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141.
Masoud Zamani Esteki Eftychia Dimitriadou Ligia Mateiu Cindy Melotte Niels Van der Aa Parveen Kumar Rakhi Das Koen Theunis Jiqiu Cheng Eric Legius Yves Moreau Sophie Debrock Thomas D’Hooghe Pieter Verdyck Martine De Rycke Karen Sermon Joris R. Vermeesch Thierry Voet 《American journal of human genetics》2015,96(6):894-912
Methods for haplotyping and DNA copy-number typing of single cells are paramount for studying genomic heterogeneity and enabling genetic diagnosis. Before analyzing the DNA of a single cell by microarray or next-generation sequencing, a whole-genome amplification (WGA) process is required, but it substantially distorts the frequency and composition of the cell’s alleles. As a consequence, haplotyping methods suffer from error-prone discrete SNP genotypes (AA, AB, BB) and DNA copy-number profiling remains difficult because true DNA copy-number aberrations have to be discriminated from WGA artifacts. Here, we developed a single-cell genome analysis method that reconstructs genome-wide haplotype architectures as well as the copy-number and segregational origin of those haplotypes by employing phased parental genotypes and deciphering WGA-distorted SNP B-allele fractions via a process we coin haplarithmisis. We demonstrate that the method can be applied as a generic method for preimplantation genetic diagnosis on single cells biopsied from human embryos, enabling diagnosis of disease alleles genome wide as well as numerical and structural chromosomal anomalies. Moreover, meiotic segregation errors can be distinguished from mitotic ones. 相似文献
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144.
Thomas Saucède Huw Griffiths Camille Moreau Jennifer A. Jackson Chester Sands Rachel Downey Adam Reed Melanie Mackenzie Paul Geissler Katrin Linse 《ZooKeys》2015,(504):1-10
Information regarding the echinoids in this dataset is based on the Agassiz Trawl (AGT) and epibenthic sledge (EBS) samples collected during the British Antarctic Survey cruise JR275 on the RRS James Clark Ross in the austral summer 2012. A total of 56 (1 at the South Orkneys and 55 in the Eastern Weddell Sea) Agassiz Trawl and 18 (2 at the South Orkneys and 16 in the Eastern Weddell Sea) epibenthic sledge deployments were performed at depths ranging from ~280 to ~2060 m. This presents a unique collection for the Antarctic benthic biodiversity assessment of an important group of benthic invertebrates. In total 487 specimens belonging to six families, 15 genera, and 22 morphospecies were collected. The species richness per station varied between one and six. Total species richness represents 27% of the 82 echinoid species ever recorded in the Southern Ocean (David et al. 2005b, Pierrat et al. 2012, Saucède et al. 2014). The Cidaridae (sub-family Ctenocidarinae) and Schizasteridae are the two most speciose families in the dataset. They comprise seven and nine species respectively. This is illustrative of the overall pattern of echinoid diversity in the Southern Ocean where 65% of Antarctic species belong to the families Schizasteridae and Cidaridae (Pierrat et al. 2012). 相似文献
145.
Crustal fluid and ash alteration impacts on the biosphere of Shikoku Basin sediments,Nankai Trough,Japan
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M. E. Torres T. Cox W.‐L. Hong J. McManus J. C. Sample C. Destrigneville H. M. Gan H. Y. Gan J. W. Moreau 《Geobiology》2015,13(6):562-580
We present data from sediment cores collected from IODP Site C0012 in the Shikoku Basin. Our site lies at the Nankai Trough, just prior to subduction of the 19 Ma Philippine Sea plate. Our data indicate that the sedimentary package is undergoing multiple routes of electron transport and that these differing pathways for oxidant supply generate a complex array of metabolic routes and microbial communities involved in carbon cycling. Numerical simulations matched to pore water data document that Ca2+ and Cl1‐ are largely supplied via diffusion from a high‐salinity (44.5 psu) basement fluid, which supports the presence of halophile Archean communities within the deep sedimentary package that are not observed in shallow sediments. Sulfate supply from basement supports anaerobic oxidation of methane (AOM) at a rate of ~0.2 pmol cm?3 day?1 at ~400 mbsf. We also note the disappearance of δ‐Proteobacteria at 434 mbsf, coincident with the maximum in methane concentration, and their reappearance at 463 mbsf, coinciding with the observed deeper increase in sulfate concentration toward the basement. We did not, however, find ANME representatives in any of the samples analyzed (from 340 to 463 mbsf). The lack of ANME may be due to an overshadowing effect from the more dominant archaeal phylotypes or may indicate involvement of unknown groups of archaea in AOM (i.e., unclassified Euryarchaeota). In addition to the supply of sulfate from a basement aquifer, the deep biosphere at this site is also influenced by an elevated supply of reactive iron (up to 143 μmol g?1) and manganese (up to 20 μmol g?1). The effect of these metal oxides on the sulfur cycle is inferred from an accompanying sulfur isotope fractionation much smaller than expected from traditional sulfate‐reducing pathways. The detection of the manganese‐ and iron‐reducer γ‐Proteobacteria Alteromonas at 367 mbsf is consistent with these geochemical inferences. 相似文献
146.
