Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population

Age-related changes in DNA methylation have been implicated in cellular senescence and longevity, yet the causes and functional consequences of these variants remain unclear. To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity, we tested for association between whole-blood DNA methylation patterns in 172 female twins aged 32 to 80 with age and age-related phenotypes. Twin-based DNA methylation levels at 26,690 CpG-sites showed evidence for mean genome-wide heritability of 18%, which was supported by the identification of 1,537 CpG-sites with methylation QTLs in cis at FDR 5%. We performed genome-wide analyses to discover differentially methylated regions (DMRs) for sixteen age-related phenotypes (ap-DMRs) and chronological age (a-DMRs). Epigenome-wide association scans (EWAS) identified age-related phenotype DMRs (ap-DMRs) associated with LDL (STAT5A), lung function (WT1), and maternal longevity (ARL4A, TBX20). In contrast, EWAS for chronological age identified hundreds of predominantly hyper-methylated age DMRs (490 a-DMRs at FDR 5%), of which only one (TBX20) was also associated with an age-related phenotype. Therefore, the majority of age-related changes in DNA methylation are not associated with phenotypic measures of healthy ageing in later life. We replicated a large proportion of a-DMRs in a sample of 44 younger adult MZ twins aged 20 to 61, suggesting that a-DMRs may initiate at an earlier age. We next explored potential genetic and environmental mechanisms underlying a-DMRs and ap-DMRs. Genome-wide overlap across cis-meQTLs, genotype-phenotype associations, and EWAS ap-DMRs identified CpG-sites that had cis-meQTLs with evidence for genotype-phenotype association, where the CpG-site was also an ap-DMR for the same phenotype. Monozygotic twin methylation difference analyses identified one potential environmentally-mediated ap-DMR associated with total cholesterol and LDL (CSMD1). Our results suggest that in a small set of genes DNA methylation may be a candidate mechanism of mediating not only environmental, but also genetic effects on age-related phenotypes.     

Autoreceptor control of peptide/neurotransmitter corelease from PDF neurons determines allocation of circadian activity in drosophila

Drosophila melanogaster flies concentrate behavioral activity around dawn and dusk. This organization of daily activity is controlled by central circadian clock neurons, including the lateral-ventral pacemaker neurons (LN(v)s) that secrete the neuropeptide PDF (pigment dispersing factor). Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity. Although LN(v)s also express functional PDFR, the role of these autoreceptors has remained enigmatic. Here, we show that (1) PDFR activation in LN(v)s shifts the balance of circadian activity from evening to morning, similar to behavioral responses to summer-like environmental conditions, and (2) this shift is mediated by stimulation of the Gα,s-cAMP pathway and a consequent change in PDF/neurotransmitter corelease from the LN(v)s. These results suggest another mechanism for environmental control of the allocation of circadian activity and provide new general insight into the role of neuropeptide autoreceptors in behavioral control circuits.     

Potentiation of concentric force and acceleration only occurs early during the stretch-shortening cycle

ABSTRACT: McCarthy, JP, Wood, DS, Bolding, MS, Roy, JLP, and Hunter, GR. Potentiation of concentric force and acceleration only occurs early during the stretch-shortening cycle. J Strength Cond Res 26(9): 2345-2355, 2012-The purpose of this study was to determine where stretch-shortening cycle (SSC) potentiation of force, power, velocity, and acceleration occurs across the concentric phase of ballistic leg presses. Second, we examined the influence of late eccentric phase force and length of the amortization phase on potentiated concentric phase performance variables. Twenty-one male runners (age: 31.9 ± 4.7 years) performed SSC and concentric-only (CO) ballistic leg press throws. Potentiations of concentric actions were calculated as the difference between SSC and CO contractions. An analysis splitting the concentric range of motion (ROM) into 6 equal time intervals determined force and acceleration were potentiated (p < 0.05) only during the first one-sixth time interval of concentric motion, whereas velocity and power were potentiated (p < 0.05) at all time intervals over the entire concentric motion with the exception of power over the last one-sixth time interval. A more precise analysis examining 20-millisecond time intervals across the first 200 milliseconds of concentric motion determined force was potentiated only over the first 140 milliseconds and acceleration only over the first 160 milliseconds. Eccentric force measured during the last 100 milliseconds of eccentric motion was related to potentiated force during the initial 200 milliseconds of concentric motion (r = 0.44, p < 0.05) and potentiated mean power across the full concentric ROM (r = 0.62, p < 0.01). Results indicate that in contrast to power and velocity, potentiation of force and acceleration occurs only early during the concentric phase of SSC ballistic leg presses. Correlational findings imply late eccentric phase force is important for generating force and power during the concentric phase of the SSC and thus training focusing on enhancing late phase eccentric force appears important for developing explosive force and power during SSC movements.     

