Abstract
The small subunit ribosomal RNA gene (16S rRNA) has been successfully used to catalogue and study the diversity of prokaryotic species and communities but it offers limited resolution at the ...species and finer levels, and cannot represent the whole-genome diversity and fluidity. To overcome these limitations, we introduced the Microbial Genomes Atlas (MiGA), a webserver that allows the classification of an unknown query genomic sequence, complete or partial, against all taxonomically classified taxa with available genome sequences, as well as comparisons to other related genomes including uncultivated ones, based on the genome-aggregate Average Nucleotide and Amino Acid Identity (ANI/AAI) concepts. MiGA integrates best practices in sequence quality trimming and assembly and allows input to be raw reads or assemblies from isolate genomes, single-cell sequences, and metagenome-assembled genomes (MAGs). Further, MiGA can take as input hundreds of closely related genomes of the same or closely related species (a so-called 'Clade Project') to assess their gene content diversity and evolutionary relationships, and calculate important clade properties such as the pangenome and core gene sets. Therefore, MiGA is expected to facilitate a range of genome-based taxonomic and diversity studies, and quality assessment across environmental and clinical settings. MiGA is available at http://microbial-genomes.org/.
What a strain is and how many strains make up a natural bacterial population remain elusive concepts despite their apparent importance for assessing the role of intra-population diversity in disease ...emergence or response to environmental perturbations. To advance these concepts, we sequenced 138 randomly selected Salinibacter ruber isolates from two solar salterns and assessed these genomes against companion short-read metagenomes from the same samples. The distribution of genome-aggregate average nucleotide identity (ANI) values among these isolates revealed a bimodal distribution, with four-fold lower occurrence of values between 99.2% and 99.8% relative to ANI >99.8% or <99.2%, revealing a natural "gap" in the sequence space within species. Accordingly, we used this ANI gap to define genomovars and a higher ANI value of >99.99% and shared gene-content >99.0% to define strains. Using these thresholds and extrapolating from how many metagenomic reads each genomovar uniquely recruited, we estimated that -although our 138 isolates represented about 80% of the Sal. ruber population- the total population in one saltern pond is composed of 5,500 to 11,000 genomovars, the great majority of which appear to be rare in-situ. These data also revealed that the most frequently recovered isolate in lab media was often not the most abundant genomovar in-situ, suggesting that cultivation biases are significant, even in cases that cultivation procedures are thought to be robust. The methodology and ANI thresholds outlined here should represent a useful guide for future microdiversity surveys of additional microbial species.
We studied the blood pressure lowering effects of a bout of exercise and/or antihypertensive medicine with the goal of studying if exercise could substitute or enhance pharmacologic hypertension ...treatment. Twenty‐three hypertensive metabolic syndrome patients chronically medicated with angiotensin II receptor 1 blockade antihypertensive medicine underwent 24‐hr monitoring in four separated days in a randomized order; (a) after taking their habitual dose of antihypertensive medicine (AHM trial), (b) substituting their medicine by placebo medicine (PLAC trial), (c) placebo medicine with a morning bout of intense aerobic exercise (PLAC+EXER trial) and (d) combining the exercise and antihypertensive medicine (AHM+EXER trial). We found that in trials with AHM subjects had lower plasma aldosterone/renin activity ratio evidencing treatment compliance. Before exercise, the trials with AHM displayed lower systolic (130 ± 16 vs 133 ± 15 mm Hg; P = .018) and mean blood pressures (94 ± 11 vs 96 ± 10 mm Hg; P = .036) than trials with placebo medication. Acutely (ie, 30 min after treatments) combining AHM+EXER lowered systolic blood pressure (SBP) below the effects of PLAC+EXER (−8.1 ± 1.6 vs −4.9 ± 1.5 mm Hg; P = .015). Twenty‐four hour monitoring revealed no differences among trials in body motion. However, PLAC+EXER and AHM lowered SBP below PLAC during the first 10 hours, time at which PLAC+EXER effects faded out (ie, at 19 PM). Adding exercise to medication (ie, AHM+EXER) resulted in longer reductions in SBP than with exercise alone (PLAC+EXER). In summary, one bout of intense aerobic exercise in the morning cannot substitute the long‐lasting effects of antihypertensive medicine in lowering blood pressure, but their combination is superior to exercise alone.
