Abstract
Summary
Genes involved in biological pathways are often collocalised in gene clusters, the comparison of which can give valuable insights into their function and evolutionary history. ...However, comparison and visualization of gene cluster similarity is a tedious process, particularly when many clusters are being compared. Here, we present clinker, a Python based tool and clustermap.js, a companion JavaScript visualization library, which used together can automatically generate accurate, interactive, publication-quality gene cluster comparison figures directly from sequence files.
Availability and implementation
Source code and documentation for clinker and clustermap.js is available on GitHub (github.com/gamcil/clinker and github.com/gamcil/clustermap.js, respectively) under the MIT license. clinker can be installed directly from the Python Package Index via pip.
Supplementary information
Supplementary data are available at Bioinformatics online.
In this article, we present a tool and a method for measuring the psychological and cultural distance between societies and creating a distance scale with any population as the point of comparison. ...Because psychological data are dominated by samples drawn from Western, educated, industrialized, rich, and democratic (WEIRD) nations, and overwhelmingly, the United States, we focused on distance from the United States. We also present distance from China, the country with the largest population and second largest economy, which is a common cultural comparison. We applied the fixation index (FST), a meaningful statistic in evolutionary theory, to the World Values Survey of cultural beliefs and behaviors. As the extreme WEIRDness of the literature begins to dissolve, our tool will become more useful for designing, planning, and justifying a wide range of comparative psychological projects. Our code and accompanying online application allow for comparisons between any two countries. Analyses of regional diversity reveal the relative homogeneity of the United States. Cultural distance predicts various psychological outcomes.
As structure prediction methods are generating millions of publicly available protein structures, searching these databases is becoming a bottleneck. Foldseek aligns the structure of a query protein ...against a database by describing tertiary amino acid interactions within proteins as sequences over a structural alphabet. Foldseek decreases computation times by four to five orders of magnitude with 86%, 88% and 133% of the sensitivities of Dali, TM-align and CE, respectively.
We present a self-consistent, absolute isochronal age scale for young ( ≲ 200 Myr), nearby ( ≲ 100 pc) moving groups in the solar neighbourhood based on homogeneous fitting of semi-empirical ...pre-main-sequence model isochrones using the τ2 maximum-likelihood fitting statistic of Naylor & Jeffries in the M
V
, V − J colour–magnitude diagram. The final adopted ages for the groups are as follows:
$149^{+51}_{-19}\,\rm {Myr}$
for the AB Dor moving group, 24 ± 3 Myr for the β Pic moving group (BPMG),
$45^{+11}_{-7}\,\rm {Myr}$
for the Carina association,
$42^{+6}_{-4}\,\rm {Myr}$
for the Columba association, 11 ± 3 Myr for the η Cha cluster, 45 ± 4 Myr for the Tucana–Horologium moving group (Tuc–Hor), 10 ± 3 Myr for the TW Hya association and
$22^{+4}_{-3}\,\rm {Myr}$
for the 32 Ori group. At this stage we are uncomfortable assigning a final, unambiguous age to the Argus association as our membership list for the association appears to suffer from a high level of contamination, and therefore it remains unclear whether these stars represent a single population of coeval stars. Our isochronal ages for both the BPMG and Tuc–Hor are consistent with recent lithium depletion boundary (LDB) ages, which unlike isochronal ages, are relatively insensitive to the choice of low-mass evolutionary models. This consistency between the isochronal and LDB ages instils confidence that our self-consistent, absolute age scale for young, nearby moving groups is robust, and hence we suggest that these ages be adopted for future studies of these groups. Software implementing the methods described in this study is available from http://www.astro.ex.ac.uk/people/timn/tau-squared/.
Regulatory T cells (Tregs) subdue immune responses. Central to Treg activation are changes in lipid metabolism that support their survival and function. Fatty acid binding proteins (FABPs) are a ...family of lipid chaperones required to facilitate uptake and intracellular lipid trafficking. One family member, FABP5, is expressed in T cells, but its function remains unclear. We show that in Tregs, genetic or pharmacologic inhibition of FABP5 function causes mitochondrial changes underscored by decreased OXPHOS, impaired lipid metabolism, and loss of cristae structure. FABP5 inhibition in Tregs triggers mtDNA release and consequent cGAS-STING-dependent type I IFN signaling, which induces heightened production of the regulatory cytokine IL-10 and promotes Treg suppressive activity. We find evidence of this pathway, along with correlative mitochondrial changes in tumor infiltrating Tregs, which may underlie enhanced immunosuppression in the tumor microenvironment. Together, our data reveal that FABP5 is a gatekeeper of mitochondrial integrity that modulates Treg function.
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•FABP5 inhibition in Tregs alters mitochondria and enhances suppression•Disrupting FABP5 in Tregs results in mtDNA release and type I IFN signaling•cGAS/-STING-dependent type I IFN signals promote Treg IL-10 production•Tumor Tregs exhibit mitochondrial alterations and a type I IFN gene signature
Field et al. show that fatty acid binding protein 5 (FABP5) maintains mitochondrial integrity in regulatory T cells (Tregs). FABP5 inhibition results in mtDNA release, which triggers expression of IL-10 and promotes Treg suppressive capacity. These findings may have implications for therapeutically targeting Tregs in autoimmunity and cancer.
