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排序方式: 共有155条查询结果,搜索用时 15 毫秒
1.
Anoek Friskes Lisa Koob Lenno Krenning Tesa M Severson Emma
S Koeleman Xabier Vergara Michael Schubert Jeroen van
den
Berg Bastiaan Evers Anna G Manjn Stacey Joosten Yongsoo Kim Wilbert Zwart Ren
H Medema 《Nucleic acids research》2022,50(17):9930
Cells respond to double-strand breaks (DSBs) by activating DNA damage response pathways, including cell cycle arrest. We have previously shown that a single double-strand break generated via CRISPR/Cas9 is sufficient to delay cell cycle progression and compromise cell viability. However, we also found that the cellular response to DSBs can vary, independent of the number of lesions. This implies that not all DSBs are equally toxic, and raises the question if the location of a single double-strand break could influence its toxicity. To systematically investigate if DSB-location is a determinant of toxicity we performed a CRISPR/Cas9 screen targeting 6237 single sites in the human genome. Next, we developed a data-driven framework to design CRISPR/Cas9 sgRNA (crRNA) pools targeting specific chromatin features. The chromatin context was defined using ChromHMM states, Lamin-B1 DAM-iD, DNAseI hypersensitivity, and RNA-sequencing data. We computationally designed 6 distinct crRNA pools, each containing 10 crRNAs targeting the same chromatin state. We show that the toxicity of a DSB is highly similar across the different ChromHMM states. Rather, we find that the major determinants of toxicity of a sgRNA are cutting efficiency and off-target effects. Thus, chromatin features have little to no effect on the toxicity of a single CRISPR/Cas9-induced DSB. 相似文献
2.
Heng Zhang Xabier Judez Alexander Santiago Maria Martinez‐Ibaez Miguel ngel Muoz‐Mrquez Javier Carrasco Chunmei Li Gebrekidan Gebresilassie Eshetu Michel Armand 《Liver Transplantation》2019,9(25)
Amongst post‐Li‐ion battery technologies, lithium–sulfur (Li–S) batteries have captured an immense interest as one of the most appealing devices from both the industrial and academia sectors. The replacement of conventional liquid electrolytes with solid polymer electrolytes (SPEs) enables not only a safer use of Li metal (Li°) anodes but also a flexible design in the shape of Li–S batteries. However, the practical implementation of SPEs‐based all‐solid‐state Li–S batteries (ASSLSBs) is largely hindered by the shuttling effect of the polysulfide intermediates and the formation of dendritic Li° during the battery operation. Herein, a fluorine‐free noble salt anion, tricyanomethanide [C(CN)3?, TCM?], is proposed as a Li‐ion conducting salt for ASSLSBs. Compared to the widely used perfluorinated anions {e.g., bis(trifluoromethanesulfonyl)imide anion, [N(SO2CF3)2)]?, TFSI?}, the LiTCM‐based electrolytes show decent ionic conductivity, good thermal stability, and sufficient anodic stability suiting the cell chemistry of ASSLSBs. In particular, the fluorine‐free solid electrolyte interphase layer originating from the decomposition of LiTCM exhibits a good mechanical integrity and Li‐ion conductivity, which allows the LiTCM‐based Li–S cells to be cycled with good rate capability and Coulombic efficiency. The LiTCM‐based electrolytes are believed to be the most promising candidates for building cost‐effective and high energy density ASSLSBs in the near future. 相似文献
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Albert Harillo‐Baos Xabier Rodríguez‐Martínez Mariano Campoy‐Quiles 《Liver Transplantation》2020,10(1)
Organic solar cells based on ternary active layers can lead to higher power conversion efficiencies than corresponding binaries, and improved stability. The parameter space for optimization of multicomponent systems is considerably more complex than that of binaries, due to both, a larger number of parameters (e.g., two relative compositions rather than one) and intricate morphology–property correlations. Most experimental reports to date reasonably limit themselves to a relatively narrow subset of compositions (e.g., the 1:1 donor/s:acceptor/s trajectory). This work advances a methodology that allows exploration of a large fraction of the ternary phase space employing only a few (<10) samples. Each sample is produced by a designed sequential deposition of the constituent inks, and results in compositions gradients with ≈5000 points/sample that cover about 15%–25% of the phase space. These effective ternary libraries are then colocally imaged by a combination of photovoltaic techniques (laser and white light photocurrent maps) and spectroscopic techniques (Raman, photoluminescence, absorption). The generality of the methodology is demonstrated by investigating three ternary systems, namely PBDB‐T:ITIC:PC70BM, PTB7‐Th:ITIC:PC70BM, and P3HT:O‐IDFBR:O‐IDTBR. Complex performance‐structure landscapes through the ternary diagram as well as the emergence of several performance maxima are discovered. 相似文献
5.