Aerobic interval training (AIT) improves the health of metabolic syndrome patients (MetS) more than moderate intensity continuous training. However, AIT has not been shown to reverse all metabolic ...syndrome risk factors, possibly due to the limited duration of the training programs. Thus, we assessed the effects of 6 months of AIT on cardio‐metabolic health and muscle metabolism in middle‐aged MetS. Eleven MetS (54.5±0.7 years old) underwent 6 months of 3 days a week supervised AIT program on a cycle ergometer. Cardio‐metabolic health was assessed, and muscle biopsies were collected from the vastus lateralis prior and at the end of the program. Body fat mass (−3.8%), waist circumference (−1.8%), systolic (−10.1%), and diastolic (−9.3%) blood pressure were reduced, whereas maximal fat oxidation rate and VO2peak were significantly increased (38.9% and 8.0%, respectively; all P<.05). The remaining components of cardio‐metabolic health measured (body weight, blood cholesterol, triglycerides, and glucose) were not changed after the intervention, and likewise, insulin sensitivity (CSi) remained unchanged. Total AMPK (23.4%), GLUT4 (20.5%), endothelial lipase (33.3%) protein expression, and citrate synthase activity (26.0%) increased with training (P<.05). Six months of AIT in MetS raises capacity for fat oxidation during exercise and increases VO2peak in combination with skeletal muscle improvements in mitochondrial enzyme activity. Muscle proteins involved in glucose, fat metabolism, and energy cell balance improved, although this was not reflected by parallel improvements in insulin sensitivity or blood lipid profile.
Bacterial strains and clonal complexes are two cornerstone concepts for microbiology that remain loosely defined, which confuses communication and research. Here we identify a natural gap in genome ...sequence comparisons among isolate genomes of all well-sequenced species that has gone unnoticed so far and could be used to more accurately and precisely define these and related concepts compared to current methods. These findings advance the molecular toolbox for accurately delineating and following the important units of diversity within prokaryotic species and thus should greatly facilitate future epidemiological and micro-diversity studies across clinical and environmental settings.
We studied if salt and water ingestion alleviates the physiological strain caused by dehydrating exercise in the heat. Ten trained male cyclists (
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: 60 ± 7 mL/kg/min) completed three ...randomized trials in a hot‐dry environment (33 °C, 30% rh, 2.5 m/s airflow). Ninety minutes before the exercise, participants ingested 10 mL of water/kg body mass either alone (CON trial) or with salt to result in concentrations of 82 or 164 mM Na+ (ModNa+ or HighNa+ trial, respectively). Then, participants cycled at 63% of
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for 120 min immediately followed by a time‐trial. After 120 min of exercise, the reduction in plasma volume was lessened with ModNa+ and HighNa+ trials (−11.9 ± 2.1 and −9.8 ± 4.2%) in comparison with CON (−16.4 ± 3.2%; P < 0.05). However, heat accumulation or dissipation (forearm skin blood flow and sweat rate) were not improved by salt ingestion. In contrast, both salt trials maintained cardiac output (∼1.3 ± 1.4 L/min; P < 0.05) and stroke volume (∼10 ± 11 mL/beat; P < 0.05) above CON after 120 min of exercise. Furthermore, the salt trials equally improved time‐trial performance by 7.4% above CON (∼289 ± 42 vs 269 ± 50 W, respectively; P < 0.05). Our data suggest that pre‐exercise ingestion of salt plus water maintains higher plasma volume during dehydrating exercise in the heat without thermoregulatory effects. However, it maintains cardiovascular function and improves cycling performance.
