Magnitude of behavioral deficits varies with job-related chlorpyrifos exposure levels among Egyptian pesticide workers.

Chronic occupational exposure to organophosphorus pesticides (OPs) is consistently associated with deficits on behavioral tests when compared to unexposed comparison groups. However, a dose-response relationship has yet to be established, leading some to doubt an association between occupational OP exposure and behavioral deficits. Pesticide application teams in Egypt who are primarily exposed to one OP, chlorpyrifos (CPF), were recruited into a field assessment. Trail Making A and the more challenging Trail Making B tests were administered to 54 engineers (who supervise the pesticide application process, usually from the side of the field), 59 technicians (who guide the pesticide applicators in the field), 31 applicators (who mix and apply pesticides using knapsack sprayers), and 150 controls (who did not work in the fields) at two different times during the OP application season as well as immediately after applications had ended and 1.5 months later. All participants were males since only males work on pesticide application teams in Egypt. Urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, confirmed the pattern of lower to higher CPF exposures from engineers to technicians to applicators, and these were all greater than urinary metabolite levels in controls. A consistent relationship between job title and performance speed on the behavioral task was observed: Controls had the best (fastest) performance on Trail Making A and B tests throughout the application season, and applicators had significantly slower performance than engineers on Trail Making A (p = 0.015) and B (p = 0.003). However, individual urinary TCPy, blood acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) levels did not predict individual performance. This study identifies a dose-related effect based on job title, which serves as a surrogate for chronic exposure in that differing job titles exhibit varying group exposure levels. The results establish that chronic occupational exposure to chlorpyrifos is neurotoxic and suggest that the classic biomarkers of recent CPF exposure are not predictive of chronic exposure effects

Egg development, hatching rhythm and moult patterns in Paralomos spinosissima (Decapoda: Anomura: Paguroidea: Lithodidae) from South Georgia waters (Southern Ocean)

Larval release, hatching rhythms and moult patterns were examined in a captive population of the subantarctic lithodid, Paralomis spinosissima from the South Georgia and Shag Rocks region. Larvae hatched throughout the year with the majority of females starting to release larvae at the end of the austral summer and beginning of autumn. Larval release continued over a period of up to 9 weeks with high variability in the numbers that hatched each day. A similar seasonal pattern to hatching was evident in the moulting of females. Intermoult period for two adult females (CL = 63 and 85 mm) ranged from 894 to 1,120 days while an intermoult period for males was estimated to be in excess of 832 days. The results are consistent with other species of Paralomis and are discussed in relation to physiological and environmental adaptations to the cold-water conditions south of the Antarctic Convergence

Predictors of Implantable Pulse Generator Placement After Sacral Neuromodulation: Who Does Better?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107552/1/ner12109.pd

Outcomes of Sacral Neuromodulation in a Privately Insured Population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134200/1/ner12472_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134200/2/ner12472.pd

Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes

DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono-and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes

Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes

DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono-and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes

Temperature modulates compensatory responses to food limitation at metamorphosis in a marine invertebrate

Under climate change, increased temperatures combined with food limitation may be critical for species with complex life cycles, if high growth rates characterise the larval development. We studied the effect of increased temperature and food limitation on larval survival and on functional traits (developmental time, body mass, elemental composition, growth) at moulting and metamorphosis in the crab Carcinus maenas collected in the North Sea (Helgoland, Germany). We followed the approach of models of metamorphosis integrating responses of body mass and developmental time to increased temperature and food limitation. We also evaluated if body mass decreased with temperature (according to the temperature-size rule) and if developmental time followed an inverse exponential reduction (expected from some metabolic theories), as both trends are relevant for modelling effects of climate change on fitness and population connectivity. Larvae produced by four females during the reproductive period (i.e. spring-summer 2016) were reared separately from hatching to metamorphosis to the megalopa at two food conditions (ad libitum and low food availability), and at four temperatures covering the range experienced in the field (20°C). Survival and developmental rates were obtained by daily monitoring of the experiments. Biomass data (body mass and elemental composition) were obtained by sampling larvae at the zoea IV and megalopa stages and further processed with standard methods (see Torres & Giménez 2020 for details). We propose that integrative studies of traits at metamorphosis could be a basis to develop a mechanistic understanding of how species with complex life cycles will respond to climate change. Such models could eventually include hormonal and metabolic regulation of development as drivers of responses to environmental change

The Effect of Sacral Neuromodulation on Anticholinergic Use and Expenditures in a Privately Insured Population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106102/1/ner12062.pd

The qWR star HD 45166. II. Fundamental stellar parameters and evidence of a latitude-dependent wind

The enigmatic object HD 45166 is a qWR star in a binary system with an orbital period of 1.596 day, and presents a rich emission-line spectrum in addition to absorption lines from the companion star (B7 V). As the system inclination is very small (i=0.77 +- 0.09 deg), HD 45166 is an ideal laboratory for wind-structure studies. The goal of the present paper is to determine the fundamental stellar and wind parameters of the qWR star. A radiative transfer model for the wind and photosphere of the qWR star was calculated using the non-LTE code CMFGEN. The wind asymmetry was also analyzed using a recently-developed version of CMFGEN to compute the emerging spectrum in two-dimensional geometry. The temporal-variance spectrum (TVS) was calculated for studying the line-profile variations. Abundances, stellar and wind parameters of the qWR star were obtained. The qWR star has an effective temperature of Teff=50000 +- 2000 K, a luminosity of log(L/Lsun)=3.75 +- 0.08, and a corresponding photospheric radius of Rphot=1.00 Rsun. The star is helium-rich (N(H)/N(He) = 2.0), while the CNO abundances are anomalous when compared either to solar values, to planetary nebulae, or to WR stars. The mass-loss rate is Mdot = 2.2 . 10^{-7} Msun/yr, and the wind terminal velocity is vinf=425 km/s. The comparison between the observed line profiles and models computed under different latitude-dependent wind densities strongly suggests the presence of an oblate wind density enhancement, with a density contrast of at least 8:1 from equator to pole. If a high velocity polar wind is present (~1200 km/s), the minimum density contrast is reduced to 4:1. The wind parameters determined are unusual when compared to O-type stars or to typical WR stars. (abridged)Comment: 16 pages, 13 figures, accepted for publication in A&