Genomic stability over 9 years of an isoniazid resistant Mycobacterium tuberculosis outbreak strain in Sweden

In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e.g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance.     

Suspected motor problems and low preference for active play in childhood are associated with physical inactivity and low fitness in adolescence

Background

This prospective longitudinal study investigates whether suspected motor problems and low preference for active play in childhood are associated with physical inactivity and low cardiorespiratory fitness in adolescence.

Methodology/Principal Findings

The study sample consisted of the Northern Finland Birth Cohort 1986 (NFBC 1986) composed of 5,767 children whose parents responded to a postal inquiry concerning their children''s motor skills at age 8 years and who themselves reported their physical activity at age 16 years. Cardiorespiratory fitness was measured with a cycle ergometer test at age 16 years. Odds ratios (OR) and their 95% confidence intervals (95% CI) for the level of physical activity and fitness were obtained from multinomial logistic regression and adjusted for socio-economic position and body mass index. Low preference for active play in childhood was associated with physical inactivity (boys: OR 3.31, 95% CI 2.42–4.53; girls: OR 1.79, 95% CI 1.36–2.36) and low cardiorespiratory fitness (boys: OR 1.87, 95% CI 1.27–2.74; girls: OR 1.52, 95% CI 1.09–2.11) in adolescence. Suspected gross (OR 2.16, 95% CI 1.33–3.49) and fine (OR 1.88, 95% CI 1.35–2.60) motor problems were associated with physical inactivity among boys. Children with suspected motor problems and low preference for active play tended to have an even higher risk of physical inactivity in adolescence.

Conclusions/Significance

Low preference for active play in childhood was associated with physical inactivity and low cardiorespiratory fitness in adolescence. Furthermore, children with suspected motor problems and low preference for active play tended to have an even higher risk of physical inactivity in adolescence. Identification of children who do not prefer active play and who have motor problems may allow targeted interventions to support their motor learning and participation in active play and thereby promote their physical activity and fitness in later life.     

Water loss and temperature interact to compound amphibian vulnerability to climate change

Ectotherm thermal physiology is frequently used to predict species responses to changing climates, but for amphibians, water loss may be of equal or greater importance. Using physical models, we estimated the frequency of exceeding the thermal optimum (T_opt) or critical evaporative water loss (EWL_crit) limits, with and without shade‐ or water‐seeking behaviours. Under current climatic conditions (2002–2012), we predict that harmful thermal (>T_opt) and hydric (>EWL_crit) conditions limit the activity of amphibians during ~70% of snow‐free days in sunny habitats. By the 2080s, we estimate that sunny and dry habitats will exceed one or both of these physiological limits during 95% of snow‐free days. Counterintuitively, we find that while wet environments eliminate the risk of critical EWL, they do not reduce the risk of exceeding T_opt (+2% higher). Similarly, while shaded dry environments lower the risk of exceeding T_opt, critical EWL limits are still exceeded during 63% of snow‐free days. Thus, no single environment that we evaluated can simultaneously reduce both physiological risks. When we forecast both temperature and EWL into the 2080s, both physiological thresholds are exceeded in all habitats during 48% of snow‐free days, suggesting that there may be limited opportunity for behaviour to ameliorate climate change. We conclude that temperature and water loss act synergistically, compounding the ecophysiological risk posed by climate change, as the combined effects are more severe than those predicted individually. Our results suggest that predictions of physiological risk posed by climate change that do not account for water loss in amphibians may be severely underestimated and that there may be limited scope for facultative behaviours to mediate rapidly changing environments.     

The Guinea-Bissau family of Mycobacterium tuberculosis complex revisited

The Guinea-Bissau family of strains is a unique group of the Mycobacterium tuberculosis complex that, although genotypically closely related, phenotypically demonstrates considerable heterogeneity. We have investigated 414 M. tuberculosis complex strains collected in Guinea-Bissau between 1989 and 2008 in order to further characterize the Guinea-Bissau family of strains. To determine the strain lineages present in the study sample, binary outcomes of spoligotyping were compared with spoligotypes existing in the international database SITVIT2. The major circulating M. tuberculosis clades ranked in the following order: AFRI (n = 195, 47.10%), Latin-American-Mediterranean (LAM) (n = 75, 18.12%), ill-defined T clade (n = 53, 12.8%), Haarlem (n = 37, 8.85%), East-African-Indian (EAI) (n = 25, 6.04%), Unknown (n = 12, 2.87%), Beijing (n = 7, 1.68%), X clade (n = 4, 0.96%), Manu (n = 4, 0.97%), CAS (n = 2, 0.48%). Two strains of the LAM clade isolated in 2007 belonged to the Cameroon family (SIT61). All AFRI isolates except one belonged to the Guinea-Bissau family, i.e. they have an AFRI_1 spoligotype pattern, they have a distinct RFLP pattern with low numbers of IS6110 insertions, and they lack the regions of difference RD7, RD8, RD9 and RD10, RD701 and RD702. This profile classifies the Guinea-Bissau family, irrespective of phenotypic biovar, as part of the M. africanum West African 2 lineage, or the AFRI_1 sublineage according to the spoligtyping nomenclature. Guinea-Bissau family strains display a variation of biochemical traits classically used to differentiate M. tuberculosis from M. bovis. Yet, the differential expression of these biochemical traits was not related to any genes so far investigated (narGHJI and pncA). Guinea-Bissau has the highest prevalence of M. africanum recorded in the African continent, and the Guinea-Bissau family shows a high phylogeographical specificity for Western Africa, with Guinea-Bissau being the epicenter. Trends over time however indicate that this family of strains is waning in most parts of Western Africa, including Guinea-Bissau (p = 0.048).     

