The genericity theorem for the essential dimension of tame stacks

Let X be a regular tame stack. If X is locally of finite type over a field, we prove that the essential dimension of X is equal to its generic essential dimension; this generalizes a previous result of P. Brosnan, Z. Reichstein and the second author. Now suppose that X is locally of finite type over a 1-dimensional noetherian local domain R with fraction field K and residue field k. We prove that edk Xk ≤ edK XK if X → Spec R is smooth and edk Xk ≤ edK XK + 1 in general

Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs

Diabetes Mellitus (DM) is a multi-factorial chronic health condition that affects a large part of population and according to the World Health Organization (WHO) the number of adults living with diabetes is expected to increase. Since type 2 diabetes mellitus (T2DM) is suffered by the majority of diabetic patients (around 90-95%) and often the mono-target therapy fails in managing blood glucose levels and the other comorbidities, this review focuses on the potential drugs acting on multi-targets involved in the treatment of this type of diabetes. In particular, the review considers the main systems directly involved in T2DM or involved in diabetes comorbidities. Agonists acting on incretin, glucagon systems, as well as on peroxisome proliferation activated receptors are considered. Inhibitors which target either aldose reductase and tyrosine phosphatase 1B or sodium glucose transporters 1 and 2 are taken into account. Moreover, with a view at the multi-target approaches for T2DM some phytocomplexes are also discussed

There is no degree map for 0-cycles on Artin stacks

We show that there is no way to define degrees of 0-cycles on Artin stacks with proper good moduli spaces so that (i) the degree of an ordinary point is non-zero, and (ii) degrees are compatible with closed immersions.Comment: 3 page

Data from docking simulations to develop an efficient strategy able to evaluate the interactions between RAGE and MDA-induced albumin adducts

This data article contains the results of docking simulations performed in order to develop a suitable in silico strategy able to assess the stability of the putative complexes between RAGE and MDA induced adducts on human albumin as experimentally determined doi: 10.1016/j.redox.2016.12.017, (Degani et al., 2017) [1]. The docking simulations involved different approaches to give a simplified yet realistic representation of the protein adducts and their environment. With increasing complexity, simulations involved the corresponding albumin tripeptides and pentapeptides with the modified residue in the central position as well as pseudo-structures which were generated by collecting the albumin residues around the adducted residue within a sphere of 7.5 \uc5 and 5 \uc5 radius. The reliability of the tested approaches was assessed by monitoring the score differences between adducted and unmodified residues. The obtained results revealed the greater predictive power of the spherical pseudo-structures compared to the simple tri- or pentapeptidic sequences thus suggesting that RAGE recognition involves residues which are spatially close to the modified residue even though not necessarily adjacent in the primary sequence

Combining molecular dynamics and docking simulations to develop targeted protocols for performing optimized virtual screening campaigns on the HTRPM8 channel

Background: There is an increasing interest in TRPM8 ligands of medicinal interest, the rational design of which can be nowadays supported by structure-based in silico studies based on the recently resolved TRPM8 structures. Methods: The study involves the generation of a reliable hTRPM8 homology model, the reliability of which was assessed by a 1.0 \u3bcs MD simulation which was also used to generate multiple receptor conformations for the following structure-based virtual screening (VS) campaigns; docking simulations utilized different programs and involved all monomers of the selected frames; the so computed docking scores were combined by consensus approaches based on the EFO algorithm. Results: The obtained models revealed very satisfactory performances; LiGen\u2122 provided the best results among the tested docking programs; the combination of docking results from the four monomers elicited a markedly beneficial effect on the computed consensus models. Conclusions: The generated hTRPM8 model appears to be amenable for successful structure-based VS studies; cross-talk modulating effects between interacting monomers on the binding sites can be accounted for by combining docking simulations as performed on all the monomers; this strategy can have general applicability for docking simulations involving quaternary protein structures with multiple identical binding pockets

Retrieval of magnetic medical microrobots from the bloodstream

Untethered magnetic microrobots hold the potential to penetrate hard-to-reach areas of the human body and to perform therapy in a controlled way. In the past decade, impressive advancements have been made in this field but the clinical adoption of magnetoresponsive microrobots is still hampered by safety issues. A tool appointed for magnetic microrobots retrieval within body fluids could enable a real paradigm change, fostering their clinical translation.By starting from the general problem to retrieve magnetic microrobots injected into the bloodstream, the authors introduce a magnetic capture model that allows to design retrieval tools for magnetic cores of different diameters (down to 10 nm) and in different environmental conditions (fluid speed up to 7 cms-1). The model robustness is demonstrated by the design and testing of a retrieval catheter. In its optimal configuration, the catheter includes 27 magnets and fits a 12 F catheter. The model provides a good prediction of capture efficiency for 250 nm magnetic particles (experimental data: 77.6%, model prediction: 65%) and a very good prediction for 500 nm particles (experimental data: 93.6%, model prediction: 94%). The results support the proposed model-based design approach, which can be extended to retrieve other magnetoresponsive agents from body compartments

Development of a direct ESI-MS method for measuring the tannin precipitation effect of proline-rich peptides and in silico studies on the proline role in tannin-protein interactions

Tannins are a heterogeneous class of polyphenols that are present in several plants and foods. Their ability to interact and precipitate proline-rich proteins leads to different effects such as astringency or antidiarrheal activity. Thus, evaluation of the tannin content in plant extracts plays a key role in understanding their potential use as pharmaceuticals and nutraceuticals. Several methods have been proposed to study tannin-protein interactions but few of them are focused on quantification. The purpose of the present work is to set up a suitable and time efficient method able to quantify the extent of tannin protein precipitation. Bradykinin, chosen as a model, was incubated with increasing concentrations of 1,2,3,4,6-penta-O-galloyl-\u3b2-D-glucose and tannic acid selected as reference of tannic compounds. Bradykinin not precipitated was determined by a mass spectrometer TSQ Quantum Ultra Triple Quadrupole (direct infusion analysis). The results were expressed as PC 50 , which is the concentration able to precipitate 50% of the protein. The type of tannin-protein interaction was evaluated also after precipitate solubilisation. The involvement of proline residues in tannin-protein interactions was confirmed by repeating the experiment using a synthesized peptide (RR-9) characterized by the same bradykinin sequence, but having proline residues replaced by glycine residues: no interaction occurred between the peptide and the tannins. Moreover, modelling studies on PGG-BK and PGG-RR-9 were performed to deeply investigate the involvement of prolines: a balance of hydrophobic and H-bond contacts stabilizes the PGG-BK cluster and the proline residues exert a crucial role thus allowing the PGG molecules to elicit a sticking effect