150 research outputs found

    Guaranteed Lower Eigenvalue Bound of Steklov Operator with Conforming Finite Element Methods

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    For the eigenvalue problem of the Steklov differential operator, by following Liu's approach, an algorithm utilizing the conforming finite element method (FEM) is proposed to provide guaranteed lower bounds for the eigenvalues. The proposed method requires the a priori error estimation for FEM solution to nonhomogeneous Neumann problems, which is solved by constructing the hypercircle for the corresponding FEM spaces and boundary conditions. Numerical examples are also shown to confirm the efficiency of our proposed method.Comment: 21 pages, 4 figures, 4 table

    High affinity binding of H3K14ac through collaboration of bromodomains 2, 4 and 5 is critical for the molecular and tumor suppressor functions of PBRM1.

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    Polybromo-1 (PBRM1) is an important tumor suppressor in kidney cancer. It contains six tandem bromodomains (BDs), which are specialized structures that recognize acetyl-lysine residues. While BD2 has been found to bind acetylated histone H3 lysine 14 (H3K14ac), it is not known whether other BDs collaborate with BD2 to generate strong binding to H3K14ac, and the importance of H3K14ac recognition for the molecular and tumor suppressor function of PBRM1 is also unknown. We discovered that full-length PBRM1, but not its individual BDs, strongly binds H3K14ac. BDs 2, 4, and 5 were found to collaborate to facilitate strong binding to H3K14ac. Quantitative measurement of the interactions between purified BD proteins and H3K14ac or nonacetylated peptides confirmed the tight and specific association of the former. Interestingly, while the structural integrity of BD4 was found to be required for H3K14ac recognition, the conserved acetyl-lysine binding site of BD4 was not. Furthermore, simultaneous point mutations in BDs 2, 4, and 5 prevented recognition of H3K14ac, altered promoter binding and gene expression, and caused PBRM1 to relocalize to the cytoplasm. In contrast, tumor-derived point mutations in BD2 alone lowered PBRM1\u27s affinity to H3K14ac and also disrupted promoter binding and gene expression without altering cellular localization. Finally, overexpression of PBRM1 variants containing point mutations in BDs 2, 4, and 5 or BD2 alone failed to suppress tumor growth in a xenograft model. Taken together, our study demonstrates that BDs 2, 4, and 5 of PBRM1 collaborate to generate high affinity to H3K14ac and tether PBRM1 to chromatin. Mutations in BD2 alone weaken these interactions, and this is sufficient to abolish its molecular and tumor suppressor functions

    Non-suicidal self-injury and suicidal ideation among adolescents: the chain-mediating role of rumination and decentering

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    ObjectiveTo explore the relationship between non-suicidal self-injury and suicidal ideation in adolescents and examine the roles of rumination and decentering in that relationship.MethodBy means of a questionnaire, 175 adolescent patients in a psychiatric hospital in Fujian Province were given the Functional Assessment of Self-Mutilation: Chinese Version, Positive and Negative Suicide Ideation, Ruminative Response Scale: Chinese Version, and Experiences Questionnaire: Decentering Scale.Results(1) Adolescent non-suicidal self-injury was significantly positively related to suicidal ideation and rumination and significantly negatively related to decentering. Suicidal ideation was significantly positively related to rumination and significantly negatively related to decentering. Rumination was significantly negatively related to decentering. (2) Rumination and decentering played a complete chain-mediating role between non-suicidal self-injury and suicidal ideation. Non-suicidal self-injury was found to indirectly affect suicidal ideation along three pathways: the independent mediating role of rumination (the mediating effect accounted for 40.166%), independent mediating role of decentering (the mediating effect accounted for 41.274%), and chain-mediating role of rumination and decentering (the mediating effect accounted for 14.958%).ConclusionAdolescent non-suicidal self-injury can indirectly affect suicidal ideation through rumination and decentering. In the future, mindfulness and other methods should be used to improve individuals’ levels of decentering and cultivate emotional regulation abilities, so as to reduce the incidence of non-suicidal self-injury and suicide in adolescents

    Dual-transgenic BiFC vector systems for protein-protein interaction analysis in plants

