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1.
J Colloid Interface Sci ; 659: 739-750, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38211491

RESUMO

HYPOTHESIS: The formation of distorted lamellar phases, distinguished by their arrangement of crumpled, stacked layers, is frequently accompanied by the disruption of long-range order, leading to the formation of interconnected network structures commonly observed in the sponge phase. Nevertheless, traditional scattering functions grounded in deterministic modeling fall short of fully representing these intricate structural characteristics. Our hypothesis posits that a deep learning method, in conjunction with the generalized leveled wave approach used for describing structural features of distorted lamellar phases, can quantitatively unveil the inherent spatial correlations within these phases. EXPERIMENTS AND SIMULATIONS: This report outlines a novel strategy that integrates convolutional neural networks and variational autoencoders, supported by stochastically generated density fluctuations, into a regression analysis framework for extracting structural features of distorted lamellar phases from small angle neutron scattering data. To evaluate the efficacy of our proposed approach, we conducted computational accuracy assessments and applied it to the analysis of experimentally measured small angle neutron scattering spectra of AOT surfactant solutions, a frequently studied lamellar system. FINDINGS: The findings unambiguously demonstrate that deep learning provides a dependable and quantitative approach for investigating the morphology of wide variations of distorted lamellar phases. It is adaptable for deciphering structures from the lamellar to sponge phase including intermediate structures exhibiting fused topological features. This research highlights the effectiveness of deep learning methods in tackling complex issues in the field of soft matter structural analysis and beyond.

2.
Proc Natl Acad Sci U S A ; 115(28): 7386-7391, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29941601

RESUMO

Gene duplication and deletion are pivotal processes shaping the structural and functional repertoire of genomes, with implications for disease, adaptation, and evolution. We employed a mutation accumulation (MA) framework partnered with high-throughput genomics to assess the molecular and transcriptional characteristics of newly arisen gene copy-number variants (CNVs) in Caenorhabditis elegans populations subjected to varying intensity of selection. Here, we report a direct spontaneous genome-wide rate of gene duplication of 2.9 × 10-5/gene per generation in C. elegans, the highest for any species to date. The rate of gene deletion is sixfold lower (5 × 10-6/gene per generation). Deletions of highly expressed genes are particularly deleterious, given their paucity in even the N = 1 lines with minimal efficacy of selection. The increase in average transcript abundance of new duplicates arising under minimal selection is significantly greater than twofold compared with single copies of the same gene, suggesting that genes in segmental duplications are frequently overactive at inception. The average increase in transcriptional activity of gene duplicates is greater in the N = 1 MA lines than in MA lines with larger population bottlenecks. There is an inverse relationship between the ancestral transcription levels of new gene duplicates and population size, with duplicate copies of highly expressed genes less likely to accumulate in larger populations. Our results demonstrate a fitness cost of increased transcription following duplication, which results in purifying selection against new gene duplicates. However, on average, duplications also provide a significant increase in gene expression that can facilitate adaptation to novel environmental challenges.


Assuntos
Adaptação Fisiológica/genética , Caenorhabditis elegans , Deleção de Genes , Dosagem de Genes , Duplicação Gênica , Transcrição Gênica , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Estudo de Associação Genômica Ampla
3.
J Environ Manage ; 222: 348-358, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29870963

RESUMO

The mining industry needs to treat large volumes of wastewater highly concentrated in chemical compounds that can adversely affect receiving environments. One promising method of treatment is the use of reverse osmosis to remove most of the dissolved salts. However, the resulting brine reject is a highly saline wastewater that needs further treatment to remove the toxic components, such as selenate, which is a chemical compound of great concern in coal-mining regions. Biological reduction and removal of dissolved selenium from a brine solution was achieved. Microorganisms were enriched from environmental samples collected from two mines, respectively, at different geographic locations through adaptive evolution in the laboratory. Batch treatment of typical brine was tested with two different enrichments with the addition of either of two chemical forms of iron, ferrous chloride or zero valent iron. Successful selenium removal in the presence of high nitrate and sulphate concentrations was achieved with a combination of enriched microorganisms from one particular site and the addition of zero-valent iron. The composition and metabolic potential of the enriched microorganisms revealed Clostridium, Sphaerochaeta, Synergistes and Desulfosporosinus species with the metabolic potential for selenate reduction through the YgfK enzymatic process associated with selenium detoxification.


