QMEANclust: estimation of protein model quality by combining a composite scoring function with structural density information

Background  

The selection of the most accurate protein model from a set of alternatives is a crucial step in protein structure prediction both in template-based and ab initio approaches. Scoring functions have been developed which can either return a quality estimate for a single model or derive a score from the information contained in the ensemble of models for a given sequence. Local structural features occurring more frequently in the ensemble have a greater probability of being correct. Within the context of the CASP experiment, these so called consensus methods have been shown to perform considerably better in selecting good candidate models, but tend to fail if the best models are far from the dominant structural cluster. In this paper we show that model selection can be improved if both approaches are combined by pre-filtering the models used during the calculation of the structural consensus.     

The Electron Microscopy Outreach Program: A Web-based resource for research and education

We have developed a centralized World Wide Web (WWW)-based environment that serves as a resource of software tools and expertise for biological electron microscopy. A major focus is molecular electron microscopy, but the site also includes information and links on structural biology at all levels of resolution. This site serves to help integrate or link structural biology techniques in accordance with user needs. The WWW site, called the Electron Microscopy (EM) Outreach Program (URL: http://emoutreach.sdsc.edu), provides scientists with computational and educational tools for their research and edification. In particular, we have set up a centralized resource containing course notes, references, and links to image analysis and three-dimensional reconstruction software for investigators wanting to learn about EM techniques either within or outside of their fields of expertise.     

Factors influencing in the response of <i>Schizolobium parahybum</i> (Vell) Blake to <i>Ceratocystis paradoxa</i> and <i>C. moniliformis</i>

In the Ecuadorian coast one of the most destructive diseases of the pachaco is vascular wilt or stem rot caused by Ceratocystis complex, so the aim of this study was to determine the factors that affect the efficiency of the reaction of bark pachaco to this disease. This research was conducted under laboratory conditions, using trees pachaco S38, S41, S98, AE-1, AE-2 and AE-3, and pathogenic species Ceratocystis paradoxa and C. moniliformis. The method utilized was tissue stem bark,with bark sections with 4.5 cm², and a suspension of 3x10⁴ units infection and remained in a humid chamber for 96 hours at 25 ± 5 °C. Were determined grades of resistance/ susceptibility using a scale from 0 to 4, depending on the amount of mycelia and peritecio in each plant sample. Three factors were used: four colonies obtained by several transfers from each fungal specie, four ages of colonies of each fungal specie and four volumes of inoculum applied (units of infection), using for each experiment separately Completely Randomized Design with 4 replications factorial arrangement. For comparison between treatment means was used Tukey test at 5% probability of error. For future trials using this technique, you could use 30-day colonies for C. paradoxa and 40 days for C. moniliformis, and an application volume of 100 μL/cm², it would improve the level of response for the formation of perithecium and mycelia in samples cortex.     

Towards new sources of resistance to the currant-lettuce aphid (<Emphasis Type="Italic">Nasonovia ribisnigri</Emphasis>)

Domesticated lettuce varieties encompass much morphological variation across a range of crop type groups, with large collections of cultivars and landrace accessions maintained in genebanks. Additional variation not captured during domestication, present in ancestral wild relatives, represents a potentially rich source of alleles that can deliver to sustainable crop production. However, these large collections are difficult and costly to screen for many agronomically important traits. In this paper, we describe the generation of a diversity collection of 96 lettuce and wild species accessions that are amenable to routine phenotypic analysis and their genotypic characterization with a panel of 682 newly developed expressed sequence tag (EST)-linked KASP? single nucleotide polymorphism (SNP) markers that are anchored to the draft Lactuca sativa genome assembly. To exemplify the utility of these resources, we screened the collection for putative sources of resistance to currant-lettuce aphid (Nasonovia ribisnigri) and carried out association analyses to look for potential SNPs linked to resistance.     

Empirical Study of an Adaptive Multiscale Model for Simulating Cardiac Conduction

We modify and empirically study an adaptive multiscale model for simulating cardiac action potential propagation along a strand of cardiomyocytes. The model involves microscale partial differential equations posed over cells near the action potential upstroke and macroscale partial differential equations posed over the remainder of the tissue. An important advantage of the modified model of this paper is that, unlike our original model, it does not require perfect alignment between myocytes and the macroscale computational grid. We study the effects of gap-junctional coupling, ephaptic coupling, and macroscale grid spacing on the accuracy of the multiscale model. Our simulations reveal that the multiscale method accurately reproduces both the wavespeed and the waveform, including both upstroke and recovery, of fully microscale models. They also reveal that perfect alignment between myocytes and the macroscale grid is not necessary to reproduce the dynamics of a traveling action potential. Further, our simulations suggest that the macroscale grid spacing used in an adaptive multiscale model need not be much finer than the spatial width of an action potential. These results are demonstrated to hold under high, low, and zero gap-junctional coupling regimes.     

