A structured overview of simultaneous component based data integration

Background  

Data integration is currently one of the main challenges in the biomedical sciences. Often different pieces of information are gathered on the same set of entities (e.g., tissues, culture samples, biomolecules) with the different pieces stemming, for example, from different measurement techniques. This implies that more and more data appear that consist of two or more data arrays that have a shared mode. An integrative analysis of such coupled data should be based on a simultaneous analysis of all data arrays. In this respect, the family of simultaneous component methods (e.g., SUM-PCA, unrestricted PCovR, MFA, STATIS, and SCA-P) is a natural choice. Yet, different simultaneous component methods may lead to quite different results.     

Morphology and Phylogeny of Two New Pleurostomatid Ciliates,Epiphyllum shenzhenense n. sp. and Loxophyllum spirellum n. sp. (Protozoa,Ciliophora) from A Mangrove Wetland,South China

ABSTRACT. The morphology, infraciliature, and small subunit (SSU) rRNA gene sequences of two new pleurostomatid ciliates, Epiphyllum shenzhenense n. sp. and Loxophyllum spirellum n. sp., isolated from a mangrove wetland near Shenzhen, South China, were investigated. Epiphyllum shenzhenense n. sp. is morphologically characterized by leaf‐shaped cell about 150 × 35 μm in vivo, usually with four contractile vacuoles, 20–29 right kineties and 10–26 left kineties, ca. four macronuclear nodules, and two types of extrusomes (i.e. short spindle‐shaped and long bar‐shaped). As a new species, L. spirellum n. sp. is distinguished from its congeners by its posterior dorsal margin twisted onto the left side, the distribution of extrusomes (evenly arranged along the oral slit, the posterior end, and clustered to 7–13 warts on dorsal margin), the subterminally positioned contractile vacuole, the number of kineties (8–10 on right side, 4–5 on left side), and its genetic distance from congeners. Phylogenetic trees based on the SSU rRNA gene sequence for both organisms were constructed, which indicate that Epiphyllum is a distinct genus and occupies a basal position in the Pleurostomatida clade; L. spirellum n. sp. falls well into the Loxophyllum clade, which has a close relationship with Litonotus and Spiroloxophyllum.     

Elevated dNTP levels suppress hyper-recombination in Saccharomyces cerevisiae S-phase checkpoint mutants

MEC1, the essential yeast homolog of the human ATR/ATM genes, controls the S-phase checkpoint and prevents replication fork collapse at slow zones of DNA replication. The viability of hypomorphic mec1-21 is reduced in the rad52 mutant, defective in homologous recombination, suggesting that replication generates recombinogenic lesions. We previously observed a 6-, 10- and 30-fold higher rate of spontaneous sister chromatid exchange (SCE), heteroallelic recombination and translocations, respectively, in mec1-21 mutants compared to wild-type. Here we report that the hyper-recombination phenotype correlates with lower deoxyribonucleoside triphosphate (dNTP) levels, compared to wild-type. By introducing a dun1 mutation, thus eliminating inducible expression of ribonucleotide reductase in mec1-21, rates of spontaneous SCE increased 15-fold above wild-type. All the hyper-recombination phenotypes were reduced by SML1 deletions, which increase dNTP levels. Measurements of dNTP pools indicated that, compared to wild-type, there was a significant decrease in dNTP levels in mec1-21, dun1 and mec1-21 dun1, while the dNTP levels of mec1-21 sml1, mec1-21 dun1 sml1 and sml1 mutants were ∼2-fold higher. Interestingly, higher dNTP levels in mec1-21 dun1 sml1 correlate with ∼2-fold higher rate of spontaneous mutagenesis, compared to mec1-21 dun1. We suggest that higher dNTP levels in specific checkpoint mutants suppress the formation of recombinogenic lesions.     

Accurate measurement of gene copy number for human alpha-defensin DEFA1A3

Background

Multi-allelic copy number variants include examples of extensive variation between individuals in the copy number of important genes, most notably genes involved in immune function. The definition of this variation, and analysis of its impact on function, has been hampered by the technical difficulty of large-scale but accurate typing of genomic copy number. The copy-variable alpha-defensin locus DEFA1A3 on human chromosome 8 commonly varies between 4 and 10 copies per diploid genome, and presents considerable challenges for accurate high-throughput typing.

Results

In this study, we developed two paralogue ratio tests and three allelic ratio measurements that, in combination, provide an accurate and scalable method for measurement of DEFA1A3 gene number. We combined information from different measurements in a maximum-likelihood framework which suggests that most samples can be assigned to an integer copy number with high confidence, and applied it to typing 589 unrelated European DNA samples. Typing the members of three-generation pedigrees provided further reassurance that correct integer copy numbers had been assigned. Our results have allowed us to discover that the SNP rs4300027 is strongly associated with DEFA1A3 gene copy number in European samples.

