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  • Articles  (111,960)
  • Oxford University Press  (109,913)
  • Berkeley Electronic Press (now: De Gruyter)
  • Medicine  (59,190)
  • Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition  (25,894)
  • Economics  (22,071)
  • Chemistry and Pharmacology  (20,253)
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  • 11
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    Translation of MT-ATP6 pathogenic variants reveals distinct regulatory consequences from the co-translational quality control of mitochondrial protein synthesis (2021)
    Oxford University Press
    Details
    Publication Date: 2021-10-28
    Description: Pathogenic variants that disrupt human mitochondrial protein synthesis are associated with a clinically heterogenous group of diseases. Despite an impairment in oxidative phosphorylation being a common phenotype, the underlying molecular pathogenesis is more complex than simply a bioenergetic deficiency. Currently, we have limited mechanistic understanding on the scope by which a primary defect in mitochondrial protein synthesis contributes to organelle dysfunction. Since the proteins encoded in the mitochondrial genome are hydrophobic and need co-translational insertion into a lipid bilayer, responsive quality control mechanisms are required to resolve aberrations that arise with the synthesis of truncated and misfolded proteins. Here, we show that defects in the OXA1L-mediated insertion of MT-ATP6 nascent chains into the mitochondrial inner membrane are rapidly resolved by the AFG3L2 protease complex. Using pathogenic MT-ATP6 variants, we then reveal discrete steps in this quality control mechanism and the differential functional consequences to mitochondrial gene expression. The inherent ability of a given cell type to recognize and resolve impairments in mitochondrial protein synthesis may in part contribute at the molecular level to the wide clinical spectrum of these disorders.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 12
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    DeepMP: a deep learning tool to detect DNA base modifications on Nanopore sequencing data (2021)
    Oxford University Press
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    Publication Date: 2021-10-28
    Description: Motivation DNA Methylation plays a key role in a variety of biological processes. Recently, Nanopore long-read sequencing has enabled direct detection of these modifications. As a consequence, a range of computational methods have been developed to exploit Nanopore data for methylation detection. However, current approaches rely on a human-defined threshold to detect the methylation status of a genomic position and are not optimized to detect sites methylated at low frequency. Furthermore, most methods employ either the Nanopore signals or the basecalling errors as the model input and do not take advantage of their combination. Results Here we present DeepMP, a convolutional neural network (CNN)-based model that takes information from Nanopore signals and basecalling errors to detect whether a given motif in a read is methylated or not. Besides, DeepMP introduces a threshold-free position modification calling model sensitive to sites methylated at low frequency across cells. We comprehensively benchmarked DeepMP against state-of-the-art methods on E. coli, human and pUC19 datasets. DeepMP outperforms current approaches at read-based and position-based methylation detection across sites methylated at different frequencies in the three datasets. Availability DeepMP is implemented and freely available under MIT license at https://github.com/pepebonet/DeepMP Supplementary information Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 13
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    SigTools: Exploratory Visualization For Genomic Signals (2021)
    Oxford University Press
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    Publication Date: 2021-10-28
    Description: Motivation With the advancement of sequencing technologies, genomic data sets are constantly being expanded by high volumes of different data types. One recently introduced data type in genomic science is genomic signals, which are usually short-read coverage measurements over the genome. To understand and evaluate the results of such studies, one needs to understand and analyze the characteristics of the input data. Results SigTools is an R-based genomic signals visualization package developed with two objectives: 1) to facilitate genomic signals exploration in order to uncover insights for later model training, refinement, and development by including distribution and autocorrelation plots. 2) to enable genomic signals interpretation by including correlation, and aggregation plots. In addition, our corresponding web application, SigTools-Shiny, extends the accessibility scope of these modules to people who are more comfortable working with graphical user interfaces instead of command-line tools. Availability SigTools source code, installation guide, and manual is freely available on http://github.com/shohre73.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 14
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    Greater hydraulic safety contributes to higher growth resilience to drought across seven pine species in a semi-arid environment (2021)
    Oxford University Press
