DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13? years: Project Ice Storm

Prenatal maternal stress (PNMS) in animals and humans predicts obesity and metabolic dysfunction in the offspring. Epigenetic modification of gene function is considered one possible mechanism by which PNMS results in poor outcomes in offspring. Our goal was to determine the role of maternal objective exposure and subjective distress on child BMI and central adiposity at 13½ years of age, and to test the hypothesis that DNA methylation mediates the effect of PNMS on growth. Mothers were pregnant during the January 1998 Quebec ice storm. We assessed their objective exposure and subjective distress in June 1998. At age 13½ their children were weighed and measured (n = 66); a subsample provided blood samples for epigenetic studies (n = 31). Objective and subjective PNMS correlated with central adiposity (waist-to-height ratio); only objective PNMS predicted body mass index (BMI). Bootstrapping analyses showed that the methylation level of genes from established Type-1 and -2 diabetes mellitus pathways showed significant mediation of the effect of objective PNMS on both central adiposity and BMI. However, the negative mediating effects indicate that, although greater objective PNMS predicts greater BMI and adiposity, this effect is dampened by the effects of objective PNMS on DNA methylation, suggesting a protective role of the selected genes from Type-1 and -2 diabetes mellitus pathways. We provide data supporting that DNA methylation is a potential mechanism involved in the long-term adaptation and programming of the genome in response to early adverse environmental factors.     

Coral reef crisis in deep and shallow reefs: 30 years of constancy and change in reefs of Curacao and Bonaire

Coral reefs are thought to be in worldwide decline but available data are practically limited to reefs shallower than 25 m. Zooxanthellate coral communities in deep reefs (30–40 m) are relatively unstudied. Our question is: what is happening in deep reefs in terms of coral cover and coral mortality? We compare changes in species composition, coral mortality, and coral cover at Caribbean (Curacao and Bonaire) deep (30–40 m) and shallow reefs (10–20 m) using long-term (1973–2002) data from permanent photo quadrats. About 20 zooxanthellate coral species are common in the deep-reef communities, dominated by Agaricia sp., with coral cover up to 60%. In contrast with shallow reefs, there is no decrease in coral cover or number of coral colonies in deep reefs over the last 30 years. In deep reefs, non-agaricid species are decreasing but agaricid domination will be interrupted by natural catastrophic mortality such as deep coral bleaching and storms. Temperature is a vastly fluctuating variable in the deep-reef environment with extremely low temperatures possibly related to deep-reef bleaching. An erratum to this article can be found at     

Oligogenic combinations associated with breast cancer risk in women under 53 years of age

Common, but weakly penetrant, functional polymorphisms probably account for most of the genetic risk for breast cancer in the general population. Current polygenic risk models assume that component genes act independently. To test for potential gene-gene interactions, single nucleotide polymorphisms in ten genes with known or predicted roles in breast carcinogenesis were examined in a case-control study of 631 Caucasian women diagnosed with breast cancer under the age of 53 years and 1,504 controls under the age of 53 years. Association of breast cancer risk with individual genes and with two- and three-gene combinations was analyzed. Sixty-nine oligogenotypes from 37 distinct two- and three-gene combinations met stringent criteria for significance. Significant odds ratios (ORs) covered a 12-fold range: 0.5-5.9. Of the observed ORs, 17% differed significantly from the ORs predicted by a model of independent gene action, suggesting epistasis, i.e., that these genes interact to affect breast cancer risk in a manner not predictable from single gene effects. Exploration of the biological basis for these oligogenic interactions might reveal etiologic or therapeutic insights into breast cancer and other cancers.     

What is an adequate length of baseline in research and clinical practice with chronic headache?

We examined the representativeness of baseline headache diary recording periods of 1, 2, 3, and 4 weeks for three kinds of headache disorder — tension, migraine, and combined migraine and tension. For research purposes at pretreatment, 2 weeks of diary recording are preferable for tension headache, while at least 3 weeks are preferred for migraine and combined headache. At follow-up, 1 week of diary recording appears adequate for all three headache types. Recommendations are also made for clinical practice.This research was supported by grants from NINCDS, NS-23440, and NIMH, MH-41341.     

