Feasibility and Informative Value of Environmental Sample Collection in the National Children\u27s Vanguard Study

Background: Birth cohort studies provide the opportunity to advance understanding of the impact of environmental factors on childhood health and development through prospective collection of environmental samples. Methods: We evaluated the feasibility and informative value of the environmental sample collection methodology in the initial pilot phase of the National Children\u27s Study, a planned U.S. environmental birth cohort study. Environmental samples were collected from January 2009–September 2010 at up to three home visits: pre-pregnancy (n¼306), pregnancy (n¼807), and 6-months postnatal (n¼117). Collections included air for particulate matter r2.5 mm (PM2.5), nitrogen dioxide, ozone, volatile organic compounds (VOCs), and carbonyls; vacuum dust for allergens/endotoxin; water for VOCs, trihalomethanes (THMs), and haloacetic acids (HAAs); and wipe samples for pesticides, semi-volatile organics, and metals. We characterized feasibility using sample collection rates and times and informative value using analyte detection frequencies (DF). Results: Among the 1230 home visits, environmental sample collection rates were high across all sample types (mean¼89%); all samples except the air PM2.5 samples had collection times o30 min. Informative value was low for water VOCs (median DF¼0%) and pesticide floor wipes (median DF¼5%). Informative value was moderate for air samples (median DF¼35%) and high for water THMs and HAAs (median DF¼91% and 75%, respectively). Conclusions: Though collection of environmental samples was feasible, some samples (e.g., wipe pesticides and water VOCs) yielded limited information. These results can be used in conjunction with other study design considerations, such as target population size and hypotheses of interest, to inform the method selection of future environmental health birth cohort studies

Functional polarity is introduced by Dicer processing of short substrate RNAs

Synthetic RNA duplexes that are substrates for Dicer are potent triggers of RNA interference (RNAi). Blunt 27mer duplexes can be up to 100-fold more potent than traditional 21mer duplexes (1). Not all 27mer duplexes show increased potency. Evaluation of the products of in vitro dicing reactions using electrospray ionization mass spectrometry reveals that a variety of products can be produced by Dicer cleavage. Use of asymmetric duplexes having a single 2-base 3′-overhang restricts the heterogeneity that results from dicing. Inclusion of DNA residues at the ends of blunt duplexes also limits heterogeneity. Combination of asymmetric 2-base 3′-overhang with 3′-DNA residues on the blunt end result in a duplex form which directs dicing to predictably yield a single primary cleavage product. It is therefore possible to design a 27mer duplex which is processed by Dicer to yield a specific, desired 21mer species. Using this strategy, two different 27mers can be designed that result in the same 21mer after dicing, one where the 3′-overhang resides on the antisense (AS) strand and dicing proceeds to the ‘right’ (‘R’) and one where the 3′-overhang resides on the sense (S) strand and dicing proceeds to the ‘left’ (‘L’). Interestingly, the ‘R’ version of the asymmetric 27mer is generally more potent in reducing target gene levels than the ‘L’ version 27mer. Strand targeting experiments show asymmetric strand utilization between the two different 27mer forms, with the ‘R’ form favoring S strand and the ‘L’ form favoring AS strand silencing. Thus, Dicer processing confers functional polarity within the RNAi pathway

Human box C/D snoRNAs with miRNA like functions: expanding the range of regulatory RNAs

Small nucleolar RNAs (snoRNAs) and microRNAs are two classes of non-protein-coding RNAs with distinct functions in RNA modification or post-transcriptional gene silencing. In this study, we introduce novel insights to RNA-induced gene activity adjustments in human cells by identifying numerous snoRNA-derived molecules with miRNA-like function, including H/ACA box snoRNAs and C/D box snoRNAs. In particular, we demonstrate that several C/D box snoRNAs give rise to gene regulatory RNAs, named sno-miRNAs here. Our data are complementing the increasing number of studies in the field of small RNAs with regulatory functions. In massively deep sequencing of small RNA fractions we identified high copy numbers of sub-sequences from >30 snoRNAs with lengths of ≥18 nt. RNA secondary structure prediction indicated for a majority of candidates a location in predicted stem regions. Experimental analysis revealed efficient gene silencing for 11 box C/D sno-miRNAs, indicating cytoplasmic processing and recruitment to the RNA silencing machinery. Assays in four different human cell lines indicated variations in both the snoRNA levels and their processing to active sno-miRNAs. In addition we show that box D elements are predominantly flanking at least one of the sno-miRNA strands, while the box C element locates within the sequence of the sno-miRNA guide strand

Particular thanks and obligations’: The communications made by women to the society of antiquaries between 1776 and 1837, and their significance

This paper brings together the evidence bearing on the relationship between the Society of Antiquaries and the women who contributed to it during a significant period when archaeology, through the work of such men as Samuel Lysons and Richard Colt Hoare, was beginning to emerge as a distinct field with its own conceptual and technical systems. It takes its departure from the first substantial appearance by a woman in the Society's publications in 1776, and continues until the accession of a female monarch, Victoria, in 1837, a period of just over sixty years. It explores what women did and what reception they received and assesses the significance of this within the wider processes of the development of an understanding of the past and the shaping of gender relationships through the medium of material culture, in a period that saw fundamental changes in many areas of intellectual and social life, including levels of material consumption and the sentiments surrounding consumerism

Comparison of Single-Point and Continuous Sampling Methods for Estimating Residential Indoor Temperature and Humidity

Residential temperature and humidity are associated with multiple health effects. Studies commonly use single-point measures to estimate indoor temperature and humidity exposures, but there is little evidence to support this sampling strategy. This study evaluated the relationship between single-point and continuous monitoring of air temperature, apparent temperature, relative humidity, and absolute humidity over four exposure intervals (5-min, 30-min, 24-hr, and 12-days) in 9 northern Utah homes, from March-June 2012. Three homes were sampled twice, for a total of 12 observation periods. Continuous data-logged sampling was conducted in homes for 2–3 wks, and simultaneous single-point measures (n = 114) were collected using handheld thermo-hygrometers. Time-centered single-point measures were moderately correlated with short-term (30-min) data logger mean air temperature (r = 0.76, β = 0.74), apparent temperature (r = 0.79, β = 0.79), relative humidity (r = 0.70, β = 0.63), and absolute humidity (r = 0.80, β = 0.80). Data logger 12-day means were also moderately correlated with single-point air temperature (r = 0.64, β = 0.43) and apparent temperature (r = 0.64, β = 0.44), but were weakly correlated with single-point relative humidity (r = 0.53, β = 0.35) and absolute humidity (r = 0.52, β = 0.39). Of the single-point RH measures, 59 (51.8%) deviated more than ±5%, 21 (18.4%) deviated more than ±10%, and 6 (5.3%) deviated more than ±15% from data logger 12-day means. Where continuous indoor monitoring is not feasible, single-point sampling strategies should include multiple measures collected at prescribed time points based on local conditions