Prevalence,Comorbidity and Heritability of Hoarding Symptoms in Adolescence: A Population Based Twin Study in 15-Year Olds

Background

Hoarding Disorder (HD) is often assumed to be an ‘old age’ problem, but many individuals diagnosed with HD retrospectively report first experiencing symptoms in childhood or adolescence. We examined the prevalence, comorbidity and etiology of hoarding symptoms in adolescence.

Methods

To determine the presence of clinically significant hoarding symptoms, a population-based sample of 15-year old twins (N = 3,974) completed the Hoarding Rating Scale-Self Report. Co-occurring Obsessive Compulsive Disorder (OCD), Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) were estimated from parental report. Model-fitting analyses divided hoarding symptom scores into additive genetic, shared, and non-shared environmental effects.

Results

The prevalence of clinically significant hoarding symptoms was 2% (95% CI 1.6–2.5%), with a significantly higher prevalence in girls than boys. Exclusion of the clutter criterion (as adolescents do not have control over their environment) increased the prevalence rate to 3.7% (95% CI 3.1–4.3%). Excessive acquisition was reported by 30–40% among those with clinically significant hoarding symptoms. The prevalence of co-occurring OCD (2.9%), ASD (2.9%) and ADHD (10.0%) was comparable in hoarding and non-hoarding teenagers. Model-fitting analyses suggested that, in boys, additive genetic (32%; 95% CI 13–44%) and non-shared environmental effects accounted for most of the variance. In contrast, among girls, shared and non-shared environmental effects explained most of the variance, while additive genetic factors played a negligible role.

Conclusions

Hoarding symptoms are relatively prevalent in adolescents, particularly in girls, and cause distress and/or impairment. Hoarding was rarely associated with other common neurodevelopmental disorders, supporting its DSM-5 status as an independent diagnosis. The relative importance of genetic and shared environmental factors for hoarding differed across sexes. The findings are suggestive of dynamic developmental genetic and environmental effects operating from adolescence onto adulthood.     

Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity

Background

Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women.

Methodology/Principal Findings

Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data.

Conclusions/Significance

This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation.     

Longitudinal,genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance

Background

The extent to which development- and age-associated epigenetic changes are influenced by genetic, environmental and stochastic factors remains to be discovered. Twins provide an ideal model with which to investigate these influences but previous cross-sectional twin studies provide contradictory evidence of within-pair epigenetic drift over time. Longitudinal twin studies can potentially address this discrepancy.

Results

In a pilot, genome-scale study of DNA from buccal epithelium, a relatively homogeneous tissue, we show that one-third of the CpGs assayed show dynamic methylation between birth and 18 months. Although all classes of annotated genomic regions assessed show an increase in DNA methylation over time, probes located in intragenic regions, enhancers and low-density CpG promoters are significantly over-represented, while CpG islands and high-CpG density promoters are depleted among the most dynamic probes. Comparison of co-twins demonstrated that within-pair drift in DNA methylation in our cohort is specific to a subset of pairs, who show more differences at 18 months. The rest of the pairs show either minimal change in methylation discordance, or more similar, converging methylation profiles at 18 months. As with age-associated regions, sites that change in their level of within-pair discordance between birth and 18 months are enriched in genes involved in development, but the average magnitude of change is smaller than for longitudinal change.

Conclusions

Our findings suggest that DNA methylation in buccal epithelium is influenced by non-shared stochastic and environmental factors that could reflect a degree of epigenetic plasticity within an otherwise constrained developmental program.     

On the Origin of Rheumatoid Arthritis: The Impact of Environment and Genes—A Population Based Twin Study

Background

Rheumatoid arthritis (RA) is an autoimmune disease with a complex origin. Previous studies have reported heritability estimates on RA at about 60%. Only 16% of the genetic background of the disease has been disclosed so far. The purpose of the present investigation was to provide an optimized estimate on the heritability of RA and to study the recurrence risk in a nationwide Caucasian twin population.