Assuntos
Bactérias Anaeróbias , Ácido Selênico/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Ferro , Sais , Ácido Selênico/metabolismo , Poluentes Químicos da Água/metabolismo
4.
PLoS One ; 13(4): e0196032, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29694379

RESUMO

We investigated the impacts of the Mount Polley tailings impoundment failure on chemical, physical, and microbial properties of substrates within the affected watershed, comprised of 70 hectares of riparian wetlands and 40 km of stream and lake shore. We established a biomonitoring network in October of 2014, two months following the disturbance, and evaluated riparian and wetland substrates for microbial community composition and function via 16S and full metagenome sequencing. A total of 234 samples were collected from substrates at 3 depths and 1,650,752 sequences were recorded in a geodatabase framework. These data revealed a wealth of information regarding watershed-scale distribution of microbial community members, as well as community composition, structure, and response to disturbance. Substrates associated with the impact zone were distinct chemically as indicated by elevated pH, nitrate, and sulphate. The microbial community exhibited elevated metabolic capacity for selenate and sulfate reduction and an abundance of chemolithoautotrophs in the Thiobacillus thiophilus/T. denitrificans/T. thioparus clade that may contribute to nitrate attenuation within the affected watershed. The most impacted area (a 6 km stream connecting two lakes) exhibited 30% lower microbial diversity relative to the remaining sites. The tailings impoundment failure at Mount Polley Mine has provided a unique opportunity to evaluate functional and compositional diversity soon after a major catastrophic disturbance to assess metabolic potential for ecosystem recovery.


Assuntos
Bactérias/classificação , Metagenômica/métodos , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/metabolismo , Biodiversidade , Concentração de Íons de Hidrogênio , Mineração , Nitratos/metabolismo , Análise de Sequência de DNA , Solo/química , Água/química , Áreas Alagadas
5.
G3 (Bethesda) ; 8(5): 1535-1544, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29507057

RESUMO

In a genetic screen to identify genes that promote GLP-1/Notch signaling in Caenorhabditis elegans germline stem cells, we found a single mutation, om40, defining a gene called ego-3. ego-3(om40) causes several defects in the soma and the germline, including paralysis during larval development, sterility, delayed proliferation of germline stem cells, and ectopic germline stem cell proliferation. Whole genome sequencing identified om40 as an allele of hsp-90, previously known as daf-21, which encodes the C. elegans ortholog of the cytosolic form of HSP90. This protein is a molecular chaperone with a central position in the protein homeostasis network, which is responsible for proper folding, structural maintenance, and degradation of proteins. In addition to its essential role in cellular function, HSP90 plays an important role in stem cell maintenance and renewal. Complementation analysis using a deletion allele of hsp-90 confirmed that ego-3 is the same gene. hsp-90(om40) is an I→N conservative missense mutation of a highly conserved residue in the middle domain of HSP-90 RNA interference-mediated knockdown of hsp-90 expression partially phenocopied hsp-90(om40), confirming the loss-of-function nature of hsp-90(om40) Furthermore, reduced HSP-90 activity enhanced the effect of reduced function of both the GLP-1 receptor and the downstream LAG-1 transcription factor. Taken together, our results provide the first experimental evidence of an essential role for HSP90 in Notch signaling in development.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Células Germinativas/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Chaperonas Moleculares/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ligação a DNA , Proteínas de Choque Térmico HSP90/química , Proteínas de Choque Térmico HSP90/genética , Mutação com Perda de Função/genética , Fenótipo , Mapeamento Físico do Cromossomo
6.
Chemosphere ; 183: 536-545, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28570897

