Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling

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Pharmacologic modulation of RNA splicing enhances anti-tumor immunity

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The Role of Habitat Complexity in Community Development Is Mediated by Resource Availability

Habitat complexity strongly affects the structure and dynamics of ecological communities, with increased complexity often leading to greater species diversity and abundance. However, habitat complexity changes as communities develop, and some species alter their environment to themselves provide habitat for other species. Most experimental studies manipulate basal substrate complexity, and while the importance of complexity likely changes during community development, few studies have examined the temporal dynamics of this variable. We used two experiments to quantify the importance of basal substrate complexity to sessile marine invertebrate community development through space and time. First, we compared effects of substrate complexity at 70 sites across ten estuaries. Sites differed in recruitment and community development rates, and after three months provided spatial variation in community development stage. Second, we tested for effects of substrate complexity at multiple times at a single site. In both experiments, complexity affected marine sessile invertebrate community composition in the early stages of community development when resource availability was high. Effects of complexity diminished through time as the amount of available space (the primary limiting resource) declined. Our work suggests the presence of a bare-space threshold, at which structural complexity of the basal substrate is overwhelmed by secondary biotic complexity. This threshold will be met at different times depending on local recruitment and growth rates and is likely to vary with productivity gradients.     

Environmental and seasonal influences on red raspberry flavour volatiles and identification of quantitative trait loci (QTL) and candidate genes

Raspberry volatiles are important for perceptions of sensory quality, mould resistance and some have nutraceutical activities. Twelve raspberry character volatiles were quantified, 11 of them in fruit from two seasons, from plants from the Glen Moy × Latham mapping population growing in both open field and under cover (polytunnels). Effects of season and environment were examined for their impact on the content of α-ionone, α-ionol, β-ionone, β-damascenone, linalool, geraniol, benzyl alcohol, (Z)-3-hexenol, acetoin, acetic and hexanoic acids, whilst raspberry ketone was measured in one season. A significant variation was observed in fruit volatiles in all progeny between seasons and method of cultivation. Quantitative trait loci were determined and mapped to six of the seven linkage groups, as were candidate genes in the volatiles pathways.     

Promoting Smoke-Free Homes: A Novel Behavioral Intervention Using Real-Time Audio-Visual Feedback on Airborne Particle Levels

Interventions are needed to protect the health of children who live with smokers. We pilot-tested a real-time intervention for promoting behavior change in homes that reduces second hand tobacco smoke (SHS) levels. The intervention uses a monitor and feedback system to provide immediate auditory and visual signals triggered at defined thresholds of fine particle concentration. Dynamic graphs of real-time particle levels are also shown on a computer screen. We experimentally evaluated the system, field-tested it in homes with smokers, and conducted focus groups to obtain general opinions. Laboratory tests of the monitor demonstrated SHS sensitivity, stability, precision equivalent to at least 1 µg/m³, and low noise. A linear relationship (R² = 0.98) was observed between the monitor and average SHS mass concentrations up to 150 µg/m³. Focus groups and interviews with intervention participants showed in-home use to be acceptable and feasible. The intervention was evaluated in 3 homes with combined baseline and intervention periods lasting 9 to 15 full days. Two families modified their behavior by opening windows or doors, smoking outdoors, or smoking less. We observed evidence of lower SHS levels in these homes. The remaining household voiced reluctance to changing their smoking activity and did not exhibit lower SHS levels in main smoking areas or clear behavior change; however, family members expressed receptivity to smoking outdoors. This study established the feasibility of the real-time intervention, laying the groundwork for controlled trials with larger sample sizes. Visual and auditory cues may prompt family members to take immediate action to reduce SHS levels. Dynamic graphs of SHS levels may help families make decisions about specific mitigation approaches.     

