Corrélations de vitesse lagrangienne et échelle intégrale temporelle en simulation des grandes échelles

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RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase.

Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. The mechanism by which AID triggers SHM and CSR has been explained by two distinct models. In the DNA deamination model, AID converts cytidine bases in DNA into uridine. The uridine is recognized by the DNA repair system, which produces DNA strand breakages and point mutations. In the alternative model, RNA edited by AID is responsible for triggering CSR and SHM. However, RNA deamination by AID has not been demonstrated. Here we found that C-to-T and G-to-A mutations accumulated in hepatitis B virus (HBV) nucleocapsid DNA when AID was expressed in HBV-replicating hepatic cell lines. AID expression caused C-to-T mutations in the nucleocapsid DNA of RNase H-defective HBV, which does not produce plus-strand viral DNA. Furthermore, the RT-PCR products of nucleocapsid viral RNA from AID-expressing cells exhibited significant C-to-T mutations, whereas viral RNAs outside the nucleocapsid did not accumulate C-to-U mutations. Moreover, AID was packaged within the nucleocapsid by forming a ribonucleoprotein complex with HBV RNA and the HBV polymerase protein. The encapsidation of the AID protein with viral RNA and DNA provides an efficient environment for evaluating AID's RNA and DNA deamination activities. A bona fide RNA-editing enzyme, apolipoprotein B mRNA editing catalytic polypeptide 1, induced a similar level of C-to-U mutations in nucleocapsid RNA as AID. Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV

Automatic Data Transformation Using Large Language Model: An Experimental Study on Building Energy Data

Existing approaches to automatic data transformation are insufficient to meet the requirements in many real-world scenarios, such as the building sector. First, there is no convenient interface for domain experts to provide domain knowledge easily. Second, they require significant training data collection overheads. Third, the accuracy suffers from complicated schema changes. To bridge this gap, we present a novel approach that leverages the unique capabilities of large language models (LLMs) in coding, complex reasoning, and zero-shot learning to generate SQL code that transforms the source datasets into the target datasets. We demonstrate the viability of this approach by designing an LLM-based framework, termed SQLMorpher, which comprises a prompt generator that integrates the initial prompt with optional domain knowledge and historical patterns in external databases. It also implements an iterative prompt optimization mechanism that automatically improves the prompt based on flaw detection. The key contributions of this work include (1) pioneering an end-to-end LLM-based solution for data transformation, (2) developing a benchmark dataset of 105 real-world building energy data transformation problems, and (3) conducting an extensive empirical evaluation where our approach achieved 96% accuracy in all 105 problems. SQLMorpher demonstrates the effectiveness of utilizing LLMs in complex, domain-specific challenges, highlighting the potential of their potential to drive sustainable solutions.Comment: 10 pages, 7 figure

Chemical-scissor-mediated structural editing of layered transition metal carbides

Intercalation of non-van der Waals (vdW) layered materials can produce new 2D and 3D materials with unique properties, but it is difficult to achieve. Here, we describe a structural editing protocol for 3D non-vdW layered ternary carbides and nitrides (MAX phases) and their 2D vdW derivatives (MXenes). Gap-opening and species-intercalating stages were mediated by chemical scissors and guest intercalants, creating a large family of layered materials with unconventional elements and structures in MAX phases, as well as MXenes with versatile termination species. Removal of surface terminations by metal scissors and stitching of carbide layers by metal atoms leads to a reverse transformation from MXenes to MAX phases, and metal-intercalated 2D carbides. This scissor-mediated structural editing may enable structural and chemical tailoring of other layered ceramics

RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase

Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. The mechanismby which AID triggers SHMand CSR has been explained by two distinct models. In the DNA deamination model, AID converts cytidine bases in DNA into uridine. The uridine is recognized by the DNA repair system, which produces DNA strand breakages and point mutations. In the alternative model, RNA edited by AID is responsible for triggering CSR and SHM. However, RNA deamination by AID has not been demonstrated. Here we found that C-to-T and G-to-A mutations accumulated in hepatitis B virus (HBV) nucleocapsid DNA when AID was expressed in HBV replicating hepatic cell lines. AID expression caused C-to-T mutations in the nucleocapsid DNA of RNase H-defective HBV, which does not produce plus-strand viral DNA. Furthermore, the RT-PCR products of nucleocapsid viral RNA from AID-expressing cells exhibited significant C-to-T mutations, whereas viral RNAs outside the nucleocapsid did not accumulate C-to-U mutations. Moreover, AID was packaged within the nucleocapsid by forming a ribonucleoprotein complex with HBV RNA and the HBV polymerase protein. The encapsidation of the AID protein with viral RNA and DNA provides an efficient environment for evaluating AID\u27s RNA and DNA deamination activities. A bona fide RNA-editing enzyme, apolipoprotein B mRNA editing catalytic polypeptide 1, induced a similar level of C-to-U mutations in nucleocapsid RNA as AID. Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV

