Circadian Dysregulation Disrupts Bile Acid Homeostasis

BACKGROUND:Bile acids are potentially toxic compounds and their levels of hepatic production, uptake and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis. METHODOLOGY/PRINCIPAL FINDINGS:Both restricted feeding, which phase shifts peripheral clocks, and genetic ablation in Per1(-/-)/Per2(-/-) (PERDKO) mice disrupted normal bile acid control and resulted in hepatic cholestasis. Restricted feeding caused a dramatic, transient elevation in hepatic bile acid levels that was associated with activation of the xenobiotic receptors CAR and PXR and elevated serum aspartate aminotransferase (AST), indicative of liver damage. In the PERDKO mice, serum bile acid levels were elevated and the circadian expression of key bile acid synthesis and transport genes, including Cyp7A1 and NTCP, was lost. This was associated with blunted expression of a primary clock output, the transcription factor DBP, which transactivates the promoters of both genes. CONCLUSIONS/SIGNIFICANCE:We conclude that disruption of the circadian clock results in dysregulation of bile acid homeostasis that mimics cholestatic disease

Semi-leptonic form factors of Ξc→Ξ\Xi_{c}\to\Xi in QCD sum rules

There exists a significant deviation between the most recent Lattice QCD simulation and experimental measurement by Belle for $\Xi_{c}^{0}\to\Xi^{-}\ell^{+}\nu_{\ell}$. In this work, we investigate the $\Xi_{c}\to\Xi$ form factors in QCD sum rules. To this end, the two-point correlation functions of $\Xi_{c}$ and $\Xi$, and the three-point correlation functions of $\Xi_{c}\to\Xi$ are calculated. At the QCD level, contributions from up to dimension-6 four-quark operators are considered, and the leading order results of the Wilson coefficients are obtained. For the form factors, relatively stable Borel windows can be found. Our form factors are comparable with those of Lattice QCD, except for $f_{\perp}$. The obtained form factors are then used to predict the branching ratios of $\Xi_{c}\to\Xi \ell^{+}\nu_{\ell}$, and our predictions are consistent with the most recent data of ALICE and Belle, and those of Lattice QCD within error. Given that the branching ratios only contain limited information, we suggest the experimentalists directly measure the form factors of $\Xi_{c}\to\Xi$.Comment: 18 pages, 7 figures; version accepted by PR

An HI View of Galaxy Conformity: HI-rich Environment around HI-excess Galaxies

Using data taken as part of the Bluedisk project we study the connection between neutral hydrogen (HI) in the environment of spiral galaxies and that in the galaxies themselves. We measure the total HI mass present in the environment in a statistical way by studying the distribution of noise peaks in the HI data cubes obtained for 40 galaxies observed with WSRT. We find that galaxies whose HI mass fraction is high relative to standard scaling relations have an excess HI mass in the surrounding environment as well. Gas in the environment consists of gas clumps which are individually below the detection limit of our HI data. These clumps may be hosted by small satellite galaxies and\or be the high-density peaks of a more diffuse gas distribution in the inter-galactic medium. We interpret this result as an indication for a picture in which the HI-rich central galaxies accrete gas from an extended gas reservoir present in their environment.Comment: 15 pages, 13 figures. Accepted for publication in MNRA

MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer

Background We recently reported that miR-1 was one of the most significantly downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in gastric carcinogenesis. Methods We measured miR-1 expression in human GC cell lines and 90 paired primary GC samples, and analyzed the association of its status with clinicopathological features. The effect of miR-1 on GC cells was evaluated by proliferation and migration assay. To identify the target genes of miR-1, bioinformatic analysis and protein array analysis were performed. Moreover, the regulation mechanism of miR-1 with regard to these predicted targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and endothelial cell tube formation. The putative binding site of miR-1 on target genes was assessed by a reporter assay. Results Expression of miR-1 was obviously decreased in GC cell lines and primary tissues. Patients with low miR-1 expression had significantly shorter overall survival compared with those with high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited proliferation, migration, and tube formation of endothelial cells by suppressing expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1 (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low-malignancy GC cells. Conclusions MiR-1 acts as a tumor suppressor by inhibiting angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1 not only promotes cellular proliferation and migration of GC cells, but may activates proangiogenesis signaling and stimulates the proliferation and migration of endothelial cells, indicating the possibility of new strategies for GC therapy

