Effective target size for the induction of bystander effects in medium transfer experiments

Although radiation-induced bystander effects are frequently observed biological phenomena, the mechanism for these effects has not been fully determined. The target-hit theory and related concepts from microdosimetry provide a convenient formalism to help identify the nature of the targets responsible for initiating the emission of diffusible factors in medium transfer experiments. We used the microdosimetric models proposed by Stewart et al. (Radiat. Res. 165, 460-469, 2006) to analyze the results of published medium transfer experiments for gamma-ray doses in the range of 0.04 mGy to 5 Gy. The analysis suggests that the effective size of the target responsible for initiating signal emission in HPV-G human keratinocyte donor cells is approximately 2 microm.     

Analysis of rare amino acid replacements supports the Coelomata clade

The recent analysis of a novel class of rare genomic changes, RGC_CAMs (after conserved amino acids-multiple substitutions), supported the Coelomata clade of animals as opposed to the Ecdysozoa clade (Rogozin et al. 2007). A subsequent reanalysis, with the sequences from the sea anemone Nematostella vectensis included in the set of outgroup species, suggested that this result was an artifact caused by reverse amino replacements and claimed support for Ecdysozoa (Irimia et al. 2007). We show that the internal branch connecting the sea anemone to the bilaterian animals is extremely short, resulting in a weak statistical support for the Coelomata clade. Direct estimation of the level of homoplasy, combined with taxon sampling with different sets of outgroup species, reinforces the support for Coelomata, whereas the effect of reversals is shown to be relatively minor.     

A roadmap for high‐throughput sequencing studies of wild animal populations using noninvasive samples and hybridization capture

Large‐scale genomic studies of wild animal populations are often limited by access to high‐quality DNA. Although noninvasive samples, such as faeces, can be readily collected, DNA from the sample producers is usually present in low quantities, fragmented, and contaminated by microorganism and dietary DNAs. Hybridization capture can help to overcome these impediments by increasing the proportion of subject DNA prior to high‐throughput sequencing. Here we evaluate a key design variable for hybridization capture, the number of rounds of capture, by testing whether one or two rounds are most appropriate, given varying sample quality (as measured by the ratios of subject to total DNA). We used a set of 1,780 quality‐assessed wild chimpanzee (Pan troglodytes schweinfurthii) faecal samples and chose 110 samples of varying quality for exome capture and sequencing. We used multiple regression to assess the effects of the ratio of subject to total DNA (sample quality), rounds of capture and sequencing effort on the number of unique exome reads sequenced. We not only show that one round of capture is preferable when the proportion of subject DNA in a sample is above ~2%–3%, but also explore various types of bias introduced by capture, and develop a model that predicts the sequencing effort necessary for a desired data yield from samples of a given quality. Thus, our results provide a useful guide and pave a methodological way forward for researchers wishing to plan similar hybridization capture studies.     

Biallelic Mutations in the Autophagy Regulator DRAM2 Cause Retinal Dystrophy with Early Macular Involvement

Retinal dystrophies are an overlapping group of genetically heterogeneous conditions resulting from mutations in more than 250 genes. Here we describe five families affected by an adult-onset retinal dystrophy with early macular involvement and associated central visual loss in the third or fourth decade of life. Affected individuals were found to harbor disease-causing variants in DRAM2 (DNA-damage regulated autophagy modulator protein 2). Homozygosity mapping and exome sequencing in a large, consanguineous British family of Pakistani origin revealed a homozygous frameshift variant (c.140delG [p.Gly47Valfs^∗3]) in nine affected family members. Sanger sequencing of DRAM2 in 322 unrelated probands with retinal dystrophy revealed one European subject with compound heterozygous DRAM2 changes (c.494G>A [p.Trp165^∗] and c.131G>A [p.Ser44Asn]). Inspection of previously generated exome sequencing data in unsolved retinal dystrophy cases identified a homozygous variant in an individual of Indian origin (c.64_66del [p.Ala22del]). Independently, a gene-based case-control association study was conducted via an exome sequencing dataset of 18 phenotypically similar case subjects and 1,917 control subjects. Using a recessive model and a binomial test for rare, presumed biallelic, variants, we found DRAM2 to be the most statistically enriched gene; one subject was a homozygote (c.362A>T [p.His121Leu]) and another a compound heterozygote (c.79T>C [p.Tyr27His] and c.217_225del [p.Val73_Tyr75del]). DRAM2 encodes a transmembrane lysosomal protein thought to play a role in the initiation of autophagy. Immunohistochemical analysis showed DRAM2 localization to photoreceptor inner segments and to the apical surface of retinal pigment epithelial cells where it might be involved in the process of photoreceptor renewal and recycling to preserve visual function.     