TGF-β Suppression of HBV RNA through AID-Dependent Recruitment of an RNA Exosome Complex

Transforming growth factor (TGF)-β inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-β is dependent on AID expression, which significantly decreases both HBV transcripts and viral DNA, resulting in inhibition of viral replication. Immunoprecipitation reveals that AID physically associates with viral P protein that binds to specific virus RNA sequence called epsilon. AID also binds to an RNA degradation complex (RNA exosome proteins), indicating that AID, RNA exosome, and P protein form an RNP complex. Suppression of HBV transcripts by TGF-β was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-β mediated suppression of HBV RNA. Moreover, AID-mediated HBV reduction does not occur when P protein is disrupted or when viral transcription is inhibited. These results suggest that induced expression of AID by TGF-β causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner. © 2015 Liang et al

New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease

Parkinson’s disease (PD) is one of the synucleinopathies spectrum of disorders typified by the presence of intraneuronal protein inclusions. It is primarily composed of misfolded and aggregated forms of alpha-synuclein (α-syn), the toxicity of which has been attributed to the transition from an α-helical conformation to a β-sheetrich structure that polymerizes to form toxic oligomers. This could spread and initiate the formation of “LB-like aggregates,” by transcellular mechanisms with seeding and subsequent permissive templating. This hypothesis postulates that α-syn is a prion-like pathological agent and responsible for the progression of Parkinson’s pathology. Moreover, the involvement of the inflammatory response in PD pathogenesis has been reported on the excessive microglial activation and production of pro-inflammatory cytokines. At last, we describe several treatment approaches that target the pathogenic α-syn protein, especially the oligomers, which are currently being tested in advanced animal experiments or are already in clinical trials. However, there are current challenges with therapies that target α-syn, for example, difficulties in identifying varying α-syn conformations within different individuals as well as both the cost and need of long-duration large trials

Cluster-Like Headache Secondary to Anamnesis of Sphenoid Ridge Meningioma: A Case Report and Literature Review

Cluster headache is generally considered to be a primary headache; secondary cluster-like headache is quite rare, while cluster-like headache secondary to meningioma is even rarer. Here, we describe an unusual case with cluster-like headache 2.5 years after sphenoid ridge meningioma surgery. The cluster-like headache and meningioma were on the same side, and even at the same position. Furthermore, the cluster-like headache lasted for 6 months. In addition, the patient did not respond well to conventional treatments for cluster headache, such as oxygen inhalation, carbamazepine, and tramadol. Brain magnetic resonance imaging demonstrated a softening lesion, glial hyperplasia, and localized thickening and enhancement of the dura in the left frontal-temporal lobe. However, positron-emission computed tomography showed reduced metabolism in the left frontal-temporal lobe. Although the possibility of a primary headache cannot be completely eliminated, the association between cluster-like headache and probable tumor recurrence or postoperative changes should be considered

Interleukin-1 and tumor necrosis factor-α trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID).

金沢大学医薬保健研究域医学系Virus infection is restricted by intracellular immune responses in host cells, and this is typically modulated by stimulation of cytokines. The cytokines and host factors that determine the host cell restriction against hepatitis B virus (HBV) infection are not well understood. We screened 36 cytokines and chemokines to determine which were able to reduce the susceptibility of HepaRG cells to HBV infection. Here, we found that pretreatment with IL-1β and TNFα remarkably reduced the host cell susceptibility to HBV infection. This effect was mediated by activation of the NF-κB signaling pathway. A cytidine deaminase, activation-induced cytidine deaminase (AID), was up-regulated by both IL-1β and TNFα in a variety of hepatocyte cell lines and primary human hepatocytes. Another deaminase APOBEC3G was not induced by these proinflammatory cytokines. Knockdown of AID expression impaired the anti-HBV effect of IL-1β, and overexpression of AID antagonized HBV infection, suggesting that AID was one of the responsible factors for the anti-HBV activity of IL-1/TNFα. Although AID induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV activity. The antiviral effect of IL-1/TNFα was also observed on different HBV genotypes but not on hepatitis C virus. These results demonstrate that proinflammatory cytokines IL-1/TNFα trigger a novel antiviral mechanism involving AID to regulate host cell permissiveness to HBV infection