608 research outputs found

    Quasinormal modes of slowly-rotating black holes in dynamical Chern-Simons gravity

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    The detection of gravitational waves from compact binary mergers by the LIGO/Virgo collaboration has, for the first time, allowed us to test relativistic gravity in its strong, dynamical and nonlinear regime, thus opening a new arena to confront general relativity (and modifications thereof) against observations. We consider a theory which modifies general relativity by introducing a scalar field coupled to a parity-violating curvature term known as dynamical Chern-Simons gravity. In this theory, spinning black holes are different from their general relativistic counterparts and can thus serve as probes to this theory. We study linear gravito-scalar perturbations of black holes in dynamical Chern-Simons gravity at leading-order in spin and (i) obtain the perturbed field equations describing the evolution of the perturbed gravitational and scalar fields, (ii) numerically solve these equations by direct integration to calculate the quasinormal mode frequencies for the dominant and higher multipoles and tabulate them, (iii) find strong evidence that these rotating black holes are linearly stable, and (iv) present general fitting functions for different multipoles for gravitational and scalar quasinormal mode frequencies in terms of spin and Chern-Simons coupling parameter. Our results can be used to validate the ringdown of small-spin remnants of numerical relativity simulations of black hole binaries in dynamical Chern-Simons gravity and pave the way towards future tests of this theory with gravitational wave ringdown observations

    Exploration of mycorrhizal fungi as potential biofertilizer in the management of plant biotic and abiotic stresses

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    Arbuscular mycorrhizal fungi (AMF) are fungi found in the soil and it can significantly enhance plant nutrient uptake and increase resistance to various environmental stresses. Arbuscular mycorrhizal symbiosis is the most common non-pathogenic symbiosis in the soil and is found in 80% of vascular plant roots. Most of AM fungi species belong to the sub-phylum Glomeromycotina within the phylum Mucoromycota. Arbuscular mycorrhizal (AM) fungi not only enhance the phosphorus supply to plants but also boost the absorption of zinc, copper, nitrogen and iron. AM fungi limit the uptake of Na and Cl. AM fungal hyphae make significant contributions in enhancing soil structure and its ability to retain water. Additionally, these fungi demonstrate resilience against certain root diseases and display a tolerance to drought conditions. Arbuscular mycorrhizal (AM) fungi serve as crucial endosymbionts, playing a significant role in enhancing plant productivity and contributing to the overall functioning of ecosystems. Their importance is paramount in the context of sustainable crop enhancement

    cDNA-detector: detection and removal of cDNA contamination in DNA sequencing libraries

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    BACKGROUND: Exogenous cDNA introduced into an experimental system, either intentionally or accidentally, can appear as added read coverage over that gene in next-generation sequencing libraries derived from this system. If not properly recognized and managed, this cross-contamination with exogenous signal can lead to incorrect interpretation of research results. Yet, this problem is not routinely addressed in current sequence processing pipelines. RESULTS: We present cDNA-detector, a computational tool to identify and remove exogenous cDNA contamination in DNA sequencing experiments. We demonstrate that cDNA-detector can identify cDNAs quickly and accurately from alignment files. A source inference step attempts to separate endogenous cDNAs (retrocopied genes) from potential cloned, exogenous cDNAs. cDNA-detector provides a mechanism to decontaminate the alignment from detected cDNAs. Simulation studies show that cDNA-detector is highly sensitive and specific, outperforming existing tools. We apply cDNA-detector to several highly-cited public databases (TCGA, ENCODE, NCBI SRA) and show that contaminant genes appear in sequencing experiments where they lead to incorrect coverage peak calls. CONCLUSIONS: cDNA-detector is a user-friendly and accurate tool to detect and remove cDNA detection in NGS libraries. This two-step design reduces the risk of true variant removal since it allows for manual review of candidates. We find that contamination with intentionally and accidentally introduced cDNAs is an underappreciated problem even in widely-used consortium datasets, where it can lead to spurious results. Our findings highlight the importance of sensitive detection and removal of contaminant cDNA from NGS libraries before downstream analysis

    Assessing the clinical utility of cancer genomic and proteomic data across tumor types