Transient Population Dynamics of Two Epiphytic Orchid Species after Hurricane Ivan: Implications for Management

Populations of epiphytic orchids in disturbance‐prone environments rarely reach stable‐stage equilibrium. We characterized the post‐disturbance, transient dynamics of two epiphytic orchids, Broughtonia cubensis, and the leafless Dendrophylax lindenii, comparing the following indices: reactivity/first‐time attenuation, maximal amplification/attenuation, and amplified/attenuated inertia. We also assessed the effects of reintroducing only seeds or only adults, by examining the elasticity of the inertia on the vital rates. For 2006–2010, the stochastic growth rate of D. lindenii was λ_s = 0.94, or a 6 percent decrease per annum. First‐time step attenuation indicates that in 1 year, the population could decrease by an additional 16 percent, and in the worst‐case scenario could decrease by almost half, relative to the stable‐stage distribution, in 10 years. Broughtonia cubensis had a λ_s = 1.03; reactivity and first‐time step attenuation indicates that in 1 year, the population should not change by more than 14 percent of the estimated stable‐stage distribution. However, the worst‐case scenario projected a reduction of 40 percent relative to the stable‐stage distribution within 8 years. A comparison of reintroduction strategies assessed by elasticity of the population momentum showed that adults performed better when relocated to new habitats.     

Anticipating the spatio‐temporal response of plant diversity and vegetation structure to climate and land use change in a protected area

Vegetation is a key driver of ecosystem functioning (e.g. productivity and stability) and of the maintenance of biodiversity (e.g. creating habitats for other species groups). While vegetation sensitivity to climate change has been widely investigated, its spatio‐temporally response to the dual effects of land management and climate change has been ignored at landscape scale. Here we use a dynamic vegetation model called FATE‐HD, which describes the dominant vegetation dynamics and associated functional diversity, in order to anticipate vegetation response to climate and land‐use changes in both short and long‐term perspectives. Using three contrasted management scenarios for the Ecrins National Park (French Alps) developed in collaboration with the park managers, and one regional climate change scenario, we tracked the dynamics of vegetation structure (forest expansion) and functional diversity over 100 yr of climate change and a further 400 additional years of stabilization. As expected, we observed a slow upward shift in forest cover distribution, which appears to be severely impacted by pasture management (i.e. maintenance or abandonment). The time lag before observing changes in vegetation cover was the result of demographic and seed dispersal processes. However, plant diversity response to environmental changes was rapid. After land abandonment, local diversity increased and spatial turnover was reduced, whereas local diversity decreased following land use intensification. Interestingly, in the long term, as both climate and management scenarios interacted, the regional diversity declined. Our innovative spatio‐temporally explicit framework demonstrates that the vegetation may have contrasting responses to changes in the short and the long term. Moreover, climate and land‐abandonment interact extensively leading to a decrease in both regional diversity and turnover in the long term. Based on our simulations we therefore suggest a continuing moderate intensity pasturing to maintain high levels of plant diversity in this system.     

The Association between Body Mass Index and Mortality in Incident Dialysis Patients

Objectives

To study the body mass index (BMI) trajectory in patients with incident end-stage kidney disease and its association with all-cause mortality.

Methods

This longitudinal cohort study included 17022 adult patients commencing hemodialysis [HD] (n = 10860) or peritoneal dialysis [PD] (n = 6162) between 2001 and 2008 and had ≥6-month follow-up and ≥2 weight measurements, using the Australia and New Zealand Dialysis and Transplant Registry data. The association of time-varying BMI with all-cause mortality was explored using multivariate Cox regression models.

Results

The median follow-up was 2.3 years. There was a non-linear change in the mean BMI (kg/m²) over time, with an initial decrease from 27.6 (95% confidence interval [CI]: 27.5, 27.7) to 26.7 (95% CI: 26.6, 26.9) at 3-month, followed by increments to 27.1 (95% CI: 27, 27.2) at 1-year and 27.2 (95% CI: 26.8, 27.1) at 3-year, and a gradual decrease subsequently. The BMI trajectory was significantly lower in HD patients who died than those who survived, although this pattern was not observed in PD patients. Compared to the reference time-varying BMI category of 25.1–28 kg/m², the mortality risks of both HD and PD patients were greater in all categories of time-varying BMI <25 kg/m². The mortality risks were significantly lower in all categories of time-varying BMI >28.1 kg/m² among HD patients, but only in the category 28.1–31 kg/m² among PD patients.

Conclusions

BMI changed over time in a non-linear fashion in incident dialysis patients. Time-varying measures of BMI were significantly associated with mortality risk in both HD and PD patients.     

Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n?=?23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n?=?10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n?=?7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.