Methods and Findings

In a mail survey addressed to 56.707 twin individuals, RA was reported by 479 individuals, mean age 52 (range 16–73). Respondents underwent an interview and clinical examination. Ascertainment probability was 80%. RA was confirmed in 162 twin individuals yielding a prevalence at 0.37% (95% CI 0.31–0.43). The mean discordance time was 19 years (range 0–57). The concordance was 9.1% (95% CI 1.9 to 24.3) in MZ, 6.4% (95% CI 2.1 to 14.3) in DZss. The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6 to 35.4 in MZ twins and 17.3 to 31.6 in DZss twins. The correlation coefficients were 0.60 (0.33 to 0.78) in monozygotic (MZ) and 0.55 (0.33 to 0.72) in dizygotic same sexed (DZss) pairs. Twelve percent (95% CI 0–76%) of the phenotypic variance in the liability to RA was due to additive genetic effects, 50% (95% CI 0–72%) to shared environmental effects and 38% (95% CI 17–61%) to non-shared environmental effects.

Conclusions

This study emphasizes that family factors are important for the development of RA. Although genetic effectors are important, shared and non-shared environmental triggers and/or epigenetic stochastic events seem to be even more significant. However, it should be borne in mind that the genetic and non-genetic components may not be the same across disease subsets.     

Genetic and environmental effects on age at menarche,and its relationship with reproductive health in twins

INTRODUCTION:

Menarche or first menstrual period is a landmark in reproductive life span and it is the most prominent change of puberty. The timing of menarche can be under the influence of genes as well as individual environmental factors interacting with genetic factors.

OBJECTIVE:

Our study objectives were (a) to investigate the heritability of age of menarche in twins, (b) to obtain the association between age of menarche and childhood factors, and reproductive events/behavior, (c) to examine whether or not having a male co-twin affects early/late menarche.

METHODOLOGY:

A group of female-female identical (n = 108, 54 pairs), non-identical twins (n = 68, 34 pairs) and 17 females from opposite-sex twin sets were identified from twin registries of Malaysia and Iran. Genetic analysis was performed via two methods of Falconers’ formula and maximum likelihood.

RESULTS:

Heritability was found to be 66% using Falconers’ formula and 15% using univariate twin analysis. Model analysis revealed that shared environmental factors have a major contribution in determining the age of menarche (82%) followed by non-shared environment (18%).

DISCUSSION:

Result of this study is consistent with that of the literature. Timing of menarche could be under the influence of shared and non-shared environmental effects. Hirsutism was found to have a higher frequency among subjects with late menarche. There was no significant difference in age of menarche between females of opposite-sex twins and females of same-sex twins.

CONCLUSION:

It is concluded that twin models provide a powerful means of examining the total genetic contribution to age of menarche. Longitudinal studies of twins may clarify the type of environmental effects that determine the age of menarche.     

Socioeconomic status (SES) and children's intelligence (IQ): in a UK-representative sample SES moderates the environmental, not genetic, effect on IQ

Background

The environment can moderate the effect of genes - a phenomenon called gene-environment (GxE) interaction. Several studies have found that socioeconomic status (SES) modifies the heritability of children''s intelligence. Among low-SES families, genetic factors have been reported to explain less of the variance in intelligence; the reverse is found for high-SES families. The evidence however is inconsistent. Other studies have reported an effect in the opposite direction (higher heritability in lower SES), or no moderation of the genetic effect on intelligence.

Methods

Using 8716 twin pairs from the Twins Early Development Study (TEDS), we attempted to replicate the reported moderating effect of SES on children''s intelligence at ages 2, 3, 4, 7, 9, 10, 12 and 14: i.e., lower heritability in lower-SES families. We used a twin model that allowed for a main effect of SES on intelligence, as well as a moderating effect of SES on the genetic and environmental components of intelligence.

Results

We found greater variance in intelligence in low-SES families, but minimal evidence of GxE interaction across the eight ages. A power calculation indicated that a sample size of about 5000 twin pairs is required to detect moderation of the genetic component of intelligence as small as 0.25, with about 80% power - a difference of 11% to 53% in heritability, in low- (−2 standard deviations, SD) and high-SES (+2 SD) families. With samples at each age of about this size, the present study found no moderation of the genetic effect on intelligence. However, we found the greater variance in low-SES families is due to moderation of the environmental effect – an environment-environment interaction.

Conclusions

In a UK-representative sample, the genetic effect on intelligence is similar in low- and high-SES families. Children''s shared experiences appear to explain the greater variation in intelligence in lower SES.     

Brain Structural Correlates of Reward Sensitivity and Impulsivity in Adolescents with Normal and Excess Weight

Introduction

Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups.

Methods

Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex).

