Developmental and dominance-associated differences in mushroom body structure in the paper wasp Mischocyttarus mastigophorus

Primitively eusocial paper wasps exhibit considerable plasticity in their division of labor. Dominance interactions among nest mates play a strong role in determining the task performance patterns of adult females. We asked whether dominance status and task performance differences were associated with the development of subregions of the mushroom bodies (MB) of female Mischocyttarus mastigophorus queens and workers. We found that the MB calycal neuropils were better developed (relative to the Kenyon cell body layer) in the dominant females that spent more time on the nest. Increased MB calyx development was more strongly associated with social dominance than with high rates of foraging. The MB of queens resembled those of dominant workers. The results suggest that social interactions are particularly relevant to M. mastigophorus females' cognition. By examining the MB of newly emerged females, we also found evidence for significant age-related changes in MB structure.     

Dopamine Transporter Is Required for In Vivo MPTP Neurotoxicity: Evidence from Mice Lacking the Transporter

Abstract: The neurotoxic effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was tested on mice lacking the dopamine (DA) transporter (DAT−/− mice). Striatal tissue DA content and glial fibrillary acidic protein (GFAP) mRNA expression were assessed as markers of MPTP neurotoxicity. MPTP (30 mg/kg, s.c., b.i.d.) produced an 87% decrease in tissue DA levels and a 29-fold increase in the level of GFAP mRNA in the striatum of wild-type animals 48 h after administration. Conversely, there were no significant changes in either parameter in DAT−/− mice. Heterozygotes demonstrated partial sensitivity to MPTP administration as shown by an intermediate value (48%) of tissue DA loss. Direct intrastriatal infusion of the active metabolite of MPTP, 1-methyl-4-phenylpyridinium (MPP⁺; 10 m M ), via a microdialysis probe produced a massive efflux of DA in wild-type mice (>320-fold). In the DAT−/− mice the same treatment produced a much smaller increase in extracellular DA (sixfold), which is likely secondary to tissue damage due to the implantation of the dialysis probe. These observations show that the DAT is a mandatory component for expression of MPTP toxicity in vivo.     

Oxidation of polychlorinated benzenes by genetically engineered CYP101 (cytochrome P450(cam)).

Polychlorinated benzenes are recalcitrant environmental pollutants primarily because they are resistant to attack by dioxygenases commonly used by micro-organisms for the biodegradation of aromatic compounds. We have investigated the oxidation of polychlorinated benzenes by mutants of the haem mono-oxygenase CYP101 (cytochrome P450(cam)) from Pseudomonas putida with the aim of generating novel systems for their biodegradation. Wild-type CYP101 had low activity for the oxidation of dichlorobenzenes and trichlorobenzenes to the chlorophenols, but no products were detected for the heavily chlorinated benzenes. Increasing the active-site hydrophobicity with the Y96F mutation increased the activity up to 100-fold, and both pentachlorobenzene and hexachlorobenzene were oxidized slowly to pentachlorophenol. Decreasing the space available at the top of the active site with the F87W mutation to force the substrate to be bound closer to the haem resulted in a further 10-fold increase in activity with most substrates. Introducing the F98W mutation, also at the top of the active site, decreased the NADH-turnover rates but increased the coupling efficiencies, and > 90% coupling was observed for 1,3-dichlorobenzene and 1,3,5-trichlorobenzene with the F87W--Y96F--F98W mutant. The V247L mutation generally increased the NADH-turnover rates, and the F87W--Y96F--V247L mutant showed reasonably fast NADH turnover (229 min(-1)) with the highly insoluble pentachlorobenzene without the need for surfactants or organic cosolvents. As all chlorophenols are degraded by micro-organisms, novel biodegradation systems could be constructed in which CYP101 mutants convert the inert polychlorinated benzenes to the phenols, which are then readily degraded by natural pathways.     

