Tissue engineering a fetal membrane

The aim of this study was to construct an artificial fetal membrane (FM) by combination of human amniotic epithelial stem cells (hAESCs) and a mechanically enhanced collagen scaffold containing encapsulated human amniotic stromal fibroblasts (hASFs). Such a tissue-engineered FM may have the potential to plug structural defects in the amniotic sac after antenatal interventions, or to prevent preterm premature rupture of the FM. The hAESCs and hASFs were isolated from human fetal amniotic membrane (AM). Magnetic cell sorting was used to enrich the hAESCs by positive ATP-binding cassette G2 selection. We investigated the use of a laminin/fibronectin (1:1)-coated compressed collagen gel as a novel scaffold to support the growth of hAESCs. A type I collagen gel was dehydrated to form a material mimicking the mechanical properties and ultra-structure of human AM. hAESCs successfully adhered to and formed a monolayer upon the biomimetic collagen scaffold. The resulting artificial membrane shared a high degree of similarity in cell morphology, protein expression profiles, and structure to normal fetal AM. This study provides the first line of evidence that a compacted collagen gel containing hASFs could adequately support hAESCs adhesion and differentiation to a degree that is comparable to the normal human fetal AM in terms of structure and maintenance of cell phenotype.

Hillslope scale surface runoff, sediment, and nutrient losses associated with tramline wheelings

Research on arable sandy loam and silty clay loam soils on 4° slopes in England has shown that tramlines (i.e. the unseeded wheeling areas used to facilitate spraying operations in cereal crops) can represent the most important pathway for phosphorus and sediment loss from moderately sloping fields. Detailed monitoring over the October–March period in winters 2005–2006 and 2006–2007 included event-based sampling of surface runoff, suspended and particulate sediment, and dissolved and particulate phosphorus from hillslope segments (each ∼300–800 m2) established in a randomized block design with four replicates of each treatment at each of two sites on lighter and heavier soils. Experimental treatments assessed losses from the cropped area without tramlines, and from the uncropped tramline area, and were compared to losses from tramlines which had been disrupted once in the autumn with a shallow tine. On the lighter soil, the effects of removal or shallow incorporation of straw residues was also determined. Research on both sandy and silty clay loam soils across two winters showed that tramline wheelings represented the dominant pathway for surface runoff and transport of sediment, phosphorus and nitrogen from cereal crops on moderate slopes. Results indicated 5·5–15·8% of rainfall lost as runoff, and losses of 0·8–2·9 kg TP ha−1 and 0·3–4·8 t ha−1 sediment in tramline treatments, compared to only 0·2–1·7% rainfall lost as runoff, and losses of 0·0–0·2 kg TP ha−1 and 0·003–0·3 t ha−1 sediment from treatments without tramlines or those where tramlines had been disrupted. The novel shallow disruption of tramline wheelings using a tine once following the autumn spray operation consistently and dramatically reduced (p < 0·001) surface runoff and loads of sediment, total nitrogen and total phosphorus to levels similar to those measured in cropped areas between tramlines. Results suggest that options for managing tramline wheelings warrant further refinement and evaluation with a view to incorporating them into spatially-targeted farm-level management planning using national or catchment-based agri-environment policy instruments aimed at reducing diffuse pollution from land to surface water systems. Copyright © 2010 John Wiley & Sons, Ltd.

