The protective role of melanin against UV damage in human skin

Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.     

On the photophysics of polyenes. 1. Bathochromic shifts in their 1Ag --> 1Bu electronic transitions caused by the polarizability of the medium

As shown in this study, the solvatochromic behavior of polyenes depends exclusively on the polarizability of the medium and, even more interestingly, their solvatochromism increases markedly with increasing length of the polyene chain. By virtue of the electronic nature of the interaction of polyenes with the medium, their solvatochromic response to a polarizability change is instantaneous, making these compounds extremely effective polarizability probes for molecular environments. The extreme sensitivity of polyenes to the polarizability of their environment is consistent with the fact that changes in molecular architecture such as those occurring in photosynthetic systems can give rise to polarizability gradients resulting in red shifts in the 1Ag --> 1Bu transition, thereby opening up new channels directing the energy transfer involved to energy trapping sites in such systems.     

β-N-Heterocyclic Cyclobutane Carboximides: Synthesis through a Tandem Base-Catalyzed Amidation/aza-Michael Addition Protocol and Facile Transformations

A stereoselective one-pot double derivatization of cyclobutene-1-carboxylic acid via a mild organic base catalyzed amidation/aza-Michael addition of benzo[d]oxazol-2(3H)-ones has been developed. This unprecedented tandem reaction provides access to novel β-N-heterocyclic cyclobutane carboximide derivatives with a trans geometry. The carboximide moiety reacts smoothly with nucleophiles, allowing access to diverse derivatives of trans-β-N-heterocyclic cyclobutanecarboxylic acid, including peptidomimetic structures.     

In-situ investigation of the adsorption of globular model proteins on stimuli-responsive binary polyelectrolyte brushes

Binary brushes constituted from two incompatible polymers can be used in the form of ultrathin polymeric layers as a versatile tool for surface engineering to tune physicochemical surface characteristics such as wettability, surface charge, chemical composition, and morphology and furthermore to create responsive surface properties. Mixed brushes of oppositely charged weak polyelectrolytes represent a special case of responding surfaces that are sensitive to changes in the pH value of the aqueous environment and therefore represent interesting tools for biosurface engineering. The polyelectrolyte brushes used for this study were composed of two oppositely charged polyelelctrolytes poly(2-vinylpyridine) (P2VP) and poly(acrylic acid) (PAA). The in-situ properties and surface characteristics such as as surface charge, surface tension, and extent of swelling of these brush layers are functions of the pH value of the surrounding aqueous solution. To test the behavior of the mixed polylelctrolyte brushes in contact with biosystems, protein adsorption experiments with globular model proteins were performed at different pH values and salt concentrations (confinement of counterions) of the buffer solutions. The influence of the pH value, buffer salt concentration, and isoelectric points (IEP) of the brush and protein on the adsorbed amount and the interfacial tension during protein adsorption as well as the protein adsorption mechanism postulated in reference to recently developed theories of protein adsorption on polyelectrolyte brushes is discussed. In the salted regime, protein adsorption was found to be similar to the often-described adsorption at hydrophobic surfaces. However, in the osmotic regime the balance of electrostatic repulsion and a strong entropic driving force, "counterion release", was found to be the main influence on protein adsorption.     

Voltage-dependent anion channel transports calcium ions through biomimetic membranes

The mitochondrial outer membrane channel (VDAC), a central player in mitochondria and cell death, was reconstituted in polymer-supported phospholipid bilayers. Highly purified VDAC was first reconstituted in vesicles; channel properties and NADH-ferricyanide reductase activity were ascertained before deposition onto solid substrates. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-N-hydroxysuccinimide mixed vesicles containing VDAC were linked onto amine-grafted surfaces (glass and gold) and disrupted to form a VDAC-containing polymer-tethered planar bilayer. Surface plasmon spectroscopy, fluorescence microscopy, and atomic force microscopy measurements ascertained the membrane thickness, fluidity, and continuity. VDAC reconstituted in bilayers efficiently transported calcium ions and was modulable by two channel blockers, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and l-glutamate. The novel setup may allow the study of the assembly of a polyprotein complex centered on VDAC and its role in mitochondrial biology, calcium fluxes, and apoptosis.     

Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone,RIC-3

Nicotinic acetylcholine receptors (nAChRs) are widely expressed in or on various cell types and have diverse functions. In immune cells nAChRs regulate proliferation, differentiation and cytokine release. Specifically, activation of the α7 nAChR reduces inflammation as part of the cholinergic anti-inflammatory pathway. Here we review numerous effects of α7 nAChR activation on immune cell function and differentiation. Further, we also describe evidence implicating this receptor and its chaperone RIC-3 in diseases of the central nervous system and in neuroinflammation, focusing on multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Deregulated neuroinflammation due to dysfunction of α7 nAChR provides one explanation for involvement of this receptor and of RIC-3 in neurodegenerative diseases. In this review, we also provide evidence implicating α7 nAChRs and RIC-3 in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) involving neuroinflammation. Besides, we will describe the therapeutic implications of activating the cholinergic anti-inflammatory pathway for diseases involving neuroinflammation.     

New Tripodal, “Supercharged” Analogues of Adenosine Nucleotides: Inhibitors for the Fhit Ap3A Hydrolase

Methanetrisphosphonic acids provide a branch point for synthetic nucleotide analogues which can be exploited either to generate novel tripodal nucleotides or to incorporate additional negative charge into linear analogues relative to the parent nucleotide, as exemplified in the picture for ATP and diadenosine tetraphosphate (Ap₄A). These compounds show valuable discriminatory behavior as competitive inhibitors for the tumor suppressor protein Fhit and a second Ap_nA pyrophosphohydrolase. X=H, Cl, F.     

Enantioselective Preparation of γ-Amino Acids and γ-Lactams from Nitro Olefins and Carboxylic Acids,with the Valine-Derived 4-Isopropyl-5,5-diphenyl-1,3-oxazolidin-2-one as an Auxiliary

Titanium enolates of acyl-oxazolidinones 1 , derived from acetic, propanoic, 3-methylbutanoic, and 4-methylpentanoic acids and 4-isopropyl-5,5-diphenyl-1,3-oxazolidin-2-one, are added to aliphatic and aromatic nitro olefins in the presence of TiCl₄ (Schemes 2 – 4). The products, 4-nitro carboxylic-acid derivatives 2 , are formed in high diastereoselectivities (ds 80 to >99%) and in good yields (50 – 75% of purified samples of ds >98%). Hydrogenation over Raney-Ni of the NO₂ group in the adducts leads directly to the corresponding γ-lactams ( 3 and 8 ; 80 – 92%), with recovery of the insoluble auxiliary (ca. 95%). Ring opening is achieved through the N-Boc-lactams ( 4 ), which are converted to N-Boc-protected γ-amino acids 5 or to their benzyl and methyl esters ( 6 and 7 ; Scheme 5). The configuration of the products (containing up to three new stereogenic centers; Scheme 1) is assigned by comparison with literature data, by X-ray crystal-structure analysis (for 2c , g , f , 8 , Fig.), and by analogy. Thus, the (S)-auxiliary gives rise to combination of the trigonal centers of enolate and nitro olefin with Si/Si topicity (relative topicity all-lk; cf. A ).     

Investigating the high-energy QCD approaches for prompt-photon production at the LHC

We investigate the rapidity and transverse-momentum distributions of the prompt photon production at the CERN LHC energies considering the current perturbative QCD approaches for this scattering process. Namely, we compare the predictions from the usual NLO pQCD calculations to the color-dipole formalism, using distinct dipole cross sections. Special attention is paid to parton-saturation models at high energies, which are expected to be important at the forward rapidities in pp collisions (  TeV) at the LHC.