The rapid spread of rusty crayfish (Orconectes rusticus) with observations on native crayfish declines in Wisconsin (U.S.A.) over the past 130 years

The rusty crayfish, Orconectes rusticus, is one of America’s best-known non-indigenous crayfishes, having been identified as extirpating native crayfishes and disrupting local aquatic ecosystems. Over the past 40–50 years, rusty crayfish have spread from its historical range in the Ohio River drainage (U.S.A.), to waters throughout much of Illinois, Michigan, Wisconsin, and Minnesota and parts of 11 other states, Ontario (Canada) and the Laurentian Great Lakes. Using a comprehensive dataset based on all known historical records and extensive present-day surveys (n = 2775) this study reports on the invasion history of rusty crayfish, with observations on concomitant declines of native crayfishes in Wisconsin over the past 130 years (1870–2004). We found that rusty crayfish occurrences have increased from 7% of all crayfish records collected during the first 20 years of their invasion (1965–1984) to 36% of all records during the last 20 years, and that rusty crayfish have replaced the northern clearwater crayfish (O. propinquus) and virile crayfish (O. virilis) as the most dominant member of the contemporary crayfish fauna. In light of our results we discuss the introduction, establishment and integration phases of the rusty crayfish invasion and provide preliminary predictions of the potential distribution of rusty crayfish in Wisconsin lakes based on critical environmental requirements.     

Survival of Staphylococcus aureus ST398 in the Human Nose after Artificial Inoculation

There is evidence that MRSA ST398 of animal origin is only capable of temporarily occupying the human nose, and it is therefore, often considered a poor human colonizer.We inoculated 16 healthy human volunteers with a mixture of the human MSSA strain 1036 (ST931, CC8) and the bovine MSSA strain 5062 (ST398, CC398), 7 weeks after a treatment with mupirocin and chlorhexidine-containing soap. Bacterial survival was studied by follow-up cultures over 21 days. The human strain 1036 was eliminated faster (median 14 days; range 2–21 days) than the bovine strain 5062 (median 21 days; range 7–21 days) but this difference was not significant (p = 0.065). The bacterial loads were significantly higher for the bovine strain on day 7 and day 21. 4/14 volunteers (28.6%) showed elimination of both strains within 21 days. Of the 10 remaining volunteers, 5 showed no differences in bacterial counts between both strains, and in the other 5 the ST398 strain far outnumbered the human S. aureus strain. Within the 21 days of follow-up, neither human strain 1036 nor bovine strain 5062 appeared to acquire or lose any mobile genetic elements. In conclusion, S. aureus ST398 strain 5062 is capable of adequately competing for a niche with a human strain and survives in the human nose for at least 21 days.     

Environmental change over two decades since dredging and excavation of the lower Boro River, Okavango Delta, Botswana

The Okavango Delta, southern Africa's largest wetland, is situated on the fringe of the semi-arid Kalahari Desert. It is a large alluvial fan, occupying a graben structure which is an extension of the East African Rift system. Of the 16 km³ of water which enters the Delta each year, 96% is lost to the atmosphere by evapotranspiration, 2% to groundwater and only 2% leaves as surface flow. In order to increase surface outflow to meet human needs, the distal Boro channel–floodplain system was dredged, excavated and bunded between 1971 and 1974. The immediate impact of these measures was the destruction of in-channel flora. After 20 years, the aquatic flora has recovered in the excavated channel. However, little recovery has occurred along the channel reach which was dredged. Moreover, there has been significant encroachment of terrestrial species onto the floodplain in the region of the dredged channel. In addition, dredging created a nick point which has been migrating upstream by headward erosion since dredging ceased. The average rate of advance of the nick point has been about 500 m per year. Incision associated with nick point migration has produced a channel which is indistinguishable in form from the dredged channel and, like the dredged channel, is almost completely devoid of in-channel aquatic flora. The adverse environmental impact of dredging has therefore continued to propagate in an upstream direction, although the height of the nick point has decreased, suggesting a natural attenuation process. This is likely to result in eventual elimination of the nick point.     

Identifying hotspots of alien plant naturalisation in Australia: approaches and predictions

The early detection of newly naturalised alien species is vital to ensuring the greatest chance of their successful eradication. Understanding where species naturalise most frequently is the first stage in allocating surveillance effort. Using Australia’s Virtual Herbarium, we compiled the collection records for all plant species in Australia. We controlled for potential spatial biases in collection effort to identify areas that have an elevated rate of first records of alien species’ occurrence in Australia. Collection effort was highly variable across Australia, but the most intense collection effort occurred either close to herbaria (located in cities) or in remote natural environments. Significant clusters of first records of occurrence were identified around each state’s capital city, coinciding with higher collection effort. Using Poisson point process modelling, we were able to determine the relative influence of environmental and anthropogenic factors on the spatial variation in the risk of species naturalisation. Effort-corrected naturalisation risk appeared to be strongly related to land use, road and human population densities, as well as environmental factors such as average temperature and rainfall. Our paper illustrates how the risk of naturalisation at a location can be estimated quantitatively. Improved understanding of factors that contribute to naturalisation risk enhances allocation of surveillance effort, thereby detecting novel species sooner, and increasing the likelihood of their eventual eradication.