can be identified in bacterial genome sequences using their highly conserved genetic features. We analyzed an unprecedented 1,566 bacterial genomes from Bacillus species and identified nearly 20,000 BGCs. By comparing these BGCs to one another as well as a curated set of known specialized metabolite BGCs, we discovered that the majority of Bacillus natural products are comprised of a small set of highly conserved, well-distributed, known natural product compounds. Most of these metabolites have important roles influencing the physiology and development of Bacillus species. We identified, in addition to these characterized compounds, many unique, weakly conserved BGCs scattered across the genus that are predicted to encode unknown natural products. Many of these "singleton" BGCs appear to have been acquired via horizontal gene transfer. Based on this large-scale characterization of metabolite production in the Bacilli , we go on to connect the alkylpyrones, natural products that are highly conserved but previously biologically uncharacterized, to a role in Bacillus physiology: inhibiting spore development. IMPORTANCE Bacilli are capable of producing a diverse array of specialized metabolites, many of which have gained attention for their roles as signals that affect bacterial physiology and development. Up to this point, however, the Bacillus genus's metabolic capacity has been underexplored. We undertook a deep genomic analysis of 1,566 Bacillus genomes to understand the full spectrum of metabolites that this bacterial group can make. We discovered that the majority of the specialized metabolites produced by Bacillus species are highly conserved, known compounds with important signaling roles in the physiology and development of this bacterium. Additionally, there is significant unique biosynthetic machinery distributed across the genus that might lead to new, unknown metabolites with diverse biological functions. Inspired by the findings of our genomic analysis, we speculate that the highly conserved alkylpyrones might have an important biological activity within this genus. We go on to validate this prediction by demonstrating that these natural products are developmental signals in Bacillus and act by inhibiting sporulation.

A Predictive Model of Intein Insertion Site for Use in the Engineering of Molecular Switches

PubMed Central

Apgar, James; Ross, Mary; Zuo, Xiao; Dohle, Sarah; Sturtevant, Derek; Shen, Binzhang; de la Vega, Humberto; Lessard, Philip; Lazar, Gabor; Raab, R. Michael

2012-01-01

Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch. PMID:22649521

Computational approach for predicting the conserved B-cell epitopes of hemagglutinin H7 subtype influenza virus.

PubMed

Wang, Xiangyu; Sun, Qi; Ye, Zhonghua; Hua, Ying; Shao, Na; Du, Yanli; Zhang, Qiwei; Wan, Chengsong

2016-10-01

An avian-origin influenza H7N9 virus epidemic occurred in China in 2013-2014, in which >422 infected people suffered from pneumonia, respiratory distress syndrome and septic shock. H7N9 viruses belong to the H7 subtype of avian-origin influenza viruses (AIV-H7). Hemagglutinin (HA) is a vital membrane protein of AIV that has an important role in host recognition and infection. The epitopes of HA are significant determinants of the regularity of epidemic and viral mutation and recombination mechanisms. The present study aimed to predict the conserved B-cell epitopes of AIV-H7 HA using a bioinformatics approach, including the three most effective epitope prediction softwares available online: Artificial Neural Network based B-cell Epitope Prediction (ABCpred), B-cell Epitope Prediction (BepiPred) and Linear B-cell Epitope Prediction (LBtope). A total of 24 strains of Euro-Asiatic AIV-H7 that had been associated with a serious poultry pandemic or had infected humans in the past 30 years were selected to identify the conserved regions of HA. Sequences were obtained from the National Center for Biotechnology Information and Global Initiative on Sharing Avian Influenza Data databases. Using a combination of software prediction and sequence comparisons, the conserved epitopes of AIV-H7 were predicted and clarified. A total of five conserved epitopes [amino acids (aa) 37-52, 131-142, 215-234, 465-484 and 487-505] with a suitable length, high antigenicity and minimal variation were predicted and confirmed. Each obtained a score of >0.80 in ABCpred, 60% in LBtope and a level of 0.35 in Bepipred. In addition, a representative amino acid change (glutamine 235 -to-leucine 235 ) in the HA protein of the 2013 AIV-H7N9 was discovered. The strategy adopted in the present study may have profound implications on the rapid diagnosis and control of infectious disease caused by H7N9 viruses, as well as by other virulent viruses, such as the Ebola virus.

Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging

PubMed Central

Stewart, H.; Bingham, R.J.; White, S. J.; Dykeman, E. C.; Zothner, C.; Tuplin, A. K.; Stockley, P. G.; Twarock, R.; Harris, M.

2016-01-01

The specific packaging of the hepatitis C virus (HCV) genome is hypothesised to be driven by Core-RNA interactions. To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We postulated that interactions of these motifs, as well as sub-motifs which were present in HCV genomes at statistically significant levels, with the Core protein may drive virion assembly. We mutated 8 of these predicted motifs within the HCV infectious molecular clone JFH-1, thereby producing a range of mutant viruses predicted to possess altered RNA secondary structures. RNA replication and viral titre were unaltered in viruses possessing only one mutated structure. However, infectivity titres were decreased in viruses possessing a higher number of mutated regions. This work thus identified multiple novel RNA motifs which appear to contribute to genome packaging. We suggest that these structures act as cooperative packaging signals to drive specific RNA encapsidation during HCV assembly. PMID:26972799

Conservation of the Human Integrin-Type Beta-Propeller Domain in Bacteria

PubMed Central

Chouhan, Bhanupratap; Denesyuk, Alexander; Heino, Jyrki; Johnson, Mark S.; Denessiouk, Konstantin

2011-01-01

Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and sometimes two tandem copies are found. PMID:22022374

A New Approach to Extreme Value Estimation Applicable to a Wide Variety of Random Variables

NASA Technical Reports Server (NTRS)

Holland, Frederic A., Jr.

1997-01-01

Designing reliable structures requires an estimate of the maximum and minimum values (i.e., strength and load) that may be encountered in service. Yet designs based on very extreme values (to insure safety) can result in extra material usage and hence, uneconomic systems. In aerospace applications, severe over-design cannot be tolerated making it almost mandatory to design closer to the assumed limits of the design random variables. The issue then is predicting extreme values that are practical, i.e. neither too conservative or non-conservative. Obtaining design values by employing safety factors is well known to often result in overly conservative designs and. Safety factor values have historically been selected rather arbitrarily, often lacking a sound rational basis. To answer the question of how safe a design needs to be has lead design theorists to probabilistic and statistical methods. The so-called three-sigma approach is one such method and has been described as the first step in utilizing information about the data dispersion. However, this method is based on the assumption that the random variable is dispersed symmetrically about the mean and is essentially limited to normally distributed random variables. Use of this method can therefore result in unsafe or overly conservative design allowables if the common assumption of normality is incorrect.

Spatio-temporal variation in age structure and abundance of the endangered snail kite: Pooling across regions masks a declining and aging population

USGS Publications Warehouse

Reichert, Brian E.; Kendall, William L.; Fletcher, Robert J.; Kitchens, Wiley M.

2016-01-01

While variation in age structure over time and space has long been considered important for population dynamics and conservation, reliable estimates of such spatio-temporal variation in age structure have been elusive for wild vertebrate populations. This limitation has arisen because of problems of imperfect detection, the potential for temporary emigration impacting assessments of age structure, and limited information on age. However, identifying patterns in age structure is important for making reliable predictions of both short- and long-term dynamics of populations of conservation concern. Using a multistate superpopulation estimator, we estimated region-specific abundance and age structure (the proportion of individuals within each age class) of a highly endangered population of snail kites for two separate regions in Florida over 17 years (1997–2013). We find that in the southern region of the snail kite—a region known to be critical for the long-term persistence of the species—the population has declined significantly since 1997, and during this time, it has increasingly become dominated by older snail kites (> 12 years old). In contrast, in the northern region—a region historically thought to serve primarily as drought refugia—the population has increased significantly since 2007 and age structure is more evenly distributed among age classes. Given that snail kites show senescence at approximately 13 years of age, where individuals suffer higher mortality rates and lower breeding rates, these results reveal an alarming trend for the southern region. Our work illustrates the importance of accounting for spatial structure when assessing changes in abundance and age distribution and the need for monitoring of age structure in imperiled species.

Spatial models reveal the microclimatic buffering capacity of old-growth forests

PubMed Central

Frey, Sarah J. K.; Hadley, Adam S.; Johnson, Sherri L.; Schulze, Mark; Jones, Julia A.; Betts, Matthew G.

2016-01-01

Climate change is predicted to cause widespread declines in biodiversity, but these predictions are derived from coarse-resolution climate models applied at global scales. Such models lack the capacity to incorporate microclimate variability, which is critical to biodiversity microrefugia. In forested montane regions, microclimate is thought to be influenced by combined effects of elevation, microtopography, and vegetation, but their relative effects at fine spatial scales are poorly known. We used boosted regression trees to model the spatial distribution of fine-scale, under-canopy air temperatures in mountainous terrain. Spatial models predicted observed independent test data well (r = 0.87). As expected, elevation strongly predicted temperatures, but vegetation and microtopography also exerted critical effects. Old-growth vegetation characteristics, measured using LiDAR (light detection and ranging), appeared to have an insulating effect; maximum spring monthly temperatures decreased by 2.5°C across the observed gradient in old-growth structure. These cooling effects across a gradient in forest structure are of similar magnitude to 50-year forecasts of the Intergovernmental Panel on Climate Change and therefore have the potential to mitigate climate warming at local scales. Management strategies to conserve old-growth characteristics and to curb current rates of primary forest loss could maintain microrefugia, enhancing biodiversity persistence in mountainous systems under climate warming. PMID:27152339

In silico study of breast cancer associated gene 3 using LION Target Engine and other tools.

PubMed

León, Darryl A; Cànaves, Jaume M

2003-12-01

Sequence analysis of individual targets is an important step in annotation and validation. As a test case, we investigated human breast cancer associated gene 3 (BCA3) with LION Target Engine and with other bioinformatics tools. LION Target Engine confirmed that the BCA3 gene is located on 11p15.4 and that the two most likely splice variants (lacking exon 3 and exons 3 and 5, respectively) exist. Based on our manual curation of sequence data, it is proposed that an additional variant (missing only exon 5) published in a public sequence repository, is a prediction artifact. A significant number of new orthologs were also identified, and these were the basis for a high-quality protein secondary structure prediction. Moreover, our research confirmed several distinct functional domains as described in earlier reports. Sequence conservation from multiple sequence alignments, splice variant identification, secondary structure predictions, and predicted phosphorylation sites suggest that the removal of interaction sites through alternative splicing might play a modulatory role in BCA3. This in silico approach shows the depth and relevance of an analysis that can be accomplished by including a variety of publicly available tools with an integrated and customizable life science informatics platform.

Spatial models reveal the microclimatic buffering capacity of old-growth forests.

PubMed

Frey, Sarah J K; Hadley, Adam S; Johnson, Sherri L; Schulze, Mark; Jones, Julia A; Betts, Matthew G

2016-04-01

Climate change is predicted to cause widespread declines in biodiversity, but these predictions are derived from coarse-resolution climate models applied at global scales. Such models lack the capacity to incorporate microclimate variability, which is critical to biodiversity microrefugia. In forested montane regions, microclimate is thought to be influenced by combined effects of elevation, microtopography, and vegetation, but their relative effects at fine spatial scales are poorly known. We used boosted regression trees to model the spatial distribution of fine-scale, under-canopy air temperatures in mountainous terrain. Spatial models predicted observed independent test data well (r = 0.87). As expected, elevation strongly predicted temperatures, but vegetation and microtopography also exerted critical effects. Old-growth vegetation characteristics, measured using LiDAR (light detection and ranging), appeared to have an insulating effect; maximum spring monthly temperatures decreased by 2.5°C across the observed gradient in old-growth structure. These cooling effects across a gradient in forest structure are of similar magnitude to 50-year forecasts of the Intergovernmental Panel on Climate Change and therefore have the potential to mitigate climate warming at local scales. Management strategies to conserve old-growth characteristics and to curb current rates of primary forest loss could maintain microrefugia, enhancing biodiversity persistence in mountainous systems under climate warming.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rushton, Phillip S.; Olek, Anna T.; Makowski, Lee

The crystallographic structure of a rice (Oryza sativa) cellulose synthase, OsCesA8, plant-conserved region (P-CR), one of two unique domains in the catalytic domain of plant CesAs, was solved to 2.4 Å resolution. Two antiparallel α-helices form a coiled-coil domain linked by a large extended connector loop containing a conserved trio of aromatic residues. The P-CR structure was fit into a molecular envelope for the P-CR domain derived from small-angle X-ray scattering data. The P-CR structure and molecular envelope, combined with a homology-based chain trace of the CesA8 catalytic core, were modeled into a previously determined CesA8 small-angle X-ray scattering molecularmore » envelope to produce a detailed topological model of the CesA8 catalytic domain. The predicted position for the P-CR domain from the molecular docking models places the P-CR connector loop into a hydrophobic pocket of the catalytic core, with the coiled-coil aligned near the entrance of the substrate UDP-glucose into the active site. In this configuration, the P-CR coiled-coil alone is unlikely to regulate substrate access to the active site, but it could interact with other domains of CesA, accessory proteins, or other CesA catalytic domains to control substrate delivery.« less

Structural characterization and evolutionary analysis of fish-specific TLR27.

PubMed

Wang, Jinlan; Zhang, Zheng; Liu, Jing; Li, Fang; Chang, Fen; Fu, Hui; Zhao, Jing; Yin, Deling

2015-08-01

Toll-like receptors (TLRs) are critical components of the innate immune response of fish. In a phylogenetic analysis, TLR27 from three fish species, which belongs to TLR family 1, clustered with TLR14/18 and TLR25 on the evolutionary tree. The ectodomain of TLR27 is predicted to include 19 leucine-rich repeat (LRR) modules. Structural modeling showed that the TLR27 ectodomain can be divided into three distinctive sections. The lack of conserved asparagines on the concave surface of the central subdomain causes a structural transition in the middle of the ectodomain, forming a distinct hydrophobic pocket at the border between the central subdomain and the C-terminal subdomain. We infer that, like other functionally characterized TLRs in family 1, the hydrophobic pocket located between LRR11 and LRR12 participates in ligand recognition by TLR27. An evolutionary analysis showed that the dN/dS value at the TLR27 locus was very low. Approximately one quarter of the total number of TLR27 sites are under significant negatively selection pressure, whereas only two sites are under positive selection. Consequently, TLR27 is highly evolutionarily conserved and probably plays an extremely important role in the innate immune systems of fishes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biochemical Regulatory Features of Activation-Induced Cytidine Deaminase Remain Conserved from Lampreys to Humans

PubMed Central

King, Justin J.; Amemiya, Chris T.; Hsu, Ellen

2017-01-01

ABSTRACT Activation-induced cytidine deaminase (AID) is a genome-mutating enzyme that initiates class switch recombination and somatic hypermutation of antibodies in jawed vertebrates. We previously described the biochemical properties of human AID and found that it is an unusual enzyme in that it exhibits binding affinities for its substrate DNA and catalytic rates several orders of magnitude higher and lower, respectively, than a typical enzyme. Recently, we solved the functional structure of AID and demonstrated that these properties are due to nonspecific DNA binding on its surface, along with a catalytic pocket that predominantly assumes a closed conformation. Here we investigated the biochemical properties of AID from a sea lamprey, nurse shark, tetraodon, and coelacanth: representative species chosen because their lineages diverged at the earliest critical junctures in evolution of adaptive immunity. We found that these earliest-diverged AID orthologs are active cytidine deaminases that exhibit unique substrate specificities and thermosensitivities. Significant amino acid sequence divergence among these AID orthologs is predicted to manifest as notable structural differences. However, despite major differences in sequence specificities, thermosensitivities, and structural features, all orthologs share the unusually high DNA binding affinities and low catalytic rates. This absolute conservation is evidence for biological significance of these unique biochemical properties. PMID:28716949

Tilapia and human CLIC2 structures are highly conserved.

PubMed

Zeng, Jiao; Li, Zhengjun; Lui, Eei Yin; Lam, Siew Hong; Swaminathan, Kunchithapadam

2018-01-08

Chloride intracellular channels (CLICs) exist in soluble and membrane bound forms. We have determined the crystal structure of soluble Clic2 from the euryhaline teleost fish Oreochromis mossambicus. Structural comparison of tilapia and human CLIC2 with other CLICs shows that these proteins are highly conserved. We have also compared the expression levels of clic2 in selected osmoregulatory organs of tilapia, acclimated to freshwater, seawater and hypersaline water. Structural conservation of vertebrate CLICs implies that they might play conserved roles. Also, tissue-specific responsiveness of clic2 suggests that it might be involved in iono-osmoregulation under extreme conditions in tilapia. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

Sudha, Govindarajan; Singh, Prashant; Swapna, Lakshmipuram S; Srinivasan, Narayanaswamy

2015-01-01

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. PMID:26311309

RGAugury: a pipeline for genome-wide prediction of resistance gene analogs (RGAs) in plants.

PubMed

Li, Pingchuan; Quan, Xiande; Jia, Gaofeng; Xiao, Jin; Cloutier, Sylvie; You, Frank M

2016-11-02

Resistance gene analogs (RGAs), such as NBS-encoding proteins, receptor-like protein kinases (RLKs) and receptor-like proteins (RLPs), are potential R-genes that contain specific conserved domains and motifs. Thus, RGAs can be predicted based on their conserved structural features using bioinformatics tools. Computer programs have been developed for the identification of individual domains and motifs from the protein sequences of RGAs but none offer a systematic assessment of the different types of RGAs. A user-friendly and efficient pipeline is needed for large-scale genome-wide RGA predictions of the growing number of sequenced plant genomes. An integrative pipeline, named RGAugury, was developed to automate RGA prediction. The pipeline first identifies RGA-related protein domains and motifs, namely nucleotide binding site (NB-ARC), leucine rich repeat (LRR), transmembrane (TM), serine/threonine and tyrosine kinase (STTK), lysin motif (LysM), coiled-coil (CC) and Toll/Interleukin-1 receptor (TIR). RGA candidates are identified and classified into four major families based on the presence of combinations of these RGA domains and motifs: NBS-encoding, TM-CC, and membrane associated RLP and RLK. All time-consuming analyses of the pipeline are paralleled to improve performance. The pipeline was evaluated using the well-annotated Arabidopsis genome. A total of 98.5, 85.2, and 100 % of the reported NBS-encoding genes, membrane associated RLPs and RLKs were validated, respectively. The pipeline was also successfully applied to predict RGAs for 50 sequenced plant genomes. A user-friendly web interface was implemented to ease command line operations, facilitate visualization and simplify result management for multiple datasets. RGAugury is an efficiently integrative bioinformatics tool for large scale genome-wide identification of RGAs. It is freely available at Bitbucket: https://bitbucket.org/yaanlpc/rgaugury .