Results

Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents.

Conclusion

Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.     

Qualitative Approach to Attempted Suicide by Adolescents and Young Adults: The (Neglected) Role of Revenge

Background

Suicide by adolescents and young adults is a major public health concern, and repetition of self-harm is an important risk factor for future suicide attempts.

Objective

Our purpose is to explore the perspective of adolescents directly involved in suicidal acts.

Methods

Qualitative study involving 16 purposively selected adolescents (sex ratio1∶1) from 3 different centers. Half had been involved in repeated suicidal acts, and the other half only one. Data were gathered through semistructured interviews and analyzed according to Interpretative Phenomenological Analysis.

Results

We found five main themes, organized in two superordinate themes. The first theme (individual dimensions of the suicide attempt) describes the issues and explanations that the adolescents saw as related to themselves; it includes the subthemes: (1) negative emotions toward the self and individual impasse, and (2) the need for some control over their lives. The second main theme (relational dimensions of attempted suicide) describes issues that adolescents mentioned that were related to others and includes three subthemes: (3) perceived impasse in interpersonal relationships, (4) communication, and (5) revenge.

Conclusions

Adolescents involved in suicidal behavior are stuck in both an individual and a relational impasse from which there is no exit and no apparent way to reach the other. Revenge can bridge this gap and thus transforms personal distress into a relational matter. This powerful emotion has been neglected by both clinicians and researchers.     

Comparison of the Web-Based and Digital Questionnaires of the Spanish and Catalan Versions of the KIDSCREEN-52

Background

The objectives of the study were to develop web-based Spanish and Catalan versions of the KIDSCREEN, and to compare scores and psychometric properties with the paper version.

Methods

Internet and paper Spanish and Catalan versions of the KIDSCREEN-52 were included in a cross-sectional study in school-age children. Web-based and paper Spanish or Catalan versions of the KIDSCREEN-52 were administered to students aged 8 to 18 years from primary and secondary schools in Palafolls (Barcelona, Spain, n = 923). All students completed both web-based and paper versions during school time with an interval of at least 2 hours between administrations. The order of administration was randomized. The KIDSCREEN-52, the Strengths and Difficulties Questionnaire (SDQ), and sociodemographic variables were collected. Missing values, floor and ceiling effects, and internal consistency were compared between both versions, as well as mean score differences, level of agreement, and known groups and construct validity.

Results

Participation rate was 77% (n = 715). Web-based and paper versions showed low percentage of missing values and similar high ceiling effect (range 0 to 44%). Mean score differences showed an effect size (ES) lower than 0.2 in all dimensions. Internal consistency ranged from 0.7 to 0.88, and degree of agreement was excellent (Intraclass correlation coefficient [ICC] range 0.75 to 0.87). Expected differences were seen by sex, age, socioeconomic status and mental health status.

Conclusions

The web-based KIDSCREEN-52 showed similar scale score and reliability and validity than the paper version. It will incorporate the child population in the assessment of quality of life providing a more attractive format.     

Natural variation in germination responses of Arabidopsis to seasonal cues and their associated physiological mechanisms

Background and Aims

Despite the intense interest in phenological adaptation to environmental change, the fundamental character of natural variation in germination is almost entirely unknown. Specifically, it is not known whether different genotypes within a species are germination specialists to particular conditions, nor is it known what physiological mechanisms of germination regulation vary in natural populations and how they are associated with responses to particular environmental factors.

Methods

We used a set of recombinant inbred genotypes of Arabidopsis thaliana, in which linkage disequilibrium has been disrupted over seven generations, to test for genetic variation and covariation in germination responses to distinct environmental factors. We then examined physiological mechanisms associated with those responses, including seed-coat permeability and sensitivity to the phytohormones gibberellic acid (GA) and abscisic acid (ABA).

Key Results

Genetic variation for germination was environment-dependent, but no evidence for specialization of germination to different conditions was found. Hormonal sensitivities also exhibited significant genetic variation, but seed-coat properties did not. GA sensitivity was associated with germination responses to multiple environmental factors, but seed-coat permeability and ABA sensitivity were associated with specific germination responses, suggesting that an evolutionary change in GA sensitivity could affect germination in multiple environments, but that of ABA sensitivity may affect germination under more restricted conditions.