The Effect of Conflicting Pressures on the Evolution of Division of Labor

Within nature, many groups exhibit division of labor. Individuals in these groups are under seemingly antagonistic pressures to perform the task most directly beneficial to themselves and to potentially perform a less desirable task to ensure the success of the group. Performing experiments to study how these pressures interact in an evolutionary context is challenging with organic systems because of long generation times and difficulties related to group propagation and fine-grained control of within-group and between-group pressures. Here, we use groups of digital organisms (i.e., self-replicating computer programs) to explore how populations respond to antagonistic multilevel selection pressures. Specifically, we impose a within-group pressure to perform a highly-rewarded role and a between-group pressure to perform a diverse suite of roles. Thus, individuals specializing on highly-rewarded roles will have a within-group advantage, but groups of such specialists have a between-group disadvantage. We find that digital groups could evolve to be either single-lineage or multi-lineage, depending on experimental parameters. These group compositions are reminiscent of different kinds of major evolutionary transitions that occur within nature, where either relatives divide labor (fraternal transitions) or multiple different organisms coordinate activities to form a higher-level individual (egalitarian transitions). Regardless of group composition, organisms embraced phenotypic plasticity as a means for genetically similar individuals to perform different roles. Additionally, in multi-lineage groups, organisms from lineages performing highly-rewarded roles also employed reproductive restraint to ensure successful coexistence with organisms from other lineages.     

Measurement and Selection of Parasitoid Quality for Mass-Reared Trichogramma minutum Riley Used in Inundative Release

Parasitoid quality, subject to both genetic and environmental influences, is critical to the success of any biological control program, however, its measurement and improvement is poorly understood. In this study, a classic genetic approach is taken to develop two indices, namely a character index and a fitness index, for the measurement and selection of high quality parasitoids used in inundative release. Six life-history traits and corresponding fitness components in 33 inbred strains of Trichogramma minutum were used to generate both genotypic and phenotypic variance-covariance matrices that then allowed for the construction of the indices. Most traits and their fitness components were positively correlated, both phenotypically and genotypically, with lifetime fecundity and the number of female offspring appearing to have an important influence. Selection of the top three strains showed that parasitoid quality could be improved by 36% using the character index and possibly up to 150% using the fitness index. The two indices were linearly correlated suggesting that either could be used to measure quality. The character index is recommended because it requires information on only three life-history traits (fecundity, number of female offspring, and number of male offspring) and has highly correlated responses of fitness components. Our work demonstrates that the best quality T. minutum will be obtained by using the character index to select for inbred strains which have high fecundity and number of female offspring.     

Predictors of Weight Loss in Adults with Topiramate‐Treated Epilepsy

Objective: We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults. Research Methods and Procedures: In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial‐onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment. Results: In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) ≥ 30 kg/m²], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007). Discussion: Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.     

A re-investigation of the ribonuclease sensitivity of a DNA demethylation reaction in chicken embryo and G8 mouse myoblasts.

Recently published results (Nucleic Acids Res. 26, 5573-5580, 1998) suggest that the ribonuclease sensitivity of the DNA demethylation reaction may be an experimental artifact due to the possible tight binding of the nucleases to the methylated DNA substrate. Using an improved protocol we show for two different systems that demethylation of hemimethylated DNA is indeed sensitive to micrococcal nuclease, requires RNA and is not an experimental artifact. The purified 5-MeC-DNA glycosylase from chicken embryos and G8 mouse myoblasts was first incubated for 5 min at 37 degrees C with micrococcal nuclease in the presence of Ca2+ in the absence of the DNA substrate. Upon blocking the nuclease activity by the addition of 25 mM EGTA, the DNA demethylation reaction was initiated by adding the labeled hemimethylated DNA substrate to the reaction mixture. Under these conditions the DNA demethylation reaction was abolished. In parallel controls, where the purified 5-MeC-DNA glycosylase was pre-incubated at 37 degrees C with the nuclease, Ca2+ and EGTA or with the nuclease and EGTA, RNA was not degraded and no inhibition of the demethylation reaction was obtained. As has already been shown for chicken embryos, the loss of 5-MeC-DNA glycosylase activity from G8 myoblasts following nuclease treatment can also be restored by the addition of synthetic RNA complementary to the methylated strand of the substrate DNA. No reactivation of 5-MeC-DNA glycosylase is obtained by complementation with a random RNA sequence, the RNA sequence complementary to the non-methylated strand or DNA, thus ruling out a non-specific competition of the RNA for the binding of the nuclease to the labeled DNA substrate.