Crucial nesting habitat for gunnison sage-grouse: A spatially explicit hierarchical approach

USGS Publications Warehouse

Aldridge, Cameron L.; Saher, D.J.; Childers, T.M.; Stahlnecker, K.E.; Bowen, Z.H.

2012-01-01

Gunnison sage-grouse (Centrocercus minimus) is a species of special concern and is currently considered a candidate species under Endangered Species Act. Careful management is therefore required to ensure that suitable habitat is maintained, particularly because much of the species' current distribution is faced with exurban development pressures. We assessed hierarchical nest site selection patterns of Gunnison sage-grouse inhabiting the western portion of the Gunnison Basin, Colorado, USA, at multiple spatial scales, using logistic regression-based resource selection functions. Models were selected using Akaike Information Criterion corrected for small sample sizes (AIC c) and predictive surfaces were generated using model averaged relative probabilities. Landscape-scale factors that had the most influence on nest site selection included the proportion of sagebrush cover >5%, mean productivity, and density of 2 wheel-drive roads. The landscape-scale predictive surface captured 97% of known Gunnison sage-grouse nests within the top 5 of 10 prediction bins, implicating 57% of the basin as crucial nesting habitat. Crucial habitat identified by the landscape model was used to define the extent for patch-scale modeling efforts. Patch-scale variables that had the greatest influence on nest site selection were the proportion of big sagebrush cover >10%, distance to residential development, distance to high volume paved roads, and mean productivity. This model accurately predicted independent nest locations. The unique hierarchical structure of our models more accurately captures the nested nature of habitat selection, and allowed for increased discrimination within larger landscapes of suitable habitat. We extrapolated the landscape-scale model to the entire Gunnison Basin because of conservation concerns for this species. We believe this predictive surface is a valuable tool which can be incorporated into land use and conservation planning as well the assessment of future land-use scenarios. ?? 2011 The Wildlife Society.

Identification of DNA-Binding Proteins Using Structural, Electrostatic and Evolutionary Features

PubMed Central

Nimrod, Guy; Szilágyi, András; Leslie, Christina; Ben-Tal, Nir

2009-01-01

Summary DNA binding proteins (DBPs) often take part in various crucial processes of the cell's life cycle. Therefore, the identification and characterization of these proteins are of great importance. We present here a random forests classifier for identifying DBPs among proteins with known three-dimensional structures. First, clusters of evolutionarily conserved regions (patches) on the protein's surface are detected using the PatchFinder algorithm; previous studies showed that these regions are typically the proteins' functionally important regions. Next, we train a classifier using features like the electrostatic potential, cluster-based amino acid conservation patterns and the secondary structure content of the patches, as well as features of the whole protein including its dipole moment. Using 10-fold cross validation on a dataset of 138 DNA-binding proteins and 110 proteins which do not bind DNA, the classifier achieved a sensitivity and a specificity of 0.90, which is overall better than the performance of previously published methods. Furthermore, when we tested 5 different methods on 11 new DBPs which did not appear in the original dataset, only our method annotated all correctly. The resulting classifier was applied to a collection of 757 proteins of known structure and unknown function. Of these proteins, 218 were predicted to bind DNA, and we anticipate that some of them interact with DNA using new structural motifs. The use of complementary computational tools supports the notion that at least some of them do bind DNA. PMID:19233205

Identification of DNA-binding proteins using structural, electrostatic and evolutionary features.

PubMed

Nimrod, Guy; Szilágyi, András; Leslie, Christina; Ben-Tal, Nir

2009-04-10

DNA-binding proteins (DBPs) participate in various crucial processes in the life-cycle of the cells, and the identification and characterization of these proteins is of great importance. We present here a random forests classifier for identifying DBPs among proteins with known 3D structures. First, clusters of evolutionarily conserved regions (patches) on the surface of proteins were detected using the PatchFinder algorithm; earlier studies showed that these regions are typically the functionally important regions of proteins. Next, we trained a classifier using features like the electrostatic potential, cluster-based amino acid conservation patterns and the secondary structure content of the patches, as well as features of the whole protein, including its dipole moment. Using 10-fold cross-validation on a dataset of 138 DBPs and 110 proteins that do not bind DNA, the classifier achieved a sensitivity and a specificity of 0.90, which is overall better than the performance of published methods. Furthermore, when we tested five different methods on 11 new DBPs that did not appear in the original dataset, only our method annotated all correctly. The resulting classifier was applied to a collection of 757 proteins of known structure and unknown function. Of these proteins, 218 were predicted to bind DNA, and we anticipate that some of them interact with DNA using new structural motifs. The use of complementary computational tools supports the notion that at least some of them do bind DNA.

Assessing the multi-scale predictive ability of ecosystem functional attributes for species distribution modelling.

PubMed

Arenas-Castro, Salvador; Gonçalves, João; Alves, Paulo; Alcaraz-Segura, Domingo; Honrado, João P

2018-01-01

Global environmental changes are rapidly affecting species' distributions and habitat suitability worldwide, requiring a continuous update of biodiversity status to support effective decisions on conservation policy and management. In this regard, satellite-derived Ecosystem Functional Attributes (EFAs) offer a more integrative and quicker evaluation of ecosystem responses to environmental drivers and changes than climate and structural or compositional landscape attributes. Thus, EFAs may hold advantages as predictors in Species Distribution Models (SDMs) and for implementing multi-scale species monitoring programs. Here we describe a modelling framework to assess the predictive ability of EFAs as Essential Biodiversity Variables (EBVs) against traditional datasets (climate, land-cover) at several scales. We test the framework with a multi-scale assessment of habitat suitability for two plant species of conservation concern, both protected under the EU Habitats Directive, differing in terms of life history, range and distribution pattern (Iris boissieri and Taxus baccata). We fitted four sets of SDMs for the two test species, calibrated with: interpolated climate variables; landscape variables; EFAs; and a combination of climate and landscape variables. EFA-based models performed very well at the several scales (AUCmedian from 0.881±0.072 to 0.983±0.125), and similarly to traditional climate-based models, individually or in combination with land-cover predictors (AUCmedian from 0.882±0.059 to 0.995±0.083). Moreover, EFA-based models identified additional suitable areas and provided valuable information on functional features of habitat suitability for both test species (narrowly vs. widely distributed), for both coarse and fine scales. Our results suggest a relatively small scale-dependence of the predictive ability of satellite-derived EFAs, supporting their use as meaningful EBVs in SDMs from regional and broader scales to more local and finer scales. Since the evaluation of species' conservation status and habitat quality should as far as possible be performed based on scalable indicators linking to meaningful processes, our framework may guide conservation managers in decision-making related to biodiversity monitoring and reporting schemes.

Towards a damage tolerance philosophy for composite materials and structures

NASA Technical Reports Server (NTRS)

O'Brien, T. Kevin

1990-01-01

A damage-threshold/fail-safe approach is proposed to ensure that composite structures are both sufficiently durable for economy of operation, as well as adequately fail-safe or damage tolerant for flight safety. Matrix cracks are assumed to exist throughout the off-axis plies. Delamination onset is predicted using a strain energy release rate characterization. Delamination growth is accounted for in one of three ways: either analytically, using delamination growth laws in conjunction with strain energy release rate analyses incorporating delamination resistance curves; experimentally, using measured stiffness loss; or conservatively, assuming delamination onset corresponds to catastrophic delamination growth. Fail-safety is assessed by accounting for the accumulation of delaminations through the thickness. A tension fatigue life prediction for composite laminates is presented as a case study to illustrate how this approach may be implemented. Suggestions are made for applying the damage-threshold/fail-safe approach to compression fatigue, tension/compression fatigue, and compression strength following low velocity impact.

Multiparticle collision simulations of two-dimensional one-component plasmas: Anomalous transport and dimensional crossovers

NASA Astrophysics Data System (ADS)

Di Cintio, Pierfrancesco; Livi, Roberto; Lepri, Stefano; Ciraolo, Guido

2017-04-01

By means of hybrid multiparticle collsion-particle-in-cell (MPC-PIC) simulations we study the dynamical scaling of energy and density correlations at equilibrium in moderately coupled two-dimensional (2D) and quasi-one-dimensional (1D) plasmas. We find that the predictions of nonlinear fluctuating hydrodynamics for the structure factors of density and energy fluctuations in 1D systems with three global conservation laws hold true also for 2D systems that are more extended along one of the two spatial dimensions. Moreover, from the analysis of the equilibrium energy correlators and density structure factors of both 1D and 2D neutral plasmas, we find that neglecting the contribution of the fluctuations of the vanishing self-consistent electrostatic fields overestimates the interval of frequencies over which the anomalous transport is observed. Such violations of the expected scaling in the currents correlation are found in different regimes, hindering the observation of the asymptotic scaling predicted by the theory.

Towards a damage tolerance philosophy for composite materials and structures

NASA Technical Reports Server (NTRS)

Obrien, T. Kevin

1988-01-01

A damage-threshold/fail-safe approach is proposed to ensure that composite structures are both sufficiently durable for economy of operation, as well as adequately fail-safe or damage tolerant for flight safety. Matrix cracks are assumed to exist throughout the off-axis plies. Delamination onset is predicted using a strain energy release rate characterization. Delamination growth is accounted for in one of three ways: either analytically, using delamination growth laws in conjunction with strain energy release rate analyses incorporating delamination resistance curves; experimentally, using measured stiffness loss; or conservatively, assuming delamination onset corresponds to catastrophic delamination growth. Fail-safety is assessed by accounting for the accumulation of delaminations through the thickness. A tension fatigue life prediction for composite laminates is presented as a case study to illustrate how this approach may be implemented. Suggestions are made for applying the damage-threshold/fail-safe approach to compression fatigue, tension/compression fatigue, and compression strength following low velocity impact.

Fast and Accurate Multivariate Gaussian Modeling of Protein Families: Predicting Residue Contacts and Protein-Interaction Partners

PubMed Central

Feinauer, Christoph; Procaccini, Andrea; Zecchina, Riccardo; Weigt, Martin; Pagnani, Andrea

2014-01-01

In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation) have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids), exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i) the prediction of residue-residue contacts in proteins, and (ii) the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website http://areeweb.polito.it/ricerca/cmp/code. PMID:24663061

Effects of preference heterogeneity among landowners on spatial conservation prioritization.

PubMed

Nielsen, Anne Sofie Elberg; Strange, Niels; Bruun, Hans Henrik; Jacobsen, Jette Bredahl

2017-06-01

The participation of private landowners in conservation is crucial to efficient biodiversity conservation. This is especially the case in settings where the share of private ownership is large and the economic costs associated with land acquisition are high. We used probit regression analysis and historical participation data to examine the likelihood of participation of Danish forest owners in a voluntary conservation program. We used the results to spatially predict the likelihood of participation of all forest owners in Denmark. We merged spatial data on the presence of forest, cadastral information on participation contracts, and individual-level socioeconomic information about the forest owners and their households. We included predicted participation in a probability model for species survival. Uninformed and informed (included land owner characteristics) models were then incorporated into a spatial prioritization for conservation of unmanaged forests. The choice models are based on sociodemographic data on the entire population of Danish forest owners and historical data on their participation in conservation schemes. Inclusion in the model of information on private landowners' willingness to supply land for conservation yielded at intermediate budget levels up to 30% more expected species coverage than the uninformed prioritization scheme. Our landowner-choice model provides an example of moving toward more implementable conservation planning. © 2016 Society for Conservation Biology.

Innovating Conservation Agriculture: The Case of No-Till Cropping

ERIC Educational Resources Information Center

Coughenour, C. Milton

2003-01-01

The extensive sociological studies of conservation agriculture have provided considerable understanding of farmers' use of conservation practices, but attempts to develop predictive models have failed. Reviews of research findings question the utility of the conceptual and methodological perspectives of prior research. The argument advanced here…

Characterization of cDNAs and genomic DNAs for human threonyl- and cysteinyl-tRNA synthetases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cruzen, M.E.

1993-01-01

Techniques of molecular biology were used to clone, sequence and map two human aminoacyl-tRNA synthetase (aaRS) cDNAs: threonyl-tRNA synthetase (ThrRS) a class II enzyme and cysteinyl-tRNA synthetase (CysRS) a class I enzyme. The predicted protein sequence of human ThrRS is highly homologous to that of lower eukaryotic and prokaryotic ThRSs, particularly in the regions containing the three structural motifs common to all class II synthetases. Signature regions 1 and 2, which characterize the class IIa subgroup (SerRS, ThrRS and HisRS) are highly conserved from bacteria to human. Structural predictions for human ThrRS based on the known structure of the closelymore » related SerRS from E.coli implicate strongly conserved residues in the signature sequences to be important in substrate binding. The amino terminal 100 residues of the deduced amino acid sequence of ThrRS shares structural similarity to SerRS consistent with forming an antiparallel helix implicated in tRNA binding. The 5' untranslated sequence of the human ThrRS gene shares short stretches of common sequence with the gene for hamster HisRS including a binding site for the promoter specific transcription factor sp-1. The deduced amino acid sequence of human CysRS has a high degree of sequence identify to E. coli CysRS. Human CysRS possesses the classic characteristics of a class I synthetase and is most closely related to the MetRS subgroup. The amino terminal half of human CysRS can be modeled as a nucleotide binding fold and shares significant sequence and structural similarity to the other enzymes in this subgroup. The CysRS structural gene (CARS) was mapped to human chromosome 11p15.5 by fluorescent in situ hybridization. CARS is the first aaRS gene to be mapped to chromosome 11. The steady state of both CysRS and ThrRs mRNA were quantitated in several human tissues. Message levels for these enzymes appear to be subjected to differential regulation in different cell types.« less

FoldGPCR: structure prediction protocol for the transmembrane domain of G protein-coupled receptors from class A.

PubMed

Michino, Mayako; Chen, Jianhan; Stevens, Raymond C; Brooks, Charles L

2010-08-01

Building reliable structural models of G protein-coupled receptors (GPCRs) is a difficult task because of the paucity of suitable templates, low sequence identity, and the wide variety of ligand specificities within the superfamily. Template-based modeling is known to be the most successful method for protein structure prediction. However, refinement of homology models within 1-3 A C alpha RMSD of the native structure remains a major challenge. Here, we address this problem by developing a novel protocol (foldGPCR) for modeling the transmembrane (TM) region of GPCRs in complex with a ligand, aimed to accurately model the structural divergence between the template and target in the TM helices. The protocol is based on predicted conserved inter-residue contacts between the template and target, and exploits an all-atom implicit membrane force field. The placement of the ligand in the binding pocket is guided by biochemical data. The foldGPCR protocol is implemented by a stepwise hierarchical approach, in which the TM helical bundle and the ligand are assembled by simulated annealing trials in the first step, and the receptor-ligand complex is refined with replica exchange sampling in the second step. The protocol is applied to model the human beta(2)-adrenergic receptor (beta(2)AR) bound to carazolol, using contacts derived from the template structure of bovine rhodopsin. Comparison with the X-ray crystal structure of the beta(2)AR shows that our protocol is particularly successful in accurately capturing helix backbone irregularities and helix-helix packing interactions that distinguish rhodopsin from beta(2)AR. (c) 2010 Wiley-Liss, Inc.

Functional formation of domain V of the poliovirus noncoding region: significance of unpaired bases.

PubMed

Rowe, A; Burlison, J; Macadam, A J; Minor, P D

2001-10-10

Previously we have shown that polioviruses with mutations that disrupt the predicted secondary structure of the 5' noncoding region of domain V are temperature sensitive for growth. Non-temperature-sensitive revertant viruses had mutations that re-formed secondary structure by a direct back mutation of changes in the opposite strand. We mutated unpaired regions and selected revertants of viruses with single base deletions, where no obvious back mutation was available in order to gain information on secondary structure. Results indicated that conservation of length of a three base loop between two double-stranded stems was essential for a functional domain V to form. The requirement for the unpaired "hinge" base at 484 which is implicated in the attenuation of Sabin 2 was also confirmed. Results also underline the necessity for functional folding over local secondary structure stability. Copyright 2001 Academic Press.

An Evolution-Based Approach to De Novo Protein Design and Case Study on Mycobacterium tuberculosis

PubMed Central

Brender, Jeffrey R.; Czajka, Jeff; Marsh, David; Gray, Felicia; Cierpicki, Tomasz; Zhang, Yang

2013-01-01

Computational protein design is a reverse procedure of protein folding and structure prediction, where constructing structures from evolutionarily related proteins has been demonstrated to be the most reliable method for protein 3-dimensional structure prediction. Following this spirit, we developed a novel method to design new protein sequences based on evolutionarily related protein families. For a given target structure, a set of proteins having similar fold are identified from the PDB library by structural alignments. A structural profile is then constructed from the protein templates and used to guide the conformational search of amino acid sequence space, where physicochemical packing is accommodated by single-sequence based solvation, torsion angle, and secondary structure predictions. The method was tested on a computational folding experiment based on a large set of 87 protein structures covering different fold classes, which showed that the evolution-based design significantly enhances the foldability and biological functionality of the designed sequences compared to the traditional physics-based force field methods. Without using homologous proteins, the designed sequences can be folded with an average root-mean-square-deviation of 2.1 Å to the target. As a case study, the method is extended to redesign all 243 structurally resolved proteins in the pathogenic bacteria Mycobacterium tuberculosis, which is the second leading cause of death from infectious disease. On a smaller scale, five sequences were randomly selected from the design pool and subjected to experimental validation. The results showed that all the designed proteins are soluble with distinct secondary structure and three have well ordered tertiary structure, as demonstrated by circular dichroism and NMR spectroscopy. Together, these results demonstrate a new avenue in computational protein design that uses knowledge of evolutionary conservation from protein structural families to engineer new protein molecules of improved fold stability and biological functionality. PMID:24204234

Lessons from (co-)evolution in the docking of proteins and peptides for CAPRI Rounds 28-35.