RESUMO

Increasing selenium concentrations in aquatic environments downstream of mine sites is of great concern due to selenium's bioaccumulation propensity and teratogenic toxicity. Removal of selenium from mine influenced water is complicated by the presence of nitrate, which is also elevated in mine influenced water due to the use of explosives in mining. In many biological treatment processes, nitrate as a thermodynamically more preferable electron acceptor inhibits selenate reduction. Here we report on an enrichment of a bacterial assemblage from a mine impacted natural marsh sediment that was capable of simultaneous selenate reduction and denitrification. Selenate reduction followed first order kinetics with respect to the concentration of total dissolved selenium. The kinetic rate constant was independent of initial nitrate concentration over the range 3-143 mg L-1-NO3--N. The initial concentration of selenate inhibited selenate reduction kinetics over the range 1-24 mg-Se L-1. Dominant taxa that grew in selenate only medium were classified in the genera Pseudomonas, Lysinibacillus and Thauera. When nitrate was introduced in addition to selenate, previously rare taxa that became dominant were relatives of Exiguobacterium, Tissierella and Clostridium. Open reading frames (ORFs) associated with dissimilatory denitrification were identified for Pseudomonas, Thauera and Clostridium. In addition, ORFs were found that were homologous with known selenate reductase subunits (SerA and SerB). These findings suggest that native mine site bacteria can be used for removing selenate and nitrate from mine wastewater.


Assuntos
Consórcios Microbianos , Mineração , Nitratos/análise , Ácido Selênico/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Bactérias Anaeróbias/genética , Bactérias Anaeróbias/crescimento & desenvolvimento , Desnitrificação , Cinética , Oxirredução , Oxirredutases/genética
7.
G3 (Bethesda) ; 6(7): 2125-34, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27185398

RESUMO

Notch-type signaling mediates cell-cell interactions important for animal development. In humans, reduced or inappropriate Notch signaling activity is associated with various developmental defects and disease states, including cancers. Caenorhabditis elegans expresses two Notch-type receptors, GLP-1 and LIN-12. GLP-1 mediates several cell-signaling events in the embryo and promotes germline proliferation in the developing and adult gonad. LIN-12 acts redundantly with GLP-1 in certain inductive events in the embryo and mediates several cell-cell interactions during larval development. Recovery of genetic suppressors and enhancers of glp-1 or lin-12 loss- or gain-of-function mutations has identified numerous regulators of GLP-1 and LIN-12 signaling activity. Here, we report the molecular identification of sog-1, a gene identified in screens for recessive suppressors of conditional glp-1 loss-of-function mutations. The sog-1 gene encodes UBR-5, the sole C. elegans member of the UBR5/Hyd family of HECT-type E3 ubiquitin ligases. Molecular and genetic analyses indicate that the loss of ubr-5 function suppresses defects caused by reduced signaling via GLP-1 or LIN-12. In contrast, ubr-5 mutations do not suppress embryonic or larval lethality associated with mutations in a downstream transcription factor, LAG-1. In the gonad, ubr-5 acts in the receiving cells (germ cells) to limit GLP-1 signaling activity. SEL-10 is the F-box component of SCF(SEL-10) E3 ubiquitin-ligase complex that promotes turnover of Notch intracellular domain. UBR-5 acts redundantly with SEL-10 to limit Notch signaling in certain tissues. We hypothesize that UBR-5 activity limits Notch-type signaling by promoting turnover of receptor or limiting its interaction with pathway components.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Receptores Notch/genética , Ubiquitina-Proteína Ligases/genética , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Gônadas/crescimento & desenvolvimento , Gônadas/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Mutação , Receptores Notch/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/metabolismo
8.
BMC Genomics ; 16: 1044, 2015 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-26645535

RESUMO

BACKGROUND: Gene copy-number variation (CNVs), which provides the raw material for the evolution of novel genes, is widespread in natural populations. We investigated whether CNVs constitute a common mechanism of genetic change during adaptation in experimental Caenorhabditis elegans populations. Outcrossing C. elegans populations with low fitness were evolved for >200 generations. The frequencies of CNVs in these populations were analyzed by oligonucleotide array comparative genome hybridization, quantitative PCR, PCR, DNA sequencing across breakpoints, and single-worm PCR. RESULTS: Multiple duplications and deletions rose to intermediate or high frequencies in independent populations. Several lines of evidence suggest that these changes were adaptive: (i) copy-number changes reached high frequency or were fixed in a short time, (ii) many independent populations harbored CNVs spanning the same genes, and (iii) larger average size of CNVs in adapting populations relative to spontaneous CNVs. The latter is expected if larger CNVs are more likely to encompass genes under selection for a change in gene dosage. Several convergent CNVs originated in populations descended from different low fitness ancestors as well as high fitness controls. CONCLUSIONS: We show that gene copy-number changes are a common class of adaptive genetic change. Due to the high rates of origin of spontaneous duplications and deletions, copy-number changes containing the same genes arose readily in independent populations. Duplications that reached high frequencies in these adapting populations were significantly larger in span. Many convergent CNVs may be general adaptations to laboratory conditions. These results demonstrate the great potential borne by CNVs for evolutionary adaptation.


