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Beige adipocytes in white adipose tissue (WAT) are similar to classical brown adipocytes in that they can burn lipids to produce heat. Thus, an increase in beige adipocyte content in WAT browning would raise energy expenditure and reduce adiposity. Here we report that adipose-specific inactivation of Notchl or its signaling mediator Rbpj in mice results in browning of WAT and elevated expression of uncoupling protein 1 (Ucp1), a key regulator of thermogenesis. Consequently, as compared to wild-type mice, Notch mutants exhibit elevated energy expenditure, better glucose tolerance and improved insulin sensitivity and are more resistant to high fat diet-induced obesity. By contrast, adipose-specific activation of Notch1 leads to the opposite phenotypes. At the molecular level, constitutive activation of Notch signaling inhibits, whereas Notch inhibition induces, Ppargc1a and Prdm16 transcription in white adipocytes. Notably, pharmacological inhibition of Notch signaling in obese mice ameliorates obesity, reduces blood glucose and increases Ucp1 expression in white fat. Therefore, Notch signaling may be therapeutically targeted to treat obesity and type 2 diabetes., The global epidemic of obesity and its associated risks of chronic diseases, including type 2 diabetes, pose formidable challenges to human health. Classical brown adipose tissue (BAT) found prominently in [...]

Simple Summary: Polycythemia vera (PV) is a malignant neoplastic disease. Abnormal cell metabolism is a new feature of malignant proliferation of tumor cells. Our study described the global metabolic profile of PV patients, analyzed their relationship with cell proliferation, screened prognosis-related metabolic biomarkers. Notably, fatty acid metabolism, glucose metabolism, sphingolipid metabolism, and amino acid metabolism were significantly altered in PV. In addition, Cer(d18:2/22:6-2OH(7S, 17S)) and SM(d18:0/PGF1α) were closely associated with JAK2 mutations, which may contribute to the proliferation of peripheral blood cells in PV patients. The elevated levels of four potential biomarkers may provide a reference for poor prognosis in PV patients. Polycythemia vera (PV) is a malignant clonal hematological disease of hematopoietic stem cells characterized by the proliferation of peripheral blood cells, and JAK2 mutation is one of the main causes of PV peripheral blood cell proliferation. Abnormal cell metabolism is a new feature of malignant proliferation of tumor cells, but the role of metabolism in the pathogenesis and prognosis of PV remains unclear. We analyzed metabolic differences of peripheral blood sera between 32 PV patients and 20 healthy controls (HCs) by liquid chromatography–mass spectrometry (LC–MS) to investigate their relationship with cell proliferation and to screen for prognosis-related metabolic biomarkers. Compared to HC, 33 endogenous metabolites were significantly changed in PV and were involved in fatty acid metabolism, glucose metabolism, sphingolipid metabolism, and amino acid metabolism pathways. Among them, seven metabolites were closely associated with JAK2 mutations, 2 of which may contribute to the proliferation of peripheral blood cells in PV patients. A set of potential prognostic metabolic biomarkers containing four metabolites was identified by a receiver operating characteristic (ROC) curve according to the risk stratification of the PV patients and their combined AUC value of 0.952, with a sensitivity of 90.905% and specificity of 90.909% at the optimal cutoff point. Metabonomics is an important tool for the study of the pathogenesis of PV and the relationship between JAK2 gene mutation. Furthermore, the potential biomarkers of this study may provide a reference for the prognosis of PV. [ABSTRACT FROM AUTHOR]

Two-photon Ca2+ imaging is a widely used technique for investigating brain functions across multiple spatial scales. However, the recording of neuronal activities is affected by movement of the brain during tasks in which the animal is behaving normally. Although post-hoc image registration is the commonly used approach, the recent developments of online neuroscience experiments require real-time image processing with efficient motion correction performance, posing new challenges in neuroinformatics. We propose a fast and accurate image density feature-based motion correction method to address the problem of imaging animal during behaviors. This method is implemented by first robustly estimating and clustering the density features from two-photon images. Then, it takes advantage of the temporal correlation in imaging data to update features of consecutive imaging frames with efficient calculations. Thus, motion artifacts can be quickly and accurately corrected by matching the features and obtaining the transformation parameters for the raw images. Based on this efficient motion correction strategy, our algorithm yields promising computational efficiency on imaging datasets with scales ranging from dendritic spines to neuronal populations. Furthermore, we show that the proposed motion correction method outperforms other methods by evaluating not only computational speed but also the quality of the correction performance. Specifically, we provide a powerful tool to perform motion correction for two-photon Ca2+ imaging data, which may facilitate online imaging experiments in the future. [ABSTRACT FROM AUTHOR]