PubMed

Yu, Jinchao; Andreani, Jessica; Ochsenbein, Françoise; Guerois, Raphaël

2017-03-01

Computational protein-protein docking is of great importance for understanding protein interactions at the structural level. Critical assessment of prediction of interactions (CAPRI) experiments provide the protein docking community with a unique opportunity to blindly test methods based on real-life cases and help accelerate methodology development. For CAPRI Rounds 28-35, we used an automatic docking pipeline integrating the coarse-grained co-evolution-based potential InterEvScore. This score was developed to exploit the information contained in the multiple sequence alignments of binding partners and selectively recognize co-evolved interfaces. Together with Zdock/Frodock for rigid-body docking, SOAP-PP for atomic potential and Rosetta applications for structural refinement, this pipeline reached high performance on a majority of targets. For protein-peptide docking and interfacial water position predictions, we also explored different means of taking evolutionary information into account. Overall, our group ranked 1 st by correctly predicting 10 targets, composed of 1 High, 7 Medium and 2 Acceptable predictions. Excellent and Outstanding levels of accuracy were reached for each of the two water prediction targets, respectively. Altogether, in 15 out of 18 targets in total, evolutionary information, either through co-evolution or conservation analyses, could provide key constraints to guide modeling towards the most likely assemblies. These results open promising perspectives regarding the way evolutionary information can be valuable to improve docking prediction accuracy. Proteins 2017; 85:378-390. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prioritizing Conservation of Ungulate Calving Resources in Multiple-Use Landscapes

PubMed Central

Dzialak, Matthew R.; Harju, Seth M.; Osborn, Robert G.; Wondzell, John J.; Hayden-Wing, Larry D.; Winstead, Jeffrey B.; Webb, Stephen L.

2011-01-01

Background Conserving animal populations in places where human activity is increasing is an ongoing challenge in many parts of the world. We investigated how human activity interacted with maternal status and individual variation in behavior to affect reliability of spatially-explicit models intended to guide conservation of critical ungulate calving resources. We studied Rocky Mountain elk (Cervus elaphus) that occupy a region where 2900 natural gas wells have been drilled. Methodology/Principal Findings We present novel applications of generalized additive modeling to predict maternal status based on movement, and of random-effects resource selection models to provide population and individual-based inference on the effects of maternal status and human activity. We used a 2×2 factorial design (treatment vs. control) that included elk that were either parturient or non-parturient and in areas either with or without industrial development. Generalized additive models predicted maternal status (parturiency) correctly 93% of the time based on movement. Human activity played a larger role than maternal status in shaping resource use; elk showed strong spatiotemporal patterns of selection or avoidance and marked individual variation in developed areas, but no such pattern in undeveloped areas. This difference had direct consequences for landscape-level conservation planning. When relative probability of use was calculated across the study area, there was disparity throughout 72–88% of the landscape in terms of where conservation intervention should be prioritized depending on whether models were based on behavior in developed areas or undeveloped areas. Model validation showed that models based on behavior in developed areas had poor predictive accuracy, whereas the model based on behavior in undeveloped areas had high predictive accuracy. Conclusions/Significance By directly testing for differences between developed and undeveloped areas, and by modeling resource selection in a random-effects framework that provided individual-based inference, we conclude that: 1) amplified selection or avoidance behavior and individual variation, as responses to increasing human activity, complicate conservation planning in multiple-use landscapes, and 2) resource selection behavior in places where human activity is predictable or less dynamic may provide a more reliable basis from which to prioritize conservation action. PMID:21297866

A Proteome-wide Domain-centric Perspective on Protein Phosphorylation *

PubMed Central

Palmeri, Antonio; Ausiello, Gabriele; Ferrè, Fabrizio; Helmer-Citterich, Manuela; Gherardini, Pier Federico

2014-01-01

Phosphorylation is a widespread post-translational modification that modulates the function of a large number of proteins. Here we show that a significant proportion of all the domains in the human proteome is significantly enriched or depleted in phosphorylation events. A substantial improvement in phosphosites prediction is achieved by leveraging this observation, which has not been tapped by existing methods. Phosphorylation sites are often not shared between multiple occurrences of the same domain in the proteome, even when the phosphoacceptor residue is conserved. This is partly because of different functional constraints acting on the same domain in different protein contexts. Moreover, by augmenting domain alignments with structural information, we were able to provide direct evidence that phosphosites in protein-protein interfaces need not be positionally conserved, likely because they can modulate interactions simply by sitting in the same general surface area. PMID:24830415

Cloning, expression and phylogenetic analysis of Hemolin, from the Chinese oak silkmoth, Antheraea pernyi.

PubMed

Li, Wenli; Terenius, Olle; Hirai, Makoto; Nilsson, Anders S; Faye, Ingrid

2005-01-01

The Chinese oak silk moth Antheraea pernyi is an important silk producer. To understand microbial resistance of this moth, we cloned Hemolin, encoding a multifunctional immune protein belonging to the immunoglobulin superfamily, and examined the expression in gonads and fat body. The ApHemolin amino acid sequence was compared to other Hemolin sequences in order to predict functional sites. Several sites were conserved; among them a phosphate binding site, which according to 3D structure modelling does not appear in neuroglian, the phylogenetically closest related protein. In addition, two conserved KDG sequences in the C-C' loop of immunoglobulin domains 1 and 3, give rise to gamma-turns, which is a common motif in the C'-C'' loop of the hypervariable region L2 in vertebrate immunoglobulins. The comparisons also show variable regions of specific interest for future studies of hemolin and its interaction with microbial entities.

DsaV methyltransferase and its isoschizomers contain a conserved segment that is similar to the segment in Hhai methyltransferase that is in contact with DNA bases.

PubMed Central

Gopal, J; Yebra, M J; Bhagwat, A S

1994-01-01

The methyltransferase (MTase) in the DsaV restriction--modification system methylates within 5'-CCNGG sequences. We have cloned the gene for this MTase and determined its sequence. The predicted sequence of the MTase protein contains sequence motifs conserved among all cytosine-5 MTases and is most similar to other MTases that methylate CCNGG sequences, namely M.ScrFI and M.SsoII. All three MTases methylate the internal cytosine within their recognition sequence. The 'variable' region within the three enzymes that methylate CCNGG can be aligned with the sequences of two enzymes that methylate CCWGG sequences. Remarkably, two segments within this region contain significant similarity with the region of M.HhaI that is known to contact DNA bases. These alignments suggest that many cytosine-5 MTases are likely to interact with DNA using a similar structural framework. Images PMID:7971279

Selection of the simplest RNA that binds isoleucine

PubMed Central

LOZUPONE, CATHERINE; CHANGAYIL, SHANKAR; MAJERFELD, IRENE; YARUS, MICHAEL

2003-01-01

We have identified the simplest RNA binding site for isoleucine using selection-amplification (SELEX), by shrinking the size of the randomized region until affinity selection is extinguished. Such a protocol can be useful because selection does not necessarily make the simplest active motif most prominent, as is often assumed. We find an isoleucine binding site that behaves exactly as predicted for the site that requires fewest nucleotides. This UAUU motif (16 highly conserved positions; 27 total), is also the most abundant site in successful selections on short random tracts. The UAUU site, now isolated independently at least 63 times, is a small asymmetric internal loop. Conserved loop sequences include isoleucine codon and anticodon triplets, whose nucleotides are required for amino acid binding. This reproducible association between isoleucine and its coding sequences supports the idea that the genetic code is, at least in part, a stereochemical residue of the most easily isolated RNA–amino acid binding structures. PMID:14561881

Laplace-Runge-Lenz vector in quantum mechanics in noncommutative space

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gáliková, Veronika; Kováčik, Samuel; Prešnajder, Peter

2013-12-15

The main point of this paper is to examine a “hidden” dynamical symmetry connected with the conservation of Laplace-Runge-Lenz vector (LRL) in the hydrogen atom problem solved by means of non-commutative quantum mechanics (NCQM). The basic features of NCQM will be introduced to the reader, the key one being the fact that the notion of a point, or a zero distance in the considered configuration space, is abandoned and replaced with a “fuzzy” structure in such a way that the rotational invariance is preserved. The main facts about the conservation of LRL vector in both classical and quantum theory willmore » be reviewed. Finally, we will search for an analogy in the NCQM, provide our results and their comparison with the QM predictions. The key notions we are going to deal with are non-commutative space, Coulomb-Kepler problem, and symmetry.« less

Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies.

PubMed

Zhang, Shuxiao; Ross, Kevin D; Seidner, Glen A; Gorman, Michael R; Poon, Tiffany H; Wang, Xiaobo; Keithley, Elizabeth M; Lee, Patricia N; Martindale, Mark Q; Joiner, William J; Hamilton, Bruce A

2015-07-01

Many protein-coding genes identified by genome sequencing remain without functional annotation or biological context. Here we define a novel protein-coding gene, Nmf9, based on a forward genetic screen for neurological function. ENU-induced and genome-edited null mutations in mice produce deficits in vestibular function, fear learning and circadian behavior, which correlated with Nmf9 expression in inner ear, amygdala, and suprachiasmatic nuclei. Homologous genes from unicellular organisms and invertebrate animals predict interactions with small GTPases, but the corresponding domains are absent in mammalian Nmf9. Intriguingly, homozygotes for null mutations in the Drosophila homolog, CG45058, show profound locomotor defects and premature death, while heterozygotes show striking effects on sleep and activity phenotypes. These results link a novel gene orthology group to discrete neurological functions, and show conserved requirement across wide phylogenetic distance and domain level structural changes.

Computing Axisymmetric Jet Screech Tones Using Unstructured Grids

NASA Technical Reports Server (NTRS)

Jorgenson, Philip C. E.; Loh, Ching Y.

2002-01-01

The space-time conservation element and solution element (CE/SE) method is used to solve the conservation law form of the compressible axisymmetric Navier-Stokes equations. The equations are time marched to predict the unsteady flow and the near-field screech tone noise issuing from an underexpanded circular jet. The CE/SE method uses an unstructured grid based data structure. The unstructured grids for these calculations are generated based on the method of Delaunay triangulation. The purpose of this paper is to show that an acoustics solution with a feedback loop can be obtained using truly unstructured grid technology. Numerical results are presented for two different nozzle geometries. The first is considered to have a thin nozzle lip and the second has a thick nozzle lip. Comparisons with available experimental data are shown for flows corresponding to several different jet Mach numbers. Generally good agreement is obtained in terms of flow physics, screech tone frequency, and sound pressure level.

Science communication and vernal pool conservation: a study of local decision maker attitudes in a knowledge-action system.

PubMed

McGreavy, Bridie; Webler, Thomas; Calhoun, Aram J K

2012-03-01

In this study, we describe local decision maker attitudes towards vernal pools to inform science communication and enhance vernal pool conservation efforts. We conducted interviews with town planning board and conservation commission members (n = 9) from two towns in the State of Maine in the northeastern United States. We then mailed a questionnaire to a stratified random sample of planning board members in August and September 2007 with a response rate of 48.4% (n = 320). The majority of survey respondents favored the protection and conservation of vernal pools in their towns. Decision makers were familiar with the term "vernal pool" and demonstrated positive attitudes to vernal pools in general. General appreciation and willingness to conserve vernal pools predicted support for the 2006 revisions to the Natural Resource Protection Act regulating Significant Vernal Pools. However, 48% of respondents were unaware of this law and neither prior knowledge of the law nor workshop attendance predicted support for the vernal pool law. Further, concerns about private property rights and development restrictions predicted disagreement with the vernal pool law. We conclude that science communication must rely on specific frames of reference, be sensitive to cultural values, and occur in an iterative system to link knowledge and action in support of vernal pool conservation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Marker genes that are less conserved in their sequences are useful for predicting genome-wide similarity levels between closely related prokaryotic strains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lan, Yemin; Rosen, Gail; Hershberg, Ruth

The 16s rRNA gene is so far the most widely used marker for taxonomical classification and separation of prokaryotes. Since it is universally conserved among prokaryotes, it is possible to use this gene to classify a broad range of prokaryotic organisms. At the same time, it has often been noted that the 16s rRNA gene is too conserved to separate between prokaryotes at finer taxonomic levels. In this paper, we examine how well levels of similarity of 16s rRNA and 73 additional universal or nearly universal marker genes correlate with genome-wide levels of gene sequence similarity. We demonstrate that themore » percent identity of 16s rRNA predicts genome-wide levels of similarity very well for distantly related prokaryotes, but not for closely related ones. In closely related prokaryotes, we find that there are many other marker genes for which levels of similarity are much more predictive of genome-wide levels of gene sequence similarity. Finally, we show that the identities of the markers that are most useful for predicting genome-wide levels of similarity within closely related prokaryotic lineages vary greatly between lineages. However, the most useful markers are always those that are least conserved in their sequences within each lineage. In conclusion, our results show that by choosing markers that are less conserved in their sequences within a lineage of interest, it is possible to better predict genome-wide gene sequence similarity between closely related prokaryotes than is possible using the 16s rRNA gene. We point readers towards a database we have created (POGO-DB) that can be used to easily establish which markers show lowest levels of sequence conservation within different prokaryotic lineages.« less

Marker genes that are less conserved in their sequences are useful for predicting genome-wide similarity levels between closely related prokaryotic strains

DOE PAGES

Lan, Yemin; Rosen, Gail; Hershberg, Ruth

2016-05-03

The 16s rRNA gene is so far the most widely used marker for taxonomical classification and separation of prokaryotes. Since it is universally conserved among prokaryotes, it is possible to use this gene to classify a broad range of prokaryotic organisms. At the same time, it has often been noted that the 16s rRNA gene is too conserved to separate between prokaryotes at finer taxonomic levels. In this paper, we examine how well levels of similarity of 16s rRNA and 73 additional universal or nearly universal marker genes correlate with genome-wide levels of gene sequence similarity. We demonstrate that themore » percent identity of 16s rRNA predicts genome-wide levels of similarity very well for distantly related prokaryotes, but not for closely related ones. In closely related prokaryotes, we find that there are many other marker genes for which levels of similarity are much more predictive of genome-wide levels of gene sequence similarity. Finally, we show that the identities of the markers that are most useful for predicting genome-wide levels of similarity within closely related prokaryotic lineages vary greatly between lineages. However, the most useful markers are always those that are least conserved in their sequences within each lineage. In conclusion, our results show that by choosing markers that are less conserved in their sequences within a lineage of interest, it is possible to better predict genome-wide gene sequence similarity between closely related prokaryotes than is possible using the 16s rRNA gene. We point readers towards a database we have created (POGO-DB) that can be used to easily establish which markers show lowest levels of sequence conservation within different prokaryotic lineages.« less

Landscapes for Energy and Wildlife: Conservation Prioritization for Golden Eagles across Large Spatial Scales

PubMed Central

Tack, Jason D.; Fedy, Bradley C.

2015-01-01

Proactive conservation planning for species requires the identification of important spatial attributes across ecologically relevant scales in a model-based framework. However, it is often difficult to develop predictive models, as the explanatory data required for model development across regional management scales is rarely available. Golden eagles are a large-ranging predator of conservation concern in the United States that may be negatively affected by wind energy development. Thus, identifying landscapes least likely to pose conflict between eagles and wind development via shared space prior to development will be critical for conserving populations in the face of imposing development. We used publically available data on golden eagle nests to generate predictive models of golden eagle nesting sites in Wyoming, USA, using a suite of environmental and anthropogenic variables. By overlaying predictive models of golden eagle nesting habitat with wind energy resource maps, we highlight areas of potential conflict among eagle nesting habitat and wind development. However, our results suggest that wind potential and the relative probability of golden eagle nesting are not necessarily spatially correlated. Indeed, the majority of our sample frame includes areas with disparate predictions between suitable nesting habitat and potential for developing wind energy resources. Map predictions cannot replace on-the-ground monitoring for potential risk of wind turbines on wildlife populations, though they provide industry and managers a useful framework to first assess potential development. PMID:26262876

Landscapes for energy and wildlife: conservation prioritization for golden eagles across large spatial scales

USGS Publications Warehouse

Tack, Jason D.; Fedy, Bradley C.

2015-01-01

Proactive conservation planning for species requires the identification of important spatial attributes across ecologically relevant scales in a model-based framework. However, it is often difficult to develop predictive models, as the explanatory data required for model development across regional management scales is rarely available. Golden eagles are a large-ranging predator of conservation concern in the United States that may be negatively affected by wind energy development. Thus, identifying landscapes least likely to pose conflict between eagles and wind development via shared space prior to development will be critical for conserving populations in the face of imposing development. We used publically available data on golden eagle nests to generate predictive models of golden eagle nesting sites in Wyoming, USA, using a suite of environmental and anthropogenic variables. By overlaying predictive models of golden eagle nesting habitat with wind energy resource maps, we highlight areas of potential conflict among eagle nesting habitat and wind development. However, our results suggest that wind potential and the relative probability of golden eagle nesting are not necessarily spatially correlated. Indeed, the majority of our sample frame includes areas with disparate predictions between suitable nesting habitat and potential for developing wind energy resources. Map predictions cannot replace on-the-ground monitoring for potential risk of wind turbines on wildlife populations, though they provide industry and managers a useful framework to first assess potential development.

Landscapes for Energy and Wildlife: Conservation Prioritization for Golden Eagles across Large Spatial Scales.

PubMed

Tack, Jason D; Fedy, Bradley C

2015-01-01

Proactive conservation planning for species requires the identification of important spatial attributes across ecologically relevant scales in a model-based framework. However, it is often difficult to develop predictive models, as the explanatory data required for model development across regional management scales is rarely available. Golden eagles are a large-ranging predator of conservation concern in the United States that may be negatively affected by wind energy development. Thus, identifying landscapes least likely to pose conflict between eagles and wind development via shared space prior to development will be critical for conserving populations in the face of imposing development. We used publically available data on golden eagle nests to generate predictive models of golden eagle nesting sites in Wyoming, USA, using a suite of environmental and anthropogenic variables. By overlaying predictive models of golden eagle nesting habitat with wind energy resource maps, we highlight areas of potential conflict among eagle nesting habitat and wind development. However, our results suggest that wind potential and the relative probability of golden eagle nesting are not necessarily spatially correlated. Indeed, the majority of our sample frame includes areas with disparate predictions between suitable nesting habitat and potential for developing wind energy resources. Map predictions cannot replace on-the-ground monitoring for potential risk of wind turbines on wildlife populations, though they provide industry and managers a useful framework to first assess potential development.

Prediction of active sites of enzymes by maximum relevance minimum redundancy (mRMR) feature selection.