Innominato PF Giacchetti S Moreau T Smaaland R Focan C Bjarnason GA Garufi C Iacobelli S Tampellini M Tumolo S Carvalho C Karaboué A Lévi F;ARTBC International Chronotherapy Group 《Chronobiology international》2011,28(7):586-600
Circadian clocks control cellular proliferation and drug metabolism over the 24?h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N?=?556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p?.0001), and G3-4 were 7% and 25%, respectively (p < .0001). Neutropenia was significantly more frequent in women than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median survival was 20.7 mo in patients with G3-4 neutropenia versus 12.5 mo in neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7 and 19.4 mo, respectively, on chronoFLO4 (p?=?.36). Multivariate analysis confirmed occurrence of severe neutropenia independently predicted for better overall survival on FOLFOX2 (HR?=?0.56; p = .015), and worse survival on chronoFLO4 (HR?=?1.77, p = .06), with a significant interaction test (p < .0001). Prediction of better survival in neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy. 相似文献
147.
Luaine Bandounas Nick JP Wierckx Johannes H de Winde Harald J Ruijssenaars 《BMC biotechnology》2011,11(1):1-11
Background
The number of biotransformations that use nicotinamide recycling systems is exponentially growing. For this reason one of the current challenges in biocatalysis is to develop and optimize more simple and efficient cofactor recycling systems. One promising approach to regenerate NAD+ pools is the use of NADH-oxidases that reduce oxygen to hydrogen peroxide while oxidizing NADH to NAD+. This class of enzymes may be applied to asymmetric reduction of prochiral substrates in order to obtain enantiopure compounds.Results
The NADH-oxidase (NOX) presented here is a flavoenzyme which needs exogenous FAD or FMN to reach its maximum velocity. Interestingly, this enzyme is 6-fold hyperactivated by incubation at high temperatures (80°C) under limiting concentrations of flavin cofactor, a change that remains stable even at low temperatures (37°C). The hyperactivated form presented a high specific activity (37.5 U/mg) at low temperatures despite isolation from a thermophile source. Immobilization of NOX onto agarose activated with glyoxyl groups yielded the most stable enzyme preparation (6-fold more stable than the hyperactivated soluble enzyme). The immobilized derivative was able to be reactivated under physiological conditions after inactivation by high solvent concentrations. The inactivation/reactivation cycle could be repeated at least three times, recovering full NOX activity in all cases after the reactivation step. This immobilized catalyst is presented as a recycling partner for a thermophile alcohol dehydrogenase in order to perform the kinetic resolution secondary alcohols.Conclusion
We have designed, developed and characterized a heterogeneous and robust biocatalyst which has been used as recycling partner in the kinetic resolution of rac-1-phenylethanol. The high stability along with its capability to be reactivated makes this biocatalyst highly re-useable for cofactor recycling in redox biotransformations. 相似文献148.
