The polyphenol epigallocatechin gallate lowers circulating catecholamine concentrations and alters lipid metabolism during graded exercise in man: a randomized cross-over study.

PURPOSE: Physical exercise is shown to mitigate catecholamine metabolites; however, it is unknown if exercise-induced increases in sympatho-adrenal activity or catecholamine metabolites are influenced by ingestion of specific catechins found within green tea. This study explored the impact of epigallocatechin gallate (EGCG) ingestion on catecholamine metabolism during graded cycle exercise in humans. METHODS: Eight males (22.4 ± 3.3 years, BMI:25.7 ± 2.4 kg.m2) performed a randomised, placebo-controlled, single-blind, cross-over trial after consumption (1450 mg) of either EGCG or placebo (PLAC) and performed graded cycling to volitional exhaustion. Venous bloods were taken at rest, 2 h post-ingestion and after every 3-min stage. Blood variables were analysed for catecholamines, catecholamine metanephrines and metabolic variables at rest, 2 h post-ingestion (POST-ING), peak rate of lipid oxidation (FATpeak), lactate threshold (LT) and peak rate of oxygen consumption (VO2peak). Data were analysed using SPSS (Version 26). RESULTS: Resting catecholamine and metanephrines were similar between trials. Plasma adrenaline (AD) was lower in ECGC treatment group between trials at FATpeak (P < 0.05), LT (P < 0.001) and VO2peak (P < 0.01). Noradrenaline (NA) was lower under EGCG at POST (P < 0.05), FATpeak (P < 0.05), LT (P < 0.01) and VO2peak (P < 0.05) compared to PLAC. Metanephrines, glucose and lactate increased similarly with exercise intensity in both trials. Lipid oxidation rate was 32% lower in EGCG at FATpeak (EGCG 0.33 ± 0.14 vs. PLAC 0.49 ± 0.11 g.min-1, P < 0.05). Cycle time to exhaustion was similar (NS). CONCLUSION: Acute EGCG supplementation reduced circulating catecholamines but not; metanephrine, glucose or lactates, response to graded exercise. Lower circulating catecholamines may explain a lower lipid oxidation rate.

A Predictor of Early Disease Recurrence in Patients With Breast Cancer Using a Cell-free RNA and Protein Liquid Biopsy.

INTRODUCTION: Circulating biomarkers have been increasingly used in the clinical management of breast cancer. The present study evaluated whether RNAs and a protein present in the plasma of patients with breast cancer might have utility as prognostic biomarkers complementary to existing clinical tests. PATIENTS AND METHODS: We performed microarray profiling of small noncoding RNAs in plasma samples from 30 patients with breast cancer and 10 control individuals. Two small noncoding RNAs, including microRNA (miR)-923, were selected and quantified in plasma samples from an evaluation cohort of 253 patients with breast cancer, using droplet digital polymerase chain reaction. We also measured cancer antigen (CA) 15-3 protein levels in these samples. Cox regression survival analysis was used to determine which markers were associated with patient prognosis. RESULTS: As independent markers of prognosis, the plasma levels of miR-923 and CA 15-3 at the time of surgery for breast cancer were significantly associated with prognosis, irrespective of treatment (Cox proportional hazards, P = 3.9 × 10-3 and 1.9 × 10-9, respectively). After building a multivariable model with standard clinical and pathological features, the addition of miR-923 and CA 15-3 information into the model resulted in a significantly better predictor of disease recurrence in patients, irrespective of treatment, compared with the use of clinicopathological data alone (area under the curve at 3 years, 0.858 vs. 0.770 with clinicopathological markers only; P = .017). CONCLUSION: We propose that the plasma levels of miR-923 and CA 15-3, combined with standard clinicopathological predictors, could be used as a preoperative, noninvasive estimate of patient prognosis to identify which women might need more aggressive treatment or closer surveillance after surgery for breast cancer.

Comparison of Huntington's disease CAG Repeat Length Stability in Human Motor Cortex and Cingulate Gyrus.

