Maternal Filaggrin Mutations Increase the Risk of Atopic Dermatitis in Children: An Effect Independent of Mutation Inheritance

Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome''s influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1_{meta-analysis} = 2.4, P = 1.0 x 10⁻³⁶), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, P_{meta-analysis} = 8.4 x 10⁻⁸). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS). Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring’s susceptibility to a common human disease.     

Evolution of the Northern Rockweed,Fucus distichus,in a Regime of Glacial Cycling: Implications for Benthic Algal Phylogenetics

Northern hemisphere rockweeds (Fucus) are thought to have evolved in the North Pacific and then spread to the North Atlantic following the opening of the Bering Strait. They have dispersed and widely speciated in the North Atlantic and its tributary seas. Fucus distichus is likely near the ancestral member of this genus, and studies have shown that there are several species/subspecies in this complex (i.e. F. evanescens and F. gardneri). We used phylogenetic and haplotype analyses to test the phylogenetic relationships and biogeography of F. distichus. Our data and subsequent analyses demonstrate that, unlike previous studies that lacked samples from an extensive geographical area of the Arctic and Subarctic, there is a distinct Arctic haplotype that is the source of subspecies in both the North Pacific and North Atlantic. Fucus distichus occupies a low tide zone habitat, and in Arctic/Subarctic regions it is adapted to the severe stress of sea ice coverage and disturbance during many months per year. We hypothesize that the very large geographic area of Arctic and Subarctic rocky shores available to this species during interglacials, supported by large Arctic/Subarctic fringe areas as well as unglaciated refugia during glacial cycles, provided a robust population and gene pool (described by the Thermogeographic Model). This gene pool dilutes that of the more fragmented and area-limited Temperate/Boreal area populations when they are brought together during glacial cycles. We suggest that similar subspecies complexes for a variety of Arctic/Subarctic shore biota should be examined further in this context, rather than arbitrarily being split up into numerous species.     

Plant invasions differentially affected by diversity and dominant species in native‐ and exotic‐dominated grasslands

Plant invasions are an increasingly serious global concern, especially as the climate changes. Here, we explored how plant invasions differed between native‐ and novel exotic‐dominated grasslands with experimental addition of summer precipitation in Texas in 2009. Exotic species greened up earlier than natives by an average of 18 days. This was associated with a lower invasion rate early in the growing season compared to native communities. However, invasion rate did not differ significantly between native and exotic communities across all sampling times. The predictors of invasion rate differed between native and exotic communities, with invasion being negatively influenced by species richness in natives and by dominant species in exotics. Interestingly, plant invasions matched the bimodal pattern of precipitation in Temple, Texas, and did not respond to the pulse of precipitation during the summer. Our results suggest that we will need to take different approaches in understanding of invasion between native and exotic grasslands. Moreover, with anticipated increasing variability in precipitation under global climate change, plant invasions may be constrained in their response if the precipitation pulses fall outside the normal growing period of invaders.     

From Reef to Table: Social and Ecological Factors Affecting Coral Reef Fisheries,Artisanal Seafood Supply Chains,and Seafood Security

Ocean and coastal ecosystems provide critical fisheries, coastal protection, and cultural benefits to communities worldwide, but these services are diminishing due to local and global threats. In response, place-based strategies involve communities and resource users in management have proliferated. Here, we present a transferable community-based approach to assess the social and ecological factors affecting resource sustainability and food security in a small-scale, coral reef fishery. Our results show that this small-scale fishery provides large-scale benefits to communities, including 7,353 ± 1547 kg yr^-1 (mean ± SE) of seafood per year, equating to >30,000 meals with an economic value of $78,432. The vast majority of the catch is used for subsistence, contributing to community food security: 58% is kept, 33.5% is given away, and 8.5% is sold. Our spatial analysis assesses the geographic distribution of community beneficiaries from the fishery (the “food shed” for the fishery), and we document that 20% of seafood procured from the fishery is used for sociocultural events that are important for social cohesion. This approach provides a method for assessing social, economic, and cultural values provided by small-scale food systems, as well as important contributions to food security, with significant implications for conservation and management. This interdisciplinary effort aims to demonstrate a transferable participatory research approach useful for resource-dependent communities as they cope with socioeconomic, cultural, and environmental change.     

Characterization of Bacterial Communities Associated with the Tyrian Purple Producing Gland in a Marine Gastropod

Dicathais orbita is a marine mollusc recognised for the production of anticancer compounds that are precursors to Tyrian purple. This study aimed to assess the diversity and identity of bacteria associated with the Tyrian purple producing hypobranchial gland, in comparison with foot tissue, using a high-throughput sequencing approach. Taxonomic and phylogenetic analysis of variable region V1-V3 of 16S rRNA bacterial gene amplicons in QIIME and MEGAN were carried out. This analysis revealed a highly diverse bacterial assemblage associated with the hypobranchial gland and foot tissues of D. orbita. The dominant bacterial phylum in the 16S rRNA bacterial profiling data set was Proteobacteria followed by Bacteroidetes, Tenericutes and Spirochaetes. In comparison to the foot, the hypobranchial gland had significantly lower bacterial diversity and a different community composition, based on taxonomic assignment at the genus level. A higher abundance of indole producing Vibrio spp. and the presence of bacteria with brominating capabilities in the hypobranchial gland suggest bacteria have a potential role in biosynthesis of Tyrian purple in D. orbita.     

Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical Ketosis

The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA) and ketone bodies.Therefore, in the present study, a DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first investigation BI 14332 treatment (intravenous injection at dosages of up to 3 mg/kg body weight) was well tolerated in healthy lactating pluriparous cows (n = 6) with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days) or the control group. Under condition of subclinical ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic lipid content remained unaffected, but NEFA and triglyceride concentrations were decreased after treatment. Owing to lower NEFA, the revised quantitative insulin sensitivity check index (surrogate marker for insulin sensitivity) increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4⁺/CD8⁺ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic control like it is shown in humans, but was able to impact hyperlipemia, as NEFA and TG decreased.     

Public Opinions about Overdiagnosis: A National Community Survey

BackgroundDespite evidence about the "modern epidemic" of overdiagnosis, and expanding disease definitions that medicalize more people, data are lacking on public views about these issues. Our objective was to measure public perceptions about overdiagnosis and views about financial ties of panels setting disease definitions.MethodsWe conducted a 15 minute Computer Assisted Telephone Interview with a randomly selected community sample of 500 Australians in January 2014. We iteratively developed and piloted a questionnaire, with a convenience sample (n=20), then with participants recruited by a research company (n=20). Questions included whether respondents had been informed about overdiagnosis; opinions on informing people; and views about financial ties among panels writing disease definitions.FindingsOur sample was generally representative, but included a higher proportion of females and seniors, typical of similar surveys. American Association for Public Opinion Research response rate was 20% and cooperation rate was 44%. Only 10% (95% CI 8%–13%) of people reported ever being told about overdiagnosis by a doctor. 18% (95% CI 11%–28%) of men who reported having prostate cancer screening, and 10% (95% CI 6%–15%) of women who reported having mammography said they were told about overdiagnosis. 93% (95% CI 90%–95%) agreed along with screening benefits, people should be informed about overdiagnosis. On panels setting disease definitions, 78% (95% CI 74%–82%) felt ties to pharmaceutical companies inappropriate, and 91% (95% CI 82%–100%) believed panels should have a minority or no members with ties. Limitations included questionnaire novelty and complexity.ConclusionsA small minority of Australians surveyed, including those reporting being screened for prostate or breast cancer, reported being informed of overdiagnosis; most believed people should be informed; and a majority felt it inappropriate that doctors with ties to pharmaceutical companies write disease definitions. Results suggest strategies to better inform people about overdiagnosis, and review disease definition processes, have significant public sympathy.     

Cross‐resistance of chrysanthemum to western flower thrips,celery leafminer,and two‐spotted spider mite

Chrysanthemum [Chrysanthemum × morifolium Ramat. (Asteraceae)] is one of the economically most important greenhouse ornamentals worldwide. A major constraint in chrysanthemum production is adequate pest management, requiring the use of different tactics, such as improving host plant resistance, in the framework of an integrated pest management (IPM) approach. In this study, we investigated cross‐resistance of chrysanthemum to its three major pests: western flower thrips [Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae)], celery leafminer [Liriomyza trifolii (Burgess) (Diptera: Agromyzidae)], and two‐spotted spider mite [Tetranychus urticae Koch (Acari: Tetranychidae)]. We quantified resistance to each pest by performing greenhouse bioassays with a broad range of chrysanthemum types from commercial germplasm provided by Dutch breeding companies. Considerable variation was detected among the chrysanthemum cultivars in thrips silver damage and growth damage, leafminer damage, measured as number of mines and pupae, and spider mite numbers and damage. We observed significant positive correlations between thrips damage (both silver and growth damage) vs. leafminer numbers (both mines and pupae), and between leafminer numbers (both mines and pupae) vs. spider mite numbers. Our results indicate an overlap in resistance to all three herbivores. The important implications of this result for chrysanthemum breeding are discussed.     

Porcine proximal tubular cells (LLC‐PK1) are able to tolerate high levels of lithium chloride in vitro: assessment of the influence of 1–20 mM LiCl on cell death and alterations in cell biology and biochemistry

Lithium, a prophylactic drug for the treatment of bipolar disorder, is prescribed with caution due to its side effects, including renal damage. In this study porcine LLC‐PK₁ renal tubular cells were used to establish the direct toxicity of lithium on proximal cells and gain insights into the molecular mechanisms involved. In the presence of LiCl, cell proliferation exhibited insignificant decreases in a concentration‐dependent manner, but once confluent, constant cell numbers were observed. Cell cycle studies indicated a small dose‐dependant accumulation of cells in the G₂/M stage after 24 h, as well as an increase in cells in the G₀/G₁ phase after treatment with 1–10 mM LiCl, but not at 20 mM LiCl. No evidence of apoptosis was observed based on cell morphology or DNA fragmentation studies, or evidence of protein expression changes for Bax, Bcl‐2, and p53 proteins using immunocytochemistry. In addition caspases 3, 8 and 9 activity remained unaltered between control and lithium‐treated cultures. To conclude, exposure to high concentrations of lithium did not result in overt toxic effects to LLC‐PK₁ renal cells, although LiCl did alter some aspects of cell behaviour, which could potentially influence function over time.