Plant community responses to 5 years of simulated climate change in meadow and heath ecosystems at a subarctic-alpine site

Climate change was simulated by increasing temperature and nutrient availability in an alpine landscape. We conducted a field experiment of BACI-design (before/after control/impact) running for five seasons in two alpine communities (heath and meadow) with the factors temperature (increase of ca. 1.5–3.0°C) and nutrients (5 g N, 5 g P per m²) in a fully factorial design in northern Swedish Lapland. The response variables were abundances of plant species and functional types. Plant community responses to the experimental perturbations were investigated, and the responses of plant functional types were examined in comparison to responses at the species level. Nutrient addition, exclusively and in combination with enhanced temperature increase, exerted the most pronounced responses at the species-specific and community levels. The main responses to nutrient addition were increases in graminoids and forbs, whereas deciduous shrubs, evergreen shrubs, bryophytes, and lichens decreased. The two plant communities of heath or meadow showed different vegetation responses to the environmental treatments despite the fact that both communities were located on the same subarctic-alpine site. Furthermore, we showed that the abundance of forbs increased in response to the combined treatment of temperature and nutrient addition in the meadow plant community. Within a single-plant functional type, most species responded similarly to the enhanced treatments although there were exceptions, particularly in the moss and lichen functional types. Plant community structure showed BACI responses in that vegetation dominance relationships in the existing plant functional types changed to varying degrees in all plots, including control plots. Betula nana and lichens increased in the temperature-increased enhancements and in control plots in the heath plant community during the treatment period. The increases in control plots were probably a response to the observed warming during the treatment period in the region. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Prominent ears in children younger than 4 years of age: what is the appropriate timing for otoplasty?

The present study was conducted to determine whether otoplasty performed in children younger than 4 years of age has an acceptable long-term outcome. This two-part study consisted of (1) a questionnaire mailed to 481 members of the American Association of Plastic Surgeons to ask their opinion on the timing of otoplasty, and (2) a consecutive series of 12 patients who had otoplasty performed before the age of 4 years. The survey demonstrated that the majority (57 percent) of the respondents perform otoplasty on patients who are aged 5 years or older. The prospective series consisted of 12 patients ranging in age from 9 months to 3 years at the time of the procedure. Otoplasty was bilateral in nine patients and unilateral in three patients. Length of follow-up ranged from 21 months to 7(1/2) years, with a median follow-up of 41 months. Growth following otoplasty was evaluated in three patients who underwent unilateral otoplasty by measuring the length of both ears at the time of final follow-up. No difference in ear length was noted between the sides that were and were not operated on during a follow-up period of 46 to 63 months. Noticeable recurrence was noted in only one (8 percent) of 12 patients. In response to a follow-up questionnaire to the patients' families, all respondents (n = 10) stated that if again asked to choose the timing of otoplasty in their children, they would opt to have it performed at the same age of younger than 4 years. Otoplasty can be safely performed at ages younger than previously thought without interfering with growth of the operated ear.     

Self-perception of self-regulatory skills in children with attention-deficit/hyperactivity disorder aged 8–10 years

Several studies have reported a characteristic "positive illusory bias" in the self-evaluation of children with ADHD. However, results are controversial. The aim of the present study was to investigate whether children with ADHD aged 8 to 10 years can rate their self-regulatory skills accurately when assessed with an age appropriate instrument. Twenty-seven children with ADHD and 27 matched normal control children completed the Self-rating Scale of Self-regulatory Function (SelfReg), a new rating scale that has been specifically designed for this age group. As expected, children with ADHD rated themselves significantly more dysfunctional than control children. In most domains, self-ratings of children with ADHD did not diverge from parent and teacher ratings to a greater extent than self-ratings of control children, although overall results indicated a moderate tendency toward a positive bias. When a cluster analysis based on discrepancies between children's and adults' evaluations was carried out, three groups with different self-rating patterns emerged: A "positive bias" group containing exclusively children with ADHD, a "negative bias" group containing both children with ADHD and control children, and the largest group of accurate self-raters which also included children from both diagnostic groups. It is concluded that overly positive self-judgments are not a ubiquitous finding in ADHD, but may be confined to a specific subgroup of children whose specific characteristics remain to be determined.     