We propose a closed-form quasi-maiximum likelihood (QML) estimator of bid-ask spread from daily high-low ranges under both near-ideal and overnight theoretical frameworks. As is shown that the high-low spread estimator is more precise than that only using closing prices, we pay attention to investigating the statistical properties of such kind of range-based spread estimators, and further demonstrating that our estimator is free from overnight adjustment with higher estimation efficiency. Simulation studies show that the QML estimator has relatively lower bias and RMSE, compared with other prevalent low-frequency measures, and the results are more significant under overnight conditions. [ABSTRACT FROM AUTHOR]

This study reported the synthesis process of SmFe0.5Cr0.5O3 by the sol-gel method, and its structure, hyperfine parameters and magnetic properties are also studied. X-ray diffraction (XRD) revealed the Pbnm(62) spatial group characteristics of the nanoscale size and orthogonally distorted perovskite structure of the samples. The Mössbauer spectrum shows the characteristics of trivalent hexacoordinated high spin (s = 5/2) of 57Fe in the sample and the distorted octahedron symmetric structure environment of triangle or quadrilateral. Magnetization data and Mössbauer spectra record magnetic phase transition at about 250 K (TN = 250 K). Under the Néel temperature, the system exhibits a frustrated spin glass state. Monte Carlo simulation of magnetization curves based on 3D Heisenberg model modified by Dzyaloshinskii-Moriya (DM) interaction results in the main exchange constants in the sample (JFe-Cr/kB = 16.04 K) and magnetic phase transition temperature (~250 K). Highlights: Preparation of SmFe0.5Cr0.5O3 Perovskite Nanoparticles by Sol-Gel Method. The structure and magnetic properties of the prepared SmFe0.5Cr0.5O3 nanoparticles were characterized by XRD, Mössbauer spectrometer, and VSM. Based on the three-dimensional Heisenberg model modified by Dzyaloshinskii–Moriya interaction, the magnetization curve was simulated by Monte Carlo method to obtain the exchange constant and magnetic ordering temperature. [ABSTRACT FROM AUTHOR]

In this work, BiFe 1 − x Co x O 3 (x = 0, 0.08) nanoparticles were synthesized by the solution method and their structural differences were studied. X-ray diffraction results show that the rhombohedral R3c space group and perovskite structures are detected in both samples, accompanied by an impurity phase. The (104) and (110) peaks merge when cobalt ions are doped. The decrease in lattice parameters indicates that the microstructure of the nanoparticles becomes gradually distorted. Mössbauer spectroscopy analysis at room temperature reveals an additional doublet due to the oxygen vacancies in BiFe 0. 9 2 Co 0. 0 8 O 3 . Hyperfine interactions, spatial spin-modulated structures and oxygen deficiencies around iron ions are also reflected in the observed spectra and variations in hyperfine parameters. [ABSTRACT FROM AUTHOR]

Aims Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miRs) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown. Methods and results Out of 172 screened CAD patients, 31 patients with CAD + CKD were identified and matched with 31 CAD patients without CKD. Additionally, 13 controls without CAD and CKD were included. Large EVs from CAD + CKD patients contained significantly lower levels of the vasculo-protective miR-130a-3p and miR-126-3p compared to CAD patients and controls. Flow cytometric analysis of plasma-derived EVs revealed significantly higher numbers of endothelial cell-derived EVs in CAD and CAD + CKD patients compared to controls. EVs from CAD + CKD patients impaired target human coronary artery endothelial cell (HCAEC) proliferation upon incubation in vitro. Consistent with the clinical data, treatment with the uraemia toxin indoxyl sulfate (IS)-reduced miR-130a-3p levels in HCAEC-derived EVs. EVs from IS-treated donor HCAECs-reduced proliferation and re-endothelialization in EV-recipient cells and induced an anti-angiogenic gene expression profile. In a mouse-experiment, intravenous treatment with EVs from IS-treated endothelial cells significantly impaired endothelial regeneration. On the molecular level, we found that IS leads to an up-regulation of the heterogenous nuclear ribonucleoprotein U (hnRNPU), which retains miR-130a-3p in the cell leading to reduced vesicular miR-130a-3p export and impaired EV-recipient cell proliferation. Conclusion Our findings suggest that EV-miR-mediated vascular intercellular communication is altered in patients with CAD and CKD, promoting CKD-induced endothelial dysfunction. [ABSTRACT FROM AUTHOR]