PubMed

Gao, Yu-Fei; Li, Bi-Qing; Cai, Yu-Dong; Feng, Kai-Yan; Li, Zhan-Dong; Jiang, Yang

2013-01-27

Identification of catalytic residues plays a key role in understanding how enzymes work. Although numerous computational methods have been developed to predict catalytic residues and active sites, the prediction accuracy remains relatively low with high false positives. In this work, we developed a novel predictor based on the Random Forest algorithm (RF) aided by the maximum relevance minimum redundancy (mRMR) method and incremental feature selection (IFS). We incorporated features of physicochemical/biochemical properties, sequence conservation, residual disorder, secondary structure and solvent accessibility to predict active sites of enzymes and achieved an overall accuracy of 0.885687 and MCC of 0.689226 on an independent test dataset. Feature analysis showed that every category of the features except disorder contributed to the identification of active sites. It was also shown via the site-specific feature analysis that the features derived from the active site itself contributed most to the active site determination. Our prediction method may become a useful tool for identifying the active sites and the key features identified by the paper may provide valuable insights into the mechanism of catalysis.

The impact of p53 protein core domain structural alteration on ovarian cancer survival.

PubMed

Rose, Stephen L; Robertson, Andrew D; Goodheart, Michael J; Smith, Brian J; DeYoung, Barry R; Buller, Richard E

2003-09-15

Although survival with a p53 missense mutation is highly variable, p53-null mutation is an independent adverse prognostic factor for advanced stage ovarian cancer. By evaluating ovarian cancer survival based upon a structure function analysis of the p53 protein, we tested the hypothesis that not all missense mutations are equivalent. The p53 gene was sequenced from 267 consecutive ovarian cancers. The effect of individual missense mutations on p53 structure was analyzed using the International Agency for Research on Cancer p53 Mutational Database, which specifies the effects of p53 mutations on p53 core domain structure. Mutations in the p53 core domain were classified as either explained or not explained in structural or functional terms by their predicted effects on protein folding, protein-DNA contacts, or mutation in highly conserved residues. Null mutations were classified by their mechanism of origin. Mutations were sequenced from 125 tumors. Effects of 62 of the 82 missense mutations (76%) could be explained by alterations in the p53 protein. Twenty-three (28%) of the explained mutations occurred in highly conserved regions of the p53 core protein. Twenty-two nonsense point mutations and 21 frameshift null mutations were sequenced. Survival was independent of missense mutation type and mechanism of null mutation. The hypothesis that not all missense mutations are equivalent is, therefore, rejected. Furthermore, p53 core domain structural alteration secondary to missense point mutation is not functionally equivalent to a p53-null mutation. The poor prognosis associated with p53-null mutation is independent of the mutation mechanism.

Novel high-performance purification protocol of recombinant CNBP suitable for biochemical and biophysical characterization.

PubMed

Challier, Emilse; Lisa, María-Natalia; Nerli, Bibiana B; Calcaterra, Nora B; Armas, Pablo

2014-01-01

Cellular nucleic acid binding protein (CNBP) is a highly conserved multi-zinc knuckle protein that enhances c-MYC expression, is related to certain human muscular diseases and is required for proper rostral head development. CNBP binds to single-stranded DNA (ssDNA) and RNA and acts as nucleic acid chaperone. Despite the advances made concerning CNBP biological roles, a full knowledge about the structure-function relationship has not yet been achieved, likely due to difficulty in obtaining pure and tag-free CNBP. Here, we report a fast, simple, reproducible, and high-performance expression and purification protocol that provides recombinant tag-free CNBP from Escherichia coli cultures. We determined that tag-free CNBP binds its molecular targets with higher affinity than tagged-CNBP. Furthermore, fluorescence spectroscopy revealed the presence of a unique and conserved tryptophan, which is exposed to the solvent and involved, directly or indirectly, in nucleic acid binding. Size-exclusion HPLC revealed that CNBP forms homodimers independently of nucleic acid binding and coexist with monomers as non-interconvertible forms or in slow equilibrium. Circular dichroism spectroscopy showed that CNBP has a secondary structure dominated by random-coil and β-sheet coincident with the sequence-predicted repetitive zinc knuckles motifs, which folding is required for CNBP structural stability and biochemical activity. CNBP structural stability increased in the presence of single-stranded nucleic acid targets similar to other unstructured nucleic acid chaperones. Altogether, data suggest that CNBP is a flexible protein with interspersed structured zinc knuckles, and acquires a more rigid structure upon nucleic acid binding. Copyright © 2013 Elsevier Inc. All rights reserved.

Modular structural elements in the replication origin region of Tetrahymena rDNA.

PubMed Central

Du, C; Sanzgiri, R P; Shaiu, W L; Choi, J K; Hou, Z; Benbow, R M; Dobbs, D L

1995-01-01

Computer analyses of the DNA replication origin region in the amplified rRNA genes of Tetrahymena thermophila identified a potential initiation zone in the 5'NTS [Dobbs, Shaiu and Benbow (1994), Nucleic Acids Res. 22, 2479-2489]. This region consists of a putative DNA unwinding element (DUE) aligned with predicted bent DNA segments, nuclear matrix or scaffold associated region (MAR/SAR) consensus sequences, and other common modular sequence elements previously shown to be clustered in eukaryotic chromosomal origin regions. In this study, two mung bean nuclease-hypersensitive sites in super-coiled plasmid DNA were localized within the major DUE-like element predicted by thermodynamic analyses. Three restriction fragments of the 5'NTS region predicted to contain bent DNA segments exhibited anomalous migration characteristic of bent DNA during electrophoresis on polyacrylamide gels. Restriction fragments containing the 5'NTS region bound Tetrahymena nuclear matrices in an in vitro binding assay, consistent with an association of the replication origin region with the nuclear matrix in vivo. The direct demonstration in a protozoan origin region of elements previously identified in Drosophila, chick and mammalian origin regions suggests that clusters of modular structural elements may be a conserved feature of eukaryotic chromosomal origins of replication. Images PMID:7784181

Predicting effects of climate change on the composition and function of soil microbial communities

NASA Astrophysics Data System (ADS)

Dubinsky, E.; Brodie, E.; Myint, C.; Ackerly, D.; van Nostrand, J.; Bird, J.; Zhou, J.; Andersen, G.; Firestone, M.

2008-12-01

Complex soil microbial communities regulate critical ecosystem processes that will be altered by climate change. A critical step towards predicting the impacts of climate change on terrestrial ecosystems is to determine the primary controllers of soil microbial community composition and function, and subsequently evaluate climate change scenarios that alter these controllers. We surveyed complex soil bacterial and archaeal communities across a range of climatic and edaphic conditions to identify critical controllers of soil microbial community composition in the field and then tested the resulting predictions using a 2-year manipulation of precipitation and temperature using mesocosms of California annual grasslands. Community DNA extracted from field soils sampled from six different ecosystems was assayed for bacterial and archaeal communities using high-density phylogenetic microarrays as well as functional gene arrays. Correlations among the relative abundances of thousands of microbial taxa and edaphic factors such as soil moisture and nutrient content provided a basis for predicting community responses to changing soil conditions. Communities of soil bacteria and archaea were strongly structured by single environmental predictors, particularly variables related to soil water. Bacteria in the Actinomycetales and Bacilli consistently demonstrated a strong negative response to increasing soil moisture, while taxa in a greater variety of lineages responded positively to increasing soil moisture. In the climate change experiment, overall bacterial community structure was impacted significantly by total precipitation but not by plant species. Changes in soil moisture due to decreased rainfall resulted in significant and predictable alterations in community structure. Over 70% of the bacterial taxa in common with the cross-ecosystem study responded as predicted to altered precipitation, with the most conserved response from Actinobacteria. The functional consequences of these predictable changes in community composition were measured with functional arrays that detect genes involved in the metabolism of carbon, nitrogen and other elements. The response of soil microbial communities to altered precipitation can be predicted from the distribution of microbial taxa across moisture gradients.

Using changes in agricultural utility to quantify future climate-induced risk to conservation.

PubMed

Estes, Lyndon D; Paroz, Lydie-Line; Bradley, Bethany A; Green, Jonathan M H; Hole, David G; Holness, Stephen; Ziv, Guy; Oppenheimer, Michael G; Wilcove, David S

2014-04-01

Much of the biodiversity-related climate change impacts research has focused on the direct effects to species and ecosystems. Far less attention has been paid to the potential ecological consequences of human efforts to address the effects of climate change, which may equal or exceed the direct effects of climate change on biodiversity. One of the most significant human responses is likely to be mediated through changes in the agricultural utility of land. As farmers adapt their practices to changing climates, they may increase pressure on some areas that are important to conserve (conservation lands) whereas lessening it on others. We quantified how the agricultural utility of South African conservation lands may be altered by climate change. We assumed that the probability of an area being farmed is linked to the economic benefits of doing so, using land productivity values to represent production benefit and topographic ruggedness as a proxy for costs associated with mechanical workability. We computed current and future values of maize and wheat production in key conservation lands using the DSSAT4.5 model and 36 crop-climate response scenarios. Most conservation lands had, and were predicted to continue to have, low agricultural utility because of their location in rugged terrain. However, several areas were predicted to maintain or gain high agricultural utility and may therefore be at risk of near-term or future conversion to cropland. Conversely, some areas were predicted to decrease in agricultural utility and may therefore prove easier to protect from conversion. Our study provides an approximate but readily transferable method for incorporating potential human responses to climate change into conservation planning. © 2013 Society for Conservation Biology.

Comparison of five modelling techniques to predict the spatial distribution and abundance of seabirds

USGS Publications Warehouse

O'Connell, Allan F.; Gardner, Beth; Oppel, Steffen; Meirinho, Ana; Ramírez, Iván; Miller, Peter I.; Louzao, Maite

2012-01-01

Knowledge about the spatial distribution of seabirds at sea is important for conservation. During marine conservation planning, logistical constraints preclude seabird surveys covering the complete area of interest and spatial distribution of seabirds is frequently inferred from predictive statistical models. Increasingly complex models are available to relate the distribution and abundance of pelagic seabirds to environmental variables, but a comparison of their usefulness for delineating protected areas for seabirds is lacking. Here we compare the performance of five modelling techniques (generalised linear models, generalised additive models, Random Forest, boosted regression trees, and maximum entropy) to predict the distribution of Balearic Shearwaters (Puffinus mauretanicus) along the coast of the western Iberian Peninsula. We used ship transect data from 2004 to 2009 and 13 environmental variables to predict occurrence and density, and evaluated predictive performance of all models using spatially segregated test data. Predicted distribution varied among the different models, although predictive performance varied little. An ensemble prediction that combined results from all five techniques was robust and confirmed the existence of marine important bird areas for Balearic Shearwaters in Portugal and Spain. Our predictions suggested additional areas that would be of high priority for conservation and could be proposed as protected areas. Abundance data were extremely difficult to predict, and none of five modelling techniques provided a reliable prediction of spatial patterns. We advocate the use of ensemble modelling that combines the output of several methods to predict the spatial distribution of seabirds, and use these predictions to target separate surveys assessing the abundance of seabirds in areas of regular use.

Hydration in drug design. 3. Conserved water molecules at the ligand-binding sites of homologous proteins

NASA Astrophysics Data System (ADS)

Poornima, C. S.; Dean, P. M.

1995-12-01

Water molecules are known to play an important rôle in mediating protein-ligand interactions. If water molecules are conserved at the ligand-binding sites of homologous proteins, such a finding may suggest the structural importance of water molecules in ligand binding. Structurally conserved water molecules change the conventional definition of `binding sites' by changing the shape and complementarity of these sites. Such conserved water molecules can be important for site-directed ligand/drug design. Therefore, five different sets of homologous protein/protein-ligand complexes have been examined to identify the conserved water molecules at the ligand-binding sites. Our analysis reveals that there are as many as 16 conserved water molecules at the FAD binding site of glutathione reductase between the crystal structures obtained from human and E. coli. In the remaining four sets of high-resolution crystal structures, 2-4 water molecules have been found to be conserved at the ligand-binding sites. The majority of these conserved water molecules are either bound in deep grooves at the protein-ligand interface or completely buried in cavities between the protein and the ligand. All these water molecules, conserved between the protein/protein-ligand complexes from different species, have identical or similar apolar and polar interactions in a given set. The site residues interacting with the conserved water molecules at the ligand-binding sites have been found to be highly conserved among proteins from different species; they are more conserved compared to the other site residues interacting with the ligand. These water molecules, in general, make multiple polar contacts with protein-site residues.

High diversification of CD94 by alternative splicing in New World primates.

PubMed

Galindo, John A; Cadavid, Luis F

2013-04-01

CD94 forms heterodimers with NKG2A, -C, or -E to constitute lectin-like natural killer cell receptors for MHC-E. Its structure differs from other C-type lectins in that the second α-helix is replaced by a loop that forms the interacting interface with the NKG2 molecules. Although CD94 has remained highly conserved mammals, several alternative splicing variants have been detected in some species. To evaluate the prevalence and significance of this phenomenon, we have cloned and sequenced CD94 cDNAs in six species of New World primates from the Cebidae and Atelidae families. Full-length sequences had a mean similarity of 96 % amongst New World primates and of 90 % to the human orthologue, with little variation in the residues interacting with NKG2 or MHC-E molecules. Despite this high conservation, a total of 14 different splice variants were identified, half of which were shared by two or more primate species. Homology-based modeling of the C-type lectin domain showed that most isoforms folded stably, although they had modifications that prevented its interaction with NKG2 and MHC-E. Two isoforms were predicted to replace the typical CD94 loop by a second α-helix, evidencing a domain fold transition from a CD94 structure to a canonical C-type lectin. These two structures were more similar to members of the CLEC lectin family than to the native CD94. Thus, CD94 has remained conserved in primates to maintain functional interactions with NKG2 and MHC-E, while at the same time has diversified by alternative splicing potentially providing additional functional scenarios.

Characterization of stress-responsive lncRNAs in Arabidopsis thaliana by integrating expression, epigenetic and structural features.

PubMed

Di, Chao; Yuan, Jiapei; Wu, Yue; Li, Jingrui; Lin, Huixin; Hu, Long; Zhang, Ting; Qi, Yijun; Gerstein, Mark B; Guo, Yan; Lu, Zhi John

2014-12-01

Recently, in addition to poly(A)+ long non-coding RNAs (lncRNAs), many lncRNAs without poly(A) tails, have been characterized in mammals. However, the non-polyA lncRNAs and their conserved motifs, especially those associated with environmental stresses, have not been fully investigated in plant genomes. We performed poly(A)- RNA-seq for seedlings of Arabidopsis thaliana under four stress conditions, and predicted lncRNA transcripts. We classified the lncRNAs into three confidence levels according to their expression patterns, epigenetic signatures and RNA secondary structures. Then, we further classified the lncRNAs to poly(A)+ and poly(A)- transcripts. Compared with poly(A)+ lncRNAs and coding genes, we found that poly(A)- lncRNAs tend to have shorter transcripts and lower expression levels, and they show significant expression specificity in response to stresses. In addition, their differential expression is significantly enriched in drought condition and depleted in heat condition. Overall, we identified 245 poly(A)+ and 58 poly(A)- lncRNAs that are differentially expressed under various stress stimuli. The differential expression was validated by qRT-PCR, and the signaling pathways involved were supported by specific binding of transcription factors (TFs), phytochrome-interacting factor 4 (PIF4) and PIF5. Moreover, we found many conserved sequence and structural motifs of lncRNAs from different functional groups (e.g. a UUC motif responding to salt and a AU-rich stem-loop responding to cold), indicated that the conserved elements might be responsible for the stress-responsive functions of lncRNAs. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Hamiltonian structures for systems of hyperbolic conservation laws

NASA Astrophysics Data System (ADS)

Olver, Peter J.; Nutku, Yavuz

1988-07-01

The bi-Hamiltonian structure for a large class of one-dimensional hyberbolic systems of conservation laws in two field variables, including the equations of gas dynamics, shallow water waves, one-dimensional elastic media, and the Born-Infeld equation from nonlinear electrodynamics, is exhibited. For polytropic gas dynamics, these results lead to a quadri-Hamiltonian structure. New higher-order entropy-flux pairs (conservation laws) and higher-order symmetries are exhibited.

Flight-determined stability analysis of multiple-input-multiple-output control systems

NASA Technical Reports Server (NTRS)

Burken, John J.

1992-01-01

Singular value analysis can give conservative stability margin results. Applying structure to the uncertainty can reduce this conservatism. This paper presents flight-determined stability margins for the X-29A lateral-directional, multiloop control system. These margins are compared with the predicted unscaled singular values and scaled structured singular values. The algorithm was further evaluated with flight data by changing the roll-rate-to-aileron command-feedback gain by +/- 20 percent. Minimum eigenvalues of the return difference matrix which bound the singular values are also presented. Extracting multiloop singular values from flight data and analyzing the feedback gain variations validates this technique as a measure of robustness. This analysis can be used for near-real-time flight monitoring and safety testing.

Flight-determined stability analysis of multiple-input-multiple-output control systems

NASA Technical Reports Server (NTRS)

Burken, John J.

1992-01-01

Singular value analysis can give conservative stability margin results. Applying structure to the uncertainty can reduce this conservatism. This paper presents flight-determined stability margins for the X-29A lateral-directional, multiloop control system. These margins are compared with the predicted unscaled singular values and scaled structured singular values. The algorithm was further evaluated with flight data by changing the roll-rate-to-aileron-command-feedback gain by +/- 20 percent. Also presented are the minimum eigenvalues of the return difference matrix which bound the singular values. Extracting multiloop singular values from flight data and analyzing the feedback gain variations validates this technique as a measure of robustness. This analysis can be used for near-real-time flight monitoring and safety testing.

Predictive Computational Modeling of Chromatin Folding

NASA Astrophysics Data System (ADS)

di Pierro, Miichele; Zhang, Bin; Wolynes, Peter J.; Onuchic, Jose N.

In vivo, the human genome folds into well-determined and conserved three-dimensional structures. The mechanism driving the folding process remains unknown. We report a theoretical model (MiChroM) for chromatin derived by using the maximum entropy principle. The proposed model allows Molecular Dynamics simulations of the genome using as input the classification of loci into chromatin types and the presence of binding sites of loop forming protein CTCF. The model was trained to reproduce the Hi-C map of chromosome 10 of human lymphoblastoid cells. With no additional tuning the model was able to predict accurately the Hi-C maps of chromosomes 1-22 for the same cell line. Simulations show unknotted chromosomes, phase separation of chromatin types and a preference of chromatin of type A to sit at the periphery of the chromosomes.