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    Publication Date: 2021-10-28
    Description: Quantifying inter-specific variations of tree resilience to drought and revealing the underlying mechanisms are of great importance to the understanding of forest functionality particularly in water-limited regions. So far, comprehensive studies incorporating investigations in inter-specific variations of long-term growth patterns of trees and the underlying physiological mechanisms are very limited. Here, in a semi-arid site of northern China, tree radial growth rate, inter-annual tree-ring growth responses to climate variability, as well as physiological characteristics pertinent to xylem hydraulics, carbon assimilation and drought tolerance were analyzed in seven pine species growing in a common environment. Considerable inter-specific variations in radial growth rate, growth response to drought and physiological characteristics were observed among the studied species. Differently, the studied species exhibited similar degrees of resistance to drought-induced branch xylem embolism with water potential corresponding to 50% loss hydraulic conductivity ranged from −2.31 to −2.96 MPa. We found that higher branch hydraulic efficiency is related to greater leaf photosynthetic capacity, smaller hydraulic safety margin and lower woody density (P  0.05). Rather, species with higher hydraulic conductivity and photosynthetic capacity was more sensitive to drought stress and tended to show weaker growth resistance to extreme drought events as quantified by tree-ring analyses, which is at least partially due to a trade-off between hydraulic efficiency and safety across species. This study thus demonstrates the importance of drought resilience rather than instantaneous water and carbon flux capacity in determining tree growth in water-limited environments.
    Print ISSN: 0829-318X
    Electronic ISSN: 1758-4469
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Published by Oxford University Press
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  • 15
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    The Jun-dependent axon regeneration gene program: Jun promotes regeneration over plasticity (2021)
    Oxford University Press
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    Publication Date: 2021-10-28
    Description: The regeneration-associated gene (RAG) expression program is activated in injured peripheral neurons after axotomy and enables long-distance axon re-growth. Over 1000 genes are regulated, and many transcription factors are upregulated or activated as part of this response. However, a detailed picture of how RAG expression is regulated is lacking. In particular the transcriptional targets and specific functions of the various transcription factors are unclear. Jun was the first regeneration-associated transcription factor identified and the first shown to be functionally important. Here we fully define the role of Jun in the RAG expression program in regenerating facial motor neurons. At 1, 4, and 14 days after axotomy, Jun upregulates 11%, 23% and 44% of the RAG program, respectively. Jun functions relevant to regeneration include cytoskeleton production, metabolic functions and cell activation, and the down-regulation of neurotransmission machinery. In silico analysis of promoter regions of Jun targets identifies stronger over-representation of AP1-like sites than CRE-like sites, although CRE sites were also over-represented in regions flanking AP1 sites. Strikingly, in motor neurons lacking Jun, an alternative SRF-dependent gene expression program is initiated after axotomy. The promoters of these newly expressed genes exhibit over-representation of CRE sites in regions near to SRF target sites. This alternative gene expression program includes plasticity-associated transcription factors, and leads to an aberrant early increase in synapse density on motor neurons. Jun thus has the important function in the early phase after axotomy of pushing the injured neuron away from a plasticity response and towards a regenerative phenotype.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 16
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    CpG Transformer for imputation of single-cell methylomes (2021)
    Oxford University Press
    Details
    Publication Date: 2021-10-28
    Description: Motivation The adoption of current single-cell DNA methylation sequencing protocols is hindered by incomplete coverage, outlining the need for effective imputation techniques. The task of imputing single-cell (methylation) data requires models to build an understanding of underlying biological processes. Results We adapt the transformer neural network architecture to operate on methylation matrices through combining axial attention with sliding window self-attention. The obtained CpG Transformer displays state-of-the-art performances on a wide range of scBS-seq and scRRBS-seq datasets. Furthermore, we demonstrate the interpretability of CpG Transformer and illustrate its rapid transfer learning properties, allowing practitioners to train models on new datasets with a limited computational and time budget. Availability and Implementation CpG Transformer is freely available at https://github.com/gdewael/cpg-transformer. Supplementary information Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 17
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    Heterozygous Tropomodulin 3 mice have improved lung vascularization after chronic hypoxia. (2021)
