DNA methyltransferase expression in the mouse germ line during periods of de novo methylation

DNA methyltransferase (DNMT) 3A and DNMT3B are both active de novo DNA methyltransferases required for development, whereas DNMT3L, which has no demonstrable methyltransferase activity, is required for methylation of imprinted genes in the oocyte. We show here that different mechanisms are used to restrict access by these proteins to their targets during germ cell development. Transcriptional control of the Dnmt3l promoter guarantees that message is low or absent except during periods of de novo activity. Use of an alternative promoter at the Dnmt3a locus produces the shorter Dnmt3a2 transcript in the germ line and postimplantation embryo only, whereas alternative splicing of the Dnmt3b transcript ensures that Dnmt3b1 is absent in the male prospermatogonia. Control of subcellular protein localization is a common theme for DNMT3A and DNMT3B, as proteins were seen in the nucleus only when methylation was occurring. These mechanisms converge to ensure that the only time that functional products from each locus are present in the germ cell nuclei is around embryonic day 17.5 in males and after birth in the growing oocytes in females.

Determining optimal duration of seed translocation periods for benthic mussel (Mytilus edulis) cultivation using physiological and behavioural measures of stress

During the benthic cultivation process of Mytilus edulis (blue mussels), wild mussel seed is often transplanted from naturally occurring subtidal beds to sheltered in-shore waters to be grown to a commercial size. The survival of these relaid mussels is ultimately a function of their quality and physiological condition upon relaying and it has been recognised that mussels can suffer from a loss in condition following transportation. We investigated whether the process of being transported to ongrowing plots had a negative effect on the physiological health and resultant behaviour of mussels by simulating transportation conditions in a controlled experiment. Mussels were kept, out of water, in plastic piping to recreate translocation conditions and further, we tested if depth held in a ship hold (0, 1.5 and 3 m) and length of time emersed (12, 24 and 48 h) affected mussel condition and behaviour. Physiological condition was assessed by quantifying mussel tissue pH and whole tissue glucose, glycogen, succinate and propionate concentrations. The rate of byssogenesis was also quantified to estimate recovery following a period of re-immersion. The depth at which mussels were held did not affect any of the physiological indicators of mussel stress but short-term byssus production was affected. Mussels held at 3 m produced fewer byssus threads during the first 72 h following re-immersion compared with mussels at 0 m (i.e. not buried) suggesting that depth held can impede recovery following transportation. Duration of emersion affected all stress indicators. Specifically, mussels held out of water for 48 h had a reduced physiological condition compared with those emersed for just 12 h. This work has practical implications for the benthic cultivation industry and based on these results we recommend that mussels are held out of water for less than 24 h prior to relaying to ensure physiological health and resultant condition is preserved.

Energy compensation in the real world: Good compensation for small portions of chocolate and biscuits over short time periods in complicit consumers using commercially available foods

While investigations using covert food manipulations tend to suggest that individuals are poor at adjusting for previous energy intake, in the real world adults rarely consume foods of which they are ill-informed. This study investigated the impact in fully complicit consumers of consuming commercially available dark chocolate, milk chocolate, sweet biscuits and fruit bars on subsequent appetite. Using a repeated measures design, participants received four small portions (4 × 10-11 g) of either dark chocolate, milk chocolate, sweet biscuits, fruit bars or no food throughout five separate study days (counterbalanced in order), and test meal intake, hunger, liking and acceptability were measured. Participants consumed significantly less at lunch following dark chocolate, milk chocolate and sweet biscuits compared to no food (smallest t(19) = 2.47, p = 0.02), demonstrating very good energy compensation (269-334%). No effects were found for fruit bars (t(19) = 1.76, p = 0.09), in evening meal intakes (F(4,72) = 0.62, p = 0.65) or in total intake (lunch + evening meal + food portions) (F(4,72) = 0.40, p = 0.69). No differences between conditions were found in measures of hunger (largest F(4,76) = 1.26, p = 0.29), but fruit bars were significantly less familiar than all other foods (smallest t(19) = 3.14, p = 0.01). These findings demonstrate good compensation over the short term for small portions of familiar foods in complicit consumers. Findings are most plausibly explained as a result of participant awareness and cognitions, although the nature of these cognitions cannot be discerned from this study. These findings however, also suggest that covert manipulations may have limited transfer to real world scenarios.

Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium

BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.

METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.

RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.

CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

Are older people prescribed antidepressants on the basis of fewer symptoms of depression, and for longer periods of time? A survey of 1825 New Zealanders

Aims: To determine whether older people are prescribed antidepressants at lower levels of depression and with fewer symptoms, and whether they are more likely to engage in chronic usage. Methods: An online survey about experiences with, and opinions about, depression and antidepressants, was completed by 1,825 New Zealand adults who had been prescribed antidepressants in the preceding five years. Results: Participants over 55 were prescribed antidepressants with significantly fewer symptoms and were significantly less likely to meet DSM criteria for depression. They were also significantly more likely to have used the drugs for three years and still be using them. Conclusions: Prescribing physicians and their older patients might benefit from discussing the pros and cons of antidepressants (including the additional risk factors with this age group) and the alternatives; and, if prescription does occur, careful monitoring to avoid unnecessary, potentially damaging, long-term use is recommended.