Huntington's disease is caused by expansion of the CAG repeat in Huntingtin. This repeat has shown tissue-specific instability in mouse models and in a small number of post-mortem human samples. We used small-pool PCR to generate a modified instability index to quantify CAG instability within two brain regions from six human samples where cell loss has been associated with motor and mood symptoms: the motor cortex and cingulate gyrus. The expanded allele demonstrated instability in both regions, with minimal instability in the unexpanded allele. Region-specific differences were not observed, suggesting symptomatology may not be determined by repeat length instability.

The complete mitochondrial genomes of two chiton species (Sypharochiton pelliserpentis and Sypharochiton sinclairi) obtained using Illumina next generation sequencing.

Using an Illumina platform, we shot-gun sequenced the complete mitochondrial genomes of two sister chiton species (Sypharochiton pelliserpentis and Sypharochiton sinclairi) to an average coverage of 172× and 60×, respectively. We performed a de novo assembly using SOAPdenovo2 and determined the total mitogenome lengths to be 15,048 and 15,028 bps, respectively. The gene organization was similar to that of other chitons, with 13 protein-coding genes, 24 transfer RNAs and 2 ribosomal RNAs. These data will contribute for resolving the taxonomy and population genetic structures of these species.

High coverage of the complete mitochondrial genome of the rare Gray's beaked whale (Mesoplodon grayi) using Illumina next generation sequencing.

Using an Illumina platform, we shot-gun sequenced the complete mitochondrial genome of Gray's beaked whale (Mesoplodon grayi) to an average coverage of 152X. We performed a de novo assembly using SOAPdenovo2 and determined the total mitogenome length to be 16,347 bp. The nucleotide composition was asymmetric (33.3% A, 24.6% C, 12.6% G, 29.5% T) with an overall GC content of 37.2%. The gene organization was similar to that of other cetaceans with 13 protein-coding genes, 2 rRNAs (12S and 16S), 22 predicted tRNAs and 1 control region or D-loop. We found no evidence of heteroplasmy or nuclear copies of mitochondrial DNA in this individual. Beaked whales within the genus Mesoplodon are rarely seen at sea and their basic biology is poorly understood. These data will contribute to resolving the phylogeography and population ecology of this speciose group.

Identification of regions associated with variation in sensitivity to food-related odors in the human genome.

Humans vary in their ability to smell numerous odors [1-3], including those associated with food [4-6]. Odor sensitivity is heritable [7-11], with examples linking genetic variation for sensitivity to specific odors typically located near olfactory receptor (OR) genes [12-16]. However, with thousands of aromas and few deorphaned ORs [17, 18], there has been little progress toward linking variation at OR loci to odor sensitivity [19, 20]. We hypothesized that OR genes contain the variation that explains much of the differences in sensitivity for odors, paralleling the genetics of taste [21, 22], which affect the flavor experience of foods [23-25]. We employed a genome-wide association approach for ten food-related odors and identified genetic associations to sensitivity for 2-heptanone (p = 5.1 × 10(-8)), isobutyraldehyde (p = 6.4 × 10(-10)), ß-damascenone (p = 1.6 × 10(-7)), and ß-ionone (p = 1.4 × 10(-31)). Each locus is located in/near distinct clusters of OR genes. These findings increase the number of olfactory sensitivity loci to nine and demonstrate the importance of OR-associated variation in sensory acuity for food-related odors. Analysis of genotype frequencies across human populations implies that variation in sensitivity for these odors is widespread. Furthermore, each participant possessed one of many possible combinations of sensitivities for these odors, supporting the notion that everyone experiences their own unique "flavor world."

Chemical discovery and global gene expression analysis in zebrafish.

The zebrafish (Danio rerio) provides an excellent model for studying vertebrate development and human disease because of its ex utero, optically transparent embryogenesis and amenability to in vivo manipulation. The rapid embryonic developmental cycle, large clutch sizes and ease of maintenance at large numbers also add to the appeal of this species. Considerable genomic data has recently become publicly available that is aiding the construction of zebrafish microarrays, thus permitting global gene expression analysis. The zebrafish is also suitable for chemical genomics, in part as a result of the permeability of its embryos to small molecules and consequent avoidance of external confounding maternal effects. Finally, there is increasing characterization and analysis of zebrafish models of human disease. Thus, the zebrafish offers a high-quality, high-throughput bioassay tool for determining the biological effect of small molecules as well as for dissecting biological pathways.