    Oxford University Press
    Details
    Publication Date: 2021-10-28
    Description: The molecular mechanisms leading to high altitude pulmonary hypertension (HAPH) remains poorly understood. We previously analyzed the whole genome sequence of Kyrgyz highland population and identified eight genomic intervals having a potential role in HAPH. Tropomodulin 3 gene (TMOD3) which encodes a protein that binds and caps the pointed ends of actin filaments and inhibits cell migration, was one of the top candidates. Here we systematically sought additional evidence to validate the functional role of TMOD3. In-silico analysis reveals that some of the SNPs in HAPH associated genomic intervals were positioned in a regulatory region that could result in alternative splicing of TMOD3. In order to functionally validate the role of TMOD3 in HAPH, we exposed Tmod3−/+ mice to 4 weeks of constant hypoxia, i.e. 10% O2 and analyzed both functional (hemodynamic measurements) and structural (angiography) parameters related to HAPH. The hemodynamic measurements, such as right ventricular systolic pressure, a surrogate measure for pulmonary arterial systolic pressure, and right ventricular contractility (RV- ± dP/dt), increases with hypoxia did not separate between Tmod3−/+ and control mice. Remarkably, there was a significant increase in the number of lung vascular branches and total length of pulmonary vascular branches (p 
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 18
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    LocalNgsRelate: a software tool for inferring IBD sharing along the genome between pairs of individuals from low-depth NGS data (2021)
    Oxford University Press
    Details
    Publication Date: 2021-10-28
    Description: Motivation Inference of Identity-by-descent (IBD) sharing along the genome between pairs of individuals has important uses. But all existing inference methods are based on genotypes, which is not ideal for low-depth Next Generation Sequencing (NGS) data from which genotypes can only be called with high uncertainty. Results We present a new probabilistic software tool, LocalNgsRelate, for inferring IBD sharing along the genome between pairs of individuals from low-depth NGS data. Its inference is based on genotype likelihoods instead of genotypes, and thereby it takes the uncertainty of the genotype calling into account. Using real data from the 1000 Genomes project, we show that LocalNgsRelate provides more accurate IBD inference for low-depth NGS data than two state-of-the-art genotype based methods, Albrechtsen et al. (2009) and hap-IBD. We also show that the method works well for NGS data down to a depth of 2X. Availability LocalNgsRelate is freely available at https://github.com/idamoltke/LocalNgsRelate Supplementary Data Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 19
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    Rival guests or defiant hosts? The local economic impact of hosting refugees (2021)
    Oxford University Press
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    Publication Date: 2021-10-28
    Description: This article investigates the local economic cost of hosting refugees. Using administrative data in France, we show that the opening of small housing centers for refugees decreases the economic activity in hosting municipalities. We demonstrate that this downturn is related to a decline in the population by around 2% due to fewer people moving to hosting municipalities. We show that this avoidance behavior of natives results from prejudices, and is unlikely to be driven by a labor market supply shock from the arrival of refugees. We also estimate the aggregate cost of hosting refugees.
    Print ISSN: 1468-2702
    Electronic ISSN: 1468-2710
    Topics: Geography , Economics
    Published by Oxford University Press
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  • 20
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    Corn ethanol in the Midwestern USA: Local competition, entry and agglomeration (2021)
    Oxford University Press
    Details
    Publication Date: 2021-10-28
    Description: This article analyzes the entry of corn-ethanol plants in the Midwestern USA, where the majority of corn in the USA is grown, during the second US ethanol boom. In particular, we examine whether the presence of existing ethanol plants affects ethanol plant entry decisions at the county level using discrete response panel models. There are two main channels through which existing ethanol plants may affect ethanol plant entry decisions: a competition effect and an agglomeration effect. Our results show that existing ethanol plants have a negative effect on the probability of ethanol plant entry in a given county. The net negative competition effect dissipates with distance. We also find that existing conglomerates and large ethanol producing firms in neighboring counties have a positive effect on ethanol plant entry, while existing singlet plants in neighboring counties do not. These results provide evidence for both local competition among ethanol plants within counties, as well as possible agglomeration benefits from existing conglomerates and large ethanol producing firms in neighboring counties.
    Print ISSN: 1468-2702
    Electronic ISSN: 1468-2710
    Topics: Geography , Economics
    Published by Oxford University Press
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