Fetal testosterone influences sexually dimorphic gray matter in the human brain

In nonhuman species, testosterone is known to have permanent organizing effects early in life that predict later expression of sex differences in brain and behavior. However, in humans, it is still unknown whether such mechanisms have organizing effects on neural sexual dimorphism. In human males, we show that variation in fetal testosterone (FT) predicts later local gray matter volume of specific brain regions in a direction that is congruent with sexual dimorphism observed in a large independent sample of age-matched males and females from the NIH Pediatric MRI Data Repository. Right temporoparietal junction/posterior superior temporal sulcus (RTPJ/pSTS), planum temporale/parietal operculum (PT/PO), and posterior lateral orbitofrontal cortex (plOFC) had local gray matter volume that was both sexually dimorphic and predicted in a congruent direction by FT. That is, gray matter volume in RTPJ/pSTS was greater for males compared to females and was positively predicted by FT. Conversely, gray matter volume in PT/PO and plOFC was greater in females compared to males and was negatively predicted by FT. Subregions of both amygdala and hypothalamus were also sexually dimorphic in the direction of Male > Female, but were not predicted by FT. However, FT positively predicted gray matter volume of a non-sexually dimorphic subregion of the amygdala. These results bridge a long-standing gap between human and nonhuman species by showing that FT acts as an organizing mechanism for the development of regional sexual dimorphism in the human brain.

Catchment phosphorous losses: an export coefficient modelling approach with scenario analysis for water management

This paper presents the development of an export coefficient model to characterise the rates and sources of P export from land to water in four reservoir systems located in a semi-arid rural region in southern of Portugal. The model was developed to enable effective management of these important water resource systems under the EU Water Framework Directive. This is the first time such an approach has been fully adapted for the semi-arid systems typical of Mediterranean Europe. The sources of P loading delivered to each reservoir from its catchment were determined and scenario analysis was undertaken to predict the likely impact of catchment management strategies on the scale of rate of P loading delivered to each water body from its catchment. The results indicate the importance of farming and sewage treatment works/collective septic tanks discharges as the main contributors to the total diffuse and point source P loading delivered to the reservoirs, respectively. A reduction in the total P loading for all study areas would require control of farming practices and more efficient removal of P from human wastes prior to discharge to surface waters. The scenario analysis indicates a strategy based solely on reducing the agricultural P surplus may result in only a slow improvement in water quality, which would be unlikely to support the generation of good ecological status in reservoirs. The model application indicates that a reduction of P-inputs to the reservoirs should first focus on reducing P loading from sewage effluent discharges through the introduction of tertiary treatment (P-stripping) in all major residential areas. The fully calibrated export coefficient modelling approach transferred well to semi-arid regions, with the only significant limitation being the availability of suitable input data to drive the model. Further studies using this approach in semi-arid catchments are now needed to increase the knowledge of nutrient export behaviours in semi-arid regions.

Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans

BACKGROUND: Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fetal development influences later neural sensitivity to valenced facial cues and approach-avoidance behavioral tendencies. METHODS: With functional magnetic resonance imaging we scanned 25 8-11-year-old children while viewing happy, fear, neutral, or scrambled faces. Fetal testosterone (FT) was measured via amniotic fluid sampled between 13 and 20 weeks gestation. Behavioral approach-avoidance tendencies were measured via parental report on the Sensitivity to Punishment and Sensitivity to Rewards questionnaire. RESULTS: Increasing FT predicted enhanced selectivity for positive compared with negatively valenced facial cues in reward-related regions such as caudate, putamen, and nucleus accumbens but not the amygdala. Statistical mediation analyses showed that increasing FT predicts increased behavioral approach tendencies by biasing caudate, putamen, and nucleus accumbens but not amygdala to be more responsive to positive compared with negatively valenced cues. In contrast, FT was not predictive of behavioral avoidance tendencies, either through direct or neurally mediated paths. CONCLUSIONS: This work suggests that testosterone in humans acts as a fetal programming mechanism on the reward system and influences behavioral approach tendencies later in life. As a mechanism influencing atypical development, FT might be important across a range of neuropsychiatric conditions that asymmetrically affect the sexes, the reward system, emotion processing, and approach behavior.

