A possible role of HMGB1 in DNA demethylation in CD4+ T Cells from patients with systemic lupus erythematosus

The aberrant activity of CD4(+) T cells in patients with systemic lupus erythematosus (SLE) is associated with DNA hypomethylation of the regulatory regions in CD11a and CD70 genes. Our previous studies demonstrated that Gadd45a contributes to the development of SLE by promoting DNA demethylation in CD4(+) T cells. In this study, we identified proteins that bind to Gadd45a in CD4(+) T cells during SLE flare by using the method of co-immunoprecipitation and mass spectrometry, High mobility group box protein 1 (HMGB1) is one of identified proteins. Furthermore, gene and protein expression of HMGB1 was significantly increased in SLE CD4(+) T cells compared to controls, and HMGB1 mRNA was correlated with CD11a and CD70 mRNA. A significant, positive correlation was found between HMGB1 mRNA and SLEDAI for SLE patients. Our data demonstrate that HMGB1 binds to Gadd45a and may be involved in DNA demethylation in CD4(+) T cells during lupus flare.published_or_final_versio

Phylogenomic Analyses and Reclassification of Species within the Genus Tsukamurella: Insights to Species Definition in the Post-genomic Era

published_or_final_versio

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society

The interactive effects of selenomethionine and methylmercury on their absorption, disposition, and elimination in juvenile white sturgeon

[[abstract]]Selenium (Se) and mercury (Hg) are prevalent pollutants of industrialized watersheds. However, when co-administered, Se has protective effects on organisms from Hg. The mechanism is not fully understood, but it is thought that Se reduces Hg availability, either by forming biologically inert complexes and/or associating with selenoproteins. Despite concerns with aquatic contaminations, relatively little information is available on the interaction in aquatic organisms. In the present study, the interactive effects of Se and Hg on their absorption, disposition, and elimination were examined in juvenile white sturgeon, a benthic fish species at high risk to exposures of both contaminants. Selenium and Hg were provided as l-selenomethionine (SeMet) and methylmercury (MeHg), respectively. Groups of 10 sturgeon were orally intubated with a single dose of either 0 (control), SeMet (500 μg Se/kg body weight; BW), MeHg (850 μg Hg/kg BW), or their combination (Se/Hg; 500 μg Se/kg and 850 μg Hg/kg BW). The blood was repeatedly sampled and urine collected from the fish, over a 48 h post intubation period. At 48 h, the fish were sacrificed for Se and Hg tissue concentration and distribution. The co-administration of SeMet and MeHg significantly (p < 0.05) lowered blood concentrations of both Se and Hg and tissue Se concentrations. Similarly, assimilation of Se and Hg was also reduced significantly. The interaction has a more quantitative effect on Se metabolism because the reduction in the overall tissue Se is a consequence of reduced Se absorption at the gut and not from the metabolic effects after absorption. In contrast, given the pulse increase in blood Hg concentration, tissue redistribution, and increased urinary elimination, the interactive effect on tissue Hg concentration is likely to be post-absorption. Even in the absence of exogenous SeMet, Se and Hg co-accumulated in tissue at a Se:Hg molar ratio greater than 1. Thus, similar to mammals, maintaining at least a 1:1 molar ratio of Se and Hg is of great physiological importance in the white sturgeon. Interestingly, SeMet did not divert Hg from the brain. Allocation of Se from the kidneys may have occurred in order to maintain the high Se:Hg molar ratios in the brain of white sturgeon. In the current study, the combined use of kinetic analysis and that of the conventional approach of measuring tissue concentration changes provided a comprehensive understanding of the interactive effect of SeMet and MeHg on their respective metabolic processes in juvenile white sturgeo

Absorption, distribution, and elimination of graded oral doses of methylmercury in juvenile white sturgeon