Conclusions

The physiological mechanisms of germination responses to specific environmental factors therefore can influence the ability to adapt to diverse seasonal environments encountered during colonization of new habitats or with future predicted climate change.     

Examining the Genetic and Environmental Associations between Autistic Social and Communication Deficits and Psychopathic Callous-Unemotional Traits

Background

Difficulties in appropriate social interaction are characteristic of both children with autism spectrum disorders and children with callous-unemotional traits (who are at risk of developing psychopathy). Extant experimental studies suggest that the nature of atypical social cognition that characterises these two profiles is not identical. However, ‘empathizing’ difficulties have been hypothesised for both groups, raising questions about the degree of aetiological separation between social impairments that characterize each disorder. This study explored the relative contribution of independent vs. shared aetiological influences to social and communication impairments associated with autistic traits and callous-unemotional traits, indexed by parent-report in a population-based cohort of twins.

Methods

Participants were over 5,000 twin pairs from a UK cohort (the Twins Early Development Study; TEDS), assessed for callous-unemotional traits at 7 years and autistic social and communication impairments at 8 years. Multivariate model-fitting was used to explore the relative contribution of independent vs. overlapping genetic/environmental influences on these traits.

Results

Both social and communication impairments and callous-unemotional traits were highly heritable, although the genetic and environmental influences accounting for individual differences on each domain were predominantly independent.

Conclusions

Extant evidence from experimental and neuro-imaging studies has suggested that, despite some superficially overlapping behaviours, the social difficulties seen in children with autism spectrum disorders and callous-unemotional traits are largely distinct. The current study is the first to demonstrate considerable aetiological independence of the social interaction difficulties seen in children with autism spectrum disorders and those with callous-unemotional traits.     

The genetic liability to disability retirement: a 30-year follow-up study of 24,000 Finnish twins

Background

No previous studies on the effect of genetic factors on the liability to disability retirement have been carried out. The main aim of this study was to investigate the contribution of genetic factors on disability retirement due to the most common medical causes, including depressive disorders.

Methods

The study sample consisted of 24 043 participants (49.7% women) consisting of 11 186 complete same-sex twin pairs including 3519 monozygotic (MZ) and 7667dizygotic (DZ) pairs. Information on retirement events during 1.1.1975–31.12.2004, including disability pensions (DPs) with diagnoses, was obtained from the Finnish nationwide official pension registers. Correlations in liability for MZ and DZ twins and discrete time correlated frailty model were used to investigate the genetic liability to age at disability retirement.

Results

The 30 year cumulative incidence of disability retirement was 20%. Under the best fitting genetic models, the heritability estimate for DPs due to any medical cause was 0.36 (95% CI 0.32–0.40), due to musculoskeletal disorders 0.37 (0.30–0.43), cardiovascular diseases 0.48 (0.39–0.57), mental disorders 0.42 (0.35–0.49) and all other reasons 0.24 (0.17–0.31). The effect of genetic factors decreased with increasing age of retirement. For DP due to depressive disorders, 28% of the variance was explained by environmental factors shared by family members (95% CI 21–36) and 58% of the variance by the age interval specific environmental factors (95% CI 44–71).

Conclusions

A moderate genetic contribution to the variation of disability retirement due to any medical cause was found. The genetic effects appeared to be stronger at younger ages of disability retirement suggesting the increasing influence of environmental factors not shared with family members with increasing age. Familial aggregation in DPs due to depressive disorders was best explained by the common environmental factors and genetic factors were not needed to account for the pattern of familial aggregation.     

Determinants of Physiological and Perceived Physiological Stress Reactivity in Children and Adolescents

Aims

Abnormal physiological stress reactivity is increasingly investigated as a vulnerability marker for various physical and psychological health problems. However, studies are inconsistent in taking into account potential covariates that may influence the developing stress system. We systematically tested determinants (individual, developmental, environmental and substance use-related) of physiological and perceived physiological stress reactivity. We also examined the relation between physiological and perceived physiological stress reactivity.

Method

In a stratified sample of 363 children (7–12 years) and 344 adolescents (13–20 years) from the general population, we examined cortisol, heart rate, respiratory sinus arrhythmia and perceived physiological stress reactivity to a psychosocial stress procedure.