Assuntos
Caenorhabditis elegans/genética , Variações do Número de Cópias de DNA , Evolução Molecular , Dosagem de Genes , Adaptação Biológica/genética , Animais , Cruzamentos Genéticos , Deleção de Genes , Duplicação Gênica , Aptidão Genética , Variação Genética , Genética Populacional , Mutação , Sequências Repetitivas de Ácido Nucleico
9.
J Chem Phys ; 143(17): 174703, 2015 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-26547178

RESUMO

An iron based Fischer-Tropsch synthesis catalyst is evaluated using CO hydrogenation at ambient pressure as a test reaction and is characterised by a combination of inelastic neutron scattering (INS), powder X-ray diffraction, temperature-programmed oxidation, Raman scattering, and transmission electron microscopy. The INS spectrum of the as-prepared bulk iron oxide pre-catalyst (hematite, α-Fe2O3) is distinguished by a relatively intense band at 810 cm(-1), which has previously been tentatively assigned as a magnon (spinon) feature. An analysis of the neutron scattering intensity of this band as a function of momentum transfer unambiguously confirms this assignment. Post-reaction, the spinon feature disappears and the INS spectrum is characterised by the presence of a hydrocarbonaceous overlayer. A role for the application of INS in magnetic characterisation of iron based FTS catalysts is briefly considered.


Assuntos
Monóxido de Carbono/química , Compostos Férricos/química , Magnetismo , Nêutrons , Catálise , Hidrogenação , Microscopia Eletrônica de Transmissão , Análise Espectral Raman
10.
BMC Genomics ; 16: 210, 2015 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-25880765

RESUMO

BACKGROUND: Whole and partial chromosome losses or gains and structural chromosome changes are hallmarks of human tumors. Guanine-rich DNA, which has a potential to form a G-quadruplex (G4) structure, is particularly vulnerable to changes. In Caenorhabditis elegans, faithful transmission of G-rich DNA is ensured by the DOG-1/FANCJ deadbox helicase. RESULTS: To identify a spectrum of mutations, after long-term propagation, we combined whole genome sequencing (WGS) and oligonucleotide array Comparative Genomic Hybridization (oaCGH) analysis of a C. elegans strain that was propagated, in the absence of DOG-1 and MDF-1/MAD1, for a total of 470 generations, with samples taken for long term storage (by freezing) in generations 170 and 270. We compared the genomes of F170 and F470 strains and identified 94 substitutions, 17 InDels, 3 duplications, and 139 deletions larger than 20 bp. These homozygous variants were predicted to impact 101 protein-coding genes. Phenotypic analysis of this strain revealed remarkable fitness recovery indicating that mutations, which have accumulated in the strain, are not only tolerated but also cooperate to achieve long-term population survival in the absence of DOG-1 and MDF-1. Furthermore, deletions larger than 20 bp were the only variants that frequently occurred in G-rich DNA. We showed that 126 of the possible 954 predicted monoG/C tracts, larger than 14 bp, were deleted in unc-46 mdf-1 such-4; dog-1 F470 (JNC170). CONCLUSIONS: Here, we identified variants that accumulated in C. elegans' genome after long-term propagation in the absence of DOG-1 and MDF-1. We showed that DNA sequences, with G4-forming potential, are vulnerable to deletion-formation in this genetic background.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , DNA Helicases/genética , Genoma , Animais , Caenorhabditis elegans/metabolismo , Hibridização Genômica Comparativa , Quadruplex G , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Mutação , Fenótipo , Análise de Sequência de DNA , Deleção de Sequência
12.
Cell Cycle ; 13(19): 3089-199, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25486568

