1,056 research outputs found
INDIGO - INtegrated Data Warehouse of MIcrobial GenOmes with Examples from the Red Sea Extremophiles.
Background: The next generation sequencing technologies substantially increased the throughput of microbial
genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and
computational methods are used. Integration of information from different sources is a powerful approach to enhance
such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially
depends on this annotation but it is hampered by the current lack of suitable information integration and exploration
systems for microbial genomes.
Results: We developed a data warehouse system (INDIGO) that enables the integration of annotations for
exploration and analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to construct complex
queries and combine annotations from multiple sources starting from genomic sequence to protein domain, gene
ontology and pathway levels. This data warehouse is aimed at being populated with information from genomes of
pure cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently, INDIGO contains information
from Salinisphaera shabanensis, Haloplasma contractile, and Halorhabdus tiamatea - extremophiles isolated from
deep-sea anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to gain new insights into
specific aspects on the unique lifestyle and adaptations of these organisms to extreme environments.
Conclusions: We developed a data warehouse system, INDIGO, which enables comprehensive integration of
information from various resources to be used for annotation, exploration and analysis of microbial genomes. It will
be regularly updated and extended with new genomes. It is aimed to serve as a resource dedicated to the Red Sea
microbes. In addition, through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG) pipeline.
The INDIGO web server is freely available at http://www.cbrc.kaust.edu.sa/indigo.IA and AAK were supported from the KAUST CBRC Base Fund of VBB. WBa and VBB were supported from the KAUST Base Funds of VBB. US was supported by the KAUST Base Fund of US. This study was partly supported by the Saudi Economic and Development Company (SEDCO) Research Excellence award to US and VBB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Structural and spectroscopic characterization of a HdrA-like subunit from Hyphomicrobium denitrificans
Funding Information: We thank Laurenz Heidrich for help with statistical analyses. This work was supported by grant Da 351/8â1 (to CD) from the Deutsche Forschungsgemeinschaft and Fundação para a CiĂȘncia e Tecnologia (Portugal) (grant PTDC/BIAâBQM/29118 and R&D units MOSTMICROâITQB (UIDB/04612/2020 and UIDP/04612/2020), and European Union's Horizon 2020 research and innovation program (grant agreement No 810856). Open access funding enabled and organized by Projekt DEAL. Publisher Copyright: © 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Many bacteria and archaea employ a novel pathway of sulfur oxidation involving an enzyme complex that is related to the heterodisulfide reductase (Hdr or HdrABC) of methanogens. As a first step in the biochemical characterization of Hdr-like proteins from sulfur oxidizers (sHdr), we structurally analyzed the recombinant sHdrA protein from the Alphaproteobacterium Hyphomicrobium denitrificans at 1.4 Ă
resolution. The sHdrA core structure is similar to that of methanogenic HdrA (mHdrA) which binds the electron-bifurcating flavin adenine dinucleotide (FAD), the heart of the HdrABC-[NiFe]-hydrogenase catalyzed reaction. Each sHdrA homodimer carries two FADs and two [4Feâ4S] clusters being linked by electron conductivity. Redox titrations monitored by electron paramagnetic resonance and visible spectroscopy revealed a redox potential between â203 and â188 mV for the [4Feâ4S] center. The potentials for the FADHâą/FADHâ and FAD/FADHâą pairs reside between â174 and â156 mV and between â81 and â19 mV, respectively. The resulting stable semiquinone FADHâą species already detectable in the visible and electron paramagnetic resonance spectra of the as-isolated state of sHdrA is incompatible with basic principles of flavin-based electron bifurcation such that the sHdr complex does not apply this new mode of energy coupling. The inverted one-electron FAD redox potentials of sHdr and mHdr are clearly reflected in the different FAD-polypeptide interactions. According to this finding and the assumption that the sHdr complex forms an asymmetric HdrAAâČB1C1B2C2 hexamer, we tentatively propose a mechanism that links protein-bound sulfane oxidation to sulfite on HdrB1 with NAD+ reduction via lipoamide disulfide reduction on HdrB2. The FAD of HdrA thereby serves as an electron storage unit. Database: Structural data are available in PDB database under the accession number 6TJR.publishe
Dimension-specific attention directs learning and listening on auditory training tasks
The relative contributions of bottom-up versus top-down sensory inputs to auditory learning are not well established. In our experiment, listeners were instructed to perform either a frequency discrimination (FD) task ("FD-train group") or an intensity discrimination (ID) task ("ID-train group") during training on a set of physically identical tones that were impossible to discriminate consistently above chance, allowing us to vary top-down attention whilst keeping bottom-up inputs fixed. A third, control group did not receive any training. Only the FD-train group improved on a FD probe following training, whereas all groups improved on ID following training. However, only the ID-train group also showed changes in performance accuracy as a function of interval with training on the ID task. These findings suggest that top-down, dimension-specific attention can direct auditory learning, even when this learning is not reflected in conventional performance measures of threshold change
High Density of Tumor-Associated Macrophage Staining Correlates with Poor Clinicopathologic Markers in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis
Background: Head and neck squamous cell carcinoma (HNSCC) develops within a complex cellular microenvironment that promotes tumor growth, but also represents many potential therapeutic targets. Macrophage presence within that environment has been implicated in the growth, aggression, and persistence of HNSCC. Current literature reports variable degrees of association between tumor-associated macrophage (TAMs) density and clinicopathologic markers of disease.Inconsistent findings may result from grouping of TAM subtypes, which include both M1 (pro-inflammatory) and M2 (immunosuppressive). Our aim is to define the prognostic significance of the phenotypes of tumor-associated macrophages in HNSCC.