Results

Using multivariate linear regression models, we found that individual, developmental, environmental and substance use-related factors were related to each of the stress response indices. These determinant factors were different for each of the stress reactivity indices, and different in children versus adolescents. Perceived physiological stress reactivity predicted cortisol reactivity in adolescents only. All other relations between perceived physiological and physiological stress reactivity were not significant.

Conclusions

As physiological stress variables are often examined as vulnerability markers for the development of health problems, we maintain that it is essential that future studies take into consideration factors that may account for found relations. Our study provides an overview and indication of which variables should be considered in the investigation of the relation between physiological stress indices and illness.     

Heritability and Clinical Determinants of Serum Indoxyl Sulfate and p-Cresyl Sulfate,Candidate Biomarkers of the Human Microbiome Enterotype

Background

Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden.

Objective and Design

Information on clinical determinants and heritability of indoxyl sulfate and p-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and p-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study).

Results

Serum levels of indoxyl sulfate and p-cresyl sulfate amounted to 3.1 (2.4–4.3) and 13.0 (7.4–21.5) μM, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h² = 0.17) and p-cresyl sulfate (h² = 0.18) concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites.

Limitations

Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded.

Conclusions

The heritability of indoxyl sulfate and p-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.     

A Twin Study of Early-Childhood Asthma in Puerto Ricans

Background

The relative contributions of genetics and environment to asthma in Hispanics or to asthma in children younger than 3 years are not well understood.

Objective

To examine the relative contributions of genetics and environment to early-childhood asthma by performing a longitudinal twin study of asthma in Puerto Rican children ≤3 years old.

Methods

678 twin infants from the Puerto Rico Neo-Natal Twin Registry were assessed for asthma at age 1 year, with follow-up data obtained for 624 twins at age 3 years. Zygosity was determined by DNA microsatellite profiling. Structural equation modeling was performed for three phenotypes at ages 1 and 3 years: physician-diagnosed asthma, asthma medication use in the past year, and ≥1 hospitalization for asthma in the past year. Models were additionally adjusted for early-life environmental tobacco smoke exposure, sex, and age.

Results

The prevalences of physician-diagnosed asthma, asthma medication use, and hospitalization for asthma were 11.6%, 10.8%, 4.9% at age 1 year, and 34.1%, 40.1%, and 8.5% at 3 years, respectively. Shared environmental effects contributed to the majority of variance in susceptibility to physician-diagnosed asthma and asthma medication use in the first year of life (84%–86%), while genetic effects drove variance in all phenotypes (45%–65%) at age 3 years. Early-life environmental tobacco smoke, sex, and age contributed to variance in susceptibility.

Conclusion

Our longitudinal study in Puerto Rican twins demonstrates a changing contribution of shared environmental effects to liability for physician-diagnosed asthma and asthma medication use between ages 1 and 3 years. Early-life environmental tobacco smoke reduction could markedly reduce asthma morbidity in young Puerto Rican children.     

Uncoupled geographical variation between leaves and flowers in a South-Andean Proteaceae

Background and Aims

Geographical variation in foliar and floral traits and their degree of coupling can provide relevant information on the relative importance of abiotic, biotic and even neutral factors acting at geographical scales as generators of evolutionary novelty. Geographical variation was studied in leaves and flowers of Embothrium coccineum, a species that grows along abrupt environmental gradients and exhibits contrasting pollinator assemblages in the southern Andes.

Methods

Five foliar and eight floral morphological characters were considered from 32 populations, and their patterns of variation and covariation were analysed within and among populations, together with their relationship with environmental variables, using both univariate and multivariate methods. The relationships between foliar and floral morphological variation and geographical distance between populations were compared with Mantel permutation tests.

Key Results

Leaf and flower traits were clearly uncoupled within populations and weakly associated among populations. Whereas geographical variation in foliar traits was mostly related to differences in precipitation associated with geographical longitude, variation in floral traits was not.