Changing patterns of first injection across key periods of the French Harm Reduction Policy: PrimInject, a cross sectional analysis

Background: Monitoring of emerging modes of drug consumption in France has identified new patterns of injection among youths with diverse social backgrounds, which may explain the persistence of high rates of hepatitis C virus infection. The circumstances surrounding the first injection have been poorly documented in the group of heavy drug users and in the context of the French opioid substitution treatment (OST) policy that provides expanded access to high-dosage buprenorphine (BHD). Methods: An Internet survey (Priminject) was conducted from October 2010 to March 2011 with French drug users. Four time periods were compared based on critical dates throughout the implementation of the Harm Reduction Policy in France. Results: Compared with drug users who injected for the first time prior to 1995, the aspects of drug use for users who recently injected for the first time were as follows: (1) experimentation with miscellaneous drugs before the first injection; (2) an older age at the time of first injection; (3) heroin as the drug of choice for an individual’s first injection, notwithstanding the increased usage of stimulant drugs; (4) BHD did not appear to be a pathway to injection; and (5) an increased number of users who injected their first time alone, without the help or presence of another individual. Conclusion: The PrimInject study showed that there is a group of injection drug users that is larger than the group of injection drug users observed in previous studies; therefore, it is necessary to diversify programs to reach the entire spectrum of high-risk users.

Dynamic adaptation of stability periods for service level agreements

A QoS adaptation to dynamically changing system conditions that takes into consideration the user’s constraints on the stability of service provisioning is presented. The goal is to allow the system to make QoS adaptation decisions in response to fluctuations in task traffic flow, under the control of the user. We pay special attention to the case where monitoring the stability period and resource load variation of Service Level Agreements for different types of services is used to dynamically adapt future stability periods, according to a feedback control scheme. System’s adaptation behaviour can be configured according to a desired confidence level on future resource usage. The viability of the proposed approach is validated by preliminary experiments.

Identifying economic periods and crisis with the multidimensional scaling

This paper applied MDS and Fourier transform to analyze different periods of the business cycle. With such purpose, four important stock market indexes (Dow Jones, Nasdaq, NYSE, S&P500) were studied over time. The analysis under the lens of the Fourier transform showed that the indexes have characteristics similar to those of fractional noise. By the other side, the analysis under the MDS lens identified patterns in the stock markets specific to each economic expansion period. Although the identification of patterns characteristic to each expansion period is interesting to practitioners (even if only in a posteriori fashion), further research should explore the meaning of such regularities and target to find a method to estimate future crisis.

Randomized observation periods for the compound Poisson risk model: Dividends

In the framework of the classical compound Poisson process in collective risk theory, we study a modification of the horizontal dividend barrier strategy by introducing random observation times at which dividends can be paid and ruin can be observed. This model contains both the continuous-time and the discrete-time risk model as a limit and represents a certain type of bridge between them which still enables the explicit calculation of moments of total discounted dividend payments until ruin. Numerical illustrations for several sets of parameters are given and the effect of random observation times on the performance of the dividend strategy is studied.

Beyond child's play : wealth, status, and the death of children in the MH-LH I periods of the Argolid, Greece

This study explores the mortuary remains of children from the MH-LH I periods of the Argolid, Greece. This examination concentrates on how the child in death acted as a tool for wealth and status display. Here, children are understood to have perpetuated, maintained, and reinforced status distinctions between families in their community. The analysis of one hundred child burials that date to these periods illustrates how the burials of children were important opportunities used by the families of children to display wealth and status. Thus, children can be viewed as important factors in the reorganization of social structure in the transition from the Middle to Late Helladic.

Queueing Theory And Other Applications Of Stochastic Processes Queueing And Inventory Models With Rest Periods

In this thesis we study the effect of rest periods in queueing systems without exhaustive service and inventory systems with rest to the server. Most of the works in the vacation models deal with exhaustive service. Recently some results have appeared for the systems without exhaustive service.

Changes in amino acid enantiomers and microbial performance in soils from a subtropical mountain oasis in Oman abandoned for different periods

An important feature of maintaining the agricultural stability in millennia-old mountain oases of northern Oman is the temporary abandonment of terraces. To analyse the effects of a fallow period on soil microbial performance, i.e. microbial activity and microbial biomass, samples of eight terrace soils abandoned for different periods were collected in situ, assigned to four fallow age classes and incubated for 30 days in the laboratory after rewetting. The younger fallow age classes of 1 and 5 years were based on the records of the farmers’ recollections, the two older fallow age classes of 10–20 and 25–60 years according to the increase in the D -to- L ratio of valine and leucine enantiomers. The increase in these two ratios was in agreement with that of the D -to- L ratio of lysine. The strongest relationship was observed between the increase in the D -to- L ratio of lysine and the decrease in soil microbial biomass C. However, the most stringent coherence between the increase in fallow age and soil properties was revealed by the decreases in cumulative respiration and net N mineralisation rates with decreasing availability of substrate to soil microorganisms. During the 30-day incubation following rewetting, relative changes in microbial activity (respiration and net N mineralisation) and microbial biomass (C and N)indices were similar in the eight terrace soils on a fallow age-class-specific level, indicating that the same basic processes occurred in all of the sandy terrace soils investigated.