While splicing changes caused by somatic mutations in SF3B1 are known, identifying full-length isoform changes may better elucidate the functional consequences of these mutations. We report nanopore ...sequencing of full-length cDNA from CLL samples with and without SF3B1 mutation, as well as normal B cell samples, giving a total of 149 million pass reads. We present FLAIR (Full-Length Alternative Isoform analysis of RNA), a computational workflow to identify high-confidence transcripts, perform differential splicing event analysis, and differential isoform analysis. Using nanopore reads, we demonstrate differential 3' splice site changes associated with SF3B1 mutation, agreeing with previous studies. We also observe a strong downregulation of intron retention events associated with SF3B1 mutation. Full-length transcript analysis links multiple alternative splicing events together and allows for better estimates of the abundance of productive versus unproductive isoforms. Our work demonstrates the potential utility of nanopore sequencing for cancer and splicing research.
How cells adapt metabolism to meet demands is an active area of interest across biology. Among a broad range of functions, the polyamine spermidine is needed to hypusinate the translation factor ...eukaryotic initiation factor 5A (eIF5A). We show here that hypusinated eIF5A (eIF5AH) promotes the efficient expression of a subset of mitochondrial proteins involved in the TCA cycle and oxidative phosphorylation (OXPHOS). Several of these proteins have mitochondrial targeting sequences (MTSs) that in part confer an increased dependency on eIF5AH. In macrophages, metabolic switching between OXPHOS and glycolysis supports divergent functional fates stimulated by activation signals. In these cells, hypusination of eIF5A appears to be dynamically regulated after activation. Using in vivo and in vitro models, we show that acute inhibition of this pathway blunts OXPHOS-dependent alternative activation, while leaving aerobic glycolysis-dependent classical activation intact. These results might have implications for therapeutically controlling macrophage activation by targeting the polyamine-eIF5A-hypusine axis.
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•The polyamine synthesis pathway and hypusinated eIF5A modulate mitochondrial OXPHOS•Hypusinated eIF5A maintains TCA cycle and ETC integrity in macrophages•Some mitochondrial enzymes depend on eIF5AH for efficient expression•Inhibition of hypusinated eIF5A blunts macrophage alternative activation
Puleston et al. show that polyamine biosynthesis modulates mitochondrial metabolism through eIF5A hypusination (eIF5AH). They find that inhibiting the polyamine-eIF5A-hypusine pathway blocks OXPHOS-dependent macrophage alternative activation, while leaving aerobic glycolysis-dependent macrophage classical activation intact. These results might have implications for therapeutically controlling macrophage activation by targeting the polyamine-eIF5A-hypusine axis.
Access to resources is a key challenge facing entrepreneurs during early venture development. Entrepreneurs’ networks serve as a principal means of identifying and acquiring needed resources. ...However, different stages of venture development may address different resource dependencies, suggesting entrepreneurs’ networks may need to change to meet changing resource requirements. By employing network theory and resource–dependence theory, we investigate how entrepreneurs may use networks to address changing resource needs during early venture development. Results illustrate how structural characteristics of entrepreneurs’ networks at venture launch are associated with network structure and content in early venture development in ways that may promote access to newly needed resources.
The global state of cataract blindness Lee, Cameron M; Afshari, Natalie A
Current opinion in ophthalmology,
2017-January, 2017-Jan, 2017-01-00, 20170101, Letnik:
28, Številka:
1
Journal Article
PURPOSE OF REVIEWCataracts are a significant cause of blindness and visual impairment worldwide. The present article reviews the literature and describes the current extent of cataracts globally, ...barriers to treatment, and recommendations for improving the treatment of cataracts.
RECENT FINDINGSPrevalence and absolute number of blind because of cataracts remain high, although rates are declining in many areas globally. The age-standardized prevalence of blindness in adults older than 50 remains highest in western sub-Saharan Africa, with a rate of 6.0%. The greatest declines in age-standardized blindness because of cataracts in adults older than 50 between 1990 and 2010 were in East Asia, tropical Latin America, and western Europe. Recent studies have largely found higher rates of cataracts in women than in men. A new simulator for training ophthalmologists in manual small-incision cataract surgery holds promise for the future.
SUMMARYThe rates of cataract surgery are increasing and postoperative outcomes are improving worldwide, yet challenges to reducing the cataract burden further remain. Cost, an insufficient number of ophthalmologists, and low government funding remain significant barriers but investment in further eye care infrastructure and training of additional ophthalmologists would improve the current situation.
X-ray tomography is an invaluable tool in biomedical imaging. It can deliver the three-dimensional internal structure of entire organisms as well as that of single cells, and even gives access to ...quantitative information, crucially important both for medical applications and for basic research. Most frequently such information is based on X-ray attenuation. Phase contrast is sometimes used for improved visibility but remains significantly harder to quantify. Here we describe an X-ray computed tomography technique that generates quantitative high-contrast three-dimensional electron density maps from phase contrast information without reverting to assumptions of a weak phase object or negligible absorption. This method uses a ptychographic coherent imaging approach to record tomographic data sets, exploiting both the high penetration power of hard X-rays and the high sensitivity of lensless imaging. As an example, we present images of a bone sample in which structures on the 100 nm length scale such as the osteocyte lacunae and the interconnective canalicular network are clearly resolved. The recovered electron density map provides a contrast high enough to estimate nanoscale bone density variations of less than one per cent. We expect this high-resolution tomography technique to provide invaluable information for both the life and materials sciences.
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