Ventilatory responses of trained and untrained subjects during running and walking

To investigate the influence of stride frequency on ventilation in different subject populations, the ventilatory responses to walking and running at similar metabolic loads were studied in 29 males. Ten of the males were well-trained, highly fit runners (HFR), ten were well-trained, highly fit cyclists (HFC), and nine were healthy low-fit males (LFM) who did not engage in any form of regular exercise. All subjects completed two separate exercise bouts, a level run and an uphill walk, at 90% of their ventilatory threshold. Stride frequency was found to increase by 49% between the walk and run trials. Minute ventilation (V̇E), tidal volume (VT), breathing frequency (f), end-tidal CO2 tension (PETCO2), end-tidal O2 tension (PETO2), and inspiratory time (TI) were all significantly different (P2, PETO2, and TI were significantly different. Only PETCO2 and TI were found to be significantly different between the walk and run trials for the LFM. These results suggest that stride frequency affects ventilation to varying degrees dependent upon the subject population and that the mechanisms for the hyperpnea of moderate exercise operating in each of these subject populations involve a complex interaction of many factors

Early markers of periodontal disease and altered oral microbiota are associated with glycemic control in children with type 1 diabetes

Objectives: To determine the relationship between periodontal disease and glycemic control in children with type 1 diabetes and to characterize the diversity and composition of their oral microbiota. Methods: Cross-sectional study including children with type 1 diabetes recruited from clinics at the Women's and Children's Hospital (Australia). Participants had a comprehensive dental assessment, periodontal examination, and buccal and gingival samples collected for 16S rRNA sequencing. Results: Seventy-seven participants (age 13.3 ± 2.6 years, 38 males, BMI z-score 0.81 ± 0.75) had a diabetes duration of 5.6 ± 3.9 years and median HbA1c of 8.5% (range 5.8–13.3), 69.4 mmol/mol (range 39.9–121.9). Thirty-eight (49%) had early markers of periodontal disease. HbA1c was positively correlated with plaque index (Rho = 0.34, P = 0.002), gingival index (Rho = 0.30, P = 0.009), bleeding on probing (Rho = 0.44, P = 0.0001) and periodontal pocket depth >3 mm (Rho = 0.21, P = 0.06). A 1% increase in HbA1c was independently associated with an average increase in bleeding on probing of 25% (P = 0.002) and with an increase in the rate of sites with pocket depth >3 mm of 54% (P = 0.003). Higher HbA1c was independently related to increased phylogenetic alpha diversity (P = 0.008) and increased compositional variation (beta diversity P = 0.02) in gingival, but not buccal, microbiota. Brushing frequency, plaque index, and gingival index had a significant effect on microbiota composition, independent of HbA1c. Conclusions: Children with type 1 diabetes showed a continuous relationship between less favorable glycemic control and increased early markers of periodontal disease. Glycemic control was also related to the complexity and richness of the plaque microbiota, with diversity increasing as HbA1c levels increase.Emilija D. Jensen, Caitlin A. Selway, Gabrielle Allen, Jana Bednarz, Laura S. Weyrich, Sam Gue, Alexia S. Peña, Jennifer Coupe

Longitudinal RNA-Seq analysis of the reeatability of gene expression and splicing in human platelets identifies a platelet <em>SELP</em> splice QTL.

Rationale:Longitudinal studies are required to distinguish within versus between-individual variation and repeatability of gene expression. They are uniquely positioned to decipher genetic signal from environmental noise, with potential application to gene variant and expression studies. However, longitudinal analyses of gene expression in healthy individuals-especially with regards to alternative splicing-are lacking for most primary cell types, including platelets.Objective:To assess repeatability of gene expression and splicing in platelets and use repeatability to identify novel platelet expression quantitative trait loci (QTLs) and splice QTLs.Methods and Results:We sequenced the transcriptome of platelets isolated repeatedly up to 4 years from healthy individuals. We examined within and between individual variation and repeatability of platelet RNA expression and exon skipping, a readily measured alternative splicing event. We find that platelet gene expression is generally stable between and within-individuals over time-with the exception of a subset of genes enriched for the inflammation gene ontology. We show an enrichment among repeatable genes for associations with heritable traits, including known and novel platelet expression QTLs. Several exon skipping events were also highly repeatable, suggesting heritable patterns of splicing in platelets. One of the most repeatable was exon 14 skipping of SELP. Accordingly, we identify rs6128 as a platelet splice QTL and define an rs6128-dependent association between SELP exon 14 skipping and race. In vitro experiments demonstrate that this single nucleotide variant directly affects exon 14 skipping and changes the ratio of transmembrane versus soluble P-selectin protein production.Conclusions:We conclude that the platelet transcriptome is generally stable over 4 years. We demonstrate the use of repeatability of gene expression and splicing to identify novel platelet expression QTLs and splice QTLs. rs6128 is a platelet splice QTL that alters SELP exon 14 skipping and soluble versus transmembrane P-selectin protein production