Alopecia in Harlequin mutant mice is associated with reduced AIF protein levels and expression of retroviral elements

Mammalian Genome - We investigated the contribution of apoptosis-inducing factor (AIF), a key regulator of mitochondrial biogenesis, in supporting hair growth. We report that pelage abnormalities...     

Conformational Ensembles of Antibodies Determine Their Hydrophobicity

A major challenge in the development of antibody biotherapeutics is their tendency to aggregate. One root cause for aggregation is exposure of hydrophobic surface regions to the solvent. Many current techniques predict the relative aggregation propensity of antibodies via precalculated scales for the hydrophobicity or aggregation propensity of single amino acids. However, those scales cannot describe the nonadditive effects of a residue’s surrounding on its hydrophobicity. Therefore, they are inherently limited in their ability to describe the impact of subtle differences in molecular structure on the overall hydrophobicity. Here, we introduce a physics-based approach to describe hydrophobicity in terms of the hydration free energy using grid inhomogeneous solvation theory (GIST). We apply this method to assess the effects of starting structures, conformational sampling, and protonation states on the hydrophobicity of antibodies. Our results reveal that high-quality starting structures, i.e., crystal structures, are crucial for the prediction of hydrophobicity and that conformational sampling can compensate errors introduced by the starting structure. On the other hand, sampling of protonation states only leads to good results when combined with high-quality structures, whereas it can even be detrimental otherwise. We conclude by pointing out that a single static homology model may not be adequate for predicting hydrophobicity.     

Cultured bacterial diversity and human impact on alpine glacier cryoconite

The anthropogenic effect on the microbial communities in alpine glacier cryoconites was investigated by cultivation and physiological characterization of bacteria from six cryoconite samples taken at sites with different amounts of human impact. Two hundred and forty seven bacterial isolates were included in Actinobacteria (9%, particularly Arthrobacter), Bacteroidetes (14%, particularly Olleya), Firmicutes (0.8%), Alphaproteobacteria (2%), Betaproteobacteria (16%, particularly Janthinobacterium), and Gammaproteobacteria (59%, particularly Pseudomonas). Among them, isolates of Arthrobacter were detected only in samples from sites with no human impact, while isolates affiliated with Enterobacteriaceae were detected only in samples from sites with strong human impact. Bacterial isolates included in Actinobacteria and Bacteroidetes were frequently isolated from pristine sites and showed low maximum growth temperature and enzyme secretion. Bacterial isolates included in Gammaproteobacteria were more frequently isolated from sites with stronger human impact and showed high maximum growth temperature and enzyme secretion. Ecotypic differences were not evident among isolates of Janthinobacterium lividum, Pseudomonas fluorescens, and Pseudomonas veronii, which were frequently isolated from sites with different degrees of anthropogenic effect.     

Involvement of the epidermal growth factor receptor in the modulation of multidrug resistance in human hepatocellular carcinoma cells in vitro

Background

The synergic action of KHCO₃ and D-ribose is tested on A72 and HTB-126 cell lines proliferation using K:D-Rib solution. Altered Na⁺/K⁺ ATPase expression and activity were shown in patients with cancer. Studies in human epithelial-derived malignancies indicate that K⁺ depletion also occurs, contributing to the increased intracellular Na⁺/K⁺ ratio [1]. D-ribose transformed to piruvate, enters into the Krebs's cycle and has a key role on energetic metabolism. The up-regulation of glycolysis in tumor cells is already well known and it is the rationale of F¹⁸-FDG PET diagnostic technique. D-ribose is synthesized by the non-oxidative transketolase PPP reaction.

Results

Results with different K:D-Rib concentrations show that MTT salt interferes with K:D-Rib solution and therefore this method is not reliable. The UV/VIS measurements show that K:D-Rib solutions reduce MTT salt to formazan in absence of cells. Cell proliferation has then been evaluated analysing the digital photos of the Giemsa stained cells with MCID? software. At 5 mM K:D-Rib concentration, the cell growth arrests between 48 h and 72 h; in fact the cell number after 48 h is around the same with respect to the control after 72 h. In case of HTB-126 human cancer cells, the growth rate was valuated counting the splitting times during 48 days: control cells were split sixteen times while 5 mM treated cells eleven times. Most relevant, the clonogenic assay shows that nine colonies are formed in the control cells while only one is formed in the 5 mM and none in 10 mM treated cells.

Conclusions

The K:D-Rib solution has an antioxidant behaviour also at low concentrations. Incubation with 5 mM K:D-Rib solution on A72 cells shows a cytostatic effect at 5 mM, but it needs more than 24 h of incubation time to evidence this effect on cell proliferation. At the same concentration on human HTB-126 cells, K:D-Rib solution shows a clear replication slowing but the cytostatic effect at 10 mM K:D-Rib solution only. Results on A72 cells indicate the K⁺ uptake could be determinant either to arrest or to slow down cell growth.     

Morphometric diagnosability of Cyprus Wheatears Oenanthe cypriaca and an unexpected occurrence on Helgoland Island

Capsule We found closely related Cyprus Wheatears Oenanthe cypriaca and Pied Wheatears Oenanthe pleschanka to differ significantly from each other in 14 external morphometric characters, supporting the independent taxonomic status of both forms. An additionally measured old specimen from Helgoland unexpectedly turned out to be a Cyprus Wheatear, the first record for Germany.