From genotype to phenotype with biothermodynamics: empirical formulas, biosynthesis reactions and thermodynamic properties of preproinsulin, proinsulin and insulin molecules.

Insulin was discovered 100 years ago and has been well studied from the perspectives of life and biomedical sciences. This paper reports chemical and biothermodynamic properties of biosynthesis of insulin. This paper reports for the first time the molecular and empirical formulas, biosynthesis reactions, and thermodynamic properties of molecules and their biosynthesis for human preproinsulin, proinsulin, insulin chain A, insulin chain B, insulin, signal peptide and intermediate peptide (C-peptide). Based on these, metabolic reactions were formulated for conversion of preproinsulin to insulin and their thermodynamic feasibility was analyzed.Communicated by Ramaswamy H. Sarma.

Anodizing/Anaphoretic Electrodeposition of Nano-Calcium Phosphate/Chitosan Lactate Multifunctional Coatings on Titanium with Advanced Corrosion Resistance, Bioactivity, and Antibacterial Properties.

The aim of this work was to investigate corrosion resistivity, bioactivity, and antibacterial activity of novel nano-amorphous calcium phosphate (ACP) potentially multifunctional composite coatings with and without chitosan oligosaccharide lactate (ChOL), ACP + ChOL/TiO2 and ACP/TiO2 ACP + ChOL/TiO2, respectively, on the titanium substrate. The coatings were obtained by new single-step in situ anodization of the substrate to generate TiO2 and the anaphoretic electrodeposition process of ACP and ChOL. The obtained coatings were around 300 ± 15 µm thick and consisted of two phases, namely, TiO2 and hybrid composite phases. Both ACP/TiO2 and ACP + ChOL/TiO2 have improved corrosion stability, whereas the ACP + ChOL/TiO2 coating showed better corrosion stability. It was shown that at the very start of the deposition process, the formation of the ChOL/TiO2 layer takes place predominantly, which is followed by the inclusion of ChOL into ACP with simultaneous growth of TiO2. This deposition mechanism resulted in the formation of strongly bonded uniform stable coating with high corrosion resistance. In vitro bioactivity was investigated by immersion of the samples in simulated body fluid (SBF). There is in-bone-like apatite formation on both ACP/TiO2 and ACP + ChOL/TiO2 surfaces upon immersion into SBF, which was proven by X-ray diffraction and Fourier transform infrared spectroscopy. While ACP/TiO2 shows no antibacterial activity, ACP + ChOL/TiO2 samples exhibited three- to fourfold decreases in the number of Staphylococcus aureus and Pseudomonas aeruginosa, respectively, after 420 min. The probable mechanism is binding ChOL with the bacterial cell wall, inhibiting its growth, altering the permeability of the cell membrane, and leading to bacterial death.

Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication.

We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest (NC) stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 copy number variants. Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in NC-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we found a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the human self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face. In so doing, we provide experimental evidence that the craniofacial and cognitive/behavioral phenotypes caused by alterations of the Williams-Beuren syndrome critical region can serve as a powerful entry point into the evolution of the modern human face and prosociality.

Investigation of metabolic properties and effects of 17ß-carboxamide glucocorticoids on human peripheral blood leukocytes.

The biological activity of three previously synthesized 17ß-carboxamide glucocorticoids (BG, BEG, and MPEA) was tested in vitro on mitogen stimulated and non-stimulated peripheral blood mononuclear cells (MNCs) and granulocytes from human healthy donors, and the results were compared to the conventional glucocorticoid dexamethasone. The tested 17ß-carboxamide glucocorticoids did not induce decreases in MNC viability and proliferation, while modulation of reactive oxygen species (ROS) synthesis in granulocytes was dependent on the cell donor. The obtained results indicate the possibility of avoidance of strong lymphocyte suppression, which is generally recognized during administration of conventional glucocorticoids. Furthermore, the metabolism of the tested derivatives was predicted in silico. The predicted metabolites were synthesized and the in silico results were confirmed by in vitro evaluation of the metabolism of BG, BEG, and MPEA in human serum and in cultures of peripheral blood MNCs. The results of the biological activity and metabolism evaluation and of previous in vivo evaluations of biological activity indicate the soft drug nature of BG, BEG, and MPEA. In order to be fully considered as soft glucocorticoids, further investigations on the toxicity and activity of the formed metabolites are required.

Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR.

Upstream of N-ras (UNR) is a conserved RNA-binding protein that regulates mRNA translation and stability by binding to sites generally located in untranslated regions (UTRs). In Drosophila, sex-specific binding of UNR to msl2 mRNA and the noncoding RNA roX is believed to play key roles in the control of X-chromosome dosage compensation in both sexes. To investigate broader sex-specific functions of UNR, we have identified its RNA targets in adult male and female flies by high-throughput RNA binding and transcriptome analysis. Here we show that UNR binds to a large set of protein-coding transcripts and to a smaller set of noncoding RNAs in a sex-specific fashion. The analyses also reveal a strong correlation between sex-specific binding of UNR and sex-specific differential expression of UTRs in target genes. Validation experiments indicate that UNR indeed recognizes sex-specifically processed transcripts. These results suggest that UNR exploits the transcript diversity generated by alternative processing and alternative promoter usage to bind and regulate target genes in a sex-specific manner.