Poly(2-oxazoline)s as materials for biomedical applications.

The conjunction of polymers and medicine enables the development of new materials that display novel features, opening new ways to administrate drugs, design implants and biosensors, to deliver pharmaceuticals impacting cancer treatment, regenerative medicine or gene therapy. Poly(2-oxazoline)s (POx) constitute a polymer class with exceptional properties for their use in a plethora of different biomedical applications and are proposed as a versatile platform for the development of new medicine. Herein, a global vision of POx as a platform for novel biomaterials is offered, by highlighting the recent advances and breakthroughs in this fascinating field.

Coarse architecture of the transient receptor potential vanilloid 1 (TRPV1) ion channel determined by fluorescence resonance energy transfer.

The transient receptor potential vanilloid 1 ion channel is responsible for the perception of high temperatures and low extracellular pH, and it is also involved in the response to some pungent compounds. Importantly, it is also associated with the perception of pain and noxious stimuli. Here, we attempt to discern the molecular organization and location of the N and C termini of the transient receptor potential vanilloid 1 ion channel by measuring FRET between genetically attached enhanced yellow and cyan fluorescent protein to the N or C terminus of the channel protein, expressed in transfected HEK 293 cells or Xenopus laevis oocytes.

Functional genomics indicates yeast requires Golgi/ER transport, chromatin remodeling, and DNA repair for low dose DMSO tolerance.

Dimethyl sulfoxide (DMSO) is frequently utilized as a solvent in toxicological and pharmaceutical investigations. It is therefore important to establish the cellular and molecular targets of DMSO in order to differentiate its intrinsic effects from those elicited by a compound of interest. We performed a genome-wide functional screen in Saccharomyces cerevisiae to identify deletion mutants exhibiting sensitivity to 1% DMSO, a concentration standard to yeast chemical profiling studies.

Cationic Ring-Opening Polymerization of 2-Propyl-2-oxazolines: Understanding Structural Effects on Polymerization Behavior Based on Molecular Modeling.

The surprising difference in the cationic ring-opening polymerization rate of 2-cyclopropyl-2-oxazoline versus 2--propyl-2-oxazoline and 2-isopropyl-2-oxazoline was investigated both experimentally and theoretically. The polymerization kinetics of all three oxazolines were experimentally measured in acetonitrile at 140 °C, and the polymerization rate constant () was found to decrease in the order -PropOx > -PropOx > -PropOx. Theoretical free energy calculations confirmed the trend for , and a set of DFT-based reactivity descriptors, electrostatics, and frontier molecular orbitals were studied to detect the factors controlling this peculiar behavior.

Solvent-dependent reversible ligand exchange in nickel complexes of a monosulfide bis(diphenylphosphino)(N-thioether)amine.

The coordination chemistry of the DPPA-type functional phosphine bis(diphenylphosphino)(N-thioether)amine N(PPh2)2(CH2)3SMe () and its monosulfide derivative, (Ph2P)N{P(S)Ph2}(CH2)3SMe (1·S), towards Ni(II) precursors has been investigated. The crystal structures of N{P(S)Ph2}2(CH2)3SMe (1·S2), [NiCl2{(Ph2P)2N(CH2)3SMe-P,P}] (2), [NiCl2((Ph2P)N{P(S)Ph2}(CH2)3SMe-P,S)] (3), [Ni((Ph2P)N{P(S)Ph2}(CH2)3SMe-P,S)2]NiCl4 (3'), [Ni((Ph2P)N{P(S)Ph2}(CH2)3SMe-P,S)2](BF4)2 (4), and [Ni((Ph2P)NH{P(S)Ph2}-P,S)2]Cl2 (5) have been determined by single-crystal X-ray diffraction. In all of the complexes with the hybrid ligand 1·S, P,S-chelation to the Ni(II) center is observed.

Metformin's performance in in vitro and in vivo genetic toxicology studies.

Metformin is a hypoglycemiant drug prescribed for the treatment and control of the type 2 diabetes mellitus. Recently, the potential efficacy of this antidiabetic drug as an anticancer agent has been demonstrated in various mammalian cancer cells. This report evaluates the mutagenic as well as the recombinogenic potentials of the metformin drug in therapeutically relevant plasma concentrations (12.

[Subconjunctival Loiasis: case reports and review of cases described in Italy].

Filariasis or Loiasis is an eye infection caused by a parasite belonging to the species Loa loa, also known as "African eye worm" since it is present in the rainforests belt of western and central Africa. The purpose of this study is the description of a clinical case presented to our department. A 40-years-old Congolese woman, in the third month of pregnancy, complained a foreign body sensation in the right eye for which she was submitted to complete ophthalmologic examination.

Circadian rhythms of embryonic development and hatching in fish: a comparative study of zebrafish (diurnal), Senegalese sole (nocturnal), and Somalian cavefish (blind).