Empirical modeling of the stellar spectrum of galaxies

An empirical method of modeling the stellar spectrum of galaxies is proposed, based on two successive applications of Principal Component Analysis (PCA). PCA is first applied to the newly available stellar library STELIB, supplemented by the J, H and K$_{s}$ magnitudes taken mainly from the 2 Micron All Sky Survey (2MASS). Next the resultant eigen-spectra are used to fit the observed spectra of a sample of 1016 galaxies selected from the Sloan Digital Sky Survey Data Release One (SDSS DR1). PCA is again applied, to the fitted spectra to construct the eigen-spectra of galaxies with zero velocity dispersion. The first 9 galactic eigen-spectra so obtained are then used to model the stellar spectrum of the galaxies in SDSS DR1, and synchronously to estimate the stellar velocity dispersion, the spectral type, the near-infrared SED, and the average reddening. Extensive tests show that the spectra of different type galaxies can be modeled quite accurately using these eigen-spectra. The method can yield stellar velocity dispersion with accuracies better than 10%, for the spectra of typical S/N ratios in SDSS DR1.Comment: 34 pages with 18 figures, submitted to A

The effect of grazing and reclamation on rodent community stability in the Alxa desert

Ecosystem stability has been of increasing interest in the past several decades as it helps predict the consequences of anthropogenic disturbances on ecosystems. A wild rodent community under reclamation and different grazing disturbances in the Alxa Desert was investigated using live trapping from 2006 to 2011. We studied the rodent community composition, community diversity, and variability of different life history strategies. These results showed that reclamation reduced rodent community stability by increasing temporal variability of community, reducing rodent community resistance as shown by decreasing dominance of KSS strategists, and increased the resistance variability of the rodent community by increasing the variability of abundance and richness for KSS strategists. Grazing reduced rodent community resilience by reducing the dominance of rRF strategists, and increased the resilience variability of the rodent community by increasing the variability of abundance and richness for rRF strategists. Those results may answer the three ecological questions about how ecosystems respond to disturbances from a diversity perspective. The ecosystems with intermediate disturbance are more stable, in other words, with higher resistance and resilience. The increase of KSS strategists means the increase of resistance of the community. The increase of rRF strategists means the increase of community resilience

Sestrin 2 Attenuates Rat Hepatic Stellate Cell (HSC) Activation and Liver Fibrosis via an mTOR/AMPK-Dependent Mechanism

Background/Aims: Sestrin 2 is associated with the pathophysiology of several diseases. The aim of this study was to investigate the effects and potential mechanisms of Sestrin 2 in rat hepatic stellate cells (HSCs) during liver fibrogenesis. Methods: In this study, Sestrin 2 protein expression was detected in rat HSC-T6 cells challenged with transforming growth factor-β (TGF-β) and in mice treated with carbon tetrachloride (CCl4), a well-known model of hepatic fibrosis. Next, HSC-T6 cells and fibrotic mice were transfected with lentivirus. The mRNA expression levels of markers of liver fibrosis [alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1)] were analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR). Cell death and proliferation were evaluated by the MTT assay, and biochemical markers of liver damage in serum [alanine transaminase (ALT) and aspartate transaminase (AST)] were also measured using a biochemical analyzer. Histopathological examination was used to evaluate the degree of liver fibrosis, and protein expression [phospho-adenosine monophosphate-activated protein kinase (p-AMPK), AMPK, phospho-mammalian target of rapamycin (p-mTOR), and mTOR] was determined by western blotting. Results: We found that Sestrin 2 was elevated in both the HSC-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of α-SMA and Col1A1, suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the ALT and AST levels as well as the α-SMA and Col1A1 protein expression in the CCl4 model of liver fibrosis. Moreover, the degree of liver fibrosis was ameliorated. Interestingly, overexpression of Sestrin 2 increased p-AMPK but decreased p-mTOR protein expression. Conclusion: Our findings indicate that Sestrin 2 may attenuate the activation of HSCs and ameliorate liver fibrosis, most likely via upregulation of AMPK phosphorylation and suppression of the mTOR signaling pathway