Sergio Cardoso Laura Valverde Miguel A. Alfonso-Sánchez Leire Palencia-Madrid Xabier Elcoroaristizabal Jaime Algorta Susana Catarino David Arteta Rene J. Herrera María Teresa Zarrabeitia José A. Pe?a Marian M. de Pancorbo 《PloS one》2013,8(7)
The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ∼10,000 years before present (YBP), with signals of expansions at ∼3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations. 相似文献
6.
Janire De-La-Torre Guillermo Quindós Cristina Marcos-Arias Xabier Marichalar-Mendia María Luisa Gainza Elena Eraso Amelia Acha-Sagredo José Manuel Aguirre-Urizar 《Revista iberoamericana de micología》2018,35(3):134-139
Background
Candida can be implicated in the pathology of chronic periodontitis.Aims
To analyze the oral Candida carriage in patients suffering from chronic periodontitis (CP) and its correlation with the severity of this condition.Methods
Microbiological samples were taken from 155 patients using the oral rinse (OR) technique and by using paper points in the periodontal pockets (GPP). These patients were divided into 3 groups: 89 patients without CP (control), 47 with moderate CP, and 19 with severe CP. Samples were cultured in a Candida chromogenic agar for Candida. Species were identified by microbiological and molecular methods.Results
Candida was isolated in the OR of 45 (50.6%), 21 (44.7%), and 11 (57.9%) patients, respectively, and in the GPP of 32 (36%), 14 (29.2%), and 10 (42.6%) patients from the control, moderate CP and severe CP groups, respectively. Candida was isolated more frequently and in a greater burden in OR than in GPP (p < 0.01). Candida albicans was the most prevalent species. GPP of patients with CP had poor fungal biodiversity (p < 0.01).Conclusions
Colonization by Candida was present in the samples of patients without CP, and with both moderate and severe CP. Nonetheless, patients with severe CP had a higher rate of Candida colonization, especially by C. albicans. 相似文献7.
Pablo García-Díaz David S. L. Ramsey Andrew P. Woolnough Marc Franch Gustavo A. Llorente Albert Montori Xabier Buenetxea Asier R. Larrinaga Matthieu Lasceve Alberto Álvarez José María Traverso Aitor Valdeón Ariñe Crespo Virginia Rada Enrique Ayllón Vicente Sancho J. Ignacio Lacomba José Vicente Bataller Miguel Lizana 《Biological invasions》2017,19(9):2739-2750
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9.
The aims of the present study were to determine whether the estimations of the frontal area of the combined cyclist-bicycle (APCB) obtained with the Heil's non-logarithmic prediction equations (NPE) in the stem position (SP), brake hoods position (BHP) and drops position (DP) are comparable to the measured APCB with the computerized planimetry (CP) method, and to analyse with the CP method and the NPE the influence of the body position on the APCB. Nineteen participants competing in the Spanish Road Cycling First division took part in the study. The NPE overestimated the APCB in the BHP and in the DP compared with the measured APCB with the CP method (6.9% and 5.1%, respectively; p<0.05). Significant differences among the three positions were obtained with the CP method. The overestimation of the APCB with the NPE in the BHP and in the DP and the less sensitivity of the NPE to show significant differences between the SP and DP suggest that the NPE are not appropriate to accurately predict the APCB. 相似文献
10.
I Zarraonaindia M Iriondo A Albaina MA Pardo C Manzano WS Grant X Irigoien A Estonba 《PloS one》2012,7(7):e42201
Geographic surveys of allozymes, microsatellites, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have detected several genetic subdivisions among European anchovy populations. However, these studies have been limited in their power to detect some aspects of population structure by the use of a single or a few molecular markers, or by limited geographic sampling. We use a multi-marker approach, 47 nDNA and 15 mtDNA single nucleotide polymorphisms (SNPs), to analyze 626 European anchovies from the whole range of the species to resolve shallow and deep levels of population structure. Nuclear SNPs define 10 genetic entities within two larger genetically distinctive groups associated with oceanic variables and different life-history traits. MtDNA SNPs define two deep phylogroups that reflect ancient dispersals and colonizations. These markers define two ecological groups. One major group of Iberian-Atlantic populations is associated with upwelling areas on narrow continental shelves and includes populations spawning and overwintering in coastal areas. A second major group includes northern populations in the North East (NE) Atlantic (including the Bay of Biscay) and the Mediterranean and is associated with wide continental shelves with local larval retention currents. This group tends to spawn and overwinter in oceanic areas. These two groups encompass ten populations that differ from previously defined management stocks in the Alboran Sea, Iberian-Atlantic and Bay of Biscay regions. In addition, a new North Sea-English Channel stock is defined. SNPs indicate that some populations in the Bay of Biscay are genetically closer to North Western (NW) Mediterranean populations than to other populations in the NE Atlantic, likely due to colonizations of the Bay of Biscay and NW Mediterranean by migrants from a common ancestral population. Northern NE Atlantic populations were subsequently established by migrants from the Bay of Biscay. Populations along the Iberian-Atlantic coast appear to have been founded by secondary waves of migrants from a southern refuge. 相似文献