Clinical characterisation and risk stratification of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy ≥50 years of age

Purpose

With the increased use of genetic testing for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), this disease is being increasingly recognised among elderly patients. However, elderly ARVD/C patients were underrepresented in prior cohorts. We aimed to describe the phenotypical characteristics and outcomes among ARVD/C patients surviving ≥50 years.

Methods

We assessed detailed phenotypical data of 29 patients who (1) presented at ≥50 years of age; and (2) fulfilled 2010 Task Force Criteria (TFC) for ARVD/C by last follow-up. Primary outcome was the occurrence of a major ventricular arrhythmia (sudden cardiac death, resuscitated sudden cardiac arrest or sustained ventricular tachycardia).

Results

The majority (55?%) of elderly ARVD/C subjects were male, with a mean age of 59.0 ± 5.8 years at presentation. Study participants fulfilled a median of six (IQR 5–8) TFC criteria by last follow-up, of which arrhythmia criteria were most frequent (97?%), followed by structural criteria (83?%), depolarisation criteria (72?%) and repolarisation criteria (69?%). By last follow-up, 15 (52?%) patients had experienced major ventricular arrhythmias. Most patients (n = 12) presented with this arrhythmia, while three experienced the event during 5.4 ± 3.2 years of follow-up. Compared with patients without an arrhythmic event, patients with major arrhythmias were more likely to be proband (p < 0.001) and male (p = 0.042). Likewise, survival free from sustained ventricular arrhythmia was lower among probands and males.

Conclusion

Phenotypic characteristics of elderly ARVD/C patients are characterised by depolarisation abnormalities and structural cardiac changes. Ventricular arrhythmias in this elderly cohort are associated with male gender and proband status.

     

Transglutaminases and their substrates in biology and human diseases: 50 years of growing

Transglutaminase is an enzyme able to play more than one enzymatic action, acting on a variety of different substrates. The growth of knowledge about the members of the enzyme transglutaminase’s family and its substrates since the last 50 years indicates a large interest and curiosity about this protein, whose function and structure was, but still is, an important object of research. On the other hand, the involvement in a number of human diseases together with the lack of knowledge about the biological functions played by some of the most studied members of this family, make this enzyme a fascinating field of study. The history of this enzyme and its substrates, whose cross-linking action was reported for the first time 50 years ago, suggests that an effort to increase knowledge and communication among researchers is required. To achieve this important result, 10 years ago an internet web page called worldwide happening around transglutaminase (WHAT) was created. Driven by these experiences, novel points-of-view to look at Transglutaminase and its substrates may be identified.     

Trisomy 21 and maternal age of menopause: does reproductive age rather than chronological age influence risk of nondisjunction?

The biological basis underlying the increased risk of nondisjunction in offspring of women of advanced maternal age is not understood. We sought to test the hypothesis that maternal reproductive age (distance in time from approaching menopause) rather than chronological age is pivotal in the etiology of nondisjunction. Our results found no difference in age of menopause between women 30 years old at delivery of a child with trisomy 21 (i.e., age-related nondisjunction) compared to controls. Among women <30 years of age at delivery of a child with trisomy 21, none underwent premature menopause. Therefore, our findings fail to support the theory that reproductive age plays a major role in the etiology of nondisjunction.     

Patterns and rates of erosion in dead Porites across the Great Barrier Reef (Australia) after 2 years and 4 years of exposure

Rates and agents of erosion were investigated experimentally at six sites located along a cross shelf transect from the northern Queensland coast out into the Coral Sea. Rates of internal and external erosion of coral blocks, and accretion by coralline algae were measured after 2 years and 4 years of exposure. Blocks were cut from live colonies of Porites sp., which were collected from the outer barrier reef in north Queensland. They were then washed, dried, measured, weighed and attached to grids that were firmly attached to dead coral substrate at depths of 7–10 m. Significant differences in all three parameters were found within and among sites, and rates increased with increasing duration of exposure. Inshore sites were characterized by low rates of external erosion compared to offshore sites. Agents responsible for internal erosion differed among sites, with boring sponges being most abundant on the two inshore reefs, and molluscs most abundant at the offshore sites. Deposit-feeding polychaetes were more abundant at the two inshore sites, while filter and surface deposit feeders were more common at the offshore sites. Net erosion rates varied among sites (1.090±0.499 to 7.846±3.218 kg m²), and the relative importance of the components of erosion changed markedly along the cross-shelf transect.     