Comparative genomics of Eucalyptus and Corymbia reveals low rates of genome structural rearrangement.

PubMed

Butler, J B; Vaillancourt, R E; Potts, B M; Lee, D J; King, G J; Baten, A; Shepherd, M; Freeman, J S

2017-05-22

Previous studies suggest genome structure is largely conserved between Eucalyptus species. However, it is unknown if this conservation extends to more divergent eucalypt taxa. We performed comparative genomics between the eucalypt genera Eucalyptus and Corymbia. Our results will facilitate transfer of genomic information between these important taxa and provide further insights into the rate of structural change in tree genomes. We constructed three high density linkage maps for two Corymbia species (Corymbia citriodora subsp. variegata and Corymbia torelliana) which were used to compare genome structure between both species and Eucalyptus grandis. Genome structure was highly conserved between the Corymbia species. However, the comparison of Corymbia and E. grandis suggests large (from 1-13 MB) intra-chromosomal rearrangements have occurred on seven of the 11 chromosomes. Most rearrangements were supported through comparisons of the three independent Corymbia maps to the E. grandis genome sequence, and to other independently constructed Eucalyptus linkage maps. These are the first large scale chromosomal rearrangements discovered between eucalypts. Nonetheless, in the general context of plants, the genomic structure of the two genera was remarkably conserved; adding to a growing body of evidence that conservation of genome structure is common amongst woody angiosperms.

Planning for bird conservation: a tale of two models

Treesearch

Douglas H. Johnson; Maiken Winter

2005-01-01

Planning for bird conservation has become increasingly reliant on remote sensing, geographical information systems, and, especially, models used to predict the occurrence of bird species as well as their density and demographics. We address the role of such tools by contrasting two models used in bird conservation. One, the Mallard (Anas platyrhynchos...

Estimating Landholders’ Probability of Participating in a Stewardship Program, and the Implications for Spatial Conservation Priorities

PubMed Central

Adams, Vanessa M.; Pressey, Robert L.; Stoeckl, Natalie

2014-01-01

The need to integrate social and economic factors into conservation planning has become a focus of academic discussions and has important practical implications for the implementation of conservation areas, both private and public. We conducted a survey in the Daly Catchment, Northern Territory, to inform the design and implementation of a stewardship payment program. We used a choice model to estimate the likely level of participation in two legal arrangements - conservation covenants and management agreements - based on payment level and proportion of properties required to be managed. We then spatially predicted landholders’ probability of participating at the resolution of individual properties and incorporated these predictions into conservation planning software to examine the potential for the stewardship program to meet conservation objectives. We found that the properties that were least costly, per unit area, to manage were also the least likely to participate. This highlights a tension between planning for a cost-effective program and planning for a program that targets properties with the highest probability of participation. PMID:24892520

Interactions among ecosystem stressors and their importance in conservation

PubMed Central

Darling, Emily S.; Brown, Christopher J.

2016-01-01

Interactions between multiple ecosystem stressors are expected to jeopardize biological processes, functions and biodiversity. The scientific community has declared stressor interactions—notably synergies—a key issue for conservation and management. Here, we review ecological literature over the past four decades to evaluate trends in the reporting of ecological interactions (synergies, antagonisms and additive effects) and highlight the implications and importance to conservation. Despite increasing popularity, and ever-finer terminologies, we find that synergies are (still) not the most prevalent type of interaction, and that conservation practitioners need to appreciate and manage for all interaction outcomes, including antagonistic and additive effects. However, it will not be possible to identify the effect of every interaction on every organism's physiology and every ecosystem function because the number of stressors, and their potential interactions, are growing rapidly. Predicting the type of interactions may be possible in the near-future, using meta-analyses, conservation-oriented experiments and adaptive monitoring. Pending a general framework for predicting interactions, conservation management should enact interventions that are robust to uncertainty in interaction type and that continue to bolster biological resilience in a stressful world. PMID:26865306

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase.

PubMed

Zemla, Adam T; Lang, Dorothy M; Kostova, Tanya; Andino, Raul; Ecale Zhou, Carol L

2011-06-02

Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.

Structure-sequence based analysis for identification of conserved regions in proteins

DOEpatents

Zemla, Adam T; Zhou, Carol E; Lam, Marisa W; Smith, Jason R; Pardes, Elizabeth

2013-05-28

Disclosed are computational methods, and associated hardware and software products for scoring conservation in a protein structure based on a computationally identified family or cluster of protein structures. A method of computationally identifying a family or cluster of protein structures in also disclosed herein.

Political conservatism predicts asymmetries in emotional scene memory.

PubMed

Mills, Mark; Gonzalez, Frank J; Giuseffi, Karl; Sievert, Benjamin; Smith, Kevin B; Hibbing, John R; Dodd, Michael D

2016-06-01

Variation in political ideology has been linked to differences in attention to and processing of emotional stimuli, with stronger responses to negative versus positive stimuli (negativity bias) the more politically conservative one is. As memory is enhanced by attention, such findings predict that memory for negative versus positive stimuli should similarly be enhanced the more conservative one is. The present study tests this prediction by having participants study 120 positive, negative, and neutral scenes in preparation for a subsequent memory test. On the memory test, the same 120 scenes were presented along with 120 new scenes and participants were to respond whether a scene was old or new. Results on the memory test showed that negative scenes were more likely to be remembered than positive scenes, though, this was true only for political conservatives. That is, a larger negativity bias was found the more conservative one was. The effect was sizeable, explaining 45% of the variance across subjects in the effect of emotion. These findings demonstrate that the relationship between political ideology and asymmetries in emotion processing extend to memory and, furthermore, suggest that exploring the extent to which subject variation in interactions among emotion, attention, and memory is predicted by conservatism may provide new insights into theories of political ideology. Published by Elsevier B.V.

Homology to peptide pattern for annotation of carbohydrate-active enzymes and prediction of function.

PubMed

Busk, P K; Pilgaard, B; Lezyk, M J; Meyer, A S; Lange, L

2017-04-12

Carbohydrate-active enzymes are found in all organisms and participate in key biological processes. These enzymes are classified in 274 families in the CAZy database but the sequence diversity within each family makes it a major task to identify new family members and to provide basis for prediction of enzyme function. A fast and reliable method for de novo annotation of genes encoding carbohydrate-active enzymes is to identify conserved peptides in the curated enzyme families followed by matching of the conserved peptides to the sequence of interest as demonstrated for the glycosyl hydrolase and the lytic polysaccharide monooxygenase families. This approach not only assigns the enzymes to families but also provides functional prediction of the enzymes with high accuracy. We identified conserved peptides for all enzyme families in the CAZy database with Peptide Pattern Recognition. The conserved peptides were matched to protein sequence for de novo annotation and functional prediction of carbohydrate-active enzymes with the Hotpep method. Annotation of protein sequences from 12 bacterial and 16 fungal genomes to families with Hotpep had an accuracy of 0.84 (measured as F1-score) compared to semiautomatic annotation by the CAZy database whereas the dbCAN HMM-based method had an accuracy of 0.77 with optimized parameters. Furthermore, Hotpep provided a functional prediction with 86% accuracy for the annotated genes. Hotpep is available as a stand-alone application for MS Windows. Hotpep is a state-of-the-art method for automatic annotation and functional prediction of carbohydrate-active enzymes.

Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin

PubMed Central

Bhutoria, Savita

2016-01-01

Abstract The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein‐protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV‐1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c‐MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. PMID:27261671

Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin.

PubMed

Bhutoria, Savita; Kalpana, Ganjam V; Acharya, Seetharama A

2016-09-01

The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein-protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV-1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c-MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined ββαα topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. © 2016 The Protein Society.

Type and Level of RMRP Functional Impairment Predicts Phenotype in the Cartilage Hair Hypoplasia–Anauxetic Dysplasia Spectrum

PubMed Central

Thiel, Christian T. ; Mortier, Geert ; Kaitila, Ilkka ; Reis, André ; Rauch, Anita 

2007-01-01

Mutations in the RMRP gene lead to a wide spectrum of autosomal recessive skeletal dysplasias, ranging from the milder phenotypes metaphyseal dysplasia without hypotrichosis and cartilage hair hypoplasia (CHH) to the severe anauxetic dysplasia (AD). This clinical spectrum includes different degrees of short stature, hair hypoplasia, defective erythrogenesis, and immunodeficiency. The RMRP gene encodes the untranslated RNA component of the mitochondrial RNA–processing ribonuclease, RNase MRP. We recently demonstrated that mutations may affect both messenger RNA (mRNA) and ribosomal RNA (rRNA) cleavage and thus cell-cycle regulation and protein synthesis. To investigate the genotype-phenotype correlation, we analyzed the position and the functional effect of 13 mutations in patients with variable features of the CHH-AD spectrum. Those at the end of the spectrum include a novel patient with anauxetic dysplasia who was compound heterozygous for the null mutation g.254_263delCTCAGCGCGG and the mutation g.195C→T, which was previously described in patients with milder phenotypes. Mapping of nucleotide conservation to the two-dimensional structure of the RMRP gene revealed that disease-causing mutations either affect evolutionarily conserved nucleotides or are likely to alter secondary structure through mispairing in stem regions. In vitro testing of RNase MRP multiprotein-specific mRNA and rRNA cleavage of different mutations revealed a strong correlation between the decrease in rRNA cleavage in ribosomal assembly and the degree of bone dysplasia, whereas reduced mRNA cleavage, and thus cell-cycle impairment, predicts the presence of hair hypoplasia, immunodeficiency, and hematological abnormalities and thus increased cancer risk. PMID:17701897

Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord

PubMed Central

José-Edwards, Diana S.; Oda-Ishii, Izumi; Kugler, Jamie E.; Passamaneck, Yale J.; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

2015-01-01

A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs. PMID:26684323

Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

PubMed

José-Edwards, Diana S; Oda-Ishii, Izumi; Kugler, Jamie E; Passamaneck, Yale J; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

2015-12-01

A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

Characterising and Predicting Benthic Biodiversity for Conservation Planning in Deepwater Environments

PubMed Central

Dunstan, Piers K.; Althaus, Franziska; Williams, Alan; Bax, Nicholas J.

2012-01-01

Understanding patterns of biodiversity in deep sea systems is increasingly important because human activities are extending further into these areas. However, obtaining data is difficult, limiting the ability of science to inform management decisions. We have used three different methods of quantifying biodiversity to describe patterns of biodiversity in an area that includes two marine reserves in deep water off southern Australia. We used biological data collected during a recent survey, combined with extensive physical data to model, predict and map three different attributes of biodiversity: distributions of common species, beta diversity and rank abundance distributions (RAD). The distribution of each of eight common species was unique, although all the species respond to a depth-correlated physical gradient. Changes in composition (beta diversity) were large, even between sites with very similar environmental conditions. Composition at any one site was highly uncertain, and the suite of species changed dramatically both across and down slope. In contrast, the distributions of the RAD components of biodiversity (community abundance, richness, and evenness) were relatively smooth across the study area, suggesting that assemblage structure (i.e. the distribution of abundances of species) is limited, irrespective of species composition. Seamounts had similar biodiversity based on metrics of species presence, beta diversity, total abundance, richness and evenness to the adjacent continental slope in the same depth ranges. These analyses suggest that conservation objectives need to clearly identify which aspects of biodiversity are valued, and employ an appropriate suite of methods to address these aspects, to ensure that conservation goals are met. PMID:22606271

Characterising and predicting benthic biodiversity for conservation planning in deepwater environments.

PubMed

Dunstan, Piers K; Althaus, Franziska; Williams, Alan; Bax, Nicholas J

2012-01-01

Understanding patterns of biodiversity in deep sea systems is increasingly important because human activities are extending further into these areas. However, obtaining data is difficult, limiting the ability of science to inform management decisions. We have used three different methods of quantifying biodiversity to describe patterns of biodiversity in an area that includes two marine reserves in deep water off southern Australia. We used biological data collected during a recent survey, combined with extensive physical data to model, predict and map three different attributes of biodiversity: distributions of common species, beta diversity and rank abundance distributions (RAD). The distribution of each of eight common species was unique, although all the species respond to a depth-correlated physical gradient. Changes in composition (beta diversity) were large, even between sites with very similar environmental conditions. Composition at any one site was highly uncertain, and the suite of species changed dramatically both across and down slope. In contrast, the distributions of the RAD components of biodiversity (community abundance, richness, and evenness) were relatively smooth across the study area, suggesting that assemblage structure (i.e. the distribution of abundances of species) is limited, irrespective of species composition. Seamounts had similar biodiversity based on metrics of species presence, beta diversity, total abundance, richness and evenness to the adjacent continental slope in the same depth ranges. These analyses suggest that conservation objectives need to clearly identify which aspects of biodiversity are valued, and employ an appropriate suite of methods to address these aspects, to ensure that conservation goals are met.

Herbicide and fertilizers promote analogous phylogenetic responses but opposite functional responses in plant communities

NASA Astrophysics Data System (ADS)

Pellissier, Loïc; Wisz, Mary S.; Strandberg, Beate; Damgaard, Christian

2014-01-01

Throughout the world, herbicides and fertilizers change species composition in agricultural communities, but how do the cumulative effects of these chemicals impact the functional and phylogenetic structure of non-targeted communities when they drift into adjacent semi-natural habitats? Based on long-term experiment we show that fertilizer and herbicides (glyphosate) have contrasting effects on functional structure, but can increase phylogenetic diversity in semi-natural plant communities. We found that an increase in nitrogen promoted an increase in the average specific leaf area and canopy height at the community level, but an increase in glyphosate promoted a decrease in those traits. Phylogenetic diversity of plant communities increased when herbicide and fertilizer were applied together, likely because functional traits facilitating plant success in those conditions were not phylogenetically conserved. Species richness also decreased with increasing levels of nitrogen and glyphosate. Our results suggest that predicting the cumulative effects of agrochemicals is more complex than anticipated due to their distinct selection of traits that may or may not be conserved phylogenetically. Precautionary efforts to mitigate drift of agricultural chemicals into semi-natural habitats are warranted to prevent unforeseeable biodiversity shifts.

Decadal stability in genetic variation and structure in the intertidal seaweed Fucus serratus (Heterokontophyta: Fucaceae).

PubMed

Jueterbock, Alexander; Coyer, James A; Olsen, Jeanine L; Hoarau, Galice

2018-06-15

The spatial distribution of genetic diversity and structure has important implications for conservation as it reveals a species' strong and weak points with regard to stability and evolutionary capacity. Temporal genetic stability is rarely tested in marine species other than commercially important fishes, but is crucial for the utility of temporal snapshots in conservation management. High and stable diversity can help to mitigate the predicted northward range shift of seaweeds under the impact of climate change. Given the key ecological role of fucoid seaweeds along rocky shores, the positive effect of genetic diversity may reach beyond the species level to stabilize the entire intertidal ecosystem along the temperate North Atlantic. In this study, we estimated the effective population size, as well as temporal changes in genetic structure and diversity of the seaweed F. serratus using 22 microsatellite markers. Samples were taken across latitudes and a range of temperature regimes at seven locations with decadal sampling (2000 and 2010). Across latitudes, genetic structure and diversity remained stable over 5-10 generations. Stable small-scale structure enhanced regional diversity throughout the species' range. In accordance with its biogeographic history, effective population size and diversity peaked in the species' mid-range in Brittany (France), and declined towards its leading and trailing edge to the north and south. At the species' southern edge, multi-locus-heterozygosity displayed a strong decline from 1999 to 2010. Temporally stable genetic structure over small spatial scales is a potential driver for local adaptation and species radiation in the genus Fucus. Survival and adaptation of the low-diversity leading edge of F. serratus may be enhanced by regional gene flow and 'surfing' of favorable mutations or impaired by the accumulation of deleterious mutations. Our results have clear implications for the conservation of F. serratus at its genetically unique southern edge in Northwest Iberia, where increasing temperatures are likely the major cause for the decline not only of F. serratus, but also other intertidal and subtidal macroalgae. We expect that F. serratus will disappear from Northwest Iberia by 2100 if genetic rescue is not induced by the influx of genetic variation from Brittany.

Multifunctionality and diversity of GDSL esterase/lipase gene family in rice (Oryza sativa L. japonica) genome: new insights from bioinformatics analysis

PubMed Central

2012-01-01

Background GDSL esterases/lipases are a newly discovered subclass of lipolytic enzymes that are very important and attractive research subjects because of their multifunctional properties, such as broad substrate specificity and regiospecificity. Compared with the current knowledge regarding these enzymes in bacteria, our understanding of the plant GDSL enzymes is very limited, although the GDSL gene family in plant species include numerous members in many fully sequenced plant genomes. Only two genes from a large rice GDSL esterase/lipase gene family were previously characterised, and the majority of the members remain unknown. In the present study, we describe the rice OsGELP (Oryza sativa GDSL esterase/lipase protein) gene family at the genomic and proteomic levels, and use this knowledge to provide insights into the multifunctionality of the rice OsGELP enzymes. Results In this study, an extensive bioinformatics analysis identified 114 genes in the rice OsGELP gene family. A complete overview of this family in rice is presented, including the chromosome locations, gene structures, phylogeny, and protein motifs. Among the OsGELPs and the plant GDSL esterase/lipase proteins of known functions, 41 motifs were found that represent the core secondary structure elements or appear specifically in different phylogenetic subclades. The specification and distribution of identified putative conserved clade-common and -specific peptide motifs, and their location on the predicted protein three dimensional structure may possibly signify their functional roles. Potentially important regions for substrate specificity are highlighted, in accordance with protein three-dimensional model and location of the phylogenetic specific conserved motifs. The differential expression of some representative genes were confirmed by quantitative real-time PCR. The phylogenetic analysis, together with protein motif architectures, and the expression profiling were analysed to predict the possible biological functions of the rice OsGELP genes. Conclusions Our current genomic analysis, for the first time, presents fundamental information on the organization of the rice OsGELP gene family. With combination of the genomic, phylogenetic, microarray expression, protein motif distribution, and protein structure analyses, we were able to create supported basis for the functional prediction of many members in the rice GDSL esterase/lipase family. The present study provides a platform for the selection of candidate genes for further detailed functional study. PMID:22793791

A Third Approach to Gene Prediction Suggests Thousands of Additional Human Transcribed Regions

PubMed Central

Glusman, Gustavo; Qin, Shizhen; El-Gewely, M. Raafat; Siegel, Andrew F; Roach, Jared C; Hood, Leroy; Smit, Arian F. A

2006-01-01

The identification and characterization of the complete ensemble of genes is a main goal of deciphering the digital information stored in the human genome. Many algorithms for computational gene prediction have been described, ultimately derived from two basic concepts: (1) modeling gene structure and (2) recognizing sequence similarity. Successful hybrid methods combining these two concepts have also been developed. We present a third orthogonal approach to gene prediction, based on detecting the genomic signatures of transcription, accumulated over evolutionary time. We discuss four algorithms based on this third concept: Greens and CHOWDER, which quantify mutational strand biases caused by transcription-coupled DNA repair, and ROAST and PASTA, which are based on strand-specific selection against polyadenylation signals. We combined these algorithms into an integrated method called FEAST, which we used to predict the location and orientation of thousands of putative transcription units not overlapping known genes. Many of the newly predicted transcriptional units do not appear to code for proteins. The new algorithms are particularly apt at detecting genes with long introns and lacking sequence conservation. They therefore complement existing gene prediction methods and will help identify functional transcripts within many apparent “genomic deserts.” PMID:16543943

An empirical test of a diffusion model: predicting clouded apollo movements in a novel environment.

