Selective intra-dinucleotide interactions and periodicities of bases separated by K sites: a new vision and tool for phylogeny analyses

Direct tests of the random or non-random distribution of nucleotides on genomes have been devised to test the hypothesis of neutral, nearly-neutral or selective evolution. These tests are based on the direct base distribution and are independent of the functional (coding or non-coding) or structural (repeated or unique sequences) properties of the DNA. The first approach described the longitudinal distribution of bases in tandem repeats under the Bose-Einstein statistics. A huge deviation from randomness was found. A second approach was the study of the base distribution within dinucleotides whose bases were separated by 0, 1, 2... K nucleotides. Again an enormous difference from the random distribution was found with significances out of tables and programs. These test values were periodical and included the 16 dinucleotides. For example a high ¨positive¨ (more observed than expected dinucleotides) value, found in dinucleotides whose bases were separated by (3K + 2) sites, was preceded by two smaller ¨negative¨ (less observed than expected dinucleotides) values, whose bases were separated by (3K) or (3K + 1) sites. We examined mtDNAs, prokaryote genomes and some eukaryote chromosomes and found that the significant non-random interactions and periodicities were present up to 1000 or more sites of base separation and in human chromosome 21 until separations of more than 10 millions sites. Each nucleotide has its own significant value of its distance to neutrality; this yields 16 hierarchical significances. A three dimensional table with the number of sites of separation between the bases and the 16 significances (the third dimension is the dinucleotide, individual or taxon involved) gives directly an evolutionary state of the analyzed genome that can be used to obtain phylogenies. An example is provided.

Clinical outcomes and mortality in elderly peritoneal dialysis patients

OBJECTIVES: To evaluate the clinical outcomes and identify the predictors of mortality in elderly patients undergoing peritoneal dialysis. METHODS: We conducted a retrospective study including all incident peritoneal dialysis cases in patients ≥65 years of age treated from 2001 to 2014. Demographic and clinical data on the initiation of peritoneal dialysis and the clinical events during the study period were collected. Infectious complications were recorded. Overall and technique survival rates were analyzed. RESULTS: Fifty-eight patients who began peritoneal dialysis during the study period were considered for analysis, and 50 of these patients were included in the final analysis. Peritoneal dialysis exchanges were performed by another person for 65% of the patients, whereas 79.9% of patients preferred to perform the peritoneal dialysis themselves. Peritonitis and catheter exit site/tunnel infection incidences were 20.4±16.3 and 24.6±17.4 patient-months, respectively. During the follow-up period, 40 patients were withdrawn from peritoneal dialysis. Causes of death included peritonitis and/or sepsis (50%) and cardiovascular events (30%). The mean patient survival time was 38.9±4.3 months, and the survival rates were 78.8%, 66.8%, 50.9% and 19.5% at 1, 2, 3 and 4 years after peritoneal dialysis initiation, respectively. Advanced age, the presence of additional diseases, increased episodes of peritonitis, the use of continuous ambulatory peritoneal dialysis, and low albumin levels and daily urine volumes (<100 ml) at the initiation of peritoneal dialysis were predictors of mortality. The mean technique survival duration was 61.7±5.2 months. The technique survival rates were 97.9%, 90.6%, 81.5% and 71% at 1, 2, 3 and 4 years, respectively. None of the factors analyzed were predictors of technique survival. CONCLUSIONS: Mortality was higher in elderly patients. Factors affecting mortality in elderly patients included advanced age, ...

Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide analogue-naive and nucleos(t)ide analogue-experienced chronic hepatitis B patients

BACKGROUND/AIMS: This study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF) monotherapy in nucleos(t)ide analogue (NA)-naive and NA-experienced chronic hepatitis B (CHB) patients. METHODS: CHB patients treated with TDF monotherapy (300 mg/day) for > or =12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks. RESULTS: In total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis) were included. Sixty-two patients were nucleos(t)ide (NA)-naive, and 74 patients had prior NA therapy (NA-exp group), and 31 patients in the NA-exp group had lamivudine (LAM)-resistance (LAM-R group). The baseline serum hepatitis B virus (HBV) DNA level was 4.9+/-2.3 log IU/mL (mean+/-SD), and was higher in the NA-naive group than in the NA-exp and LAM-R groups (5.9+/-2.0 log IU/mL vs 3.9+/-2.0 log IU/mL vs 4.2+/-1.7 log IU/mL, P<0.01). The complete virological response (CVR) rate at week 48 in the NA-naive group (71.4%) did not differ significantly from those in the NA-exp (71.3%) and LAM-R (66.1%) groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898), while the CVR rate did not differ with the NA experience. CONCLUSIONS: TDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.

The structure of selective dinucleotide interactions and periodicities in D melanogaster mtDNA

BACKGROUND: We found a strong selective 3-sites periodicity of deviations from randomness of the dinucleotide (DN) distribution, where both bases of DN were separated by 1, 2, K sites in prokaryotes and mtDNA. Three main aspects are studied. I) the specific 3 K-sites periodic structure of the 16 DN. II) to discard the possibility that the periodicity was produced by the highly nonrandom interactive association of contiguous bases, by studying the interaction of non-contiguous bases, the first one chosen each I sites and the second chosen J sites downstream. III) the difference between this selective periodicity of association (distance to randomness) of the four bases with the described fixed periodicities of base sequences. RESULTS: I) The 16 pairs presented a consistent periodicity in the strength of association of both bases of the pairs; the most deviated pairs are those where G and C are involved and the least deviated ones are those where A and T are involved. II) we found significant non-random interactions when the first nucleotide is chosen every I sites and the second J sites downstream until I=J=76. III) we showed conclusive differences between these internucleotide association periodicities and sequence periodicities. CONCLUSIONS: This relational selective periodicity is different from sequence periodicities and indicates that any base strongly interacts with the bases of the residual genome; this interaction and periodicity is highly structured and systematic for every pair of bases. This interaction should be destroyed in few generations by recurrent mutation; it is only compatible with the Synthetic Theory of Evolution and agrees with the Wright's adaptive landscape conception and evolution by shifting balanced adaptive peaks.

