A facile analytical method for reliable selectivity examination in cofactor NADH regeneration

This work was supported by The Royal Society (ICA\R1\180317 and IES\R3\170162).Peer reviewedPublisher PD

Assessing the environmental performance of NADH regeneration methods : A cleaner process using recyclable Pt/Fe3O4 and hydrogen

This work was supported by The Royal Society (IES\R3\170162 and RG150001) and The Binks Trust (1225).Peer reviewedPostprin

HIV testing in re-education through labour camps in Guangxi Autonomous Region, China (a cross-sectional survey)

Objective: HIV testing is mandatory in re-education-through-labour camps (laojiaosuo) in China yet no studies have reported on the process. Methods: The survey response rate was 100% although 29 detainees were excluded because they were under 18 years of age. A cross-sectional face-to-face survey was conducted in three labour camps in Guangxi, located in the south-western region of China. Results: Of the 755 detainees surveyed, 725 (96%) reported having a blood test in the labour camps of whom 493 (68%) thought this included an HIV test. 61 detainees self-reported they were HIV infected, their status confirmed by medical records, if available. Of these, 53 (87%) recalled receiving post-test HIV education, and 15 (25%) were currently receiving HIV antiretroviral therapy. Pretest education on HIV was provided to 233/725 (32%) detainees. The study further reports on detainees’ reactions and feelings towards non-disclosure and disclosure of their HIV test results in the labour camps. Conclusions: Mandatory testing is almost universal in the labour camps although a proportion of detainees were unaware that this included an HIV test. HIV test results should be disclosed to all labour camp detainees to reduce their distress of not knowing and prevent misconceptions about their HIV status. Labour camps provide another opportunity to implement universal treatment (‘Test and Treat’) to prevent the spread of HIV

Methionine Adenosyltransferase α1 Is Targeted to the Mitochondrial Matrix and Interacts with Cytochrome P450 2E1 to Lower Its Expression

Methionine adenosyltransferase α1 (MATα1, encoded by MAT1A) is responsible for hepatic biosynthesis of S‐adenosyl methionine, the principal methyl donor. MATα1 also act as a transcriptional cofactor by interacting and influencing the activity of several transcription factors. Mat1a knockout (KO) mice have increased levels of cytochrome P450 2E1 (CYP2E1), but the underlying mechanisms are unknown. The aims of the current study were to identify binding partners of MATα1 and elucidate how MATα1 regulates CYP2E1 expression. We identified binding partners of MATα1 by coimmunoprecipitation (co‐IP) and mass spectrometry. Interacting proteins were confirmed using co‐IP using recombinant proteins, liver lysates, and mitochondria. Alcoholic liver disease (ALD) samples were used to confirm relevance of our findings. We found that MATα1 negatively regulates CYP2E1 at mRNA and protein levels, with the latter being the dominant mechanism. MATα1 interacts with many proteins but with a predominance of mitochondrial proteins including CYP2E1. We found that MATα1 is present in the mitochondrial matrix of hepatocytes using immunogold electron microscopy. Mat1a KO hepatocytes had reduced mitochondrial membrane potential and higher mitochondrial reactive oxygen species, both of which were normalized when MAT1A was overexpressed. In addition, KO hepatocytes were sensitized to ethanol and tumor necrosis factor α–induced mitochondrial dysfunction. Interaction of MATα1 with CYP2E1 was direct, and this facilitated CYP2E1 methylation at R379, leading to its degradation through the proteasomal pathway. Mat1a KO livers have a reduced methylated/total CYP2E1 ratio. MATα1’s influence on mitochondrial function is largely mediated by its effect on CYP2E1 expression. Patients with ALD have reduced MATα1 levels and a decrease in methylated/total CYP2E1 ratio. Conclusion: Our findings highlight a critical role of MATα1 in regulating mitochondrial function by suppressing CYP2E1 expression at multiple levels

A Hepatic Protein, Fetuin-A, Occupies a Protective Role in Lethal Systemic Inflammation

A liver-derived protein, fetuin-A, was first purified from calf fetal serum in 1944, but its potential role in lethal systemic inflammation was previously unknown. This study aims to delineate the molecular mechanisms underlying the regulation of hepatic fetuin-A expression during lethal systemic inflammation (LSI), and investigated whether alterations of fetuin-A levels affect animal survival, and influence systemic accumulation of a late mediator, HMGB1.LSI was induced by endotoxemia or cecal ligation and puncture (CLP) in fetuin-A knock-out or wild-type mice, and animal survival rates were compared. Murine peritoneal macrophages were challenged with exogenous (endotoxin) or endogenous (IFN-γ) stimuli in the absence or presence of fetuin-A, and HMGB1 expression and release was assessed. Circulating fetuin-A levels were decreased in a time-dependent manner, starting between 26 h, reaching a nadir around 24-48 h, and returning towards base-line approximately 72 h post onset of endotoxemia or sepsis. These dynamic changes were mirrored by an early cytokine IFN-γ-mediated inhibition (up to 50-70%) of hepatic fetuin-A expression. Disruption of fetuin-A expression rendered animals more susceptible to LSI, whereas supplementation of fetuin-A (20-100 mg/kg) dose-dependently increased animal survival rates. The protection was associated with a significant reduction in systemic HMGB1 accumulation in vivo, and parallel inhibition of IFN-γ- or LPS-induced HMGB1 release in vitro.These experimental data suggest that fetuin-A is protective against lethal systemic inflammation partly by inhibiting active HMGB1 release

Observation of out-of-plane vibrations in few-layer graphene

We report the observation of layer breathing mode (LBM) vibrations in few-layer graphene (FLG) samples of thickness from 2 to 6 layers, exhibiting both Bernal (AB) and rhombohedral (ABC) stacking order. The LBM vibrations are identified using a Raman combination band lying around 1720 cm-1. From double resonance theory, we identify the feature as the LOZO' combination mode of the out-of-plane LBM (ZO') and the in-plane longitudinal optical mode (LO). The LOZO' Raman band is found to exhibit multiple peaks, with a unique line shape for each layer thickness and stacking order. These complex line shapes of the LOZO'-mode arise both from the material-dependent selection of different phonons in the double-resonance Raman process and from the detailed structure of the different branches of LBM in FLG.Comment: 17 pages, 7 figures, supplemental material include

A Novel Heat Shock Transcription Factor Family in <i>Entamoeba histolytica</i>

The HSTF is a master molecule involved in the transcriptional control of several genes during different types of stress. This transcription factor is a very conserved protein identified in different organisms from bacterial to human. <i>Entamoeba histolytica</i> is the protozoan responsible for the human amoebiasis. This parasite is exposed to different kind of stress as changes in the pH, temperature, drugs, all that situations in where the parasite needs survive. Here we identified and isolated a novel gene family of HSTFs in the protozoan parasite <i>E. histolytica</i>. Three members that we called <i>Ehhstf1</i>, <i>Ehhstf2</i> and <i>Ehhstf3</i> compose this family. Amino acid alignments and domain architecture analysis revealed that the EhHSTFs presents a conserved DNA-binding domain composed of approximately 25 residues. Interestingly this domain is shorter than the domain of the human, mouse and yeast HSTFs. Heterologous antibodies recognized four peptides of 73, 66, 47 and 23 kDa in total extracts from trophozoites growth under normal conditions. The 73, 47 and 23 kDa peptides increased their intensity when the cells were growth at 42°C by 2 h. All results together demonstrate that the amoeba present HSTFs, which may be, controlled the gene expression of this parasite under different stress situations