Comparison of the pathogenic potentials of environmental and clinical vibrio parahaemolyticus strains indicates a role for temperature regulation in virulence

Although the presence of pathogenic Vibrio spp. in estuarine environments of northern New England has been known for some time (C. H. Bartley and L. W. Slanetz, Appl. Microbiol. 21: 965-966, 1971, and K. R. O'Neil, S. H. Jones, and D. J. Grimes, FEMS Microbiol. Lett. 60:163-167, 1990), their virulence and the relative threat they may pose to human health has yet to be evaluated. In this study, the virulence potential of 33 Vibrio parahaemolyticus isolates collected from the Great Bay Estuary of New Hampshire was assessed in comparison to that of clinical strains. The environmental isolates lack thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH), which are encoded by tdh and trh, respectively. Though not hemolytic, they do possess putative virulence factors, such type III secretion system 1, and are highly cytotoxic to human gastrointestinal cells. The expression of known and putative virulence-associated traits, including hemolysin, protease, motility, biofilm formation, and cytotoxicity, by clinical reference isolates correlated with increased temperature from 28°C to 37°C. In contrast, the environmental isolates did not induce their putative virulence-associated traits in response to a temperature of 37°C. We further identified a significant correlation between hemolytic activity and growth phase among clinical strains, whereby hemolysin production decreases with increasing cell density. The introduction of a tdh::gfp promoter fusion into the environmental strains revealed that they regulate this virulence-associated gene appropriately in response to temperature, indicating that their existing regulatory mechanisms are primed to manage newly acquired virulence genes.     

Preparing to Work with Big Data in Proteomics – A Report on the HUPO‐PSI Spring Workshop

The Human Proteome Organisation Proteomics Standards Initiative (HUPO‐PSI) was established in 2002 with the aim of defining community standards for data representation in proteomics and facilitating data comparison, exchange and verification. The 2013 annual spring workshop was hosted by the University of Liverpool, UK and concentrated on updating and refining the existing standards in the light of new methodologies and technologies. To control the inflation of file sizes, strategies for file compression, particularly for mzML files, were explored. Best practices for encoding information such as protein grouping and PTM localisation were refined and documented. Additional example files for the mzQuantML format were designed to provide support for selected reaction monitoring techniques. Enhancements to the PSI Common Query Interface (PSICQUIC) and PSI‐MI XML were discussed. Finally, the group engaged in discussion on how the existing work of the HUPO‐PSI can be leveraged by the Metabolomics Standards Initiative to improve the capture of metabolite data.     

Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells

Dicer, an enzyme involved in microRNA (miRNA) maturation, is required for proper cell differentiation and embryogenesis in mammals. Recent evidence indicates that Dicer and miRNA may also regulate tumorigenesis. To better characterize the role of miRNA in primary cell growth, we generated Dicer-conditional mice. Ablation of Dicer and loss of mature miRNAs in embryonic fibroblasts up-regulated p19(Arf) and p53 levels, inhibited cell proliferation, and induced a premature senescence phenotype that was also observed in vivo after Dicer ablation in the developing limb and in adult skin. Furthermore, deletion of the Ink4a/Arf or p53 locus could rescue fibroblasts from premature senescence induced by Dicer ablation. Although levels of Ras and Myc oncoproteins appeared unaltered, loss of Dicer resulted in increased DNA damage and p53 activity in these cells. These results reveal that loss of miRNA biogenesis activates a DNA damage checkpoint, up-regulates p19(Arf)-p53 signaling, and induces senescence in primary cells.     

A novel application of entropy analysis for assessing changes in movement variability during cumulative tackles in young elite rugby league players

The aim of this study was to identify between-position (forwards vs. backs) differences in movement variability in cumulative tackle events training during both attacking and defensive roles. Eleven elite adolescent male rugby league players volunteered to participate in this study (mean ± SD, age; 18.5 ± 0.5 years, height; 179.5 ± 5.0 cm, body mass; 88.3 ± 13.0 kg). Participants performed a drill encompassing four blocks of six tackling (i.e. tackling an opponent) and six tackled (i.e. being tackled by an opponent while carrying a ball) events (i.e. 48 total tackles) while wearing a micro-technological inertial measurement unit (WIMU, Realtrack Systems, Spain). The acceleration data were used to calculate sample entropy (SampEn) to analyse the movement variability during tackles performance. In tackling actions SampEn showed significant between-position differences in block 1 (p = 0.0001) and block 2 (p = 0.0003). Significant between-block differences were observed in backs (block 1 vs 3, p = 0,0021; and block 1 vs 4, p = 0,0001) but not in forwards. When being tackled, SampEn showed significant between-position differences in block 1 (p = 0.0007) and block 3 (p = 0.0118). Significant between-block differences were only observed for backs in block 1 vs 4 (p = 0,0025). Movement variability shows a progressive reduction with cumulative tackle events, especially in backs and when in the defensive role (tackling). Forwards present lower movement variability values in all blocks, particularly in the first block, both in the attacking and defensive role. Entropy measures can be used by practitioners as an alternative tool to analyse the temporal structure of variability of tackle actions and quantify the load of these actions according to playing position.     