Mediterranean island biodiversity and climate change: the last 10,000 years and the future

Mediterranean islands (MI) are hotspots of global biodiversity and lie in one of the most susceptible to climate change (CC) areas of the world; a big challenge for any conservation strategy. In fact, there is already increasing evidence for CC in the region and associated biological responses in MI ecosystems. These include phenological changes and upward elevation shifts of species and plant communities; although evidence is frequently contrasting for different taxa. Threats are also evident, mainly for endemic species from most taxonomic groups, while communities in mountain and coastal regions are likely to be affected most. For MI conservation under CC additional factors need to be considered: (i) their position at the crossroads of three continents; with which they share common environmental characteristics, (ii) their great variability in sizes and topography and (iii) their climatic differences; with a clear west-east basin divide. CC synergies with changing tourist aspiration and agricultural practices will, in the medium term, modify island landscapes and provide further challenges for biodiversity conservation. Such a combined impact from CC, land-use change, fragmentation of habitats and tourism is difficult to predict. Furthermore, the limited space on islands (especially habitat availability and climatic range limitations) imposes a barrier to species range expansion. Thus, conservation of MI biodiversity under CC requires: (i) future research to focus on improved climate predictions linked to improved understanding of ecological (climate-biotic) responses, incorporating lessons learnt from (island) biogeography, (ii) specific adaptation measures for spatial planning and improvement in regional institutional capacities.     

Cardiovascular causes of sudden unexpected death in children and adolescents (0–17 years)

Background

Little is known about the causes of unexpected death in minors (0–17 years). In young adults an important cause is cardiovascular disease, with primary arrhythmogenic disorders, atherosclerotic events, cardiomyopathies and myocarditis as main contributors. The aim of this autopsy study was to determine the contribution of cardiovascular disease to unexpected death in minors.

Methods and results

In the Netherlands, systematic investigation of all cases of unexplained death in minors was compulsory in a nationwide governmental project during a 15-month period. Autopsies were performed according to a standardised protocol (autopsy rate 85%). A cardiovascular cause of death was found in 13/56 cases (23%). In the group <1 year, the main cardiovascular causes were various congenital defects (n?=?3) and myocarditis (n?=?2). In the 1–9 year group, no cardiovascular causes were found. In the 10–14 year group, hypertrophic cardiomyopathy (n?=?1) and ruptured ascending aortic aneurysm (n?=?1) were among the observed cardiovascular causes. In 14/56 (25%) cases autopsy revealed no structural abnormalities that could explain the sudden death, mostly in the group <1 year.

Conclusion

This national cohort with a high autopsy rate reveals a high incidence (23%) of cardiovascular diseases as the pathological substrate of sudden unexpected death in children. Another high percentage of minors (25%) showed no structural abnormalities, with the possibility of a genetic arrhythmia. These findings underline the importance of systematic autopsy in sudden death in minors, with implications for cardiogenetic screening of relatives.

     

Detection of marker–QTL associations by studying change in marker frequencies with selection

The value of selective genotyping for the detection of QTL has already been studied from a theoretical point of view but with the assumption of a negligible contribution of the QTL to the phenotypic variance. For predicting change in gene frequency, we show that this assumption is only valid for less than 0.05 and for a proportion selected higher than 1%. Therefore, we develop a study of the optimization of selective genotyping without assumption on QTL effect, with selection either of both tails (bidirectional genotyping or BSG) or only one tail (unidirectional genotyping or USG). For a given population size of phenotyped plants the optimal proportion selected for selective genotyping is around 30% for each tail. For the same investment as in ANOVA, by investing more in phenotyping than in genotyping when the cost ratio of genotyping to phenotyping is higher than 1, the optimal proportion selected appears to be between 10 and 20% for each tail. It is mainly affected by the cost ratio and decreases when the cost ratio increases. At this optimum, BSG is competitive with ANOVA, or even more powerful, when the cost ratio is higher than 1. USG can also be competitive when the cost ratio is higher than 2. Using experimental data from two populations of about 300 F4 inbred families of maize, it was verified that BSG at the optimum gives the same results as ANOVA or is better whereas USG is less powerful or equivalent.     