PubMed

Ovaskainen, Otso; Luoto, Miska; Ikonen, Iiro; Rekola, Hanna; Meyke, Evgeniy; Kuussaari, Mikko

2008-05-01

Functional connectivity is a fundamental concept in conservation biology because it sets the level of migration and gene flow among local populations. However, functional connectivity is difficult to measure, largely because it is hard to acquire and analyze movement data from heterogeneous landscapes. Here we apply a Bayesian state-space framework to parameterize a diffusion-based movement model using capture-recapture data on the endangered clouded apollo butterfly. We test whether the model is able to disentangle the inherent movement behavior of the species from landscape structure and sampling artifacts, which is a necessity if the model is to be used to examine how movements depend on landscape structure. We show that this is the case by demonstrating that the model, parameterized with data from a reference landscape, correctly predicts movements in a structurally different landscape. In particular, the model helps to explain why a movement corridor that was constructed as a management measure failed to increase movement among local populations. We illustrate how the parameterized model can be used to derive biologically relevant measures of functional connectivity, thus linking movement data with models of spatial population dynamics.

Decadal changes in the structure of Cymodocea nodosa seagrass meadows: Natural vs. human influences

NASA Astrophysics Data System (ADS)

Tuya, Fernando; Ribeiro-Leite, Luís; Arto-Cuesta, Noelia; Coca, Josep; Haroun, Ricardo; Espino, Fernando

2014-01-01

Seagrass meadows are deteriorating worldwide. However, numerous declines are still unreported, which avoid accurate evaluations of seagrass global trends. This is particularly relevant for the western African coast and nearby oceanic archipelagos in the eastern Atlantic. The seagrass Cymodocea nodosa is an 'ecological engineer' on shallow soft bottoms of the Canary Islands. A comparative decadal study was conducted in 21 C. nodosa seagrass meadows at Gran Canaria Island to compare the structure (shoot density, leaf length and cover) between 2003 and 2012. Overall, 11 meadows exhibited a severe regression, while 10 remained relatively stable. During this period, natural influences (sea surface temperature, Chlorophyll-a concentration and PAR light, as well as the number of storm episodes detaching seagrasses) had a low predictive power on temporal patterns in seagrass structure. In contrast, proximity from a range of human-mediated influences (e.g. the number of outfalls and ports) seem to be related to the loss of seagrass; the rate of seagrass erosion between 2003 and 2012 was significantly predicted by the number of human-mediated impacts around each meadow. This result highlights promoting management actions to conserve meadows of C. nodosa at the study region through efficient management of local impacts.

Multivariate Analysis of Conformational Changes Induced by Macromolecular Interactions

NASA Astrophysics Data System (ADS)

Mitra, Indranil; Alexov, Emil

2009-11-01

Understanding protein-protein binding and associated conformational changes is critical for both understanding thermodynamics of protein interactions and successful drug discovery. Our study focuses on computational analysis of plausible correlations between induced conformational changes and set of biophysical characteristics of interacting monomers. It was done by comparing 3D structures of unbound and bound monomers to calculate the RMSD which is used as measure of the structural changed induced by the binding. We correlate RMSD with volumetric and interfacial charge of the monomers, the amino acid composition, the energy of binding, and type of amino acids at the interface. as predictors. The data set was analyzed with SVM in R & SPSS which is trained on a combination of a new robust evolutionary conservation signal with the monomeric properties to predict the induced RMSD. The goal of this study is to undergo parametric tests and heirchiacal cluster and discriminant multivariate analysis to find key predictors which will be used to develop algorithm to predict the magnitude of conformational changes provided by the structure of interacting monomers. Results indicate that the most promising predictor is the net charge of the monomers, however, other parameters as the type of amino acids at the interface have significant contribution as well.

Conservation of protein structure over four billion years.

PubMed

Ingles-Prieto, Alvaro; Ibarra-Molero, Beatriz; Delgado-Delgado, Asuncion; Perez-Jimenez, Raul; Fernandez, Julio M; Gaucher, Eric A; Sanchez-Ruiz, Jose M; Gavira, Jose A

2013-09-03

Little is known about the evolution of protein structures and the degree of protein structure conservation over planetary time scales. Here, we report the X-ray crystal structures of seven laboratory resurrections of Precambrian thioredoxins dating up to approximately four billion years ago. Despite considerable sequence differences compared with extant enzymes, the ancestral proteins display the canonical thioredoxin fold, whereas only small structural changes have occurred over four billion years. This remarkable degree of structure conservation since a time near the last common ancestor of life supports a punctuated-equilibrium model of structure evolution in which the generation of new folds occurs over comparatively short periods and is followed by long periods of structural stasis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis on the Critical Rainfall Value For Predicting Large Scale Landslides Caused by Heavy Rainfall In Taiwan.

NASA Astrophysics Data System (ADS)

Tsai, Kuang-Jung; Chiang, Jie-Lun; Lee, Ming-Hsi; Chen, Yie-Ruey

2017-04-01

Analysis on the Critical Rainfall Value For Predicting Large Scale Landslides Caused by Heavy Rainfall In Taiwan. Kuang-Jung Tsai 1, Jie-Lun Chiang 2,Ming-Hsi Lee 2, Yie-Ruey Chen 1, 1Department of Land Management and Development, Chang Jung Christian Universityt, Tainan, Taiwan. 2Department of Soil and Water Conservation, National Pingtung University of Science and Technology, Pingtung, Taiwan. ABSTRACT The accumulated rainfall amount was recorded more than 2,900mm that were brought by Morakot typhoon in August, 2009 within continuous 3 days. Very serious landslides, and sediment related disasters were induced by this heavy rainfall event. The satellite image analysis project conducted by Soil and Water Conservation Bureau after Morakot event indicated that more than 10,904 sites of landslide with total sliding area of 18,113ha were found by this project. At the same time, all severe sediment related disaster areas are also characterized based on their disaster type, scale, topography, major bedrock formations and geologic structures during the period of extremely heavy rainfall events occurred at the southern Taiwan. Characteristics and mechanism of large scale landslide are collected on the basis of the field investigation technology integrated with GPS/GIS/RS technique. In order to decrease the risk of large scale landslides on slope land, the strategy of slope land conservation, and critical rainfall database should be set up and executed as soon as possible. Meanwhile, study on the establishment of critical rainfall value used for predicting large scale landslides induced by heavy rainfall become an important issue which was seriously concerned by the government and all people live in Taiwan. The mechanism of large scale landslide, rainfall frequency analysis ,sediment budge estimation and river hydraulic analysis under the condition of extremely climate change during the past 10 years would be seriously concerned and recognized as a required issue by this research. Hopefully, all results developed from this research can be used as a warning system for Predicting Large Scale Landslides in the southern Taiwan. Keywords：Heavy Rainfall, Large Scale, landslides, Critical Rainfall Value

Structural insights into xenobiotic and inhibitor binding to human aldehyde oxidase.

PubMed

Coelho, Catarina; Foti, Alessandro; Hartmann, Tobias; Santos-Silva, Teresa; Leimkühler, Silke; Romão, Maria João

2015-10-01

Aldehyde oxidase (AOX) is a xanthine oxidase (XO)-related enzyme with emerging importance due to its role in the metabolism of drugs and xenobiotics. We report the first crystal structures of human AOX1, substrate free (2.6-Å resolution) and in complex with the substrate phthalazine and the inhibitor thioridazine (2.7-Å resolution). Analysis of the protein active site combined with steady-state kinetic studies highlight the unique features, including binding and substrate orientation at the active site, that characterize human AOX1 as an important drug-metabolizing enzyme. Structural analysis of the complex with the noncompetitive inhibitor thioridazine revealed a new, unexpected and fully occupied inhibitor-binding site that is structurally conserved among mammalian AOXs and XO. The new structural insights into the catalytic and inhibition mechanisms of human AOX that we now report will be of great value for the rational analysis of clinical drug interactions involving inhibition of AOX1 and for the prediction and design of AOX-stable putative drugs.

Loading tests of a wing structure for a hypersonic aircraft

NASA Technical Reports Server (NTRS)

Fields, R. A.; Reardon, L. F.; Siegel, W. H.

1980-01-01

Room-temperature loading tests were conducted on a wing structure designed with a beaded panel concept for a Mach 8 hypersonic research airplane. Strain, stress, and deflection data were compared with the results of three finite-element structural analysis computer programs and with design data. The test program data were used to evaluate the structural concept and the methods of analysis used in the design. A force stiffness technique was utilized in conjunction with load conditions which produced various combinations of panel shear and compression loading to determine the failure envelope of the buckling critical beaded panels The force-stiffness data did not result in any predictions of buckling failure. It was, therefore, concluded that the panels were conservatively designed as a result of design constraints and assumptions of panel eccentricities. The analysis programs calculated strains and stresses competently. Comparisons between calculated and measured structural deflections showed good agreement. The test program offered a positive demonstration of the beaded panel concept subjected to room-temperature load conditions.

Structure and Self-Assembly of the Calcium Binding Matrix Protein of Human Metapneumovirus

PubMed Central

Leyrat, Cedric; Renner, Max; Harlos, Karl; Huiskonen, Juha T.; Grimes, Jonathan M.

2014-01-01

Summary The matrix protein (M) of paramyxoviruses plays a key role in determining virion morphology by directing viral assembly and budding. Here, we report the crystal structure of the human metapneumovirus M at 2.8 Å resolution in its native dimeric state. The structure reveals the presence of a high-affinity Ca2+ binding site. Molecular dynamics simulations (MDS) predict a secondary lower-affinity site that correlates well with data from fluorescence-based thermal shift assays. By combining small-angle X-ray scattering with MDS and ensemble analysis, we captured the structure and dynamics of M in solution. Our analysis reveals a large positively charged patch on the protein surface that is involved in membrane interaction. Structural analysis of DOPC-induced polymerization of M into helical filaments using electron microscopy leads to a model of M self-assembly. The conservation of the Ca2+ binding sites suggests a role for calcium in the replication and morphogenesis of pneumoviruses. PMID:24316400

Draft genome sequence of Cicer reticulatum L., the wild progenitor of chickpea provides a resource for agronomic trait improvement.

PubMed

Gupta, Sonal; Nawaz, Kashif; Parween, Sabiha; Roy, Riti; Sahu, Kamlesh; Kumar Pole, Anil; Khandal, Hitaishi; Srivastava, Rishi; Kumar Parida, Swarup; Chattopadhyay, Debasis

2017-02-01

Cicer reticulatum L. is the wild progenitor of the fourth most important legume crop chickpea (C. arietinum L.). We assembled short-read sequences into 416 Mb draft genome of C. reticulatum and anchored 78% (327 Mb) of this assembly to eight linkage groups. Genome annotation predicted 25,680 protein-coding genes covering more than 90% of predicted gene space. The genome assembly shared a substantial synteny and conservation of gene orders with the genome of the model legume Medicago truncatula. Resistance gene homologs of wild and domesticated chickpeas showed high sequence homology and conserved synteny. Comparison of gene sequences and nucleotide diversity using 66 wild and domesticated chickpea accessions suggested that the desi type chickpea was genetically closer to the wild species than the kabuli type. Comparative analyses predicted gene flow between the wild and the cultivated species during domestication. Molecular diversity and population genetic structure determination using 15,096 genome-wide single nucleotide polymorphisms revealed an admixed domestication pattern among cultivated (desi and kabuli) and wild chickpea accessions belonging to three population groups reflecting significant influence of parentage or geographical origin for their cultivar-specific population classification. The assembly and the polymorphic sequence resources presented here would facilitate the study of chickpea domestication and targeted use of wild Cicer germplasms for agronomic trait improvement in chickpea. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zemla, A; Lang, D; Kostova, T

2010-11-29

Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory - still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could overcome these difficulties and facilitatemore » the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV, a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus and demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique or that shared structural similarity with structures that are distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position.« less

Comparative analysis of CDPK family in maize, Arabidopsis, rice and sorghum revealed potential targets for drought tolerance improvement

NASA Astrophysics Data System (ADS)

Mittal, Shikha; Mallikarjuna, Mallana Gowdra; Rao, Atmakuri R.; Jain, Prashant A.; Dash, Prasanta K.; Thirunavukkarasu, Nepolean

2017-12-01

Calcium dependent protein kinases (CDPKs) play major role in regulation of plant growth and development in response to various stresses including drought. A set of 32 CDPK genes identified in maize were further used for searching of orthologs in the model plant Arabidopsis (72) and major food crops such as rice (78) and sorghum (91). We comprehensively investigated the phylogenetic relationship, annotations, gene duplications, gene structure, divergence time, 3-D protein structures and tissue-specific drought induced expression of CDPK genes in all four species. Variation in intron frequency among these species likely contributed to the functional diversity of CDPK genes to various stress responses. Protein kinase and protein kinase C phosphorylation site domains were the most conserved motifs identified in all species. Four groups were identified from the sequence-based phylogenetic analysis, in which maize CDPKs were clustered in group III. The time of divergence (Ka/Ks) analysis revealed that the CDPKs were evolved through stabilizing selection. Expression data showed that the CDPK genes were highly expressed in leaf of maize, rice, and sorghum whereas in Arabidopsis the maximum expression was observed in root. 3-D protein structure were predicted for the nine genes (Arabidopsis: 2, maize: 2, rice: 3 and sorghum: 2) showing differential expression in at least three species. The predicted 3-D structures were further evaluated and validated by Ramachandran plot, ANOLEA, ProSA and Verify-3D. The superimposed 3-D structure of drought-related orthologous proteins retained similar folding pattern owing to their conserved nature. Functional annotation revealed the involvement of CDPK genes in various pathways such as osmotic homeostasis, cell protection and root growth. The interactions of CDPK genes in various pathways play crucial role in imparting drought tolerance through different ABA and MAPK signalling cascades. Our studies suggest that these selected candidate genes could be targeted in development of drought tolerant cultivars in maize, rice and sorghum through appropriate breeding approaches. Our comparative experiments of CDPK genes could also be extended in the drought stress breeding programmes of the related species.

Quantitative structure-activity relationship modeling of rat acute toxicity by oral exposure.

PubMed

Zhu, Hao; Martin, Todd M; Ye, Lin; Sedykh, Alexander; Young, Douglas M; Tropsha, Alexander

2009-12-01

Few quantitative structure-activity relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity end points. In this study, a comprehensive data set of 7385 compounds with their most conservative lethal dose (LD(50)) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire data set was selected that included all 3472 compounds used in TOPKAT's training set. The remaining 3913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R(2) of linear regression between actual and predicted LD(50) values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R(2) ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD(50) for every compound using all five models. The consensus models afforded higher prediction accuracy for the external validation data set with the higher coverage as compared to individual constituent models. The validated consensus LD(50) models developed in this study can be used as reliable computational predictors of in vivo acute toxicity.

Developmental antecedents of political ideology: a longitudinal investigation from birth to age 18 years.

PubMed

Fraley, R Chris; Griffin, Brian N; Belsky, Jay; Roisman, Glenn I

2012-01-01

The study reported here examined the developmental antecedents of conservative versus liberal ideologies using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development and a follow-up study conducted when the sample was 18 years old. Specifically, we examined variation in conservative versus liberal ideologies at age 18 years as a function of parenting attitudes and child temperament during the first 5 years of life. Consistent with long-standing theories on the development of political attitudes, our results showed that parents' authoritarian attitudes assessed when children were 1 month old predicted conservative attitudes in those children more than 17 years later. Consistent with the findings of Block and Block (2006), our results also showed that early childhood temperament predicted variation in conservative versus liberal ideologies.

Reductions in global biodiversity loss predicted from conservation spending.

PubMed

Waldron, Anthony; Miller, Daniel C; Redding, Dave; Mooers, Arne; Kuhn, Tyler S; Nibbelink, Nate; Roberts, J Timmons; Tobias, Joseph A; Gittleman, John L

2017-11-16

Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country between 1996 and 2008. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

Sequencing Needs for Viral Diagnostics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, S N; Lam, M; Mulakken, N J

2004-01-26

We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''nearmore » neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.« less

Reductions in global biodiversity loss predicted from conservation spending

NASA Astrophysics Data System (ADS)

Waldron, Anthony; Miller, Daniel C.; Redding, Dave; Mooers, Arne; Kuhn, Tyler S.; Nibbelink, Nate; Roberts, J. Timmons; Tobias, Joseph A.; Gittleman, John L.