Methods: We conducted a meta-analysis of the existing publications investigating the relationship between TAMs (total and M2 subtype) and T stage, nodal involvement, vascular invasion, lymphatic invasion, and tumor differentiation. Forest plots and risk ratios were generated to report overall effect.
Results: Higher density of both total and M2 subtype of TAMs in the tumor microenvironment is associated with advanced T stage, increased rates of nodal positivity, presence of vascular invasion, and presence of lymphatic invasion (p \u3c 0.0001). There is no significant association between either total or M2 TAM density and tumor differentiation.
Conclusion: Increased density of TAMs, including those of the M2 phenotype, correlates with poor clinicopathologic markers in HNSCC, and therefore poor clinical prognosis. It is unknown whether this relationship is causative or correlative. Additional investigation into the mechanisms behind TAM recruitment and differentiation, and effect of TAM population manipulation on tumor behavior will help define the feasibility of TAM-targeted therapies
Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3
Mutations in CCM1, CCM2, or CCM3 lead to cerebral cavernous malformations, one of the most common hereditary vascular diseases of the brain. Endothelial cells within these lesions are the main disease compartments. Here, we show that adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures. Adenoviral CCM3 expression does not induce apoptosis under normal endothelial cell culture conditions but protects endothelial cells from staurosporine-induced cell death. Tyrosine kinase activity profiling suggests that CCM3 supports PDPK-1/Akt-mediated endothelial cell quiescence and survival
Metabolic analysis of the interaction between plants and herbivores
Insect herbivores by necessity have to deal with a large arsenal of plant defence metabolites. The levels of defence compounds may be increased by insect damage. These induced plant responses may also affect the metabolism and performance of successive insect herbivores. As the chemical nature of induced responses is largely unknown, global metabolomic analyses are a valuable tool to gain more insight into the metabolites possibly involved in such interactions. This study analyzed the interaction between feral cabbage (Brassica oleracea) and small cabbage white caterpillars (Pieris rapae) and how previous attacks to the plant affect the caterpillar metabolism. Because plants may be induced by shoot and root herbivory, we compared shoot and root induction by treating the plants on either plant part with jasmonic acid. Extracts of the plants and the caterpillars were chemically analysed using Ultra Performance Liquid Chromatography/Time of Flight Mass Spectrometry (UPLCT/MS). The study revealed that the levels of three structurally related coumaroylquinic acids were elevated in plants treated on the shoot. The levels of these compounds in plants and caterpillars were highly correlated: these compounds were defined as the âmetabolic interfaceâ. The role of these metabolites could only be discovered using simultaneous analysis of the plant and caterpillar metabolomes. We conclude that a metabolomics approach is useful in discovering unexpected bioactive compounds involved in ecological interactions between plants and their herbivores and higher trophic levels.