Over the last fifteen years, genomics has become fully integrated into prokaryotic systematics. The genomes of most type strains have been sequenced, genome sequence similarity is widely used for ...delineation of species, and phylogenomic methods are commonly used for classification of higher taxonomic ranks. Additionally, environmental genomics has revealed a vast diversity of as-yet-uncultivated taxa. In response to these developments, a new code of nomenclature, the Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode), has been developed over the last two years to allow naming of Archaea and Bacteria using DNA sequences as the nomenclatural types. The SeqCode also allows naming of cultured organisms, including fastidious prokaryotes that cannot be deposited into culture collections. Several simplifications relative to the International Code of Nomenclature of Prokaryotes (ICNP) are implemented to make nomenclature more accessible, easier to apply and more readily communicated. By simplifying nomenclature with the goal of a unified classification, inclusive of both cultured and uncultured taxa, the SeqCode will facilitate the naming of taxa in every biome on Earth, encourage the isolation and characterization of as-yet-uncultivated taxa, and promote synergies between the ecological, environmental, physiological, biochemical, and molecular biological disciplines to more fully describe prokaryotes.
To examine the relationship between changes in cardiorespiratory fitness (CRF; estimated by VO2max) and metabolic syndrome (MetS) after an exercise training intervention to confirm/contradict the ...high association found in cross-sectional observational studies.
MetS individuals (54 ± 8 yrs old; BMI of 32 ± 5) were randomly allocated (6:1 ratio) to a group that exercised trained for 16-weeks (EXER; n = 138) or a control sedentary group (CONT; n = 22). At baseline, MetS components, body composition and exercise responses were similar between groups (all P > 0.05). After 16 weeks of intervention, only EXER reduced body weight, waist circumference (−1.21 ± 0.22 kg and −2.7 ± 0.3 cm; P < 0.001), mean arterial blood pressure and hence the composite MetS Z-score (−7.06 ± 0.77 mmHg and −0.21 ± 0.03 SD; P < 0.001). In the EXER group, CRF increased by 16% (0.302 ± 0.026, 95% CI 0.346 to 0.259 LO2·min−1; P < 0.001) but was not a significant predictor of MetS Z-score improvements (r = −0.231; β = −0.024; P = 0.788). Instead, body weight reductions predicted 25% of MetS Z-score changes (r = 0.508; β = 0.360; P = 0.001).
In MetS individuals, the exercise-training increases in CRF are not predictive of the improvements in their health risk factors. Instead, body weight loss (<2%) was a significant contributor to the improved MetS Z-score and thus should be emphasized in exercise training programs.
ClinicalTrials.gov identifier: NCT03019796.
•Fat but fit paradigm favors cardiorespiratory fitness (CRF) over body fat reductions.•We exercise-trained 138 metabolic syndrome (MetS) individuals with abdominal obesity.•MetS health improvements were associated with body weight losses rather than with CRF increases.•Clinical advice should return to emphasize body weight loss in exercise programs.
To determine whether exercise training improves insulin actions through concomitant body weight loss (BWL).
Subjects (aged 55±8 years) with metabolic syndrome (MetS), prediabetes (fasting blood ...glucose: 111±2mg·dL−1, HbA1c: 5.85±0.05%) and abdominal obesity (waist circumference: 104±7.9cm) were randomly allocated to either a group performing aerobic interval training (EXER; n=76) or a sedentary group receiving lifestyle counselling (CONT; n=20) for 16 weeks.
At baseline, insulin sensitivity (according to HOMA2 and intravenous glucose tolerance test; CSI), body composition and VO2max were similar between the groups. After the intervention, both groups had similar BWL (1–2%), but only the EXER group showed decreased mean (95% CI) trunk fat mass from 18.2 (17.4–18.9) to 17.3kg (16.6–17.9); P<0.001 and HOMA2 scores from 1.6 (1.5–1.7) to 1.4 (1.3–1.5); P=0.001, and increased VO2max from 2.07 (1.92–2.21) to 2.28 (2.11–2.45) LO2·min−1; P<0.001. However, CSI did not improve in any group. Within-group subdivision by BWL (≤0%, 0–3%, ≥3%) revealed higher CSI in those with BWL≥3% in both groups. Trunk fat mass reductions were closely associated with CSI and HOMA-IR improvement (r=−0.452–0.349; P<0.001).
In obese MetS subjects with prediabetes, 3% BWL is required for consistent improvement in insulin sensitivity. Thus, exercise-training programmes should be combined with calorie restriction to achieve BWL levels that prevent the development of diabetes.
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