Metabolic restructuring during energy-limited states: insights from Artemia franciscana embryos and other animals

Many life history stages of animals that experience environmental insults enter developmental arrested states that are characterized by reduced cellular proliferation, with or without a concurrent reduction in overall metabolism. In the case of the most profound metabolic arrest reported in invertebrates, i.e., anaerobic quiescence in Artemia franciscana embryos, acidification of the intracellular milieu is a major factor governing catabolic and anabolic downregulation. Release of ions from intracellular compartments is the source for approximately 50% of the proton equivalents needed for the 1.5 unit acidification that is observed. Recovery from the metabolic arrest requires re-sequestration of the protons with a vacuolar-type ATPase (V-ATPase). The remarkable facet of this mechanism is the ability of embryonic cells to survive the dissipation of intracellular ion gradients. Across many diapause-like states, the metabolic reduction and subsequent matching of energy demand is accomplished by shifting energy metabolism from oxidative phosphorylation to aerobic glycolysis. Molecular pathways that are activated to induce these resilient hypometabolic states include stimulation of the AMP-activated protein kinase (AMPK) and insulin signaling via suite of daf (dauer formation) genes for diapause-like states in nematodes and insects. Contributing factors for other metabolically depressed states involve hypoxia-inducible factor-1 and downregulation of the pyruvate dehydrogenase complex. Metabolic similarities between natural states of stasis and some cancer phenotypes are noteworthy. Reduction of flux through oxidative phosphorylation helps prevent cell death in certain cancer types, similar to the way it increases viability of dauer stages in Caenorhabditis elegans. Mechanisms that underlie natural stasis are being used to pre-condition mammalian cells prior to cell biostabilization and storage.     

Subcellular preservation in giant ostracod sperm from an early Miocene cave deposit in Australia

Cypridoidean ostracods are one of a number of animal taxa that reproduce with giant sperm, up to 10 000 µm in length, but they are the only group to have aflagellate, filamentous giant sperm. The evolution and function of this highly unusual feature of reproduction with giant sperm are currently unknown. The hypothesis of long-term evolutionary persistence of this kind of reproduction has never been tested. We here report giant sperm discovered by propagation phase contrast X-ray synchrotron micro- and nanotomography, preserved in five Miocene ostracod specimens from Queensland, Australia. The specimens belong to the species Heterocypris collaris Matzke-Karasz et al. 2013 (one male and three females) and Newnhamia mckenziana Matzke-Karasz et al. 2013 (one female). The sperm are not only the oldest petrified gametes on record, but include three-dimensional subcellular preservation. We provide direct evidence that giant sperm have been a feature of this taxon for at least 16 Myr and provide an additional criterion (i.e. longevity) to test hypotheses relating to origin and function of giant sperm in the animal kingdom. We further argue that the highly resistant, most probably chitinous coats of giant ostracod sperm may play a role in delaying decay processes, favouring early mineralization of soft tissue.     

Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype

The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.     

Assessing multi-taxa sensitivity to the human footprint,habitat fragmentation and loss by exploring alternative scenarios of dispersal ability and population size: a simulation approach

Quantifying the effects of landscape change on population connectivity is compounded by uncertainties about population size and distribution and a limited understanding of dispersal ability for most species. In addition, the effects of anthropogenic landscape change and sensitivity to regional climatic conditions interact to strongly affect habitat fragmentation and loss. To further develop conservation theory and to understand the interplay between all of these factors, we simulated habitat fragmentation and loss across the Western United States for several hypothetical species associated with four biome types, and a range of habitat requirements and dispersal abilities. We found dispersal ability and population size of the focal species to be equally sensitive to habitat extent, while dispersal ability is more sensitive to habitat fragmentation. There were also strong critical threshold effects where habitat connectivity decreased disproportionately to decreases in life-history traits making these species near these thresholds more sensitive to changes in habitat loss and fragmentation. Overall, grassland and forest associated species are also most at risk from habitat loss and fragmentation driven by human related land-use. These two largest biome types were most sensitive at large contiguous patch sizes which is often considered most important for metapopulation viability and biodiversity conservation. Hypothetical simulation studies such as this can be of great value to scientists in further conceptualizing and developing conservation theory, and evaluating spatially-explicit scenarios of habitat connectivity. Our results are available for download in a web-based interactive mapping prototype useful for accessing the results of this study.