RESUMO

Spindle assembly checkpoint (SAC) ensures genome stability by delaying anaphase onset until all the chromosomes have achieved proper spindle attachment. Once correct attachment has been achieved, SAC must be silenced. In the absence of mdf-1/MAD1, an essential SAC component, Caenorhabditis elegans cannot propagate beyond 3 generations. Previously, in a dog-1(gk10)/FANCJ mutator background, we isolated a suppressor of mdf-1(gk2) sterility (such-4) which allowed indefinite propagation in the absence of MDF-1. We showed that such-4 is a Cyclin B3 (cyb-3) duplication. Here we analyze mdf-1 such-4; dog-1, which we propagated for 470 generations, with freezing of samples for long time storage at F170 and F270. Phenotypic analysis of this strain revealed additional suppression of sterility in the absence of MDF-1, beyond the effects of such-4. We applied oligonucleotide array Comparative Genomic Hybridization (oaCGH) and whole genome sequencing (WGS) and identified a further amplification of cyb-3 (triplication) and a new missense mutation in dynein heavy chain (dhc-1). We show that dhc-1(dot168) suppresses the mdf-1(gk2), and is the second cloned suppressor, next to cyb-3 duplication, that does not cause a delay in anaphase onset. We also show that amplification of cyb-3 and dhc-1(dot168) cooperate to increase fitness in the absence of MDF-1.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/genética , Ciclina B/metabolismo , Dineínas do Citoplasma/metabolismo , Proteínas Nucleares/genética , Sequência de Aminoácidos , Anáfase , Animais , Proteínas de Ciclo Celular/metabolismo , Hibridização Genômica Comparativa , Ciclina B/genética , Dineínas do Citoplasma/genética , DNA Helicases/genética , DNA Helicases/metabolismo , Genótipo , Humanos , Dados de Sequência Molecular , Mutação , Proteínas Nucleares/metabolismo , Fenótipo , Alinhamento de Sequência
13.
Nucl Med Commun ; 35(11): 1096-106, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25144565

RESUMO

INTRODUCTION: An audit was carried out into UK glomerular filtration rate (GFR) calculation. The results were compared with an identical 2001 audit. METHODS: Participants used their routine method to calculate GFR for 20 data sets (four plasma samples) in millilitres per minute and also the GFR normalized for body surface area. Some unsound data sets were included to analyse the applied quality control (QC) methods. Variability between centres was assessed for each data set, compared with the national median and a reference value calculated using the method recommended in the British Nuclear Medicine Society guidelines. The influence of the number of samples on variability was studied. Supplementary data were requested on workload and methodology. RESULTS: The 59 returns showed widespread standardization. The applied early exponential clearance correction was the main contributor to the observed variability. These corrections were applied by 97% of centres (50% - 2001) with 80% using the recommended averaged Brochner-Mortenson correction. Approximately 75% applied the recommended Haycock body surface area formula for adults (78% for children). The effect of the number of samples used was not significant. There was wide variability in the applied QC techniques, especially in terms of the use of the volume of distribution. CONCLUSION: The widespread adoption of the guidelines has harmonized national GFR calculation compared with the previous audit. Further standardization could further reduce variability. This audit has highlighted the need to address the national standardization of QC methods. Radionuclide techniques are confirmed as the preferred method for GFR measurement when an unequivocal result is required.


Assuntos
Auditoria Clínica , Taxa de Filtração Glomerular , Testes de Função Renal/métodos , Plasma/metabolismo , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Controle de Qualidade , Reino Unido
14.
Nat Methods ; 11(5): 529-34, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24820376

RESUMO

We have generated a recombinant Mos1 transposon that can insert up to 45-kb transgenes into the Caenorhabditis elegans genome. The minimal Mos1 transposon (miniMos) is 550 bp long and inserts DNA into the genome at high frequency (~60% of injected animals). Genetic and antibiotic markers can be used for selection, and the transposon is active in C. elegans isolates and Caenorhabditis briggsae. We used the miniMos transposon to generate six universal Mos1-mediated single-copy insertion (mosSCI) landing sites that allow targeted transgene insertion with a single targeting vector into permissive expression sites on all autosomes. We also generated two collections of strains: a set of bright fluorescent insertions that are useful as dominant, genetic balancers and a set of lacO insertions to track genome position.