Perinatal outcomes of midwife-led care,stratified by medical risk: a retrospective cohort study from British Columbia (2008–2018)

Background:Anecdotal evidence suggests that the profile of midwifery clients in British Columbia has changed over the past 20 years and that midwives are increasingly caring for clients with moderate to high medical risk. We sought to compare perinatal outcomes with a registered midwife as the most responsible provider (MRP) versus outcomes among clients with physicians as their MRP across medical risk strata.Methods:This retrospective cohort study (2008–2018) used data from the BC Perinatal Data Registry. We included all births that had a family physician, obstetrician or midwife listed as the MRP (n = 425 056) and stratified the analysis by pregnancy risk status (low, moderate or high) according to an adapted perinatal risk scoring system. We estimated differences in outcomes between MRP groups by calculating adjusted absolute and relative risks.Results:The adjusted absolute and relative risks of adverse neonatal outcomes were consistently lower among those who chose midwifery care across medical risk strata, compared with clients who had a physician as MRP. Midwifery clients experienced higher rates of spontaneous vaginal births, vaginal births after cesarean delivery and breastfeeding initiation, and lower rates of cesarean deliveries and instrumental births, with no increase in adverse neonatal outcomes. We observed an increased risk of oxytocin induction among high-risk birthers with a midwife versus an obstetrician as MRP.Interpretation:Our findings suggest that compared with other providers in BC, midwives provide safe primary care for clients with varied levels of medical risk. Future research might examine how different practice and remuneration models affect clinical outcomes, client and provider experiences, and costs to the health care system.

In British Columbia, registered midwives are autonomous, primary health care providers, regulated and integrated into the publicly funded health care system. Midwives typically work in small-team continuity-of-care models, providing medical care during pregnancy, birth and up to 3 months postpartum in the community and in hospitals. Midwives hold hospital privileges and consult with physician colleagues as medically indicated.Since the regulation of midwifery in BC in 1998, the number of pregnant people who are attended by midwives during birth has steadily increased, from 4.8% in 2004/05¹ to 15.6% in 2019/20.² In 2018/19, 1 in 4 childbearing people in BC (25.4%) had a midwife involved in their care at some point during their pregnancy, birth or postpartum period.²Several studies have examined the safety of midwifery care in BC after regulation. Janssen and colleagues analyzed the outcomes of low-risk clients from 2000 to 2004, providing important evidence for the safety of midwife-attended planned home births in the early years after regulation.³ Other researchers have described good perinatal outcomes for subsets of midwifery clients in BC, including those residing in rural areas⁴ and those planning vaginal births after cesarean (VBAC) at home.⁵ However, these studies focused on subsamples of childbearing people or did not use recent data.The benefits of midwife-led care for clients with more complex needs are beginning to emerge in BC. Using BC perinatal data, McRae and colleagues^6,7 demonstrated that those affected by low socioeconomic position, substance use and mental illness had lower odds of small-for-gestational-age babies, pretermbirth and low-birth-weight babies when they were cared for by midwives antenatally rather than by physicians.This analysis is part of a larger mixed-methods study that aimed to better understand the changing profile of midwifery clients in BC and the implications this has for education, research and practice. The goal of the current analysis is to present complete and recent data from all births in BC that had a midwife, family physician or obstetrician listed as the most responsible provider (MRP). Specifically, we sought to document neonatal and maternal outcomes of childbearing people who had a mid-wife as their MRP compared with those who had a physician as the MRP, with similar medical risk profiles.