The Alzheimer beta-peptide shows temperature-dependent transitions between left-handed 3-helix, beta-strand and random coil secondary structures

The temperature-induced structural transitions of the full length Alzheimer amyloid beta-peptide [A(beta)(1-40) peptide] and fragments of it were studied using CD and 1H NMR spectroscopy. The full length peptide undergoes an overall transition from a state with a prominent population of left-handed 3(1) (polyproline II; PII)-helix at 0 degrees C to a random coil state at 60 degrees C, with an average DeltaH of 6.8 +/- 1.4 kJ.mol(-1) per residue, obtained by fitting a Zimm-Bragg model to the CD data. The transition is noncooperative for the shortest N-terminal fragment A(beta)(1-9) and weakly cooperative for A(beta)(1-40) and the longer fragments. By analysing the temperature-dependent 3J(HNH(alpha)) couplings and hydrodynamic radii obtained by NMR for A(beta)(1-9) and A(beta)(12-28), we found that the structure transition includes more than two states. The N-terminal hydrophilic A(beta)(1-9) populates PII-like conformations at 0 degrees C, then when the temperature increases, conformations with dihedral angles moving towards beta-strand at 20 degrees C, and approaches random coil at 60 degrees C. The residues in the central hydrophobic (18-28) segment show varying behaviour, but there is a significant contribution of beta-strand-like conformations at all temperatures below 20 degrees C. The C-terminal (29-40) segment was not studied by NMR, but from CD difference spectra we concluded that it is mainly in a random coil conformation at all studied temperatures. These results on structural preferences and transitions of the segments in the monomeric form of A(beta) may be related to the processes leading to the aggregation and formation of fibrils in the Alzheimer plaques.     

Children’s Respiratory Health After an Efficient Biomass Stove (Patsari) Intervention

EcoHealth - Household use of fuelwood represents a socio-ecological condition with important health effects mainly in rural areas from developing countries. One approach to tackle this problem has...     

ESR spectral analysis of the molecular motion of spin labels in lipid bilayers and membranes based on a model in terms of two angular motional parameters and rotational correlation times

Electron spin resonance (ESR) spectral line shapes are calculated for a nitroxide spin-labeled molecule undergoing rapid restricted rotations (twisting) about its long molecular axis while simultaneously tumbling within a cone. Explicit expressions are derived for the hyperfine splittings and $\text{g-}\text{values}$, as well as for the secular contributions to the motionally modulated linewidths. The present model is useful for analyzing the restricted twisting and tumbling motions, and rotational correlation times, of spin-labeled molecules in bilayers. Simulated spectra compare well with experimental spectra of lecithin bilayers marked with cholestane spin label, over a wide temperature range.     

Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis

Molecular and Cellular Biochemistry - Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed...     

Molecular and bioassay-based detection of Toxoplasma gondii oocyst uptake by mussels (Mytilus galloprovincialis)

Toxoplasma gondii is associated with morbidity and mortality in a variety of marine mammals, including fatal meningoencephalitis in the southern sea otter (Enhydra lutris nereis). The source(s) of T. gondii infection and routes of transmission in the marine environment are unknown. We hypothesise that filter-feeding marine bivalve shellfish serve as paratenic hosts by assimilation and concentration of infective T. gondii oocysts and their subsequent predation by southern sea otters is a source of infection for these animals. We developed a TaqMan PCR assay for detection of T. gondii ssrRNA and evaluated its usefulness for the detection of T. gondii in experimentally exposed mussels (Mytilus galloprovincialis) under laboratory conditions. Toxoplasma gondii-specific ssrRNA was detected in mussels as long as 21 days post-exposure to T. gondii oocysts. Parasite ssrRNA was most often detected in digestive gland homogenate (31 of 35, i.e. 89%) compared with haemolymph or gill homogenates. Parasite infectivity was confirmed using a mouse bioassay. Infections were detected in mice inoculated with any one of the mussel sample preparations (haemolymph, gill, or digestive gland), but only digestive gland samples remained bioassay-positive for at least 3 days post-exposure. For each time point, the total proportion of mice inoculated with each of the different tissues from T. gondii-exposed mussels was similar to the proportion of exposed mussels from the same treatment groups that were positive via TaqMan PCR. The TaqMan PCR assay described here is now being tested in field sampling of free-living invertebrate prey species from high-risk coastal locations where T. gondii infections are prevalent in southern sea otters.     

Biodegradation and biotransformation of explosives

Explosives now contaminate millions of hectares of land in the US alone, with global levels of contamination difficult to fully assess. Understanding the biology behind the metabolism of these toxic compounds by microorganisms and plants is imperative for managing these pollutants in the environment. Towards this aim, recent studies have identified, and are now characterizing, plant genes involved in 2,4,6-trinitrotoluene detoxification and the biochemical pathways of nitramine degradation in microorganisms. A key scientific goal continues to be identification of enzymes capable of degrading 2,4,6-trinitrotoluene and this still remains elusive, although recent reports give insights into the origin of nitrite released during biotransformation of this major contaminant. Promising phytoremediation research using transgenic model plant systems has now been transferred to poplar, a species with field applicability.