Thermal biology of genus Liolaemus: A phylogenetic approach reveals advantages of the genus to survive climate change

The trends of body temperatures in the field (T_b) and preferred body temperatures in the laboratory (T_pref) of the genus Liolaemus relative to reproductive mode, air temperature (T_air), precipitation, latitude, and elevation were studied using phylogenetic comparative analysis. Results were discussed in the framework of the evolution of thermal physiology and vulnerability to global climate change. Reproductive mode affects T_b but not T_pref. Whereas T_b and T_pref showed a significant association with T_air, there was no relationship with latitude or elevation.     

Long Telomeres in Blood Leukocytes Are Associated with a High Risk of Ascending Aortic Aneurysm

Ascending aortic aneurysm is a connective tissue disorder. Even though multiple novel gene mutations have been identified, risk profiling and diagnosis before rupture still represent a challenge. There are studies demonstrating shorter telomere lengths in the blood leukocytes of abdominal aortic aneurysm patients. The aim of this study was to measure whether relative telomere lengths are changed in the blood leukocytes of ascending aortic aneurysm patients. We also studied the expression of telomerase in aortic tissue samples of ascending aortic aneurysms. Relative lengths of leukocyte telomeres were determined from blood samples of patients with ascending aortic aneurysms and compared with healthy controls. Telomerase expression, both at the level of mRNA and protein, was quantified from the aortic tissue samples. Mean relative telomere length was significantly longer in ascending aortic aneurysm blood samples compared with controls (T/S ratio 0.87 vs. 0.61, p<0.001). Expressions of telomerase mRNA and protein were elevated in the aortic aneurysm samples (p<0.05 and p<0.01). Our study reveals a significant difference in the mean length of blood leukocyte telomeres in ascending aortic aneurysm and controls. Furthermore, expression of telomerase, the main compensating factor for telomere loss, is elevated at both the mRNA and protein level in the samples of aneurysmal aorta. Further studies will be needed to confirm if this change in telomere length can serve as a tool for assessing the risk of ascending aortic aneurysm.     

Temperament clusters in a normal population: implications for health and disease

Background

The object of this study was to identify temperament patterns in the Finnish population, and to determine the relationship between these profiles and life habits, socioeconomic status, and health.

Methods/Principal Findings

A cluster analysis of the Temperament and Character Inventory subscales was performed on 3,761 individuals from the Northern Finland Birth Cohort 1966 and replicated on 2,097 individuals from the Cardiovascular Risk in Young Finns study. Clusters were formed using the k-means method and their relationship with 115 variables from the areas of life habits, socioeconomic status and health was examined.

Results

Four clusters were identified for both genders. Individuals from Cluster I are characterized by high persistence, low extravagance and disorderliness. They have healthy life habits, and lowest scores in most of the measures for psychiatric disorders. Cluster II individuals are characterized by low harm avoidance and high novelty seeking. They report the best physical capacity and highest level of income, but also high rate of divorce, smoking, and alcohol consumption. Individuals from Cluster III are not characterized by any extreme characteristic. Individuals from Cluster IV are characterized by high levels of harm avoidance, low levels of exploratory excitability and attachment, and score the lowest in most measures of health and well-being.

Conclusions

This study shows that the temperament subscales do not distribute randomly but have an endogenous structure, and that these patterns have strong associations to health, life events, and well-being.     

Variation in telomeric repeats of Scots pine (Pinus sylvestris L.)

The shortening of telomeres, the specific structures at the end of the eukaryotic chromosomes, has been associated with ageing and loss of cell replication or regeneration capacity. The aim of this study was to determine the variation in telomeric repeats during the life-span of Scots pine (Pinus sylvestris L.) by studying different tissues and age groups ranging from immature embryos to cambium, buds, and needles of mature, 200-year-old trees. The telomeric repeats in Scots pine including interstitial and centromeric repeats ranged from 0.9 up to 25 kb, and true telomeres were evaluated to have a mean length of 19.3 kb (±SE 0.17). Telomeres were observed to shorten with increasing tissue differentiation, embryonal samples having the longest repeats with an average length of 21.1 (±0.34) to 21.7 kb (±0.42) and the needles having, on average, the shortest repeats of 18.1 kb (±0.24). After germination, ageing per se had no significant effect on the length of telomeric repeats in cambium, bud, or needle tissues. In the older trees (50–200 years of age), the telomeres in stem cambium showed shortening towards the tree top. This is the first observation on such a position-related variation in telomeric repeats. Finally, there was a remarkable genotypic variation in the length of telomeric repeats, and this was consistent over the tissue types. In the small number of tested donor trees, the genotypic differences were not related to regeneration ability in tissue culture.