2017-11-01

Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment between 1996 and 2008 reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase

PubMed Central

Qiu, Shihong; Ogino, Minako; Luo, Ming

2015-01-01

ABSTRACT Viruses have various mechanisms to duplicate their genomes and produce virus-specific mRNAs. Negative-strand RNA viruses encode their own polymerases to perform each of these processes. For the nonsegmented negative-strand RNA viruses, the polymerase is comprised of the large polymerase subunit (L) and the phosphoprotein (P). L proteins from members of the Rhabdoviridae, Paramyxoviridae, and Filoviridae share sequence and predicted secondary structure homology. Here, we present the structure of the N-terminal domain (conserved region I) of the L protein from a rhabdovirus, vesicular stomatitis virus, at 1.8-Å resolution. The strictly and strongly conserved residues in this domain cluster in a single area of the protein. Serial mutation of these residues shows that many of the amino acids are essential for viral transcription but not for mRNA capping. Three-dimensional alignments show that this domain shares structural homology with polymerases from other viral families, including segmented negative-strand RNA and double-stranded RNA (dsRNA) viruses. IMPORTANCE Negative-strand RNA viruses include a diverse set of viral families that infect animals and plants, causing serious illness and economic impact. The members of this group of viruses share a set of functionally conserved proteins that are essential to their replication cycle. Among this set of proteins is the viral polymerase, which performs a unique set of reactions to produce genome- and subgenome-length RNA transcripts. In this article, we study the polymerase of vesicular stomatitis virus, a member of the rhabdoviruses, which has served in the past as a model to study negative-strand RNA virus replication. We have identified a site in the N-terminal domain of the polymerase that is essential to viral transcription and that shares sequence homology with members of the paramyxoviruses and the filoviruses. Newly identified sites such as that described here could prove to be useful targets in the design of new therapeutics against negative-strand RNA viruses. PMID:26512087

Chlamydia trachomatis protein CT009 is a structural and functional homolog to the key morphogenesis component RodZ and interacts with division septal plane localized MreB

DOE PAGES

Kemege, Kyle E.; Hickey, John M.; Barta, Michael L.; ...

2014-11-10

Cell division in Chlamydiae is poorly understood as apparent homologs to most conserved bacterial cell division proteins are lacking and presence of elongation (rod shape) associated proteins indicate non-canonical mechanisms may be employed. The rod-shape determining protein MreB has been proposed as playing a unique role in chlamydial cell division. In other organisms, MreB is part of an elongation complex that requires RodZ for proper function. A recent study reported that the protein encoded by ORF CT009 interacts with MreB despite low sequence similarity to RodZ. The studies in this paper expand on those observations through protein structure, mutagenesis andmore » cellular localization analyses. Structural analysis indicated that CT009 shares high level of structural similarity to RodZ, revealing the conserved orientation of two residues critical for MreB interaction. Substitutions eliminated MreB protein interaction and partial complementation provided by CT009 in RodZ deficient Escherichia coli. Cellular localization analysis of CT009 showed uniform membrane staining in Chlamydia. This was in contrast to the localization of MreB, which was restricted to predicted septal planes. Finally, MreB localization to septal planes provides direct experimental observation for the role of MreB in cell division and supports the hypothesis that it serves as a functional replacement for FtsZ in Chlamydia.« less

Chlamydia trachomatis protein CT009 is a structural and functional homolog to the key morphogenesis component RodZ and interacts with division septal plane localized MreB

PubMed Central

Kemege, Kyle E.; Hickey, John M.; Barta, Michael L.; Wickstrum, Jason; Balwalli, Namita; Lovell, Scott; Battaile, Kevin P.; Hefty, P. Scott

2015-01-01

Summary Cell division in Chlamydiae is poorly understood as apparent homologs to most conserved bacterial cell division proteins are lacking and presence of elongation (rod shape) associated proteins indicate non-canonical mechanisms may be employed. The rod-shape determining protein MreB has been proposed as playing a unique role in chlamydial cell division. In other organisms, MreB is part of an elongation complex that requires RodZ for proper function. A recent study reported that the protein encoded by ORF CT009 interacts with MreB despite low sequence similarity to RodZ. The studies herein expand on those observations through protein structure, mutagenesis, and cellular localization analyses. Structural analysis indicated that CT009 shares high level of structural similarity to RodZ, revealing the conserved orientation of two residues critical for MreB interaction. Substitutions eliminated MreB protein interaction and partial complementation provided by CT009 in RodZ deficient E. coli. Cellular localization analysis of CT009 showed uniform membrane staining in Chlamydia. This was in contrast to the localization of MreB, which was restricted to predicted septal planes. MreB localization to septal planes provides direct experimental observation for the role of MreB in cell division and supports the hypothesis that it serves as a functional replacement for FtsZ in Chlamydia. PMID:25382739

Chlamydia trachomatis protein CT009 is a structural and functional homolog to the key morphogenesis component RodZ and interacts with division septal plane localized MreB.

PubMed

Kemege, Kyle E; Hickey, John M; Barta, Michael L; Wickstrum, Jason; Balwalli, Namita; Lovell, Scott; Battaile, Kevin P; Hefty, P Scott

2015-02-01

Cell division in Chlamydiae is poorly understood as apparent homologs to most conserved bacterial cell division proteins are lacking and presence of elongation (rod shape) associated proteins indicate non-canonical mechanisms may be employed. The rod-shape determining protein MreB has been proposed as playing a unique role in chlamydial cell division. In other organisms, MreB is part of an elongation complex that requires RodZ for proper function. A recent study reported that the protein encoded by ORF CT009 interacts with MreB despite low sequence similarity to RodZ. The studies herein expand on those observations through protein structure, mutagenesis and cellular localization analyses. Structural analysis indicated that CT009 shares high level of structural similarity to RodZ, revealing the conserved orientation of two residues critical for MreB interaction. Substitutions eliminated MreB protein interaction and partial complementation provided by CT009 in RodZ deficient Escherichia coli. Cellular localization analysis of CT009 showed uniform membrane staining in Chlamydia. This was in contrast to the localization of MreB, which was restricted to predicted septal planes. MreB localization to septal planes provides direct experimental observation for the role of MreB in cell division and supports the hypothesis that it serves as a functional replacement for FtsZ in Chlamydia. © 2014 John Wiley & Sons Ltd.

Improvement of rheological properties of firm acid gels by skim milk heating is conserved after stirring.

PubMed

Cayot, P; Fairise, J F; Colas, B; Lorient, D; Brulé, G

2003-11-01

The enhancement of the strength of set acid gels by heating milk was related to rheological parameters (water retention capacity, storage modulus) of corresponding stirred gels. To obtain accurate rheological data from stirred gel it was necessary to maintain a constant granulometry of gel particles and to recognize time after stirring as a contributing factor. Two hours after stirring, the gel exhibited a higher storage modulus when milk was heated above 80 degrees C. A measurement of viscosity of just-stirred yoghurt was sufficient to predict correctly the quality of a stirred gel analysed by viscoelastic measurements. Increased resistance to syneresis of just-stirred gels was related to higher viscosity. The quantity of beta-lactoglobulin (beta-Ig) bound to casein micelles explains the improvement of these gel qualities. We have considered that the structure of the initial firm gel (mesostructure level) was conserved in fragments within the stirred gel. Consequently, the explanation given by various authors for the effect of heating milk on the properties of set gels can also be applied to stirred gels. The same mechanism, described in literature for structure formation of set gels from acidified milk is purposed to explain the role of heating milk on the recovery of gel structure after stirring. The beta-Ig association with casein micelles during heating favoured micelle connections during the acidification. It also favoured the association of gel fragments after stirring during the recovery in gel structure.

What is conservation physiology? Perspectives on an increasingly integrated and essential science†

PubMed Central

Cooke, Steven J.; Sack, Lawren; Franklin, Craig E.; Farrell, Anthony P.; Beardall, John; Wikelski, Martin; Chown, Steven L.

2013-01-01

Globally, ecosystems and their constituent flora and fauna face the localized and broad-scale influence of human activities. Conservation practitioners and environmental managers struggle to identify and mitigate threats, reverse species declines, restore degraded ecosystems, and manage natural resources sustainably. Scientific research and evidence are increasingly regarded as the foundation for new regulations, conservation actions, and management interventions. Conservation biologists and managers have traditionally focused on the characteristics (e.g. abundance, structure, trends) of populations, species, communities, and ecosystems, and simple indicators of the responses to environmental perturbations and other human activities. However, an understanding of the specific mechanisms underlying conservation problems is becoming increasingly important for decision-making, in part because physiological tools and knowledge are especially useful for developing cause-and-effect relationships, and for identifying the optimal range of habitats and stressor thresholds for different organisms. When physiological knowledge is incorporated into ecological models, it can improve predictions of organism responses to environmental change and provide tools to support management decisions. Without such knowledge, we may be left with simple associations. ‘Conservation physiology’ has been defined previously with a focus on vertebrates, but here we redefine the concept universally, for application to the diversity of taxa from microbes to plants, to animals, and to natural resources. We also consider ‘physiology’ in the broadest possible terms; i.e. how an organism functions, and any associated mechanisms, from development to bioenergetics, to environmental interactions, through to fitness. Moreover, we consider conservation physiology to include a wide range of applications beyond assisting imperiled populations, and include, for example, the eradication of invasive species, refinement of resource management strategies to minimize impacts, and evaluation of restoration plans. This concept of conservation physiology emphasizes the basis, importance, and ecological relevance of physiological diversity at a variety of scales. Real advances in conservation and resource management require integration and inter-disciplinarity. Conservation physiology and its suite of tools and concepts is a key part of the evidence base needed to address pressing environmental challenges. PMID:27293585

Area, length and thickness conservation: Dogma or reality?

NASA Astrophysics Data System (ADS)

Moretti, Isabelle; Callot, Jean Paul

2012-08-01

The basic assumption of quantitative structural geology is the preservation of material during deformation. However the hypothesis of volume conservation alone does not help to predict past or future geometries and so this assumption is usually translated into bed length in 2D (or area in 3D) and thickness conservation. When subsurface data are missing, geologists may extrapolate surface data to depth using the kink-band approach. These extrapolations, preserving both thicknesses and dips, lead to geometries which are restorable but often erroneous, due to both disharmonic deformation and internal deformation of layers. First, the Bolivian Sub-Andean Zone case is presented to highlight the evolution of the concepts on which balancing is based, and the important role played by a decoupling level in enhancing disharmony. Second, analogue models are analyzed to test the validity of the balancing techniques. Chamberlin's excess area approach is shown to be on average valid. However, neither the length nor the thicknesses are preserved. We propose that in real cases, the length preservation hypothesis during shortening could also be a wrong assumption. If the data are good enough to image the decollement level, the Chamberlin excess area method could be used to compute the bed length changes.

Structural study of the Fox-1 RRM protein hydration reveals a role for key water molecules in RRM-RNA recognition

PubMed Central

Blatter, Markus; Cléry, Antoine; Damberger, Fred F.

2017-01-01

Abstract The Fox-1 RNA recognition motif (RRM) domain is an important member of the RRM protein family. We report a 1.8 Å X-ray structure of the free Fox-1 containing six distinct monomers. We use this and the nuclear magnetic resonance (NMR) structure of the Fox-1 protein/RNA complex for molecular dynamics (MD) analyses of the structured hydration. The individual monomers of the X-ray structure show diverse hydration patterns, however, MD excellently reproduces the most occupied hydration sites. Simulations of the protein/RNA complex show hydration consistent with the isolated protein complemented by hydration sites specific to the protein/RNA interface. MD predicts intricate hydration sites with water-binding times extending up to hundreds of nanoseconds. We characterize two of them using NMR spectroscopy, RNA binding with switchSENSE and free-energy calculations of mutant proteins. Both hydration sites are experimentally confirmed and their abolishment reduces the binding free-energy. A quantitative agreement between theory and experiment is achieved for the S155A substitution but not for the S122A mutant. The S155 hydration site is evolutionarily conserved within the RRM domains. In conclusion, MD is an effective tool for predicting and interpreting the hydration patterns of protein/RNA complexes. Hydration is not easily detectable in NMR experiments but can affect stability of protein/RNA complexes. PMID:28505313

Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis

PubMed Central

Lohman, Danielle C.; Forouhar, Farhad; Beebe, Emily T.; Stefely, Matthew S.; Minogue, Catherine E.; Ulbrich, Arne; Stefely, Jonathan A.; Sukumar, Shravan; Luna-Sánchez, Marta; Jochem, Adam; Lew, Scott; Seetharaman, Jayaraman; Xiao, Rong; Wang, Huang; Westphall, Michael S.; Wrobel, Russell L.; Everett, John K.; Mitchell, Julie C.; López, Luis C.; Coon, Joshua J.; Tong, Liang; Pagliarini, David J.

2014-01-01

Coenzyme Q (CoQ) is an isoprenylated quinone that is essential for cellular respiration and is synthesized in mitochondria by the combined action of at least nine proteins (COQ1–9). Although most COQ proteins are known to catalyze modifications to CoQ precursors, the biochemical role of COQ9 remains unclear. Here, we report that a disease-related COQ9 mutation leads to extensive disruption of the CoQ protein biosynthetic complex in a mouse model, and that COQ9 specifically interacts with COQ7 through a series of conserved residues. Toward understanding how COQ9 can perform these functions, we solved the crystal structure of Homo sapiens COQ9 at 2.4 Å. Unexpectedly, our structure reveals that COQ9 has structural homology to the TFR family of bacterial transcriptional regulators, but that it adopts an atypical TFR dimer orientation and is not predicted to bind DNA. Our structure also reveals a lipid-binding site, and mass spectrometry-based analyses of purified COQ9 demonstrate that it associates with multiple lipid species, including CoQ itself. The conserved COQ9 residues necessary for its interaction with COQ7 comprise a surface patch around the lipid-binding site, suggesting that COQ9 might serve to present its bound lipid to COQ7. Collectively, our data define COQ9 as the first, to our knowledge, mammalian TFR structural homolog and suggest that its lipid-binding capacity and association with COQ7 are key features for enabling CoQ biosynthesis. PMID:25339443

Efficiency of incentives to jointly increase carbon sequestration and species conservation on a landscape

Treesearch

Erik Nelson; Stephen Polasky; David J. Lewis; Andrew J. Plantinga; Eric Lonsdorf; Denis White; David Bael; Joshua Lawler

2008-01-01

We develop an integrated model to predict private land-use decisions in response to policy incentives designed to increase the provision of carbon sequestration and species conservation across heterogeneous landscapes. Using data from the Willamette Basin, Oregon, we compare the provision of carbon sequestration and species conservation under five simple policies that...

Comparison of statistical and theoretical habitat models for conservation planning: the benefit of ensemble prediction

Treesearch

D. Todd Jones-Farrand; Todd M. Fearer; Wayne E. Thogmartin; Frank R. Thompson; Mark D. Nelson; John M. Tirpak

2011-01-01

Selection of a modeling approach is an important step in the conservation planning process, but little guidance is available. We compared two statistical and three theoretical habitat modeling approaches representing those currently being used for avian conservation planning at landscape and regional scales: hierarchical spatial count (HSC), classification and...

Conserved water molecules in bacterial serine hydroxymethyltransferases.

PubMed

Milano, Teresa; Di Salvo, Martino Luigi; Angelaccio, Sebastiana; Pascarella, Stefano

2015-10-01

Water molecules occurring in the interior of protein structures often are endowed with key structural and functional roles. We report the results of a systematic analysis of conserved water molecules in bacterial serine hydroxymethyltransferases (SHMTs). SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of l-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The approach utilized in this study relies on two programs, ProACT2 and WatCH. The first software is able to categorize water molecules in a protein crystallographic structure as buried, positioned in clefts or at the surface. The other program finds, in a set of superposed homologous proteins, water molecules that occur approximately in equivalent position in each of the considered structures. These groups of molecules are referred to as 'clusters' and represent structurally conserved water molecules. Several conserved clusters of buried or cleft water molecules were found in the set of 11 bacterial SHMTs we took into account for this work. The majority of these clusters were not described previously. Possible structural and functional roles for the conserved water molecules are envisaged. This work provides a map of the conserved water molecules helpful for deciphering SHMT mechanism and for rational design of molecular engineering experiments. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ramachandran analysis of conserved glycyl residues in homologous proteins of known structure.

PubMed

Lakshmi, Balasubramanian; Sinduja, Chandrasekaran; Archunan, Govind; Srinivasan, Narayanaswamy

2014-06-01

High conservation of glycyl residues in homologous proteins is fairly frequent. It is commonly understood that glycine tends to be highly conserved either because of its unique Ramachandran angles or to avoid steric clash that would arise with a larger side chain. Using a database of aligned 3D structures of homologous proteins we identified conserved Gly in 288 alignment positions from 85 families. Ninety-six of these alignment positions correspond to conserved Gly residue with (φ, ψ) values allowed for non-glycyl residues. Reasons for this observation were investigated by in-silico mutation of these glycyl residues to Ala. We found in 94% of the cases a short contact exists between the C(β) atom of the introduced Ala with the atoms which are often distant in the primary structure. This suggests the lack of space even for a short side chain thereby explaining high conservation of glycyl residues even when they adopt (φ, ψ) values allowed for Ala. In 189 alignment positions, the conserved glycyl residues adopt (φ, ψ) values which are disallowed for Ala. In-silico mutation of these Gly residues to Ala almost always results in steric hindrance involving C(β) atom of Ala as one would expect by comparing Ramachandran maps for Ala and Gly. Rare occurrence of the disallowed glycyl conformations even in ultrahigh resolution protein structures are accompanied by short contacts in the crystal structures and such disallowed conformations are not conserved in the homologues. These observations raise the doubt on the accuracy of such glycyl conformations in proteins. © 2014 The Protein Society.

Identifying habitats at risk: simple models can reveal complex ecosystem dynamics.

PubMed

Maxwell, Paul S; Pitt, Kylie A; Olds, Andrew D; Rissik, David; Connolly, Rod M

2015-03-01

The relationship between ecological impact and ecosystem structure is often strongly nonlinear, so that small increases in impact levels can cause a disproportionately large response in ecosystem structure. Nonlinear ecosystem responses can be difficult to predict because locally relevant data sets can be difficult or impossible to obtain. Bayesian networks (BN) are an emerging tool that can help managers to define ecosystem relationships using a range of data types from comprehensive quantitative data sets to expert opinion. We show how a simple BN can reveal nonlinear dynamics in seagrass ecosystems using ecological relationships sourced from the literature. We first developed a conceptual diagram by cataloguing the ecological responses of seagrasses to a range of drivers and impacts. We used the conceptual diagram to develop a BN populated with values sourced from published studies. We then applied the BN to show that the amount of initial seagrass biomass has a mitigating effect on the level of impact a meadow can withstand without loss, and that meadow recovery can often require disproportionately large improvements in impact levels. This mitigating effect resulted in the middle ranges of impact levels having a wide likelihood of seagrass presence, a situation known as bistability. Finally, we applied the model in a case study to identify the risk of loss and the likelihood of recovery for the conservation and management of seagrass meadows in Moreton Bay, Queensland, Australia. We used the model to predict the likelihood of bistability in 23 locations in the Bay. The model predicted bistability in seven locations, most of which have experienced seagrass loss at some stage in the past 25 years providing essential information for potential future restoration efforts. Our results demonstrate the capacity of simple, flexible modeling tools to facilitate collation and synthesis of disparate information. This approach can be adopted in the initial stages of conservation programs as a low-cost and relatively straightforward way to provide preliminary assessments of.nonlinear dynamics in ecosystems.

