Airborne particulate matter and diesel engine exhaust on infrastructure construction sites in the Copenhagen metropolitan area.

Diesel engine exhaust (DEE) is carcinogenic and potentially hazardous for those working in close proximity to diesel-powered machines. This study characterizes workplace exposure to DEE and its associated particulate matter (PM) during outdoor construction activities. We sampled at 4 construction sites in the Copenhagen metropolitan area. We used portable constant-flow pumps and quartz-fiber filters to quantify personal exposure to elemental carbon (EC), and used real-time instruments to collect activity-based information about particle number and size distribution, as well as black carbon (BC) concentration. Full-shift measurements of EC concentration ranged from < 0.3 to 6.4 µg/m3. Geometric mean (GM) EC exposure was highest for ground workers (3.4 µg/m3 EC; geometric standard deviation, GSD = 1.3), followed by drilling rig operators (2.6 µg/m3 EC; GSD = 1.4). Exposure for non-drilling-rig machine operators (1.2 µg/m3 EC; GSD = 2.9) did not differ significantly from background (0.9 µg/m3 EC; GSD = 1.7). The maximum 15-min moving average concentration of BC was 17 µg/m3, and the highest recorded peak concentration was 44 µg/m3. In numbers, the particle size distributions were dominated by ultrafine particles ascribed to DEE and occasional welding activities at the sites. The average total particle number concentrations (PNCs) measured in near-field and far-field positions across all worksites were 10,600 (GSD = 3.0) and 6,000 (GSD = 2.8)/cm3, respectively. Sites with active drilling rigs saw significantly higher average total PNCs at their near-field stations (13,600, 32,000, and 9,700/cm3; GSD = 2.4, 3.4, and 2.4) than sites without (4,700/cm3; GSD = 1.6). Overall, the DEE exposures at these outdoor construction sites were below current occupational exposure limits for EC (10 µg/m3 in Denmark; 50 µg/m3 in the European Union), but extended durations of exposure to the observed DEE levels may still be a health risk.

Structure-function analysis of Cdc25Twine degradation at the Drosophila maternal-to-zygotic transition.

Downregulation of protein phosphatase Cdc25Twine activity is linked to remodelling of the cell cycle during the Drosophila maternal-to-zygotic transition (MZT). Here, we present a structure-function analysis of Cdc25Twine. We use chimeras to show that the N-terminus regions of Cdc25Twine and Cdc25String control their differential degradation dynamics. Deletion of different regions of Cdc25Twine reveals a putative domain involved in and required for its rapid degradation during the MZT. Notably, a very similar domain is present in Cdc25String and deletion of the DNA replication checkpoint results in similar dynamics of degradation of both Cdc25String and Cdc25Twine. Finally, we show that Cdc25Twine degradation is delayed in embryos lacking the left arm of chromosome III. Thus, we propose a model for the differential regulation of Cdc25 at the Drosophila MZT.

For Embryos, Mother Can Only Take You So Far.

Early embryonic development is characterized by rapid cleavage divisions, which impose significant constraints on metabolic pathways. In this issue, Song et al. (2017) show that Drosophila embryos synthesize a large fraction of nucleotides on the go and that negative feedback between dATP and ribonucleotide reductase ensures tight control of dNTP concentration.

Measuring time during early embryonic development.

In most metazoans, embryonic development is orchestrated by a precise series of cellular behaviors. Understanding how such events are regulated to achieve a stereotypical temporal progression is a fundamental problem in developmental biology. In this review, we argue that studying the regulation of the cell cycle in early embryonic development will reveal novel principles of how embryos accurately measure time. We will discuss the strategies that have emerged from studying early development of Drosophila embryos. By comparing the development of flies to that of other metazoans, we will highlight both conserved and alternative mechanisms to generate precision during embryonic development.

Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: implications for teenage smoking.

Adolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission during nicotine exposure and withdrawal in naïve adult rats compared to (1) adolescent rats and (2) adult rats that were pre-exposed to nicotine during adolescence. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAc) during nicotine exposure and precipitated withdrawal using microdialysis procedures. Adolescent (postnatal day, PND, 28-42) and adult rats (PND60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (adolescents 4.7 mg/kg/day; adults 3.2 mg/kg/day; expressed as base). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Control rats received a sham surgery. Following 13 days of nicotine exposure, the rats were implanted with microdialysis probes in the NAc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic receptor antagonist mecamylamine (1.5 and 3.0 mg/kg, i.p.) to precipitate withdrawal. A second study compared various metabolic differences in cholinergic transmission using the same treatment procedures as the first study. Following 14 days of nicotine exposure, the NAc was dissected and acetylcholinesterase (AChE) activity was compared across groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that nicotine exposure increased baseline ACh levels to a greater extent in adolescent versus adult rats. During nicotine withdrawal, ACh levels in the NAc were increased in a similar manner in adolescent versus adult rats. However, the increase in ACh that was observed in adult rats experiencing nicotine withdrawal was blunted in pre-exposed adults. These neurochemical effects do not appear to be related to nicotine metabolism, as plasma cotinine levels were similar across all groups. The second study revealed that nicotine exposure increased AChE activity in the NAc to a greater extent in adolescent versus adult rats. There was no difference in AChE activity in pre-exposed versus naïve adult rats. In conclusion, our results suggest that nicotine exposure during adolescence enhances baseline ACh in the NAc. However, the finding that ACh levels were similar during withdrawal in adolescent and adult rats suggests that the enhanced vulnerability to tobacco use during adolescence is not related to age differences in withdrawal-induced increases in cholinergic transmission. Our results also suggest that exposure to nicotine during adolescence suppresses withdrawal-induced increases in cholinergic responses during withdrawal. Taken together, this report illustrates important short- and long-term changes within cholinergic systems that may contribute to the enhanced susceptibility to tobacco use during adolescence.