Identification of the vibrational marker of tyrosine cation radical using ultrafast transient infrared spectroscopy of flavoprotein systems

Tryptophan and tyrosine radical intermediates play crucial roles in many biological charge transfer processes. Particularly in flavoprotein photochemistry, short-lived reaction intermediates can be studied by the complementary techniques of ultrafast visible and infrared spectroscopy. The spectral properties of tryptophan radical are well established, and the formation of neutral tyrosine radicals has been observed in many biological processes. However, only recently, the formation of a cation tyrosine radical was observed by transient visible spectroscopy in a few systems. Here, we assigned the infrared vibrational markers of the cationic and neutral tyrosine radical at 1483 and 1502 cm−1 (in deuterated buffer), respectively, in a variant of the bacterial methyl transferase TrmFO, and in the native glucose oxidase. In addition, we studied a mutant of AppABLUF blue-light sensor domain from Rhodobacter sphaeroides in which only a direct formation of the neutral radical was observed. Our studies highlight the exquisite sensitivity of transient infrared spectroscopy to low concentrations of specific radicals

Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: Structural and mechanistic insights

Phosphorylation adjacent to nuclear localization signals (NLSs) is involved in the regulation of nucleocytoplasmic transport. The nuclear isoform of human dUTPase, an enzyme that is essential for genomic integrity, has been shown to be phosphorylated on a serine residue (Ser11) in the vicinity of its nuclear localization signal; however, the effect of this phosphorylation is not yet known. To investigate this issue, an integrated set of structural, molecular and cell biological methods were employed. It is shown that NLS-adjacent phosphorylation of dUTPase occurs during the M phase of the cell cycle. Comparison of the cellular distribution of wild-type dUTPase with those of hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus. Isothermal titration microcalorimetry and additional independent biophysical techniques show that the interaction between dUTPase and importin-alpha, the karyopherin molecule responsible for 'classical' NLS binding, is weakened significantly in the case of the S11E hyperphosphorylation-mimicking mutant. The structures of the importin-alpha-wild-type and the importin-alpha-hyperphosphorylation-mimicking dUTPase NLS complexes provide structural insights into the molecular details of this regulation. The data indicate that the posttranslational modification of dUTPase during the cell cycle may modulate the nuclear availability of this enzyme

Hypertriglyceridemia-induced acute pancreatitis: A prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases

Background Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are inadequate and contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. Methods AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (Peer reviewe

In middle-aged and old obese patients, training intervention reduces leptin level: A meta-analysis

BACKGROUND: Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine. OBJECTIVES: We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present) were also evaluated. DATA SOURCES: 3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses. STUDY ELIGIBILITY CRITERIA: Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age) overweight or obese (body mass index above 25) individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values. STATISTICAL METHODS: We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger's test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used. RESULTS: Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight loss, indicated by unchanged serum adiponectin levels. Resistance training appears to be more efficient in reducing blood leptin level than aerobic training alone. CONCLUSIONS: Physical training, especially resistance training successfully reduces hyperleptinemia even without diet or major weight loss

A Multicenter, International Cohort Analysis of 1435 Cases to Support Clinical Trial Design in Acute Pancreatitis

L

Az endoszkópos regiszterek szerepe a minőségi betegellátásban. Az új magyar Endoszkópos Retrográd Cholangiopancreatographia (ERCP) Regiszter első eredményei

INTRODUCTION: The continuous monitoring of quality indicators in gastrointestinal endoscopy has become an essential requirement nowadays. Most of these data cannot be extracted from the currently used free text reports, therefore a structured web-based data-collecting system was developed to record the indicators of pancreatobiliary endoscopy. AIM: A structured data-collecting system, the ERCP Registry, was initiated to monitor endoscopic retrograde cholangiopancreatography (ERCP) examinations prospectively, and to verify its usability. METHOD: From January 2017, all ERCPs performed at the First Department of Medicine, University of Pecs, have been registered in the database. In the first year, the detailed data of 595 examinations were entered into the registry. After processing these data, the testing period of the registry is now finished. RESULTS: On 447 patients, 595 ERCPs were performed. The success rate of cannulation is 93.8% if all cases are considered. Difficult biliary access was noted in 32.1% of patients with native papilla, and successful cannulation was achieved in 81.0% of these cases during the first procedure. Post-ERCP pancreatitis was observed in 13 cases (2.2%), clinically significant post-papillotomy bleeding was registered in 2 cases (0.3%), while 27 patients (4.5%) developed temporary hypoxia during the procedure. 30-day follow-up was successful in 75.5% of the cases to detect late complications. All of the quality indicators determined by the American Society of Gastrointestinal Endoscopy (ASGE) were possible to monitor with the help of the registry. Our center already complies with most of these criteria. CONCLUSIONS: Continuous monitoring of the quality indicators of endoscopic interventions are not supported by the current hospital information system but it became possible with our registry. The ERCP Registry is a suitable tool to detect the quality of patient care and also useful for clinical research. Several endoscopy units have joined already this initiative and it is open for further centres through our web page ( https://tm-centre.org/hu/regiszterek/ercp-regiszter/ ). Orv Hetil. 2018; 159(37): 1506-1515