Computational identification of developmental enhancers:conservation and function of transcription factor binding-site clustersin drosophila melanogaster and drosophila psedoobscura

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berman, Benjamin P.; Pfeiffer, Barret D.; Laverty, Todd R.

2004-08-06

The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayedmore » embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the remaining 18 do not appear to have enhancer activity. We used the Drosophila pseudoobscura genome to compare patterns of evolution in and around the 15 positive and 18 false-positive predictions. Although conservation of primary sequence cannot distinguish true from false positives, conservation of binding-site clustering accurately discriminates functional binding-site clusters from those with no function. We incorporated conservation of binding-site clustering into a new genome-wide enhancer screen, and predict several hundred new regulatory sequences, including 85 adjacent to genes with embryonic patterns. Measuring conservation of sequence features closely linked to function--such as binding-site clustering--makes better use of comparative sequence data than commonly used methods that examine only sequence identity.« less

The C-terminal region of Ge-1 presents conserved structural features required for P-body localization.

PubMed

Jinek, Martin; Eulalio, Ana; Lingel, Andreas; Helms, Sigrun; Conti, Elena; Izaurralde, Elisa

2008-10-01

The removal of the 5' cap structure by the DCP1-DCP2 decapping complex irreversibly commits eukaryotic mRNAs to degradation. In human cells, the interaction between DCP1 and DCP2 is bridged by the Ge-1 protein. Ge-1 contains an N-terminal WD40-repeat domain connected by a low-complexity region to a conserved C-terminal domain. It was reported that the C-terminal domain interacts with DCP2 and mediates Ge-1 oligomerization and P-body localization. To understand the molecular basis for these functions, we determined the three-dimensional crystal structure of the most conserved region of the Drosophila melanogaster Ge-1 C-terminal domain. The region adopts an all alpha-helical fold related to ARM- and HEAT-repeat proteins. Using structure-based mutants we identified an invariant surface residue affecting P-body localization. The conservation of critical surface and structural residues suggests that the C-terminal region adopts a similar fold with conserved functions in all members of the Ge-1 protein family.

Snakes on the Balearic islands: an invasion tale with implications for native biodiversity conservation.

PubMed

Silva-Rocha, Iolanda; Salvi, Daniele; Sillero, Neftalí; Mateo, Jose A; Carretero, Miguel A

2015-01-01

Biological invasions are a major conservation threat for biodiversity worldwide. Islands are particularly vulnerable to invasive species, especially Mediterranean islands which have suffered human pressure since ancient times. In the Balearic archipelago, reptiles represent an outstanding case with more alien than native species. Moreover, in the last decade a new wave of alien snakes landed in the main islands of the archipelago, some of which were originally snake-free. The identification of the origin and colonization pathways of alien species, as well as the prediction of their expansion, is crucial to develop effective conservation strategies. In this study, we used molecular markers to assess the allochthonous status and the putative origin of the four introduced snake species (Hemorrhois hippocrepis, Malpolon monspessulanus, Macroprotodon mauritanicus and Rhinechis scalaris) as well as ecological niche models to infer their patterns of invasion and expansion based on current and future habitat suitability. For most species, DNA sequence data suggested the Iberian Peninsula as the potential origin of the allochthonous populations, although the shallow phylogeographic structure of these species prevented the identification of a restricted source-area. For all of them, the ecological niche models showed a current low habitat suitability in the Balearic, which is however predicted to increase significantly in the next few decades under climate change scenarios. Evidence from direct observations and spatial distribution of the first-occurrence records of alien snakes (but also lizards and worm lizards) suggest the nursery trade, and in particular olive tree importation from Iberian Peninsula, as the main pathway of introduction of alien reptiles in the Balearic islands. This trend has been reported also for recent invasions in NE Spain, thus showing that olive trees transplantation may be an effective vector for bioinvasion across the Mediterranean. The combination of molecular and ecological tools used in this study reveals a promising approach for the understanding of the complex invasion process, hence guiding conservation management actions.

Snakes on the Balearic Islands: An Invasion Tale with Implications for Native Biodiversity Conservation

PubMed Central

Sillero, Neftalí; Mateo, Jose A.; Carretero, Miguel A.

2015-01-01

Biological invasions are a major conservation threat for biodiversity worldwide. Islands are particularly vulnerable to invasive species, especially Mediterranean islands which have suffered human pressure since ancient times. In the Balearic archipelago, reptiles represent an outstanding case with more alien than native species. Moreover, in the last decade a new wave of alien snakes landed in the main islands of the archipelago, some of which were originally snake-free. The identification of the origin and colonization pathways of alien species, as well as the prediction of their expansion, is crucial to develop effective conservation strategies. In this study, we used molecular markers to assess the allochthonous status and the putative origin of the four introduced snake species (Hemorrhois hippocrepis, Malpolon monspessulanus, Macroprotodon mauritanicus and Rhinechis scalaris) as well as ecological niche models to infer their patterns of invasion and expansion based on current and future habitat suitability. For most species, DNA sequence data suggested the Iberian Peninsula as the potential origin of the allochthonous populations, although the shallow phylogeographic structure of these species prevented the identification of a restricted source-area. For all of them, the ecological niche models showed a current low habitat suitability in the Balearic, which is however predicted to increase significantly in the next few decades under climate change scenarios. Evidence from direct observations and spatial distribution of the first-occurrence records of alien snakes (but also lizards and worm lizards) suggest the nursery trade, and in particular olive tree importation from Iberian Peninsula, as the main pathway of introduction of alien reptiles in the Balearic islands. This trend has been reported also for recent invasions in NE Spain, thus showing that olive trees transplantation may be an effective vector for bioinvasion across the Mediterranean. The combination of molecular and ecological tools used in this study reveals a promising approach for the understanding of the complex invasion process, hence guiding conservation management actions. PMID:25853711

Comparing two remote video survey methods for spatial predictions of the distribution and environmental niche suitability of demersal fishes.

PubMed

Galaiduk, Ronen; Radford, Ben T; Wilson, Shaun K; Harvey, Euan S

2017-12-15

Information on habitat associations from survey data, combined with spatial modelling, allow the development of more refined species distribution modelling which may identify areas of high conservation/fisheries value and consequentially improve conservation efforts. Generalised additive models were used to model the probability of occurrence of six focal species after surveys that utilised two remote underwater video sampling methods (i.e. baited and towed video). Models developed for the towed video method had consistently better predictive performance for all but one study species although only three models had a good to fair fit, and the rest were poor fits, highlighting the challenges associated with modelling habitat associations of marine species in highly homogenous, low relief environments. Models based on baited video dataset regularly included large-scale measures of structural complexity, suggesting fish attraction to a single focus point by bait. Conversely, models based on the towed video data often incorporated small-scale measures of habitat complexity and were more likely to reflect true species-habitat relationships. The cost associated with use of the towed video systems for surveying low-relief seascapes was also relatively low providing additional support for considering this method for marine spatial ecological modelling.

Human somatostatin I: sequence of the cDNA.

PubMed Central

Shen, L P; Pictet, R L; Rutter, W J

1982-01-01

RNA has been isolated from a human pancreatic somatostatinoma and used to prepare a cDNA library. After prescreening, clones containing somatostatin I sequences were identified by hybridization with an anglerfish somatostatin I-cloned cDNA probe. From the nucleotide sequence of two of these clones, we have deduced an essentially full-length mRNA sequence, including the preprosomatostatin coding region, 105 nucleotides from the 5' untranslated region and the complete 150-nucleotide 3' untranslated region. The coding region predicts a 116-amino acid precursor protein (Mr, 12.727) that contains somatostatin-14 and -28 at its COOH terminus. The predicted amino acid sequence of human somatostatin-28 is identical to that of somatostatin-28 isolated from the porcine and ovine species. A comparison of the amino acid sequences of human and anglerfish preprosomatostatin I indicated that the COOH-terminal region encoding somatostatin-14 and the adjacent 6 amino acids are highly conserved, whereas the remainder of the molecule, including the signal peptide region, is more divergent. However, many of the amino acid differences found in the pro region of the human and anglerfish proteins are conservative changes. This suggests that the propeptides have a similar secondary structure, which in turn may imply a biological function for this region of the molecule. Images PMID:6126875

Modeling with uncertain science: estimating mitigation credits from abating lead poisoning in Golden Eagles.

PubMed

Fitts Cochrane, Jean; Lonsdorf, Eric; Allison, Taber D; Sanders-Reed, Carol A

2015-09-01

Challenges arise when renewable energy development triggers "no net loss" policies for protected species, such as where wind energy facilities affect Golden Eagles in the western United States. When established mitigation approaches are insufficient to fully avoid or offset losses, conservation goals may still be achievable through experimental implementation of unproven mitigation methods provided they are analyzed within a framework that deals transparently and rigorously with uncertainty. We developed an approach to quantify and analyze compensatory mitigation that (1) relies on expert opinion elicited in a thoughtful and structured process to design the analysis (models) and supplement available data, (2) builds computational models as hypotheses about cause-effect relationships, (3) represents scientific uncertainty in stochastic model simulations, (4) provides probabilistic predictions of "relative" mortality with and without mitigation, (5) presents results in clear formats useful to applying risk management preferences (regulatory standards) and selecting strategies and levels of mitigation for immediate action, and (6) defines predictive parameters in units that could be monitored effectively, to support experimental adaptive management and reduction in uncertainty. We illustrate the approach with a case study characterized by high uncertainty about underlying biological processes and high conservation interest: estimating the quantitative effects of voluntary strategies to abate lead poisoning in Golden Eagles in Wyoming due to ingestion of spent game hunting ammunition.

Identification and classification of structural soil conservation measures based on very high resolution stereo satellite data.

PubMed

Eckert, Sandra; Tesfay Ghebremicael, Selamawit; Hurni, Hans; Kohler, Thomas

2017-05-15

Land degradation affects large areas of land around the globe, with grave consequences for those living off the land. Major efforts are being made to implement soil and water conservation measures that counteract soil erosion and help secure vital ecosystem services. However, where and to what extent such measures have been implemented is often not well documented. Knowledge about this could help to identify areas where soil and water conservation measures are successfully supporting sustainable land management, as well as areas requiring urgent rehabilitation of conservation structures such as terraces and bunds. This study explores the potential of the latest satellite-based remote sensing technology for use in assessing and monitoring the extent of existing soil and water conservation structures. We used a set of very high resolution stereo Geoeye-1 satellite data, from which we derived a detailed digital surface model as well as a set of other spectral, terrain, texture, and filtered information layers. We developed and applied an object-based classification approach, working on two segmentation levels. On the coarser level, the aim was to delimit certain landscape zones. Information about these landscape zones is useful in distinguishing different types of soil and water conservation structures, as each zone contains certain specific types of structures. On the finer level, the goal was to extract and identify different types of linear soil and water conservation structures. The classification rules were based mainly on spectral, textural, shape, and topographic properties, and included object relationships. This approach enabled us to identify and separate from other classes the majority (78.5%) of terraces and bunds, as well as most hillside terraces (81.25%). Omission and commission errors are similar to those obtained by the few existing studies focusing on the same research objective but using different types of remotely sensed data. Based on our results, we estimate that the construction of the conservation structures in our study area in Eritrea required over 300,000 person-days of work, which underlines the huge efforts involved in soil and water conservation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predictive modelling of JT-60SA high-beta steady-state plasma with impurity accumulation

NASA Astrophysics Data System (ADS)

Hayashi, N.; Hoshino, K.; Honda, M.; Ide, S.

2018-06-01

The integrated modelling code TOPICS has been extended to include core impurity transport, and applied to predictive modelling of JT-60SA high-beta steady-state plasma with the accumulation of impurity seeded to reduce the divertor heat load. In the modelling, models and conditions are selected for a conservative prediction, which considers a lower bound of plasma performance with the maximum accumulation of impurity. The conservative prediction shows the compatibility of impurity seeding with core plasma with high-beta (β N  >  3.5) and full current drive conditions, i.e. when Ar seeding reduces the divertor heat load below 10 MW m‑2, its accumulation in the core is so moderate that the core plasma performance can be recovered by additional heating within the machine capability to compensate for Ar radiation. Due to the strong dependence of accumulation on the pedestal density gradient, high separatrix density is important for the low accumulation as well as the low divertor heat load. The conservative prediction also shows that JT-60SA has enough capability to explore the divertor heat load control by impurity seeding in high-beta steady-state plasmas.

Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression.

PubMed

Mars, Ruben A T; Nicolas, Pierre; Denham, Emma L; van Dijl, Jan Maarten

2016-12-01

Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5' untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such as Escherichia coli and Salmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacterium Bacillus subtilis. A recent study identified 1,583 putative regulatory RNAs in B. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation in B. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation in B. subtilis mostly involves elements at the 5' ends of mRNA molecules. These can include 5' secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs in B. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions in B. subtilis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Atomistic molecular dynamics simulations of bioactive engrailed 1 interference peptides (EN1-iPeps).

PubMed

Gandhi, Neha S; Blancafort, Pilar; Mancera, Ricardo L

2018-04-27

The neural-specific transcription factor Engrailed 1 - is overexpressed in basal-like breast tumours. Synthetic interference peptides - comprising a cell-penetrating peptide/nuclear localisation sequence and the Engrailed 1-specific sequence from the N-terminus have been engineered to produce a strong apoptotic response in tumour cells overexpressing EN1, with no toxicity to normal or non Engrailed 1-expressing cells. Here scaled molecular dynamics simulations were used to study the conformational dynamics of these interference peptides in aqueous solution to characterise their structure and dynamics. Transitions from disordered to α-helical conformation, stabilised by hydrogen bonds and proline-aromatic interactions, were observed throughout the simulations. The backbone of the wild-type peptide folds to a similar conformation as that found in ternary complexes of anterior Hox proteins with conserved hexapeptide motifs important for recognition of pre-B-cell leukemia Homeobox 1, indicating that the motif may possess an intrinsic preference for helical structure. The predicted NMR chemical shifts of these peptides are consistent with the Hox hexapeptides in solution and Engrailed 2 NMR data. These findings highlight the importance of aromatic residues in determining the structure of Engrailed 1 interference peptides, shedding light on the rational design strategy of molecules that could be adopted to inhibit other transcription factors overexpressed in other cancer types, potentially including other transcription factor families that require highly conserved and cooperative protein-protein partnerships for biological activity.

Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression

PubMed Central

Mars, Ruben A. T.; Nicolas, Pierre; Denham, Emma L.

2016-01-01

SUMMARY Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5′ untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such as Escherichia coli and Salmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacterium Bacillus subtilis. A recent study identified 1,583 putative regulatory RNAs in B. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation in B. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation in B. subtilis mostly involves elements at the 5′ ends of mRNA molecules. These can include 5′ secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs in B. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions in B. subtilis. PMID:27784798

Molecular and Mutational Analysis of a Gelsolin-Family Member Encoded by the Flightless I Gene of Drosophila Melanogaster

PubMed Central

de-Couet, H. G.; Fong, KSK.; Weeds, A. G.; McLaughlin, P. J.; Miklos, GLG.

1995-01-01

The flightless locus of Drosophila melanogaster has been analyzed at the genetic, molecular, ultrastructural and comparative crystallographic levels. The gene encodes a single transcript encoding a protein consisting of a leucine-rich amino terminal half and a carboxyterminal half with high sequence similarity to gelsolin. We determined the genomic sequence of the flightless landscape, the breakpoints of four chromosomal rearrangements, and the molecular lesions in two lethal and two viable alleles of the gene. The two alleles that lead to flight muscle abnormalities encode mutant proteins exhibiting amino acid replacements within the S1-like domain of their gelsolin-like region. Furthermore, the deduced intronexon structure of the D. melanogaster gene has been compared with that of the Caenorhabditis elegans homologue. Furthermore, the sequence similarities of the flightless protein with gelsolin allow it to be evaluated in the context of the published crystallographic structure of the S1 domain of gelsolin. Amino acids considered essential for the structural integrity of the core are found to be highly conserved in the predicted flightless protein. Some of the residues considered essential for actin and calcium binding in gelsolin S1 and villin V1 are also well conserved. These data are discussed in light of the phenotypic characteristics of the mutants and the putative functions of the protein. PMID:8582612

Distribution of functional traits in subtropical trees across environmental and forest use gradients

NASA Astrophysics Data System (ADS)

Blundo, Cecilia; Malizia, Lucio R.; González-Espinosa, Mario

2015-11-01

The relationship between functional traits and environmental factors contribute to understanding community structure and predicting which species will be able to elude environmental filters in different habitats. We selected 10 functional traits related to morphology, demography and regeneration niche in 54 subtropical premontane tree species to describe their main axes of functional differentiation. We derived species traits, environmental variables and species abundance data from 20 1-ha permanent plots established in a seasonal subtropical premontane forest in northwestern Argentina. We analyzed the relationship between species functional traits and environmental factors through RLQ and fourth-corner analyzes. We found an axis of structural differentiation that segregates understory from canopy species, and an axis of functional differentiation that segregates species that maximize resource acquisition from those that promote resource conservation. Environmental and forest use gradients operate hierarchically over subtropical premontane tree species influencing the distribution of demographic and morphological traits. The interaction between climatic and topographic factors influences the distribution of species functional traits at the regional scale. In addition, the history of forest use seems to operate at the landscape scale and explains the distribution of species traits reflecting a trade-off between resource acquisition and resource conservation strategies in secondary forests across different successional stages. Our results support the idea that functional traits may be used to analyze community structure and dynamics through niche differentiation and environmental filtering processes.

18 CFR 1304.400 - Flotation devices and material, all floating structures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Flotation devices and material, all floating structures. 1304.400 Section 1304.400 Conservation of Power and Water Resources... structures. (a) All flotation for docks, boat mooring buoys, and other water-use structures and facilities...

18 CFR 1304.400 - Flotation devices and material, all floating structures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Flotation devices and material, all floating structures. 1304.400 Section 1304.400 Conservation of Power and Water Resources... structures. (a) All flotation for docks, boat mooring buoys, and other water-use structures and facilities...