Conclusions

These patterns suggest that leaves and flowers responded to different evolutionary forces, environmental (i.e. rainfall) in the case of leaves, and biotic (i.e. pollinators) or genetic drift in the case of flowers. This study supports the view that character divergence at a geographical scale can be moulded by different factors acting in an independent fashion.Key words: Embothrium coccineum, Proteaceae, geographical variation, foliar morphology, floral morphology, uncoupling, selective forces, environmental conditions, pollinators, south Andes     

Transcutaneous Immunization System Using a Hydrotropic Formulation Induces a Potent Antigen-Specific Antibody Response

Background

Transcutaneous immunization (TCI) is a novel vaccination strategy, which is expected to have therapeutic applications. However, to develop effective TCI systems, a simple, non-invasive and safe transdermal formulation is required. This study developed a novel TCI system utilizing the co-administration of a liposoluble absorption enhancer, propylene glycol monocaprylate (PGMC) and hydrosoluble protein antigen without pretreatment of any typical adjuvants and disruption of the skin. Novel transdermal formulations were also prepared with sodium salicylate (NaSal) as a hydrotropic agent to improve the solubility of poorly water-soluble substances.

Methodology/Principal Findings

The TCI system, which used a transdermal formulation containing hen lysozyme (HEL) and PGMC, solubilized with NaSal, resulted in a substantial HEL-specific antibody response in an HEL dose-dependent manner even in the absence of potent adjuvants, such as cholera toxin (CT). We also investigated whether NaSal activates antigen-presenting cells in vitro to clarify the mechanisms of antibody production by the hydrotropic formulation. NaSal enhanced the expression of MHC class II molecules and increased the production of IL-12 and TNF-α in dendritic cells, which were stimulated by lipopolysaccharide in vitro, indicating that NaSal had an effective adjuvant-like property. Moreover, the use of NaSal in the TCI system did not induce an HEL-specific, IgE-dependent anaphylactic reaction.

Conclusion/Significance

Our TCI system using a hydrotropic formulation effectively and safely induced the intended immune response, and this system thus represents a new advantageous method that will result in improved TCI strategies.     

Niche Divergence versus Neutral Processes: Combined Environmental and Genetic Analyses Identify Contrasting Patterns of Differentiation in Recently Diverged Pine Species

Background and Aims

Solving relationships of recently diverged taxa, poses a challenge due to shared polymorphism and weak reproductive barriers. Multiple lines of evidence are needed to identify independently evolving lineages. This is especially true of long-lived species with large effective population sizes, and slow rates of lineage sorting. North American pines are an interesting group to test this multiple approach. Our aim is to combine cytoplasmic genetic markers with environmental information to clarify species boundaries and relationships of the species complex of Pinus flexilis, Pinus ayacahuite, and Pinus strobiformis.

Methods

Mitochondrial and chloroplast sequences were combined with previously obtained microsatellite data and contrasted with environmental information to reconstruct phylogenetic relationships of the species complex. Ecological niche models were compared to test if ecological divergence is significant among species.

Key Results and Conclusion

Separately, both genetic and ecological evidence support a clear differentiation of all three species but with different topology, but also reveal an ancestral contact zone between P. strobiformis and P. ayacahuite. The marked ecological differentiation of P. flexilis suggests that ecological speciation has occurred in this lineage, but this is not reflected in neutral markers. The inclusion of environmental traits in phylogenetic reconstruction improved the resolution of internal branches. We suggest that combining environmental and genetic information would be useful for species delimitation and phylogenetic studies in other recently diverged species complexes.     

Genetic and environmental contributions to weight, height, and BMI from birth to 19 years of age: an international study of over 12,000 twin pairs

Objective

To examine the genetic and environmental influences on variances in weight, height, and BMI, from birth through 19 years of age, in boys and girls from three continents.

Design and Settings

Cross-sectional twin study. Data obtained from a total of 23 twin birth-cohorts from four countries: Canada, Sweden, Denmark, and Australia. Participants were Monozygotic (MZ) and dizygotic (DZ) (same- and opposite-sex) twin pairs with data available for both height and weight at a given age, from birth through 19 years of age. Approximately 24,036 children were included in the analyses.

Results

Heritability for body weight, height, and BMI was low at birth (between 6.4 and 8.7% for boys, and between 4.8 and 7.9% for girls) but increased over time, accounting for close to half or more of the variance in body weight and BMI after 5 months of age in both sexes. Common environmental influences on all body measures were high at birth (between 74.1–85.9% in all measures for boys, and between 74.2 and 87.3% in all measures for girls) and markedly reduced over time. For body height, the effect of the common environment remained significant for a longer period during early childhood (up through 12 years of age). Sex-limitation of genetic and shared environmental effects was observed.

Conclusion

Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in pre-adolescent years and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. As gene-environment correlation and interaction is likely, it is also necessary to identify the genetic variants that may predispose individuals to obesity.