Avaliação do desempenho de frangos de corte alimentados com rações contendo probiótico e diferentes níveis de nucleotídeos / Performance evaluation of broilers fed diets containing probiotic and different nucleotides levels

objetivo deste trabalho foi avaliar o desempenho de frangos de corte alimentados com ração contendo um probiótico comercial e diferentes níveis de nucleotídeos. Foram utilizados 1050 pintos de 01 dia, machos da linhagem Ross 308 totalizando trinta e cinco aves por boxe, em um delineamento inteiramente casualizado com cinco repetições por tratamento. As aves foram criadas até 42 dias de idade, e receberam as rações experimentais a base de milho e farelo de soja contendo 6 níveis de nucleotídeos (0; 100; 200; 300; 400 e 500 gramas por tonelada de ração). Os nucleotídeos foram utilizados na fase inicial (1 a 21 dias) e fase de crescimento (22 a 35 dias). Durante a fase final (36 a 42 dias) os nucleotídeos foram removidos da ração . Houve melhora linear no desempenho dos frangos no período de 1 a 21 dias, indicando que, quanto maior o nível de nucleotídeos na dieta, maior o peso corporal das aves. A conversão alimentar também melhorou linearmente nesse período à medida que aumentou o nível de nucleotídeos na ração. O peso no período de 35 dias, também teve um comportamento linear, semelhante ao período de 1 a 21 dias, indicando que, o nível de nucleotídeos na ração melhorou o desempenho. A concentração plasmática de acido úrico demonstrou efeito quadrático no período de 1 a 21 dias, indicando 231,59 gramas de nucleotídeos por tonelada de ração, como o melhor, em níveis mínimos de ácido úrico, por outro lado, no período de 35 dias de idade, estimou-se o nível de 208,99 g de nucleotídeos por tonelada de ração; como o melhor em níveis mínimos de ácido úrico no sangue. No período final (35 a 42 dias) e período total (1 a 42 dias de idade) não foi possível o observar efeito dos contrastes testados neste trabalho.

The objective of this study was to evaluate the performance of broilers fed diets containing a commercial probiotic and different levels of nucleotides. One thousand and fifty chicks 1-d male were reared in a randomized experimental design with five replications of each treatment, distributed in 30 experimental boxes with 35 birds each. The diets contained corn and soybean meal with six different nucleotídes levels (0; 100; 200; 300; 400 and 500 grams for ton of ration), and the different nucleotides levels were used in the initial phase (1 to 21 days of age) and growth phase (22 to 35 days of age). During the final phase (36 to 42 days) nucleotides were removed from the feed. There was improvement on broilers performance in the period from 1 to 21 days of age, demonstrating proportionality between nucleotides level in the diet of broilers and body weight of the birds. Feed conversion at 21 days of age was directly proportional to nucleotides level in the diet. Body weight at 35 days of age, also had a linear behavior, similar to the period from 1 to 21 days, indicating that the nucleotides level in the feed improved the performance. Plasma uric acid concentration demonstrated quadratic effect at 21 days of age, showing that 231,59 grams of nucleotides for ton of feed had the minimum level of plasma uric acid concentration. At 35 days of age, concentration of 208,99 g of nucleotides for ton of feed had the minimum level of plasma uric acid concentration. No effects were observed in the final period (35 to 42 days of age) and total period (1 to 42 days of age) it was not demonstrated effect of the contrasts tested in this study.

New treatments for chronic hepatitis C / 대한간학회지

Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C.

Affinity labels as probes for the study of the nucleotide binding site of enzymes

Affinity labeling has proved to be a very useful tool for searching important amino acid residues located in active or allosteric sites of enzymes. In this article, the general principles and specific examples of the use of affinity labeling are discussed

Analysis of codon usage: positional preference in various organisms.

The degree of preference of the four nucleotides C, G, A and U in the three positions I, II and III of the codons of 15137 genes of various individual organisms is examined using the nucleotide sequence data obtained from the GenBank Genetic Sequence Data Bank (Release 65.0, Sep., 1990). It is found that G, A and C, are preferred maximally in the three positions respectively. Similarly, U, G and A are preferred minimally in these positions. The analysis shows a correlation in the positional base preference which discriminates against codons with the same base in all three positions or in the adjacent positions.

Los nucleótidos como nutrimentos ¿Son semiesenciales para los neonatos? / The nucleotides. It is essentials for neonates?

La adición de nucleótidos a las fórmulas de iniciación se ha hecho en base al papel que juegan estos compuestos químicos en las diferentes facetas del proceso de maduración del niño, durante los primeros meses de la vida. En este informe se revisan los estudios en que fundamenta la decisión de incluirlos en las fómulas lácteas