Potential impact of climate change on fungal distributions: analysis of 2 years of contrasting weather in the UK

The impact of climate change on fungal growth and spore production is less well documented than for allergenic pollen grains, although similar implications for respiratory tract diseases in humans occur. Fungal spores are commonly described as either “dry” or “wet” according to the type of weather associated with their occurrence in the air. This study examined the distribution of selected fungal spores (Alternaria spp., Cladosporium spp., Didymella spp., Epicoccum spp., Leptosphaeria spp. and rusts) occurring in the West Midlands of UK during 2 years of contrasting weather. Spore specimens were collected using a 7-day volumetric air sampler and then analysed with the aid of light microscopy. Distributions of spores were then studied using normality tests and Mann–Whitney U test, while relationships with meteorological parameters were investigated using Spearman’s rank test and angular-linear correlation for wind direction analysis. Our results showed that so-called wet spores were more sensitive to the weather changes showing statistically significant differences between the 2 years of study, in contrast to “dry” spores. We predict that in following years we will observe accelerated levels in allergenic fungal spore production as well as changes in species diversity. This study could be a starting point to revise the grouping system of fungal spores as either “dry” or “wet” types and their response to climate change.     

Seabed dynamics in a lage coastal embayment: 180 years of morphological change in the outer Thames estuary

This article analyses the morphological history of the outer Thames seabed, covering over 3,000 km² from Aldeburgh (Suffolk), to Southend-on-Sea (Essex) and Margate (Kent). The region has been depicted on bathymetric charts since the sixteenth century, and has been formally charted since the eighteenth century. Charts published since the early 1800s incorporate sufficient grid reference or ground control detail for georectification onto a common coordinate system (British National Grid). The morphological history of the outer seabed was thus reconstructed through the digitisation and interpolation of soundings onto a regular grid (3D surface). The evolution of seabed morphology was examined using transects, bathymetric change maps and spatial statistics. The results show considerable spatial variability in seabed behaviour. Within the central Thames, banks have experienced significant depth changes can be associated with lateral shifts in individual banks. Some of the outer banks in this region exhibit progressive elongation. Shifts in bank position across the Suffolk shoreface appear to be more subtle, and there is evidence here of both onshore and offshore migration. There is no clear evidence of any regionally coherent response to large-scale historical forcing such as sea-level rise.     

The weak effects of climatic change on Plantago pollen concentration: 17 years of monitoring in Northwestern Spain

Plantago L. species are very common in nitrified areas such as roadsides and their pollen is a major cause of pollinosis in temperate regions. In this study, we sampled airborne pollen grains in the city of León (NW, Spain) from January 1995 to December 2011, by using a Burkard® 7-day-recording trap. The percentage of Plantago pollen compared to the total pollen count ranged from 11 % (1997) to 3 % (2006) in the period under study. Peak pollen concentrations were recorded in May and June. Our 17-year analysis failed to disclose significant changes in the seasonal trend of plantain pollen concentration. In addition, there were no important changes in the start dates of pollen release and the meteorological parameters analyzed did not show significant variations in their usual trends. We analyzed the influence of several meteorological parameters on Plantago pollen concentration to explain the differences in pollen concentration trends during the study. Our results show that temperature, sun hours, evaporation, and relative humidity are the meteorological parameters best correlated to the behavior of Plantago pollen grains. In general, the years with low pollen concentrations correspond to the years with less precipitation or higher temperatures. We calculated the approximate Plantago flowering dates using the cumulative sum of daily maximum temperatures and compared them with the real bloom dates. The differences obtained were 4 days in 2009, 3 days in 2010, and 1 day in 2011 considering the complete period of pollination.