Conclusions

We have developed an accurate and robust method for measurement of DEFA1A3 copy number. Interrogation of rs4300027 and associated SNPs in Genome-Wide Association Study SNP data provides no evidence that alpha-defensin copy number is a strong risk factor for phenotypes such as Crohn’s disease, type I diabetes, HIV progression and multiple sclerosis.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-14-719) contains supplementary material, which is available to authorized users.     

NAR Breakthrough Article: Pre-activation of the genome integrity checkpoint increases DNA damage tolerance

The genome integrity checkpoint is a conserved signaling pathway that is regulated in yeast by the Mec1 (homologous to human ATR) and Rad53 (homologous to human Chk1) kinases. The pathway coordinates a multifaceted response that allows cells to cope with DNA damage and DNA replication stress. The full activation of the checkpoint blocks origin firing, stabilizes replication forks, activates DNA repair proteins and may lead to senescence or apoptosisin higher eukaryotes. We have recently demonstrated that endogenous replication stress can activate the genome integrity checkpoint in budding yeast at a low level that does not go so far as to interfere with cell cycle progression, but it does activate DNA damage-inducible proteins. Here we demonstrate that the low level pre-activation of the checkpoint, either by endogenous replication stress or by the nucleotide-depleting drug hydroxyurea, can increase damage tolerance to multiple DNA-damaging agents. These results may provide new strategies for using the checkpoint to protect normal cells from genotoxic stress.     

Biodiversity of stream insects in the Malaysian Peninsula: spatial patterns and environmental constraints

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Viscoelastic Properties of a Mixed Culture Biofilm from Rheometer Creep Analysis

The mechanical properties of mixed culture biofilms were determined by creep analysis using an AR1000 rotating disk rheometer. The biofilms were grown directly on the rheometer disks which were rotated in a chemostat for 12 d. The resulting biofilms were heterogeneous and ranged from 35?μm to 50?μm in thickness. The creep curves were all viscoelastic in nature. The close agreement between stress and strain ratio of a sample tested at 0.1 and 0.5 Pa suggested that the biofilms were tested in the linear viscoelastic range and supported the use of linear viscoelastic theory in the development of a constitutive law. The experimental data was fit to a 4-element Burger spring and dashpot model. The shear modulus (G) ranged from 0.2 to 24 Pa and the viscous coefficient (η) from 10 to 3000 Pa. These values were in the same range as those previously estimated from fluid shear deformation of biofilms in flow cells. A viscoelastic biofilm model will help to predict shear related biofilm phenomena such as elevated pressure drop, detachment, and the flow of biofilms over solid surfaces.     

A top-down view on DNA replication and recombination from 9,000 feet above sea level

A report of the Keystone Symposium 'DNA Replication and Recombination' held in Keystone, USA, 27 February to 4 March 2011.     

Taxonomy of five species of cyrtophorids (Protozoa: Ciliophora) including consideration of the phylogeny of two new genera

Cyrtophorids are a specialized group of ciliated protozoa with multitudinous morphotypes. In the present work, the morphology and infraciliature of two new and three rarely known species, including two new genera of cyrtophorid ciliates, Heterohartmannula fangi gen. et sp. nov. , Aporthotrochilia pulex (Deroux, 1976) gen. et comb. nov. , Trochilia alveolata sp. nov. , Trochochilodon flavus Deroux, 1976, and Hypocoma acinetarum Collin, 1907, are described. Heterohartmannula gen. nov. is mainly characterized by a combination of features: two circumoral kineties obliquely arranged, podite not surrounded by somatic kineties, and no distinct gap between left and right ciliary field. Aporthotrochilia gen. nov. is diagnosed mainly by: podite present, oral ciliature reduced to two fragments, several kinety fragments positioned on the right posterior of frontoventral kineties and several terminal fragments. Phylogenetic analyses based on the small subunit rRNA (SSU rRNA) gene sequences support the establishment of two new genera and indicate that Heterohartmannula is most closely related to Hartmannula, and Aporthotrochilia is basal to the Cyrtophoria‐Chonotrichia clade. Trochilia alveolata sp. nov. differs from its congeners mainly by having a conspicuous alveolar layer. In addition, detailed live and infraciliature data of Hypocoma acinetarum and Trochochilodon flavus are supplied. © 2012 The Linnean Society of London, Zoological Journal of the Linnean Society, 2012, 164 , 1–17.