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    Molecular profiling of tumors promises to advance the clinical management of cancer, but the benefits of integrating molecular data with traditional clinical variables have not been systematically studied. Here we retrospectively predict patient survival using diverse molecular data (somatic copy-number alteration, DNA methylation and mRNA, miRNA and protein expression) from 953 samples of four cancer types from The Cancer Genome Atlas project. We found that incorporating molecular data with clinical variables yielded statistically significantly improved predictions (FDR < 0.05) for three cancers but those quantitative gains were limited (2.2–23.9%). Additional analyses revealed little predictive power across tumor types except for one case. In clinically relevant genes, we identified 10,281 somatic alterations across 12 cancer types in 2,928 of 3,277 patients (89.4%), many of which would not be revealed in single-tumor analyses. Our study provides a starting point and resources, including an open-access model evaluation platform, for building reliable prognostic and therapeutic strategies that incorporate molecular data

    Epidermal mammalian target of rapamycin complex 2 controls lipid synthesis and filaggrin processing in epidermal barrier formation

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    Background: Perturbation of epidermal barrier formation will profoundly compromise overall skin function, leading to a dry and scaly, ichthyosis-like skin phenotype that is the hallmark of a broad range of skin diseases, including ichthyosis, atopic dermatitis, and a multitude of clinical eczema variants. An overarching molecular mechanism that orchestrates the multitude of factors controlling epidermal barrier formation and homeostasis remains to be elucidated. Objective: Here we highlight a specific role of mammalian target of rapamycin complex 2 (mTORC2) signaling in epidermal barrier formation. Methods: Epidermal mTORC2 signaling was specifically disrupted by deleting rapamycin-insensitive companion of target of rapamycin (Rictor), encoding an essential subunit of mTORC2 in mouse epidermis (epidermis-specific homozygous Rictor deletion [Ric(EKO)] mice). Epidermal structure and barrier function were investigated through a combination of gene expression, biochemical, morphological and functional analysis in Ric(EKO) and control mice. Results: Ric(EKO) newborns displayed an ichthyosis-like phenotype characterized by dysregulated epidermal de novo lipid synthesis, altered lipid lamellae structure, and aberrant filaggrin (FLG) processing. Despite a compensatory transcriptional epidermal repair response, the protective epidermal function was impaired in Ric(EKO) mice, as revealed by increased transepidermal water loss, enhanced corneocyte fragility, decreased dendritic epidermal T cells, and an exaggerated percutaneous immune response. Restoration of Akt-Ser473 phosphorylation in mTORC2-deficient keratinocytes through expression of constitutive Akt rescued FLG processing. Conclusion: Our findings reveal a critical metabolic signaling relay of barrier formation in which epidermal mTORC2 activity controls FLG processing and de novo epidermal lipid synthesis during cornification. Our findings provide novel mechanistic insights into epidermal barrier formation and could open up new therapeutic opportunities to restore defective epidermal barrier conditions.Peer reviewe

    In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation

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    In humans, aggregation of polyglutamine repeat (polyQ) proteins causes disorders such as Huntington’s disease. Although plants express hundreds of polyQ-containing proteins, no pathologies arising from polyQ aggregation have been reported. To investigate this phenomenon, we expressed an aggregation-prone fragment of human huntingtin (HTT) with an expanded polyQ stretch (Q69) in Arabidopsis thaliana plants. In contrast to animal models, we find that Arabidopsis sp. suppresses Q69 aggregation through chloroplast proteostasis. Inhibition of chloroplast proteostasis diminishes the capacity of plants to prevent cytosolic Q69 aggregation. Moreover, endogenous polyQ-containing proteins also aggregate on chloroplast dysfunction. We find tha

    Differential diagnosis of tuberculous meningitis from partially-treated pyogenic meningitis by cell ELISA

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    BACKGROUND: Tuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partially-treated pyogenic meningitis (PTPM). In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. We have also shown that lymphocytes from CSF of TBM patients respond differently to this antigen than do those from PTPM patients. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM. METHODS: We developed a cell enzyme-linked immunosorbant assay (Cell ELISA) to quantitatively measure production of antibodies against the 30-kD protein in B cells from CSF of TBM and PTPM patients. RESULTS: The cell ELISA yielded 92% (11/12) sensitivity and 92% (11/12) specificity for the differential diagnosis of TBM from PTPM. CONCLUSION: When induced with the 30-kD protein antigen, B cells derived from CSF of TBM patients respond to IgG production within 24 h while those derived from PTPM patients do not respond
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