The features of the spatial structure of the gramicidine A-cesium complex

AbstractEarlier obtained two-dimensional 1H-NMR spectroscopy data were used to analyze the spatial structure and conformational mobility of the double right ↑↓ ππLD7.2 helix of the complex formed by gramicidine A and Cs+ ions in an organic solvent (a chloroform-methanol mixture). Analysis of the experimental data permitted the determination of a set of conformations for each of the high-mobility residue side chains in the solution. The energy refinement of the most probable conformation of the double right ↑↓ ππLD7.2 helix was made and conformational rearrangements of the tryptophan residue side chain were studied in detail

Differential diagnostic utilities of combined testing for islet cell antibody, glutamic acid decarboxylase antibody, and tyrosine phosphatase antibody

Background. Beta-cell antibody tests are used for the differential diagnosis of diabetes mellitus. They permit to discriminate between the type 1 diabetes (T1D) and non-autoimmune diabetes types. To choose an appropriate test for ruling in or ruling out the T1D a physician needs to know how conclusive test results are. The most powerful estimate of test conclusiveness is its likelihood ratio (LHR). The higher LHR of a positive result (LHR+), the more posttest probability of T1D; the lower LHR of a negative result (LHR), the less posttest probability of T1D. Aims. To compare conclusiveness of single and combined tests for antibodies to islet cells (ICA), glutamate decarboxylase (GADA), and tyrosine phosphatase IA-2 (IA-2A), and to evaluate posttest probabilities of T1D at various pretest probabilities. Methods. All antibodies were tested in parallel in 169 children and adolescents with a new-onset T1D, and in 169 persons without this disease. ICA, GADA, and IA-2A were determined by indirect immunofluorescence, radioimmune assay, and ELISA, respectively. LHR+ and LHR were calculated with the MedCalc Statistical Software. Posttest T1D probabilities were calculated from Bayes theorem-based equation. Results. Among single tests, an ICA test had the greatest LHR+ and the smallest LHR, and consequently was the most reliable either for ruling in or ruling out the T1D. Among test combinations, an ICAGADA combination had the greatest LHR+ and was the most suitable for T1D confirmation. The triple combination ICAGADAIA-2A had the smallest LHR and was the most suitable for T1D exclusion. Conclusions. In the differential diagnosis of diabetes, the most appropriate test for ruling in the T1D is the double combination ICAGADA. With both antibodies positive, this combination provides the highest posttest T1D probabilities at any pretest probability. The most appropriate test for ruling out the T1D is the triple combination ICAGADAIA-2A. With all three antibodies negative, this combination provides the lowest posttest T1D probabilities

Bis(dicarbollide) Complexes of Transition Metals as a Platform for Molecular Switches. Study of Complexation of 8,8′-Bis(methylsulfanyl) Derivatives of Cobalt and Iron Bis(dicarbollides)

Complexation of the 8,8′-bis(methylsulfanyl) derivatives of cobalt and iron bis(dicarbollides) [8,8′-(MeS)2-3,3′-M(1,2-C2B9H10)2]− (M = Co, Fe) with copper, silver, palladium and rhodium leads to the formation of the corresponding chelate complexes, which is accompanied by a transition from the transoid to the cisoid conformation of the bis(dicarbollide) complex. This transition is reversible and can be used in design of coordination-driven molecular switches based on transition metal bis(dicarbollide) complexes. The solid-state structures of {(Ph3P)ClPd[8,8′- (MeS)2-3,3′-Co(1,2-C2B9H10)2-κ2-S,S′]} and {(COD)Rh[8,8′-(MeS)2-3,3′-Co(1,2-C2B9H10)2-κ2-S,S′]} were determined by single crystal X-ray diffraction

Monogenic diabetes associated with PAX4 gene mutations (MODY9): first description in Russia

Maturity-onset diabetes of the young (MODY) is a heterogeneous group of disorders characterised by autosomal dominant type of inheritance and caused by genetic defects leading to dysfunction of pancreatic beta-cells. To date, at least 13 subtypes of MODY have been described in the literature, the most frequent of which are MODY types 13. MODY2 and MODY3 are the most prevalent subtypes, and were previously described in our country, Russia. Several cases of rare MODY subtypes were subsequently described in the Russian literature. The current report is the first in the Russian literature to present clinical and molecular genetic characteristics of two cases of another rare MODY subtypeMODY9. This type of MODY is associated with mutations in the PAX4 gene, which encodes transcription factor PAX4, one of the factors essential for pancreatic beta-cell differentiation. Molecular genetic analysis was performed using next-generation sequencing, a new method recently applied to verify monogenic diseases and, in particular, MODY. This study reports a novel mutation in the PAX4 gene in MODY patients

Diagnostic value of islet autoantibody assays practised in Russia. 1. Classic immunofluorescence islet cell antibody assay, immunoradiometric glutamic acid decarboxylase antibody assay, and ELISA tyrosine phosphatase antibody and insulin antibody assays

Objective. To estimate performance characteristics and diagnostic value of immunofluorescent islet cell antibody (ICA) assay, immunoradiometric glutamic acid decarboxylase antibody (GADA) assay, and ELISA tyrosine phosphatase IA-2 antibody (IA-2A) and insulin antibody (IA) assays. Research Design and Methods. Antibodies were tested in 438 children and adolescents with newly diagnosed diabetes mellitus (DM) type 1, and in 891 subjects without DM type 1. ICA were determined by the classic indirect immunofluorescent method recommended by the Juvenile Diabetes Foundation International, GADA were determined with the Immunotech IRMA Anti-GAD kit, and IA-2A and IA were determined with Medizym Anti-IA2 and Orgentec Anti-Insulin ELISA kits, respectively. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the tests were estimated with contingency tables. Diagnostic accuracy was estimated from areas under receiver operating curves (AUC). Results. ICA test was of the greatest diagnostic value (Se=88%, Sp=96%, PPV=96%, NPV=94%, AUC=0,94), followed by IA-2A (Se=66%, Sp=98%, PPV=98%, NPV=59%, AUC=0,82) and GADA (Se=73%, Sp=84%, PPV=75%, NPV=83%, AUC=0,79). IA test exhibited a very low Se (4,3%) and lacked diagnostic accuracy (AUC=0,5). Conclusions. We recommend to use ICA, IA-2A and GADA tests surveyed in our study for diagnosis of DM type 1 and differential diagnosis of DM. We don’t recommend IA testing with an Orgentec Anti-Insulin ELISA kit for usage in clinical practice