Assuntos
Caenorhabditis elegans/genética , Elementos de DNA Transponíveis/genética , Proteínas de Ligação a DNA/genética , Transgenes , Transposases/genética , Animais , Animais Geneticamente Modificados , Hibridização Genômica Comparativa , Biologia Computacional , Engenharia Genética/métodos , Marcadores Genéticos/genética , Proteínas de Fluorescência Verde/metabolismo , Modelos Genéticos , Mutagênese Insercional , Proteínas Recombinantes/metabolismo , Recombinação Genética
15.
J Appl Crystallogr ; 46(Pt 6): 1755-1770, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24282332

RESUMO

A new approach to the interpretation and analysis of coherent inelastic neutron scattering from polycrystals (poly-CINS) is presented. This article describes a simulation of the one-phonon coherent inelastic scattering from a lattice model of an arbitrary crystal system. The one-phonon component is characterized by sharp features, determined, for example, by boundaries of the (Q, ω) regions where one-phonon scattering is allowed. These features may be identified with the same features apparent in the measured total coherent inelastic cross section, the other components of which (multiphonon or multiple scattering) show no sharp features. The parameters of the model can then be relaxed to improve the fit between model and experiment. This method is of particular interest where no single crystals are available. To test the approach, the poly-CINS has been measured for polycrystalline aluminium using the MARI spectrometer (ISIS), because both lattice dynamical models and measured dispersion curves are available for this material. The models used include a simple Lennard-Jones model fitted to the elastic constants of this material plus a number of embedded atom method force fields. The agreement obtained suggests that the method demonstrated should be effective in developing models for other materials where single-crystal dispersion curves are not available.

16.
Genome Res ; 23(10): 1749-62, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23800452

RESUMO

We have created a library of 2007 mutagenized Caenorhabditis elegans strains, each sequenced to a target depth of 15-fold coverage, to provide the research community with mutant alleles for each of the worm's more than 20,000 genes. The library contains over 800,000 unique single nucleotide variants (SNVs) with an average of eight nonsynonymous changes per gene and more than 16,000 insertion/deletion (indel) and copy number changes, providing an unprecedented genetic resource for this multicellular organism. To supplement this collection, we also sequenced 40 wild isolates, identifying more than 630,000 unique SNVs and 220,000 indels. Comparison of the two sets demonstrates that the mutant collection has a much richer array of both nonsense and missense mutations than the wild isolate set. We also find a wide range of rDNA and telomere repeat copy number in both sets. Scanning the mutant collection for molecular phenotypes reveals a nonsense suppressor as well as strains with higher levels of indels that harbor mutations in DNA repair genes and strains with abundant males associated with him mutations. All the strains are available through the Caenorhabditis Genetics Center and all the sequence changes have been deposited in WormBase and are available through an interactive website.


Assuntos
Caenorhabditis elegans/genética , Genes de Helmintos , Mutação , Alelos , Animais , Caenorhabditis elegans/classificação , Códon sem Sentido , Variações do Número de Cópias de DNA , DNA Ribossômico , Bases de Dados de Ácidos Nucleicos , Genes Essenciais , Genes Supressores , Variação Genética , Genoma Helmíntico , Genoma Mitocondrial , Heterozigoto , Mutação INDEL , Masculino , Mutação de Sentido Incorreto , Fenótipo , Polimorfismo de Nucleotídeo Único , Sequências de Repetição em Tandem
17.
PLoS Genet ; 9(5): e1003497, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23671424

RESUMO

Pairing of homologous chromosomes during early meiosis is essential to prevent the formation of aneuploid gametes. Chromosome pairing includes a step of homology search followed by the stabilization of homolog interactions by the synaptonemal complex (SC). These events coincide with dramatic changes in nuclear organization and rapid chromosome movements that depend on cytoskeletal motors and are mediated by SUN-domain proteins on the nuclear envelope, but how chromosome mobility contributes to the pairing process remains poorly understood. We show that defects in the mitochondria-localizing protein SPD-3 cause a defect in homolog pairing without impairing nuclear reorganization or SC assembly, which results in promiscuous installation of the SC between non-homologous chromosomes. Preventing SC assembly in spd-3 mutants does not improve homolog pairing, demonstrating that SPD-3 is required for homology search at the start of meiosis. Pairing center regions localize to SUN-1 aggregates at meiosis onset in spd-3 mutants; and pairing-promoting proteins, including cytoskeletal motors and polo-like kinase 2, are normally recruited to the nuclear envelope. However, quantitative analysis of SUN-1 aggregate movement in spd-3 mutants demonstrates a clear reduction in mobility, although this defect is not as severe as that seen in sun-1(jf18) mutants, which also show a stronger pairing defect, suggesting a correlation between chromosome-end mobility and the efficiency of pairing. SUN-1 aggregate movement is also impaired following inhibition of mitochondrial respiration or dynein knockdown, suggesting that mitochondrial function is required for motor-driven SUN-1 movement. The reduced chromosome-end mobility of spd-3 mutants impairs coupling of SC assembly to homology recognition and causes a delay in meiotic progression mediated by HORMA-domain protein HTP-1. Our work reveals how chromosome mobility impacts the different early meiotic events that promote homolog pairing and suggests that efficient homology search at the onset of meiosis is largely dependent on motor-driven chromosome movement.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans , Pareamento Cromossômico/genética , Cromossomos/genética , Proteínas Mitocondriais/genética , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Núcleo Celular , Meiose , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , Estrutura Terciária de Proteína , Complexo Sinaptonêmico/genética
18.
G3 (Bethesda) ; 2(12): 1625-41, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23275885

