Melanocyte‐Specific Immune Response in Melanoma and Vitiligo: Two Faces of the Same Coin?

The appearance of depigmentation during the course of malignant melanoma has been considered a good prognostic sign. Is it only a side‐effect, informative of the immune system's response to the treatment, or does it act as a necessary amplifier of these clinically important anti‐tumor responses? The current review will attempt to tackle this question by reviewing the current literature, as well as by posing some novel hypotheses. Understanding the nature of humoral and cellular immune responses directed against normal melanocytes and their malignant counterparts may lead to the design of improved therapeutic strategies relevant to both vitiligo and melanoma.     

Messenger RNA for glutamine synthetase

Molecular and Cellular Biochemistry - Of the various eucaryotic tissues, where glutamine synthetase (GS) mRNA and its regulation have been investigated, the induction of GS by glucocorticoids in...     

Inhibition by coumadin anticoagulants of enzymatic outer ring monodeiodination of iodothyronines

Iodothyronine outer ring monodeiodinase activity in rat kidney microsomes is strongly inhibited by the coumarin anticoagulants dicoumarol and warfarin. The inhibition is competitive with respect to the substrates and uncompetitive with respect to the thiol activator, dithiothreitol. Kinetic studies reveal that the mechanism of this inhibition is distinct from that obtained with propylthiouracil. This new class of iodine-free inhibitors may be useful in investigations of the mechanism of iodothyronine deiodination and in pharmacological studies of hormone metabolism.     

Metabarcoding of PalEnDNA as An Efficient Tool to Recover Ancient Bacterial Diversity

Past bacterial diversity of a paleosol was reconstructed using metabarcoding of paleo environmental DNA (PalEnDNA). The paleosol was subsampled from a sediment core which was excavated from a palaeo beach-ridge located 2.6?km away from present sea shore and identified that it was deposited under marine influence ～6000?years ago, using geological proxies. The bacterial community contained 37 bacterial phyla and dominated by Proteobacteria, followed by Bacteroidetes, Firmicutes, Actinobacteria, Verrucomicrobia, and Chloroflexi. The bacterial community was a mix-up of marine and terrestrial population, and thereby diversity was higher than marine populations. The result shows metabarcoding of PalEnDNA can effectively reconstruct past bacterial community structure.     

Rational design of viscosity reducing mutants of a monoclonal antibody: Hydrophobic versus electrostatic inter-molecular interactions

High viscosity of monoclonal antibody formulations at concentrations ≥100 mg/mL can impede their development as products suitable for subcutaneous delivery. The effects of hydrophobic and electrostatic intermolecular interactions on the solution behavior of MAB 1, which becomes unacceptably viscous at high concentrations, was studied by testing 5 single point mutants. The mutations were designed to reduce viscosity by disrupting either an aggregation prone region (APR), which also participates in 2 hydrophobic surface patches, or a negatively charged surface patch in the variable region. The disruption of an APR that lies at the interface of light and heavy chain variable domains, V_H and V_L, via L45K mutation destabilized MAB 1 and abolished antigen binding. However, mutation at the preceding residue (V44K), which also lies in the same APR, increased apparent solubility and reduced viscosity of MAB 1 without sacrificing antigen binding or thermal stability. Neutralizing the negatively charged surface patch (E59Y) also increased apparent solubility and reduced viscosity of MAB 1, but charge reversal at the same position (E59K/R) caused destabilization, decreased solubility and led to difficulties in sample manipulation that precluded their viscosity measurements at high concentrations. Both V44K and E59Y mutations showed similar increase in apparent solubility. However, the viscosity profile of E59Y was considerably better than that of the V44K, providing evidence that inter-molecular interactions in MAB 1 are electrostatically driven. In conclusion, neutralizing negatively charged surface patches may be more beneficial toward reducing viscosity of highly concentrated antibody solutions than charge reversal or aggregation prone motif disruption.     

Phylogeny,ecology and deep time: 2D outline analysis of anuran skulls from the Early Cretaceous to the Recent

Anurans have a long fossil record, spanning from the Early Jurassic to the Recent. However, specimens are often severely flattened, limiting their inclusion in quantitative analyses of morphological evolution. We perform a two‐dimensional morphometric analysis of anuran skull outlines, incorporating 42 Early Cretaceous to Miocene species, as well as 93 extant species in 32 families. Outlines were traced in tpsDig2 and analysed with elliptical Fourier analysis. Fourier coefficients were used in MANOVAs, phylogenetic MANOVAs (as significant phylogenetic signal was found) and disparity analyses across multiple ecological and life history groupings. The Neotropical realm showed higher disparity than the Australian, Palaearctic and Oriental realms (p = 0.007, 0.013, 0.038, respectively) suggesting concordance of disparity and diversity. Developmental strategy had a weak effect on skull shape (R² = 0.02, p = 0.039) and disparity was similar in metamorphosing and direct developing frogs. Ecological niche was a significant discriminator of skull shape (F = 1.43, p = 0.004) but not after phylogenetic correction. Evolutionary allometry had a small but significant influence on the cranial outlines of the combined extant and fossil dataset (R² = 0.05, p = 0.004). Finally, morphospace occupation appears to have changed over time (F = 1.59, p = 5 × 10^?10). However, as with ecological signal, this shift appears to be largely driven by phylogeny and was not significant after phylogenetic correction (R² = 0.26, p = 0.22). This study thus suggests that frog skull evolution is shaped more by phylogenetic constraints than by ecology.