In Situ Kinase Profiling Reveals Functionally Relevant Properties of Native Kinases

SummaryProtein kinases are intensely studied mediators of cellular signaling, yet important questions remain regarding their regulation and in vivo properties. Here, we use a probe-based chemoprotemics platform to profile several well studied kinase inhibitors against >200 kinases in native cell proteomes and reveal biological targets for some of these inhibitors. Several striking differences were identified between native and recombinant kinase inhibitory profiles, in particular, for the Raf kinases. The native kinase binding profiles presented here closely mirror the cellular activity of these inhibitors, even when the inhibition profiles differ dramatically from recombinant assay results. Additionally, Raf activation events could be detected on live cell treatment with inhibitors. These studies highlight the complexities of protein kinase behavior in the cellular context and demonstrate that profiling with only recombinant/purified enzymes can be misleading

Prenatal Exposure to Organophosphorus Pesticides and Preschool ADHD in the Norwegian Mother, Father and Child Cohort Study

Prenatal organophosphorus pesticide (OPP) exposure has been associated with child attention-deficit/hyperactivity disorder (ADHD) in agricultural communities and those that are exposed to residentially applied insecticides. To examine this association in populations that are exposed primarily through diet, we estimate the associations between prenatal OPP exposure and preschool ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa), and describe modification by paraoxonase 1 (PON1) gene variants. We used participants from the MoBa Preschool ADHD Sub-study (n = 259 cases) and a random sample of MoBa sub-cohort participants (n = 547) with birth years from 2004 to 2008. Prenatal urinary dialkylphosphate (DAP) metabolites (total diethylphosphate [∑DEP] and total dimethylphosphate [∑DMP]) were measured by an ultra-performance liquid chromatography-time-of-flight system and summed by molar concentration. Maternal DNA was genotyped for coding variants of PON1 (Q192R and L55M). We used a multivariable logistic regression to calculate the odds ratios (OR) and 95% confidence intervals, adjusted for maternal education, parity, income dependency, age, marital status, ADHD-like symptoms, pesticide use, produce consumption, and season. We found no associations between DAP metabolite concentrations and preschool ADHD. The adjusted ORs for exposure quartiles 2–4 relative to 1 were slightly inverse. No monotonic trends were observed, and the estimates lacked precision, likely due to the small sample size and variation in the population. We found no evidence of modification by PON1 SNP variation or child sex. Maternal urinary DAP concentrations were not associated with preschool ADHD

Novel Snowy Egret Foraging Behavior

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Social Cues and Environmental Conditions Influence Foraging Flight Distances of Breeding Wood Storks (Mycteria americana)

The influence of both environmental conditions and social cues on the distance flown to foraging sites was examined for breeding Wood Storks (Mycteria americana) in the Florida Everglades, USA. Adult Wood Storks (n = 73) were followed in a small plane from their nesting colony to their foraging locations during the time when adult Wood Storks were incubating and feeding chicks. On average, foraging sites were close to the nesting colony (mean = 9.6 km ± 1.1), and in shallow water (mean = 9.9 cm ± 0.7) that was receding at a moderate rate (-0.36 cm/day ± 0.13). Wood Storks landed at foraging sites already occupied by other white wading birds 99% of the time, with a mean flock size of 64 ± 14 birds. Model selection identified flock size and water recession rate as the most important variables that influenced Wood Stork foraging flight distances. Distances flown to foraging sites increased with increasing flock sizes and decreased with increasing recession rates (increasing by 39% and decreasing by 18% across the observed range of data, respectively) while accounting for colony location and water depths. These findings are particularly important because they demonstrate that both social and environmental factors play critical roles in the foraging site selection process Wood Storks use during the breeding season. Further, these results in part can be linked to management activities because at least in the case of water recession rates, managers can actively influence recession rates across much of the Everglades landscap

Resource Selection Functions for Wood Stork Foraging Habitat in the Southern Everglades

Abstract.—Modeling habitat selection of species with specific foraging requirements is an effective means evaluate landscape quality for restoration and conservation purposes. Proportional hazards regression, a discrete choice model, was used to develop resource selection functions for breeding Wood Stork in the southern Ever glades during the 2006 nesting season. Wood Storks showed the highest probability of habitat selection in a narrow range of shallow water depths. The quadratic form of water depth (depth+depth2) was an important indicator habitat selection with mean water depths between -25 and 25 cm receiving the highest probability of use (a negative water depth is below average ground elevation). Foraging sites within 20 km of nesting colonies were selected over farther sites. Shrub swamp, mangrove swamp and saltwater marsh vegetation types were used in higher proportions than they occurred in the landscape. Results exemplify the importance of shallow water depths near established stork breeding colonies throughout the breeding season

Prenatal Exposure to Organophosphorus Pesticides and Preschool ADHD in the Norwegian Mother, Father and Child Cohort Study

Prenatal organophosphorus pesticide (OPP) exposure has been associated with child attention-deficit/hyperactivity disorder (ADHD) in agricultural communities and those that are exposed to residentially applied insecticides. To examine this association in populations that are exposed primarily through diet, we estimate the associations between prenatal OPP exposure and preschool ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa), and describe modification by paraoxonase 1 (PON1) gene variants. We used participants from the MoBa Preschool ADHD Sub-study (n = 259 cases) and a random sample of MoBa sub-cohort participants (n = 547) with birth years from 2004 to 2008. Prenatal urinary dialkylphosphate (DAP) metabolites (total diethylphosphate [∑DEP] and total dimethylphosphate [∑DMP]) were measured by an ultra-performance liquid chromatography-time-of-flight system and summed by molar concentration. Maternal DNA was genotyped for coding variants of PON1 (Q192R and L55M). We used a multivariable logistic regression to calculate the odds ratios (OR) and 95% confidence intervals, adjusted for maternal education, parity, income dependency, age, marital status, ADHD-like symptoms, pesticide use, produce consumption, and season. We found no associations between DAP metabolite concentrations and preschool ADHD. The adjusted ORs for exposure quartiles 2–4 relative to 1 were slightly inverse. No monotonic trends were observed, and the estimates lacked precision, likely due to the small sample size and variation in the population. We found no evidence of modification by PON1 SNP variation or child sex. Maternal urinary DAP concentrations were not associated with preschool ADHD