Moreau M Rialland P Pelletier JP Martel-Pelletier J Lajeunesse D Boileau C Caron J Frank D Lussier B del Castillo JR Beauchamp G Gauvin D Bertaim T Thibaud D Troncy E 《Arthritis research & therapy》2011,13(3):R98-13
Introduction
The aim of this prospective, randomized, controlled, double-blind study was to evaluate the effects of tiludronate (TLN), a bisphosphonate, on structural, biochemical and molecular changes and function in an experimental dog model of osteoarthritis (OA).Methods
Baseline values were established the week preceding surgical transection of the right cranial/anterior cruciate ligament, with eight dogs serving as OA placebo controls and eight others receiving four TLN injections (2 mg/kg subcutaneously) at two-week intervals starting the day of surgery for eight weeks. At baseline, Week 4 and Week 8, the functional outcome was evaluated using kinetic gait analysis, telemetered locomotor actimetry and video-automated behaviour capture. Pain impairment was assessed using a composite numerical rating scale (NRS), a visual analog scale, and electrodermal activity (EDA). At necropsy (Week 8), macroscopic and histomorphological analyses of synovium, cartilage and subchondral bone of the femoral condyles and tibial plateaus were assessed. Immunohistochemistry of cartilage (matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS5)) and subchondral bone (cathepsin K) was performed. Synovial fluid was analyzed for inflammatory (PGE2 and nitrite/nitrate levels) biomarkers. Statistical analyses (mixed and generalized linear models) were performed with an α-threshold of 0.05.Results
A better functional outcome was observed in TLN dogs than OA placebo controls. Hence, TLN dogs had lower gait disability (P = 0.04 at Week 8) and NRS score (P = 0.03, group effect), and demonstrated behaviours of painless condition with the video-capture (P < 0.04). Dogs treated with TLN demonstrated a trend toward improved actimetry and less pain according to EDA. Macroscopically, both groups had similar level of morphometric lesions, TLN-treated dogs having less joint effusion (P = 0.01), reduced synovial fluid levels of PGE2 (P = 0.02), nitrites/nitrates (P = 0.01), lower synovitis score (P < 0.01) and a greater subchondral bone surface (P < 0.01). Immunohistochemical staining revealed lower levels in TLN-treated dogs of MMP-13 (P = 0.02), ADAMTS5 (P = 0.02) in cartilage and cathepsin K (P = 0.02) in subchondral bone.Conclusion
Tiludronate treatment demonstrated a positive effect on gait disability and joint symptoms. This is likely related to the positive influence of the treatment at improving some OA structural changes and reducing the synthesis of catabolic and inflammatory mediators. 相似文献149.
Thomas R Grimsley N Escande ML Subirana L Derelle E Moreau H 《Environmental microbiology》2011,13(6):1412-1420
Viruses are known to play a key role in the regulation of eukaryotic phytoplankton population densities; however, little is known about the mechanisms of how they interact with their hosts and how phytoplankton populations mediate their regulations. Viruses are obligate parasites that depend on host cell machinery for their dissemination in the environment (most of the time through host cell lysis that liberates many new particles). But viruses also depend on a reliable host population to carry on their replication before losing their viability. How do hosts cells survive when they coexist with their viruses? We show that clonal lines of three picoeukaryotic green algae (i.e. Bathycoccus sp., Micromonas sp., Ostreococcus tauri) reproducibly acquire resistance to their specific viruses following a round of infection. Our observations show that two mechanisms of resistance may operate in O. tauri. In the first resistant type, viruses can attach to their host cells but no new particles develop. In the second one, O. tauri acquires tolerance to its virus and releases these viruses consistently. These lines maintained their resistance over a 3‐year period, irrespective of whether or not they were re‐challenged with new viral inoculations. Co‐culturing resistant and susceptible lines revealed resistance to be associated with reduced host fitness in terms of growth rate. 相似文献
150.
Moreau D Kumar P Wang SC Chaumet A Chew SY Chevalley H Bard F 《Developmental cell》2011,21(2):231-244
Protein toxins such as Ricin and Pseudomonas exotoxin (PE) pose major public health challenges. Both toxins depend on host cell machinery for internalization, retrograde trafficking from endosomes to?the ER, and translocation to cytosol. Although both toxins follow a similar intracellular route, it is unknown how much they rely on the same genes. Here we conducted two genome-wide RNAi screens identifying genes required for intoxication and demonstrating that requirements are strikingly different between PE and Ricin, with only 13% overlap. Yet factors required by both toxins are present from the endosomes to the ER, and, at the morphological level, the toxins colocalize in multiple structures. Interestingly, Ricin, but not PE, depends on Golgi complex integrity and colocalizes significantly with a medial Golgi marker. Our data are consistent with two intertwined pathways converging and diverging at multiple points and reveal the complexity of retrograde membrane trafficking in mammalian cells. 相似文献