Oxidative Stress and Genotoxicity in Melanoma Induction: Impact on Repair Rather Than Formation of DNA Damage?

Keratinocytes and melanocytes, two cutaneous cell types located within the epidermis, are the origin of most skin cancers, namely carcinomas and melanomas. These two types of tumors differ in many ways. First, carcinomas are almost 10 times more frequent than melanomas. In addition, the affected cellular pathways, the mutated genes and the metastatic properties of the tumors are not the same. This review addresses another specificity of melanomas: the role of photo-oxidative stress. UVA efficiently produces reactive oxygen species in melanocytes, which results in more frequent oxidatively generated DNA lesions than in other cell types. The question of the respective contribution of UVB-induced pyrimidine dimers and UVA-mediated oxidatively generated lesions to mutagenesis in melanoma remains open. Recent results based on next-generation sequencing techniques strongly suggest that the mutational signature associated with pyrimidine dimers is overwhelming in melanomas like in skin carcinomas. UVA-induced oxidative stress may yet be indirectly linked to the genotoxic pathways involved in melanoma through its ability to hamper DNA repair activities.     

Chemical Antibody Mimics Inhibit Cadherin-Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy

One of the most promising strategies to treat cancer is the use of therapeutic antibodies that disrupt cell–cell adhesion mediated by dysregulated cadherins. The principal site where cell–cell adhesion occurs encompasses Trp2 found at the N-terminal region of the protein. Herein, we employed the naturally exposed highly conserved peptide Asp1-Trp2-Val3-Ile4-Pro5-Pro6-Ile7, as epitope to prepare molecularly imprinted polymer nanoparticles (MIP-NPs) to recognize cadherins. Since MIP-NPs target the site responsible for adhesion, they were more potent than commercially available therapeutic antibodies for inhibiting cell–cell adhesion in cell aggregation assays, and for completely disrupting three-dimensional tumor spheroids as well as inhibiting invasion of HeLa cells. These biocompatible supramolecular anti-adhesives may potentially be used as immunotherapeutic or sensitizing agents to enhance antitumor effects of chemotherapy.     

Heterometallic Triply‐Bridging Bis‐Borylene Complexes

Triply‐bridging bis‐{hydrido(borylene)} and bis‐borylene species of groups 6, 8 and 9 transition metals are reported. Mild thermolysis of [Fe₂(CO)₉] with an in situ produced intermediate, generated from the low‐temperature reaction of [Cp*WCl₄] (Cp*=η⁵‐C₅Me₅) and [LiBH₄?THF] afforded triply‐bridging bis‐{hydrido(borylene)}, [(μ₃‐BH)₂H₂{Cp*W(CO)₂}₂{Fe(CO)₂}] ( 1 ) and bis‐borylene, [(μ₃‐BH)₂{Cp*W(CO)₂}₂{Fe(CO)₃}] ( 2 ). The chemical bonding analyses of 1 show that the B?H interactions in bis‐{hydrido (borylene)} species is stronger as compared to the M?H ones. Frontier molecular orbital analysis shows a significantly larger energy gap between the HOMO‐LUMO for 2 as compared to 1 . In an attempt to synthesize the ruthenium analogue of 1 , a similar reaction has been performed with [Ru₃(CO)₁₂]. Although we failed to get the bis‐{hydrido(borylene)} species, the reaction afforded triply‐bridging bis‐borylene species [(μ₃‐BH)₂{WCp*(CO)₂}₂{Ru(CO)₃}] ( 2′ ), an analogue of 2 . In search for the isolation of bridging bis‐borylene species of Rh, we have treated [Co₂(CO)₈] with nido‐[(RhCp*)₂(B₃H₇)], which afforded triply‐bridging bis‐borylene species [(μ₃‐BH)₂(RhCp*)₂Co₂(CO)₄(μ‐CO)] ( 3 ). All the compounds have been characterized by means of single‐crystal X‐ray diffraction study; ¹H, ¹¹B, ¹³C NMR spectroscopy; IR spectroscopy and mass spectrometry.     

Chemical assays of end-groups displayed on the surface of poly(ethylene terephthalate) (PET) films and membranes by radiolabeling

Poly(ethylene terephthalate) (PET) films and track-etched microporous membranes naturally display, on their surfaces, reactive chain-ends, i.e. carboxyl and hydroxyl functions. These were assayed by suitable activation (reaction with carbodiimide and tosyl chloride, respectively), followed by coupling with ³H-lysine and liquid scintillation counting of the sample-associated radioactivity. Values ranging between 5 and 30 pmol/cm² (open surface) of labeled end-groups were obtained, depending on the physico-chemical nature of the samples. Basic hydrolysis enriched the PET films with both types of endings (15–25 pmol/cm²). Reduction of films with the NaBH₄-catechol complex in tetrahydrofuran enriched their surfaces with hydroxyl groups. However, this procedure was not readily applicable to the surface modification of membranes; we observed an erosion effect that was confirmed by scanning electron microscope analyses. In contrast with the reduction process, the oxidation with KMnO₄ in 1.2N H₂SO₄ could be easily applied to the modification of either films or membranes; their surfaces were significantly enriched with carboxyl groups (15–50 pmol/cm²). This surface modification strategy has been used for the covalent coupling of adhesive proteins on PET membranes developed as supports for cell cultivation.     

Numerical study of two-airfoil arrangements by a discrete vortex method

Theoretical and Computational Fluid Dynamics - The aerodynamic characteristics of two neighboring airfoils are greatly different from those of a single airfoil, for both attached and detached flow...     

Scaling Features of Two Special Markov Chains Involving Total Disasters

Journal of Statistical Physics - Catastrophe Markov chain population models have received a lot of attention in the recent past. We herewith consider two special cases of such models involving...     

Supramolecular Luminescent Lanthanide Dimers for Fluoride Sequestering and Sensing

Lanthanide complexes (Ln=Eu, Tb, and Yb) that are based on a C₂‐symmetric cyclen scaffold were prepared and characterized. The addition of fluoride anions to aqueous solutions of the complexes resulted in the formation of dinuclear supramolecular compounds in which the anion is confined into the cavity that is formed by the two complexes. The supramolecular assembly process was monitored by UV/Vis absorption, luminescence, and NMR spectroscopy and high‐resolution mass spectrometry. The X‐ray crystal structure of the europium dimer revealed that the architecture of the scaffold is stabilized by synergistic effects of the Eu? F? Eu bridging motive, π stacking interactions, and a four‐component hydrogen‐bonding network, which control the assembly of the two [EuL] entities around the fluoride ion. The strong association in water allowed for the luminescence sensing of fluoride down to a detection limit of 24 nM .