We have studied the relative positions of the frontier levels determine the main electronic properties and reaction ability, there is important necessity to compare the MO of the purine and рyrimidine bases: adenine (A), guanine (G), cytosine (C), thymine (T) and uracil (U). The donor and acceptor properties are the fundamental characteristic of the conjugated molecules and can be quantitatively estimated by relative positions of the frontier molecular orbitals. The MO’s energies can be estimated experimentally or quantum-chemically. Analysis of the relative position of the frontier levels (calibrated by the energy gap) enables the investigation of the donor/acceptor properties of the RNA/DNA bases more detailed. The index φ0 is proposed for the quantitative quantum-chemical estimation of the donor ability of the conjugated molecules: it points on the shifting of the energy gap relative to the reference electron balanced system. The RNA/DNA bases divided strictly by two groups: predominantly donors (φ0 > 0.5) and predominantly acceptors (φ0 > 0.5). Each representative base of the first group forms the stable base pair the representative base of the second group the difference of indices Δφ0 should be optimal to enables the DNA replication.

The study compared the influence of chitosan sources on rumen fermentation, methane emission and milk production in lactating dairy cows fed a glycerin-based diet. Six, lactating Holstein-Frisian crossbreeds (410 ± 5.0 kg BW, 120 ± 21 day-in-milk), were arranged in a 3 x 3 replicated Latin square design. In addition to control, a 2% chitosan extract supplement and a 2% commercial chitosan supplement of dry matter intake were the treatments. The results denoted that no significant differences on daily dry matter, nutrients or estimated energy intake were noted when cows received different sources of chitosan. Nutrient digestibility was not influenced differently by extraction based or commercial chitosan supplements. The pH, temperature, ammonia nitrogen, blood urea and microbial count were similar among treatments. The different sources of chitosan supplements did not change the totals of volatile fatty acids, acetate and butyrate; in contrast, different chitosan sources influenced (P<0.05) propionate content. The ruminal acetate to propionate ratio was markedly (P<0.05) reduced with chitosan supplement, but no change appeared between sources of chitosan. At 4 hours after feeding, the methane estimation significantly decreased with the addition of chitosan supplementation (P<0.05) compared to the control group. The purine derivatives and microbial protein synthesis were not altered by the treatments. No significant differences existed on milk yield, milk composition or milk urea nitrogen when cows received different sources of chitosan (P>0.05). In sum, supplementing extracted chitosan showed more potential than did commercial chitosan for enhancing economic efficiency and recycling shrimp residues, therefore, reducing environmental waste.

The phenomenon of decreased serum uric acid (UA) levels in patients with Parkinson’s disease (PD) and its relationship with purine metabolic pathways remain unclear. We compared inosine, hy-poxanthine, xanthine, and UA levels in serum and cerebrospinal fluid (CSF) of PD patients with those of controls, and investigated the effect of changes in the purine metabolic system on UA levels in PD. Overall, 134 samples (serum, 45 PD patients and 30 controls; CSF, 39 PD patients and 20 controls), were analyzed using liquid chromatography-tandem mass spectrometry. A general linear model (GLM) was used to investigate relationships among purine metabolites. Compared to controls, PD patients had significantly lower UA levels in the serum and CSF, and serum and CSF UA levels were significantly correlated. Additionally, in PD, decreased serum hypoxanthine levels were observed with decreased CSF inosine and hypoxanthine levels, suggesting the involvement of the purine recycling system. GLM analysis indicated that the reduced UA levels in PD were mainly due to sources other than the purine metabolic system, such as exercise, nutritional indices, muscle volume, or adipose tissue. Our results highlight the impairment of purine recycling pathways in PD, as evidenced by the decreased serum hypoxanthine and CSF inosine.

A precise understanding of the genes and associated genomes of SARS-CoV2 is important for various reasons such as discovering origin of the virus and virulence and so on. A thorough descriptive understanding of the SARS-CoV2 genomes and other coronavirus of the beta-coronavirus genus is primarily important. In this article, a set of ten genomes of four CoVs and their associated genes are considered for this present study. A spatial representations of nucleotide bases including purine-pyrimidine representations of the different genes of the corresponding genomes are quantified using Hurst exponent, Shannon entropy and density estimation of different nucleotides including GC content, in order to draw a comparison and contrast among the ten genomes of different types of CoVs which include MERS, SARS-CoV, HKU1 (Human Coronavirus) and associated their genes.

Keywords: Adrenergic signaling in cardiomyocytes; cardiac muscle contraction; Chagas disease; diabetic cardiomyopathy; dilated cardiomyopathy; glycerolipid metabolism; glycolisis/glucogenesis; hypertrophic cardiomyopathy; purine metabolism; steroid hormone biosynthesis.

A whole-exome capture and next-generation sequencing applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, severe cognitive deficit, without any identifiable Syndromic pattern, and to her parents, disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated to Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated one, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURA WT and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural confor-mation in the ~5Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA Docking corroborated these results in silico Analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, i) the energetic and stereochemical, ii) the hydropathic indices and polarity surfaces, and iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate at the atomic resolution the specific surrounding region affected by these mutations and paves the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines are not effective anymore. This highlights the urgent need for antiviral therapies even more. This article describes how the Genome-Scale Metabolic Model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7 and B.1.351. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.