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    Protein-protein interaction (PPI) play a pivotal role in cellular signal transduction. The bimolecular fluorescence complementation (BiFC) assay offers a rapid and intuitive means to ascertain the localization and interactions of target proteins within living cells. BiFC is based on fluorescence complementation by reconstitution of a functional fluorescent protein by co-expression of N- and C-terminal fragments of this protein. When fusion proteins interact, the N- and C-terminal fragments come into close proximity, leading to the reconstitution of the fluorescent protein. In the conventional approach, the N-terminal and C-terminal fragments of the fluorescent protein are typically expressed using two separate vectors, which largely relies on the efficiency of the transformation of the two vectors in the same cells. Furthermore, issues of vector incompatibility can often result in loss of one plasmid. To address these challenges, we have developed novel dual-transgenic BiFC vectors, designed as pDTQs, derived from the previously published pDT1 vector. This set of BiFC vectors offers the following advantages: 1) Both fluorescent fusion proteins are expressed sequentially within a single vector, enhancing expression efficiency; 2) Independent promoters and terminators regulate the expression of the two proteins potentially mitigating vector compatibility issues; 3) A long linker is inserted between the fluorescent protein fragment and the gene of interest, facilitating the recombination of the fused fluorescent protein into an active form; 4) Four distinct types of fluorescent proteins, namely, EYFP, mVenus, mRFP1Q66T and mCherry are available for BiFC analysis. We assessed the efficiency of the pDTQs system by investigating the oligomerization of Arabidopsis CRY2 and CRY2-BIC2 interactions in N. benthamiana. Notably, the pDTQs were found to be applicable in rice, underscoring their potential utility across various plant species

    Pressure-stabilized divalent ozonide CaO3 and its impact on Earth's oxygen cycles.

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    High pressure can drastically alter chemical bonding and produce exotic compounds that defy conventional wisdom. Especially significant are compounds pertaining to oxygen cycles inside Earth, which hold key to understanding major geological events that impact the environment essential to life on Earth. Here we report the discovery of pressure-stabilized divalent ozonide CaO3 crystal that exhibits intriguing bonding and oxidation states with profound geological implications. Our computational study identifies a crystalline phase of CaO3 by reaction of CaO and O2 at high pressure and high temperature conditions; ensuing experiments synthesize this rare compound under compression in a diamond anvil cell with laser heating. High-pressure x-ray diffraction data show that CaO3 crystal forms at 35 GPa and persists down to 20 GPa on decompression. Analysis of charge states reveals a formal oxidation state of -2 for ozone anions in CaO3. These findings unravel the ozonide chemistry at high pressure and offer insights for elucidating prominent seismic anomalies and oxygen cycles in Earth's interior. We further predict multiple reactions producing CaO3 by geologically abundant mineral precursors at various depths in Earth's mantle

    Optical Amplification at 1525 nm in BaYF 5

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    We demonstrated optical amplification in BaYF5: 20% Yb3+, 2% Er3+ (BYF) nanocrystals doped polymer waveguide. BYF nanocrystals with an average size of ∼13 nm were synthesized by a high-boiling solvent process. Intense 1.53 μm fluorescence was obtained in the nanocrystals under excitation at 980 nm. An optical polymer waveguide was fabricated by using BYF nanocrystals doped SU-8 polymer as the core material. A relative optical gain of ∼10.4 dB at 1525 nm was achieved in a 1.1 cm long waveguide for an input signal power of ∼0.09 mW and a pump power of ∼212 mW

    Antibiotic-Induced Primary Biles Inhibit SARS-CoV-2 Endoribonuclease Nsp15 Activity in Mouse Gut

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    The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids

    Foxtail Mosaic Virus-induced Flowering Assays in Monocot Crops

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    Virus-induced flowering (VIF) exploits RNA or DNA viruses to express flowering time genes to induce flowering in plants. Such plant virus-based tools have recently attracted widespread attention for their fundamental and applied uses in flowering physiology and in accelerating breeding in dicotyledonous crops and woody fruit-trees. We now extend this technology to a monocot grass and a cereal crop. Using the Foxtail mosaic virus-based VIF system, dubbed FoMViF, we showed that expression of florigenic Flowering Locus T (FT) genes can promote early flowering and spikelet development in proso millet, a C4 grass species with potential for nutritional food and biofuel resources, and in non-vermalized C3 wheat, a major food crop worldwide. Floral and spikelet/grain induction in the two monocot plants was caused by the virally expressed untagged or FLAG-tagged FT orthologues, and the florigenic activity of rice Hd3a was more pronounced than its dicotyledonous counterparts in proso millet. The FoMViF system is easy to perform and its efficacy to induce flowering and early spikelet/grain production is high. In addition to proso millet and wheat, we envisage that FoMViF will be also applicable to many economically important monocotyledonous food and biofuel crops

    Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

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    Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy
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