The Natural History of Slapton Ley Nature Reserve XVIII: nitrogen and phosphorus losses from the catchment - an export coefficient modelling approach

Nitrogen and phosphorus losses from the catchment of Slapton Ley, a small coastal lake in SW England, were calculated using an adaptation of a model developed by Jorgensen (1980). A detailed survey of the catchment revealed that its land use is dominated by both permanent and temporary grassland (respectively 38 and 32% of its total area), and that the remainder is made up of the cultivation of cereals and field vegetables, and market gardening. Livestock numbers in the catchment constitute ca. 6600 head of cattle, 10,000 sheep, 590 pigs, 1700 poultry and 58 horses. The permanent human population of the area is ca. 2000, served by two small gravity-fed sewage treatment works (STWs). Inputs to, and losses from, farmland in the catchment were computed using Jorgensen’s model, and coefficients derived from the data of Cooke (1976), Gostick (1982), Rast and Lee (1983) and Vollenweider (1968). Allowing for outputs from STWs, the total annual external load of N and P upon Slapton Ley is 160 t (35 kg ha-1) a-1 N, and 4.8 t (1.05 kg ha-1) a-1 P. Accordingly to Vollenweider (1968, 1975), such loadings exceed OECD permissible level by a factor of ca. 50 in the case of N, and ca. 5 in that of P. In order to reduce nutrient loads, attention would need to be paid to both STW and agricultural sources.

The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease.

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease involving progressive motor, cognitive and behavioural decline, leading to death approximately 20 years after motor onset. The disease is characterised pathologically by an early and progressive striatal neuronal cell loss and atrophy, which has provided the rationale for first clinical trials of neural repair using fetal striatal cell transplantation. Between 2000 and 2003, the 'NEST-UK' consortium carried out bilateral striatal transplants of human fetal striatal tissue in five HD patients. This paper describes the long-term follow up over a 3-10-year postoperative period of the patients, grafted and non-grafted, recruited to this cohort using the 'Core assessment program for intracerebral transplantations-HD' assessment protocol. No significant differences were found over time between the patients, grafted and non-grafted, on any subscore of the Unified Huntington's Disease Rating Scale, nor on the Mini Mental State Examination. There was a trend towards a slowing of progression on some timed motor tasks in four of the five patients with transplants, but overall, the trial showed no significant benefit of striatal allografts in comparison with a reference cohort of patients without grafts. Importantly, no significant adverse or placebo effects were seen. Notably, the raclopride positron emission tomography (PET) signal in individuals with transplants, indicated that there was no obvious surviving striatal graft tissue. This study concludes that fetal striatal allografting in HD is safe. While no sustained functional benefit was seen, we conclude that this may relate to the small amount of tissue that was grafted in this safety study compared with other reports of more successful transplants in patients with HD.

Projections of global warming-induced impacts on winter storm losses in the German private household sector

We present projections of winter storm-induced insured losses in the German residential building sector for the 21st century. With this aim, two structurally most independent downscaling methods and one hybrid downscaling method are applied to a 3-member ensemble of ECHAM5/MPI-OM1 A1B scenario simulations. One method uses dynamical downscaling of intense winter storm events in the global model, and a transfer function to relate regional wind speeds to losses. The second method is based on a reshuffling of present day weather situations and sequences taking into account the change of their frequencies according to the linear temperature trends of the global runs. The third method uses statistical-dynamical downscaling, considering frequency changes of the occurrence of storm-prone weather patterns, and translation into loss by using empirical statistical distributions. The A1B scenario ensemble was downscaled by all three methods until 2070, and by the (statistical-) dynamical methods until 2100. Furthermore, all methods assume a constant statistical relationship between meteorology and insured losses and no developments other than climate change, such as in constructions or claims management. The study utilizes data provided by the German Insurance Association encompassing 24 years and with district-scale resolution. Compared to 1971–2000, the downscaling methods indicate an increase of 10-year return values (i.e. loss ratios per return period) of 6–35 % for 2011–2040, of 20–30 % for 2041–2070, and of 40–55 % for 2071–2100, respectively. Convolving various sources of uncertainty in one confidence statement (data-, loss model-, storm realization-, and Pareto fit-uncertainty), the return-level confidence interval for a return period of 15 years expands by more than a factor of two. Finally, we suggest how practitioners can deal with alternative scenarios or possible natural excursions of observed losses.