During early development, most organisms display rhythmic physiological processes that are shaped by daily changes in their surrounding environment (i.e., light and temperature cycles).

Influence of a thioether function in short-bite diphosphine ligands on the nature of their silver complexes: structure of a trinuclear complex and of a coordination polymer.

New cationic Ag(I) complexes were prepared by reaction of AgBF4 with two thioether-functionalized bis(diphenylphosphino)amine ligands, Ph2PN(p-ArSMe)PPh2 (L1) and Ph2PN(n-PrSMe)PPh2 (L2), and compared with those obtained from the unfunctionalized ligands Ph2PN(Ph)PPh2 (L3) and Ph2PN(n-Bu)PPh2 (L4), respectively. The complex [Ag3(μ3-Cl)2(μ2-L1-P,P)3](BF4) (1·BF4) contains a triangular array of Ag centres supported by three bridging L1 ligands and two triply-bridging chlorides. In contrast, ligand L2 led to the coordination polymer [{Ag2(μ3-L2,-P,P,S)2(MeCN)2}{Ag2(μ2-L2-P,P)2(MeCN)2}(BF4)4]n (2) in which the tethered thioether group connects intermolecularly a Ag2 unit to the diphosphine bridging the other Ag2 unit.

Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses.

Whole-body energy metabolism is regulated by the hypothalamus and has an impact on diverse tissue functions. Here we show that selective knockdown of Sirtuin 1 Sirt1 in hypothalamic Agouti-related peptide-expressing neurons, which renders these cells less responsive to cues of low energy availability, significantly promotes CD4(+) T-cell activation by increasing production of T helper 1 and 17 proinflammatory cytokines via mediation of the sympathetic nervous system. These phenomena were associated with an impaired thymic generation of forkhead box P3 (FoxP3(+)) naturally occurring regulatory T cells and their reduced suppressive capacity in the periphery, which resulted in increased delayed-type hypersensitivity responses and autoimmune disease susceptibility in mice.

Structural modifications of polymethacrylates: impact on thermal behavior and release characteristics of glassy solid solutions.

Polymethacrylates such as Eudragit® polymers are well established as drug delivery matrix. Here, we synthesize several Eudragit E PO (n-butyl-, dimethylaminoethyl-, methyl-methacrylate-terpolymer) analogues via free radical polymerization. These polymers are processed via hot melt extrusion, followed by injection molding and evaluated as carriers to produce immediate release solid solution tablets.

Improved BM212 MmpL3 inhibitor analogue shows efficacy in acute murine model of tuberculosis infection.

1,5-Diphenyl pyrroles were previously identified as a class of compounds endowed with high in vitro efficacy against M. tuberculosis. To improve the physical chemical properties and drug-like parameters of this class of compounds, a medicinal chemistry effort was undertaken.

Meta-immunological profiling of children with type 1 diabetes identifies new biomarkers to monitor disease progression.

Type 1 diabetes is characterized by autoimmune destruction of pancreatic β-cells in genetically susceptible individuals. Triggers of islet autoimmunity, time course, and the precise mechanisms responsible for the progressive β-cell failure are not completely understood. The recent escalation of obesity in affluent countries has been suggested to contribute to the increased incidence of type 1 diabetes.

Treating refractory obsessive-compulsive disorder: what to do when conventional treatment fails?

Obsessive-compulsive disorder (OCD) is a chronic and impairing condition. A very small percentage of patients become asymptomatic after treatment. The purpose of this paper was to review the alternative therapies available for OCD when conventional treatment fails.

Does a role for selenium in DNA damage repair explain apparent controversies in its use in chemoprevention?

The trace element selenium is an essential micronutrient that has received considerable attention for its potential use in the prevention of cancer. In spite of this interest, the mechanism(s) by which selenium might function as a chemopreventive remain to be determined. Considerable experimental evidence indicates that one possible mechanism by which selenium supplementation may exert its benefits is by enhancing the DNA damage repair response, and this includes data obtained using cultured cells, animal models as well as in human clinical studies.

Alzheimer's disease-associated neurotoxic peptide amyloid-β impairs base excision repair in human neuroblastoma cells.

Alzheimer's disease (AD) is the leading cause of dementia in developed countries. It is characterized by two major pathological hallmarks, one of which is the extracellular aggregation of the neurotoxic peptide amyloid-β (Aβ), which is known to generate oxidative stress. In this study, we showed that the presence of Aβ in a neuroblastoma cell line led to an increase in both nuclear and mitochondrial DNA damage.

Leptin-induced mTOR activation defines a specific molecular and transcriptional signature controlling CD4+ effector T cell responses.

