Incorporating biologically based models into assessments of risk from chemical contaminants

The general approach to assessment of risk from chemical contaminants in drinking water involves three steps: hazard identification, exposure assessment, and dose-response assessment. Traditionally, the risks to humans associated with different levels of a chemical have been derived from the toxic responses observed in animals. It is becoming increasingly clear, however, that further information is needed if risks to humans are to be assessed accurately. Biologically based models help clarify the dose-response relationship and reduce uncertainty.     

Nanoconfined mixed Li and Mg borohydrides as materials for solid state hydrogen storage

Several mixtures of LiBH₄ and Mg(BH₄)₂ borohydrides in different stoichiometric ratios (1:0, 2:1, 1:1, 1:2, 0:1), prepared by high energy ball milling, have been investigated with X-ray powder diffraction and thermal programmed desorption (TPD) volumetric analysis to test the dehydrogenation kinetics in correlation with the physical mixture composition. Afterwards mixed and unmixed borohydrides were dispersed on high specific surface area ball milled graphite by means of the solvent infiltration technique. BET and statistical thickness methods were used to characterize the support surface properties, and SEM micrographs gave a better understanding of the preparation techniques. It has been observed by TPD volumetric measurements that the confinement of the reactive borohydrides on the nanoporous supports leads to a lower dehydrogenation temperature compared to unsupported borohydrides. Moreover, a further decrease of the dehydrogenation temperature has been observed by increasing the specific surface area of the support and the pores volume and by using the prepared mixtures instead of pure materials. The dehydrogenation process seems to be favoured by the heterogeneous nucleation on the graphite surface of decomposition products or intermediate phases from melted liquid borohydrides.     

Effect of dry‐heat treatments on the nutritional value of maize germ

Maize germ is a by‐product of the maize milling process that is characterised by a high nutritional value. Currently, heat treatments are employed to prevent full‐fat maize germ from spoilage. The aim of this research was to study the effect of five dry‐heat treatments on the nutritional value of full‐fat maize germ. The results confirmed that after each dry‐heat treatment, the lipase activity decreases but the use of high temperatures could be detrimental for phytosterol and thiamine concentrations. The main negative effects have been observed after treatments at 140 °C for 30 min and 160 °C for 10 min. No significant difference has been observed for protein, ash or fatty acid contents. The treatment at 140 °C for 20 min resulted an optimal combination between temperature and heating time to inactivate lipase without altering deeply the nutritional value and the colour of maize germ.     

Small-Molecule Inhibitors of METTL3, the Major Human Epitranscriptomic Writer

The RNA methylase METTL3 catalyzes the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM) to the N⁶ atom of adenine. We have screened a library of 4000 analogues and derivatives of the adenosine moiety of SAM by high-throughput docking into METTL3. Two series of adenine derivatives were identified in silico, and the binding mode of six of the predicted inhibitors was validated by protein crystallography. Two compounds, one for each series, show good ligand efficiency. We propose a route for their further development into potent and selective inhibitors of METTL3.     

Molecular Dynamics Simulations of Bromodomains Reveal Binding-Site Flexibility and Multiple Binding Modes of the Natural Ligand Acetyl-Lysine

Experimental protein structures provide spatial information at the atomic level. A further dimension, time, is supplemented by molecular dynamics. Since the pioneering work on the 58-residue inhibitor of bovine pancreatic trypsin in the group of Martin Karplus in the seventies, molecular dynamics simulations have shown that the intrinsic flexibility of proteins is essential for their function. Here, we review simulation studies of bromodomains. These protein modules are involved in the recognition of acetylated lysine side chains, a post-translational modification frequently observed in histone tails. The molecular dynamics simulations have unmasked: (i) the large plasticity of the loops lining the acetyl-lysine binding site (coupled to its self-occlusion), and (ii) multiple binding modes of acetyl-lysine. These simulation results suggest that recognition of histone tails by bromodomains is modulated by their intrinsic flexibility, and further corroborate the utility of molecular dynamics in understanding (macro)molecular recognition.     

Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?

Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis.     

Austenite Grain Growth in a 2.25Cr-1Mo Vanadium-Free Steel Accounting for Zener Pinning and Solute Drag: Experimental Study and Modeling

Metallurgical and Materials Transactions A - Austenite grain size has been experimentally determined for various austenitization temperatures and times in a 2.25Cr-1Mo vanadium-free steel. Three...     

Elaboration and properties of novel biobased nanocomposites with halloysite nanotubes and thermoplastic polyurethane from dimerized fatty acids

Nanocomposites of biobased thermoplastic polyurethane (TPU) from dimer fatty acids and halloysite nanotubes (HNT) were elaborated by different melt processing routes such as direct mixing (1 step process) and masterbatch/dilution (2 steps process), at different temperatures (150 and 180 °C). Rheological and transmission electron microscopy (TEM) analyses indicated that the HNT distribution and dispersion were dependent on the processing conditions: the 2 steps process produced well dispersed nanocomposites and the masterbatch dilution at 180 °C improved the HNT distribution through the TPU. Consequently, a high reinforcement was achieved, with a 40% increase in the elastic modulus and 8 °C increase in the relaxation temperature related to the glass transition of the TPU soft segments. Furthermore, a percolated network was attained, even if a large extent of HNT breaking was observed during processing, suggesting that a synergistic effect between the HNT particles and the TPU's hard segments in the molten state occurred. Thus, HNT nanotubes can be seen as highly reinforcing nanofillers when good dispersion and distribution are achieved through the polymeric matrix.