RESUMO

The nematode Caenorhabditis briggsae is an excellent model organism for the comparative analysis of gene function and developmental mechanisms. To study the evolutionary conservation and divergence of genetic pathways mediating vulva formation, we screened for mutations in C. briggsae that cause the egg-laying defective (Egl) phenotype. Here, we report the characterization of 13 genes, including three that are orthologs of Caenorhabditis elegans unc-84 (SUN domain), lin-39 (Dfd/Scr-related homeobox), and lin-11 (LIM homeobox). Based on the morphology and cell fate changes, the mutants were placed into four different categories. Class 1 animals have normal-looking vulva and vulva-uterine connections, indicating defects in other components of the egg-laying system. Class 2 animals frequently lack some or all of the vulval precursor cells (VPCs) due to defects in the migration of P-cell nuclei into the ventral hypodermal region. Class 3 animals show inappropriate fusion of VPCs to the hypodermal syncytium, leading to a reduced number of vulval progeny. Finally, class 4 animals exhibit abnormal vulval invagination and morphology. Interestingly, we did not find mutations that affect VPC induction and fates. Our work is the first study involving the characterization of genes in C. briggsae vulva formation, and it offers a basis for future investigations of these genes in C. elegans.


Assuntos
Caenorhabditis/genética , Genoma de Inseto , Vulva/crescimento & desenvolvimento , Animais , Animais Geneticamente Modificados/genética , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Núcleo Celular/metabolismo , Mapeamento Cromossômico , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Feminino , Ligação Genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Temperatura , Vulva/metabolismo
19.
Phys Chem Chem Phys ; 13(17): 7789-804, 2011 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-21442090

RESUMO

In this paper we exploit the complementarity of inelastic neutron scattering (INS), infrared and Raman spectroscopies with ab initio calculations to generate an updated assignment of the vibrational modes of C(60). We have carried out periodic-DFT calculations of the high temperature face centred cubic phase modelled as the standard structure and also of the low temperature simple cubic phase, the latter for the first time. Our assignment differs from all previous work, however, it is the only one that is able to successfully reproduce the INS spectrum in terms of both transition energies and intensities. In addition to the INS spectrum we are also able to quantitatively simulate the major features of the infrared and Raman spectra in the high temperature phase and the infrared spectrum in the low temperature phase.

20.
Genetics ; 185(2): 431-41, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20439774

RESUMO

Deep sequencing offers an unprecedented view of an organism's genome. We describe the spectrum of mutations induced by three commonly used mutagens: ethyl methanesulfonate (EMS), N-ethyl-N-nitrosourea (ENU), and ultraviolet trimethylpsoralen (UV/TMP) in the nematode Caenorhabditis elegans. Our analysis confirms the strong GC to AT transition bias of EMS. We found that ENU mainly produces A to T and T to A transversions, but also all possible transitions. We found no bias for any specific transition or transversion in the spectrum of UV/TMP-induced mutations. In 10 mutagenized strains we identified 2723 variants, of which 508 are expected to alter or disrupt gene function, including 21 nonsense mutations and 10 mutations predicted to affect mRNA splicing. This translates to an average of 50 informative mutations per strain. We also present evidence of genetic drift among laboratory wild-type strains derived from the Bristol N2 strain. We make several suggestions for best practice using massively parallel short read sequencing to ensure mutation detection.


Assuntos
Caenorhabditis elegans/genética , Mutagênese , Animais , Metanossulfonato de Etila , Etilnitrosoureia , Genoma , Mutagênicos , Mutação , Fenótipo , Trioxsaleno
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