The sensing by T cells of metabolic and energetic changes in the microenvironment can determine the differentiation, maturation, and activation of these cells. Although it is known that mammalian target of rapamycin (mTOR) gauges nutritonal and energetic signals in the extracellular milieu, it is not known how mTOR and metabolism influence CD4+CD25-FOXP3- effector T cell (Teff) responses. In this article, we show that leptin-induced activation of mTOR, which, in turn, controls leptin production and signaling, causes a defined cellular, biochemical, and transcriptional signature that determine the outcome of Teff responses, both in vitro and in vivo.

At the crossroad of T cells, adipose tissue, and diabetes.

The study of how different intracellular metabolic signaling pathways impact the control of self-immune tolerance and how metabolic dysregulation in overweight, obesity, and diabetes is able to alter self-immune tolerance are topics of intensive investigation. Recent evidence suggests that metabolic and autoimmune diseases, both characterized by chronic inflammation and an altered self-immune tolerance, are more common in affluent countries. The reasons for such phenomena are still not completely understood, but the 'metabolic pressure' induced by nutritional overload, typical of more developed countries, seems to play a role.

Encephalic photoreception and phototactic response in the troglobiont Somalian blind cavefish Phreatichthys andruzzii.

Many physiological and behavioural responses to changes in environmental lighting conditions are mediated by extraocular photoreceptors. Here we investigate encephalic photoreception in Phreatichthys andruzzii, a typical cave-dwelling fish showing an extreme phenotype with complete anophthalmy and a reduction in size of associated brain structures. We firstly identified two P.

Subcritical crack growth and in vitro lifetime prediction of resin composites with different filler distributions.

Objectives: Verify the influence of different filler distributions on the subcritical crack growth (SCG) susceptibility, Weibull parameters (m and σ(0)) and longevity estimated by the strength-probability-time (SPT) diagram of experimental resin composites.

Methods: Four composites were prepared, each one containing 59 vol% of glass powder with different filler sizes (d(50)=0.5; 0.

[A case of percutaneous coronary intervention after transfemoral implantation of a medtronic CoreValve System].

The association between aortic valve disease and coronary atherosclerosis is common. In the recent era of transcatheter aortic valve implantation there is little experience with coronary artery intervention after valve implantation. We report a case of a 80-year-old male who underwent successful coronary artery intervention few months after a Medtronic CoreValve System percutaneous implantation for severe aortic valve stenosis.

Enhanced selectivity for the hydrolysis of block copoly(2-oxazoline)s in ethanol-water resulting in linear poly(ethylene imine) copolymers.

The ability of merging the properties of poly(2-oxazoline)s and poly(ethylene imine) is of high interest for various biomedical applications, including gene delivery, biosensors, and switchable surfaces and nanoparticles. In the present research, a methodology for the controlled and selective hydrolysis of (co)poly(2-oxazoline)s is developed in an ethanol-water solvent mixture, opening the path toward a wide range of block poly(2-oxazoline-co-ethylene imine) (POx-PEI) copolymers with tunable properties. The unexpected influence of the selected ethanol-water binary solvent mixture on the hydrolysis kinetics and selectivity is highlighted in the pursue of well-defined POx-PEI block copolymers.

Ob-stopping obesity, metabolic and immune-mediated disorders.

Despite its physiological importance, no part of human leptin receptor (ObR) has been structurally characterized before. In this issue of Structure, Carpenter et al. report the crystal structure of the leptin-binding domain of human ObR in complex with the Fab fragment of an ObR-blocking monoclonal antibody (9F8 mAb).

Synthesis and structural characterisation of (aryl-BIAN)copper(I) complexes and their application as catalysts for the cycloaddition of azides and alkynes.

A series of Ar-BIAN-based copper(I) complexes (where Ar-BIAN = bis(aryl)acenaphthenequinonediimine) were synthesised and characterised by (1)H and (13)C NMR spectroscopies, FT-IR spectroscopy, MALDI-TOF-MS spectrometry, cyclic voltammetry and single crystal X-ray diffraction. The bis-chelated complexes of general formula [Cu(Ar-BIAN)(2)]BF(4) (where Ar = C(6)H(5) (1), 4-iPrC(6)H(4) (3), 2-iPrC(6)H(4) (4)) were prepared by reaction of [Cu(NCMe)(4)]BF(4) with two equivalents of the corresponding Ar-BIAN ligands, in dichloromethane, while the mono-chelated complexes of the type [Cu(Ar-BIAN)L(2)]BF(4) (where Ar = 2,6-iPr(2)C(6)H(3), L = PhCN (6); Ar = 4-iPrC(6)H(4), L = PPh(3) (7)) were readily accessible by treatment of [Cu(NCR)(4)]BF(4) (R = Me, Ph) with one equivalent of the corresponding Ar-BIAN ligands in the absence or presence of two equivalents of PPh(3), in the same solvent. The structures of complexes 3, 4, 6 and 7 were obtained by single crystal X-ray diffraction, showing distorted tetrahedral geometries around the copper centres in all cases.