Elevated fetal steroidogenic activity in autism

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.

Return periods of losses associated with European windstorm series in a changing climate

Possible future changes of clustering and return periods (RPs) of European storm series with high potential losses are quantified. Historical storm series are identified using 40 winters of reanalysis. Time series of top events (1, 2 or 5 year return levels (RLs)) are used to assess RPs of storm series both empirically and theoretically. Additionally, 800 winters of general circulation model simulations for present (1960–2000) and future (2060–2100) climate conditions are investigated. Clustering is identified for most countries, and estimated RPs are similar for reanalysis and present day simulations. Future changes of RPs are estimated for fixed RLs and fixed loss index thresholds. For the former, shorter RPs are found for Western Europe, but changes are small and spatially heterogeneous. For the latter, which combines the effects of clustering and event ranking shifts, shorter RPs are found everywhere except for Mediterranean countries. These changes are generally not statistically significant between recent and future climate. However, the RPs for the fixed loss index approach are mostly beyond the range of pre-industrial natural climate variability. This is not true for fixed RLs. The quantification of losses associated with storm series permits a more adequate windstorm risk assessment in a changing climate.

Evidence for sex differences in fetal programming of physiological stress reactivity in infancy

Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N = 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term, p = .016), and prenatal maternal anxiety predicted lower vagal reactivity only in boys (interaction term, p = .014). These findings are consistent with sex differences in fetal programming, whereby prenatal risks are associated with increased stress reactivity in females but decreased reactivity in males, with distinctive advantages and penalties for each sex.

Fetal programming of adipose tissue function: an evolutionary perspective

Obesity is an escalating threat of pandemic proportions and has risen to such unrivaled prominence in such a short period of time that it has come to define a whole generation in many countries around the globe. The burden of obesity, however, is not equally shared among the population, with certain ethnicities being more prone to obesity than others, while some appear to be resistant to obesity altogether. The reasons behind this ethnic basis for obesity resistance and susceptibility, however, have remained largely elusive. In recent years, much evidence has shown that the level of brown adipose tissue thermogenesis, which augments energy expenditure and is negatively associated with obesity in both rodents and humans, varies greatly between ethnicities. Interestingly, the incidence of low birth weight, which is associated with an increased propensity for obesity and cardiovascular disease in later life, has also been shown to vary by ethnic background. This review serves to reconcile ethnic variations in BAT development and function with ethnic differences in birth weight outcomes to argue that the variation in obesity susceptibility between ethnic groups may have its origins in the in utero programming of BAT development and function as a result of evolutionary adaptation to cold environments.

Moderate stake variations for risk and uncertainty, gains and losses: methodological implications for comparative studies

Risk attitudes are known to be sensitive to large stake variations. However, little is known on the sensitivity to moderate variations in stakes. This is important for studies that want to compare risk attitudes between countries or over time. I find that variations of ±20% affect only utility, while larger variations may affect also probability weighting. Surprisingly, the effect on weighting functions is larger for losses than for gains. It is also more pronounced for risk than for uncertainty.

I owe you: age-related similarities and differences in associative memory for gains and losses

Older adults often experience associative memory impairments but can sometimes remember important information. The current experiments investigate potential age-related similarities and differences associate memory for gains and losses. Younger and older participants were presented with faces and associated dollar amounts, which indicated how much money the person “owed” the participant, and were later given a cued recall test for the dollar amount. Experiment 1 examined face-dollar amount pairs while Experiment 2 included negative dollar amounts to examine both gains and losses. While younger adults recalled more information relative to older adults, both groups were more accurate in recalling the correct value associated with high value faces compared to lower value faces and remembered gist-information about the values. However, negative values (losses) did not have a strong impact on recall among older adults versus younger adults, illustrating important associative memory differences between younger and older adults.