Reduced branching ratio for H -> AA -> 4 tau from A - eta_b mixing
Models with an extended Higgs sector, as the NMSSM, allow for scenarios where
the Standard Model-like CP-even Higgs boson H decays dominantly as H -> AA -> 4
tau where A is a light CP-odd Higgs boson. Tight constraints on this scenario
in the form of lower bounds on M_H have recently been published by the ALEPH
group. We show that, due to A - eta_b mixing, the branching ratio H -> AA -> 4
tau is strongly reduced for M_A in the range 9 - 10.5 GeV. This is the range of
M_A in which the tension between the observed eta_b(1S) mass and its prediction
based on QCD can be resolved due to mixing, and which is thus still consistent
with a light CP-even Higgs boson H satisfying LEP constraints with a mass well
below 114 GeV. This result is practically independent from the coupling of A to
b quarks.Comment: 11 pages, 2 Figures, reference adde
Advancing Tests of Relativistic Gravity via Laser Ranging to Phobos
Phobos Laser Ranging (PLR) is a concept for a space mission designed to
advance tests of relativistic gravity in the solar system. PLR's primary
objective is to measure the curvature of space around the Sun, represented by
the Eddington parameter , with an accuracy of two parts in ,
thereby improving today's best result by two orders of magnitude. Other mission
goals include measurements of the time-rate-of-change of the gravitational
constant, and of the gravitational inverse square law at 1.5 AU
distances--with up to two orders-of-magnitude improvement for each. The science
parameters will be estimated using laser ranging measurements of the distance
between an Earth station and an active laser transponder on Phobos capable of
reaching mm-level range resolution. A transponder on Phobos sending 0.25 mJ, 10
ps pulses at 1 kHz, and receiving asynchronous 1 kHz pulses from earth via a 12
cm aperture will permit links that even at maximum range will exceed a photon
per second. A total measurement precision of 50 ps demands a few hundred
photons to average to 1 mm (3.3 ps) range precision. Existing satellite laser
ranging (SLR) facilities--with appropriate augmentation--may be able to
participate in PLR. Since Phobos' orbital period is about 8 hours, each
observatory is guaranteed visibility of the Phobos instrument every Earth day.
Given the current technology readiness level, PLR could be started in 2011 for
launch in 2016 for 3 years of science operations. We discuss the PLR's science
objectives, instrument, and mission design. We also present the details of
science simulations performed to support the mission's primary objectives.Comment: 25 pages, 10 figures, 9 table
Comparison between human fetal and adult skin
Healing of early-gestation fetal wounds results in scarless healing. Since the capacity for regeneration is probably inherent to the fetal skin itself, knowledge of the fetal skin composition may contribute to the understanding of fetal wound healing. The aim of this study was to analyze the expression profiles of different epidermal and dermal components in the human fetal and adult skin. In the human fetal skin (ranging from 13 to 22Â weeksâ gestation) and adult skin biopsies, the expression patterns of several epidermal proteins (K10, K14, K16, K17, SKALP, involucrin), basement membrane proteins, Ki-67, blood vessels and extracellular matrix proteins (fibronectin, chondroitin sulfate, elastin) were determined using immunohistochemistry. The expression profiles of K17, involucrin, dermal Ki-67, fibronectin and chondroitin sulfate were higher in the fetal skin than in adult skin. In the fetal skin, elastin was not present in the dermis, but it was found in the adult skin. The expression patterns of basement membrane proteins, blood vessels, K10, K14, K16 and epidermal Ki-67 were similar in human fetal skin and adult skin. In this systematic overview, most of the differences between fetal and adult skin were found at the level of dermal extracellular matrix molecules expression. This study suggests that, especially, dermal components are important in fetal scarless healing
Mind-wandering and alterations to default mode network connectivity when listening to naturalistic versus artificial sounds
Naturalistic environments have been demonstrated to promote relaxation and wellbeing. We assess opposing theoretical accounts for these effects through investigation of autonomic arousal and alterations of activation and functional connectivity within the default mode network (DMN) of the brain while participants listened to sounds from artificial and natural environments. We found no evidence for increased DMN activity in the naturalistic compared to artificial or control condition, however, seed based functional connectivity showed a shift from anterior to posterior midline functional coupling in the naturalistic condition. These changes were accompanied by an increase in peak high frequency heart rate variability, indicating an increase in parasympathetic activity in the naturalistic condition in line with the Stress Recovery Theory of nature exposure. Changes in heart rate and the peak high frequency were correlated with baseline functional connectivity within the DMN and baseline parasympathetic tone respectively, highlighting the importance of individual neural and autonomic differences in the response to nature exposure. Our findings may help explain reported health benefits of exposure to natural environments, through identification of alterations to autonomic activity and functional coupling within the DMN when listening to naturalistic sounds
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