The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

Nomograms of Iranian fetal middle cerebral artery Doppler waveforms and uniformity of their pattern with other populations' nomograms

<p>Abstract</p> <p>Background</p> <p>Doppler flow velocity waveform analysis of fetal vessels is one of the main methods for evaluating fetus health before labor. Doppler waves of middle cerebral artery (MCA) can predict most of the at risk fetuses in high risk pregnancies. In this study, we tried to obtain normal values and their nomograms during pregnancy for Doppler flow velocity indices of MCA in 20 – 40 weeks of normal pregnancies in Iranian population and compare their pattern with other countries' nomograms.</p> <p>Methods</p> <p>During present descriptive cross-sectional study, 1037 normal pregnant women with 20^th–40^thweek gestational age were underwent MCA Doppler study. All cases were studied by gray scale ultrasonography initially and Doppler of MCA afterward. Resistive Index (RI), Pulsative Index (PI), Systolic/Diastolic ratio (S/D ratio), and Peak Systolic Velocity (PSV) values of MCA were determined for all of the subjects.</p> <p>Results</p> <p>Results of present study showed that RI, PI, S/D ratio values of MCA decreased with parabolic pattern and PSV value increased with simple pattern, as gestational age progressed. These changes were statistically significant (P = 0.000 for all of indices) and more characteristic during late weeks of pregnancy.</p> <p>Conclusion</p> <p>Values of RI, PI and S/D ratio indices reduced toward the end of pregnancy, but PSV increased. Despite the trivial difference, nomograms of various Doppler indices in present study have similar pattern with other studies.</p

ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phosholipase C gamma 1 and protein kinase C pathways

This work was supported by the German Research Foundation DFG (SFB 850/B6) and by the Fritz-Thyssen foundation (Az.10.14.2.150) to C.-W.F and the Medical Research Council (MR/L010402/1) to D.P.K

Japanese Encephalitis—A Pathological and Clinical Perspective

Japanese encephalitis (JE) is the leading form of viral encephalitis in Asia. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. JEV is endemic to many parts of Asia, where periodic outbreaks take hundreds of lives. Despite the catastrophes it causes, JE has remained a tropical disease uncommon in the West. With rapid globalization and climatic shift, JEV has started to emerge in areas where the threat was previously unknown. Scientific evidence predicts that JEV will soon become a global pathogen and cause of worldwide pandemics. Although some research documents JEV pathogenesis and drug discovery, worldwide awareness of the need for extensive research to deal with JE is still lacking. This review focuses on the exigency of developing a worldwide effort to acknowledge the prime importance of performing an extensive study of this thus far neglected tropical viral disease. This review also outlines the pathogenesis, the scientific efforts channeled into develop a therapy, and the outlook for a possible future breakthrough addressing this killer disease

Transplantation of a hydrogen bonding network from West Nile virus protease onto Dengue-2 protease improves catalytic efficiency and sheds light on substrate specificity

10.1093/protein/gzs049Protein Engineering, Design and Selection2512843-850PEDS

The active essential CFNS3d protein complex.

The NS2B-NS3 protease complex is essential for the replication of dengue virus, which is the etiologic agent of dengue and hemorrhagic fevers, diseases that are a burden for the tropical and subtropical areas of the world. The active form of the NS3 protease linked to the 40 residues of the NS2B cofactor shows highly flexible and disordered region(s) that are responsible for its high propensity to aggregate at the concentrations necessary for NMR spectroscopy studies or for crystallization. Limited proteolysis of this active form of the protease enabled us to obtain a folded and new essential form of the NS2B-NS3 protease complex. We found that the region from residues D50 to E80 of NS2B interacts directly and strongly with the NS3 protease domain. The proteolytic activity of the noncovalently binding complex was determined by a rapid and continuous fluorescence resonance energy transfer activity assay using a depsipeptide substrate. The new protein-cofactor complex obtained, encompassing the NS2B fragment (D50-E80) and the NS3 protease, shows proteolytic activity. The H-1-N-15-heteronuclear single quantum coherence spectrum of the isotopically enriched protein complex shows good cross-peak dispersion; this is indicative of a stable folded state. Our results significantly complement the X-ray structure of the NS2B-NS3pro complex published recently. Moreover, these results open the way to performing direct structural and interaction studies in solution on a new active NS2B-NS3pro complex with libraries of substrates and inhibitors in order to identify new drugs that prevent viral polyprotein processing

Probing the substrate specificity of the dengue virus type 2 NS3 serine protease by using internally quenched fluorescent peptides

The NS3 (dengue virus non-structural protein 3) serine protease of dengue virus is an essential component for virus maturation, thus representing an attractive target for the development of antiviral drugs directed at the inhibition of polyprotein processing. In the present study, we have investigated determinants of substrate specificity of the dengue virus NS3 protease by using internally quenched fluorogenic peptides containing Abz (o-aminobenzoic acid; synonymous to anthranilic acid) and 3-nitrotyrosine (nY) representing both native and chimaeric polyprotein cleavage site sequences. By using this combinatorial approach, we were able to describe the substrate preferences and determinants of specificity for the dengue virus NS2B(H)–NS3pro protease. Kinetic parameters (k(cat)/K(m)) for the hydrolysis of peptide substrates with systematic truncations at the prime and non-prime side revealed a length preference for peptides spanning the P4–P3′ residues, and the peptide Abz-RRRRSAGnY-amide based on the dengue virus capsid protein processing site was discovered as a novel and efficient substrate of the NS3 protease (k(cat)/K(m)=11087 M(−1)·s(−1)). Thus, while having confirmed the exclusive preference of the NS3 protease for basic residues at the P1 and P2 positions, we have also shown that the presence of basic amino acids at the P3 and P4 positions is a major specificity-determining feature of the dengue virus NS3 protease. Investigation of the substrate peptide Abz-KKQRAGVLnY-amide based on the NS2B/NS3 polyprotein cleavage site demonstrated an unexpected high degree of cleavage efficiency. Chimaeric peptides with combinations of prime and non-prime sequences spanning the P4–P4′ positions of all five native polyprotein cleavage sites revealed a preponderant effect of non-prime side residues on the K(m) values, whereas variations at the prime side sequences had higher impact on k(cat)