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Abstract Reactive astrocytes play a pivotal role in the pathogenesis of neurological diseases; however, their functional phenotype and the downstream molecules by which they modify disease pathogenesis remain unclear. Here, we genetically increase P2Y1 receptor (P2Y1R) expression, which is upregulated in reactive astrocytes in several neurological diseases, in astrocytes of male mice to explore its function and the downstream molecule. This astrocyte-specific P2Y1R overexpression causes neuronal hyperexcitability by increasing both astrocytic and neuronal Ca2+ signals. We identify insulin-like growth factor-binding protein 2 (IGFBP2) as a downstream molecule of P2Y1R in astrocytes; IGFBP2 acts as an excitatory signal to cause neuronal excitation. In neurological disease models of epilepsy and stroke, reactive astrocytes upregulate P2Y1R and increase IGFBP2. The present findings identify a mechanism underlying astrocyte-driven neuronal hyperexcitability, which is likely to be shared by several neurological disorders, providing insights that might be relevant for intervention in diverse neurological disorders.

We introduce sparse-ir, a collection of libraries to efficiently handle imaginary-time propagators, a central object in finite-temperature quantum many-body calculations. We leverage two concepts: firstly, the intermediate representation (IR), an optimal compression of the propagator with robust a priori error estimates, and secondly, sparse sampling, near-optimal grids in imaginary time and imaginary frequency from which the propagator can be reconstructed and on which diagrammatic equations can be solved. IR and sparse sampling are packaged into stand-alone, easy-to-use Python, Julia and Fortran libraries, which can readily be included into existing software. We also include an extensive set of sample codes showcasing the library for typical many-body and ab initio methods.

BackgroundDespite the broad global use of antibiotics, there is no established definition of early antibiotic treatment failure (EATF) to aid clinical evaluation of treatment, which leads to inconsistent assessments of drug effectiveness.AimThis scoping review aims to identify common components of EATF definitions by synthesizing studies mentioning EATF and its relevant thesaurus matches.DesignScoping review.MethodsThis scoping review was conducted following the PRISMA Scoping review guidelines. A systematic literature search was conducted using MEDLINE (PubMed), CENTRAL, CINAHL, and Web of Science, as well as a manual Google search. Search terms were EATF and its thesaurus matches. After removing duplications, candidate studies were screened by title and abstract prior to full text searches, and quality analysis was performed on eligible studies using the Critical Appraisal Skills Programme. From each eligible study, the timing of evaluation, basic components, and detailed information for each definition of EATF were collected. The components of each definition for EATF were then summarized and counted, and finally the most common essential components were identified.ResultsOur systematic literature search found 2,472 candidate studies. After title and abstract screening, full text search and quality assessment, 61 studies, including 56 original studies and five reviews, were eligible for our analysis. Of these 56 original studies, 43 mentioned the timing of EATF evaluation 72 hours after the start of treatment with antibiotics. From these 43 studies, the most common indicators of EATF were extracted, among which a set of essential components for a definition of EATF were identified: mortality, vital signs, fever, symptoms, and additional treatment.ConclusionsOur scoping review uncovered five essential factors for EATF. Further study is needed to evaluate the validity of our findings.

Abstract We propose the sparse modeling method to estimate the spectral function from the smeared correlation functions. We give a description of how to obtain the shear viscosity from the correlation function of the renormalized energy-momentum tensor (EMT) measured by the gradient flow method (C (t, τ )) for the quenched QCD at finite temperature. The measurement of the renormalized EMT in the gradient flow method reduces a statistical uncertainty thanks to its property of the smearing. However, the smearing breaks the sum rule of the spectral function and the over-smeared data in the correlation function may have to be eliminated from the analyzing process of physical observables. In this work, we demonstrate the sparse modeling analysis in the intermediate-representation basis (IR basis), which connects between the Matsubara frequency data and real frequency data. It works well even using very limited data of C (t, τ ) only in the fiducial window of the gradient flow. We utilize the ADMM algorithm which is useful to solve the LASSO problem under some constraints. We show that the obtained spectral function reproduces the input smeared correlation function at finite flow-time. Several systematic and statistical errors and the flow-time dependence are also discussed.

Rab proteins are small GTPases that act as molecular switches for intracellular vesicle trafficking. Although their function is mainly regulated by regulatory proteins such as GTPase-activating proteins and guanine nucleotide exchange factors, recent studies have shown that some Rab proteins are physiologically phosphorylated in the switch II region by Rab kinases. As the switch II region of Rab proteins undergoes a conformational change depending on the bound nucleotide, it plays an essential role in their function as a ‘switch’. Initially, the phosphorylation of Rab proteins in the switch II region was shown to inhibit the association with regulatory proteins. However, recent studies suggest that it also regulates the binding of Rab proteins to effector proteins, determining which pathways to regulate. These findings suggest that the regulation of the Rab function may be more dynamically regulated by phosphorylation than just through the association with regulatory proteins. In this review, we summarize the recent findings and discuss the physiological and pathological roles of Rab phosphorylation.