Induced Effects of Sodium Ions on Dopaminergic G-Protein Coupled Receptors

G-protein coupled receptors, the largest family of proteins in the human genome, are involved in many complex signal transduction pathways, typically activated by orthosteric ligand binding and subject to allosteric modulation. Dopaminergic receptors, belonging to the class A family of G-protein coupled receptors, are known to be modulated by sodium ions from an allosteric binding site, although the details of sodium effects on the receptor have not yet been described. In an effort to understand these effects, we performed microsecond scale all-atom molecular dynamics simulations on the dopaminergic D₂ receptor, finding that sodium ions enter the receptor from the extracellular side and bind at a deep allosteric site (Asp2.50). Remarkably, the presence of a sodium ion at this allosteric site induces a conformational change of the rotamer toggle switch Trp6.48 which locks in a conformation identical to the one found in the partially inactive state of the crystallized human β₂ adrenergic receptor. This study provides detailed quantitative information about binding of sodium ions in the D₂ receptor and reports a possibly important sodium-induced conformational change for modulation of D₂ receptor function.     

Cu(II) ion interaction with teicoplanin-vancomycin’s analog

Teicoplanin, a member of the “last chance” antibiotic family has a similar structure and the same mechanism of action as parent drug vancomycin, which is proved to be an effective binder of Cu(II) ions. However, the potentiometric and spectroscopic studies (UV-visible, CD, NMR) have shown that the modification of the N-terminal structure of the peptide backbone in teicoplanin affects considerably the binding ability towards Cu(II) ions. While vancomycin forms almost instantly the stable 3 N complex species involving the N-terminal and two amide nitrogen donors, in case of teicoplanin only two nitrogen donors derived from the N-terminal amino group and adjacent peptide bond are coordinated to Cu(II) ion within the whole pH range studied. The major factor influencing the binding mode is most likely the structure of the N-terminus of the peptide unit in the antibiotic ligand.     

Detection by multiplex polymerase chain reaction and typing of Chlamydia trachomatis isolates

Abstract The multiplex polymerase chain reaction (PCR) was applied for the detection of the Chlamydia trachomatis chromosome and plasmid. The multiplex PCR demonstrated a sensitivity of 0.8 fg of chlamydial DNA, corresponding to the detection of about 5 copies of the plasmid. Analysis of 195 genital specimens collected randomly from a female population, showed that the multiplex PCR is more sensitive and rapid than culturing for detecting Chlamydia trachomatis . Moreover, sequencing of the II variable domain of the ompl gene, directly from DNA of the clinical specimens, appears to be a simple and rapid method for determining serovar isolates.     

The effect of binding divalent metal ions on the conformation of human angiotensin-II in solution as probed by nuclear and electron paramagnetic resonance investigations

The interaction between human angiotensin-II and Mn(II) ions in water solution has been deline-ated by nmr and esr experiments. A pH-dependent binding interaction with the imidazole moiety of His 6 has been shown, ratifying the suggestion that His 6 is involved in intramolecular structuring within the peptide molecule.     

Weather-Related Flood and Landslide Damage: A Risk Index for Italian Regions

The frequency of natural hazards has been increasing in the last decades in Europe and specifically in Mediterranean regions due to climate change. For example heavy precipitation events can lead to disasters through the interaction with exposed and vulnerable people and natural systems. It is therefore necessary a prevention planning to preserve human health and to reduce economic losses. Prevention should mainly be carried out with more adequate land management, also supported by the development of an appropriate risk prediction tool based on weather forecasts. The main aim of this study is to investigate the relationship between weather types (WTs) and the frequency of floods and landslides that have caused damage to properties, personal injuries, or deaths in the Italian regions over recent decades. In particular, a specific risk index (WT-FLARI) for each WT was developed at national and regional scale. This study has identified a specific risk index associated with each weather type, calibrated for each Italian region and applicable to both annual and seasonal levels. The risk index represents the seasonal and annual vulnerability of each Italian region and indicates that additional preventive actions are necessary for some regions. The results of this study represent a good starting point towards the development of a tool to support policy-makers, local authorities and health agencies in planning actions, mainly in the medium to long term, aimed at the weather damage reduction that represents an important issue of the World Meteorological Organization mission.     

The water proton spin-lattice relaxation times in virus-infected cells.

The water proton spin-lattice relaxation times in HEp-2 cell cultures were determined immediately after 1 h of polio-virus adsorption. The shortening of the water T1 was closely related to the multiplicity of infection, allowing direct inspections of the virus--cell interaction since the first steps of the infectious cycle. Virus-induced structural and conformational changes of cell constituents were suggested to be detectable by NMR investigation of cell water.