[[abstract]]Mercury (Hg) is toxic and is released into the environment from a wide variety of anthropogenic sources. Methylmercury (MeHg), a product of microbial methylation, enables rapid Hg bioaccumulation and biomagnification in the biota. Methylmercury is sequestered and made available to the rest of the biota through the benthic-detrital component leading to the high risk of exposure to benthic fish species, such as white sturgeon (Acipenser transmontanus). In the present study, a combined technique of stomach intubation, dorsal aorta cannulation, and urinary catheterization was utilized to characterize the absorption, distribution, and elimination of Hg in white sturgeon over a 48. h exposure. Mercury, as methylmercury chloride, at either 0, 250, 500, or 1000 μg. Hg/kg body weight, was orally intubated into white sturgeon, in groups of five. The blood was repeatedly sampled and urine collected from the fish over the 48. h post intubation period, and at 48. h, the fish were sacrificed for Hg tissue concentration and distribution determinations. The fractional rate of absorption (K), blood Hg concentration (μg/ml), tissue concentration (μg/g dry weight) and distribution (%), and urinary Hg elimination flux (μg/kg/h) are significantly different (p kidney > spleen > gill > heart > liver > brain > white muscle and remaining whole body. At 48. h, Hg was found to be preferentially distributed to metabolically active tissues. Digestibility is highest at the lowest MeHg dose. Measurable urinary Hg was observed in the fish treated with the highest MeHg dose, and a significant increase in the elimination flux was observed between 3 and 12. h post intubation

Clustering of Schizotypal Features in Unaffected First-Degree Relatives of Schizophrenia Patients

Meehl conceptualized schizotypy as the phenotypic manifestations of a neural integrative defect resulting from a schizophrenia diathesis. The majority of schizotypy studies recruited subjects from the general population and revealed a multidimensional construct. This 2-phase investigation first examined the clustering of schizotypy in 194 unaffected relatives of schizophrenia patients using the Chapman Psychosis Proneness scales and then directly compared the cognitive profiles of negative schizotypal individuals and positive schizotypal individuals with schizophrenia patients and controls. In the first phase, cluster analysis categorized 194 unaffected relatives of schizophrenia patients into positive schizotypy (n = 33), negative schizotypy (n = 66), mixed schizotypy (n = 27), and low schizotypy (n = 64). Positive schizotypal participants showed more self-report pleasure experiences than negative schizotypal participants, replicating earlier cluster analytic findings. In the second phase, 27 negative schizotypal individuals, 18 positive schizotypal individuals, 19 schizophrenia patients, and 29 controls were recruited. Although the groups were matched in terms of age, gender, and IQ, they differed significantly in cognitive profiles. While schizophrenia patients exhibited the broadest cognitive impairments, negative schizotypal participants exhibited visual memory, working memory, and verbal fluency impairments, and positive schizotypal participants exhibited logical memory, visual memory, working memory, and theory-of-mind impairments. Among people with familial risk of schizophrenia, individuals exhibiting positive rather than negative schizotypal features resembled schizophrenia patients in cognitive profiles. Using the psychometric-familial method to identify schizotypy, our findings support the heterogeneity of schizotypy as well as the potential utility of the positive schizotypy dimension in genetically high-risk individuals to predict the risk of developing schizophrenia.No Full Tex

Molecular wheels of ruthenium and osmium with bridging chalcogenolate ligands: edge-shared-octahedron structures and metal-ion binding

Inventing new wheels: Reaction of [M 3(CO) 12] (M=Ru, Os) with 4-RC 6H 4SH afforded [{M(S-4-RC 6H 4) 2(CO) 2} 8] (R=H; I) or [{M(S-4-RC 6H 4) 2(CO) 2} 6] (R=Me, iPr; II; see scheme), all of which have been structurally characterized. The octamers I are unique metal molecular wheels featuring skew-edge-shared octahedra with a central planar M 8 octagon. [{Ru(S-4-iPrC 6H 4) 2(CO) 2} 6] selectively binds a Cu + or Ag + ion to form [M′{Ru(S(4-iPr- C 6H 4)) 2(CO) 2} 6] + (III). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.link_to_subscribed_fulltex

Trapping reactive metal-carbene complexes by a bis-pocket porphyrin: X-ray crystal structures of Ru=CHCO 2et and trans-[Ru(CHR)(CO)] species and highly selective carbenoid transfer reaction

What's in my pockets? By employing Suslick's bis-pocket porphyrin (ttppp), a reactive M=CHCO 2Et complex and a trans-[M(CHR)(CO)] (M = Ru) complex have been structurally characterized by X-ray crystal analysis. The sterically encumbered ttppp ligand has a significant impact on both the diastereoselectivity and chemoselectivity in metalloporphyrin-catalyzed reactions of ethyl diazoacetate with conjugated aryl dienes. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.link_to_subscribed_fulltex