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Seven governing principles in biology

In physical science such as physics and chemistry, there are governing principles that are universal and applicable to all relevant systems, including energy conservation, entropy increase, uncertainty principle in quantum mechanics, and chemical equilibrium. However, what are governing principles in biology that are unique to all living systems? After collecting opinions and thoughts from diverse scientists and engineers all over the world, I summarize seven governing principles or laws in biology: central dogma, evolution, biological robustness, regeneration, reproduction, development, and causality. Some of these are not necessarily unique in biological systems from a reductionist’s point of view (e.g., causality), and others are applicable predominantly to eukaryotes (e.g., reproduction and development). Notably, many engineering systems have mimicked biological systems to enhance their performance. In this perspective article, I discuss these principles to better understand the rules of life and help construct improved engineering systems that we can use and control in an ethical, safe, and rational way.

Moon, Tae Seok↗

Leptospira borgpetersenii serovar Hardjo and Leptospira santarosai serogroup Pyrogenes isolated from bovine dairy herds in Puerto Rico

Leptospirosis is one of the most common zoonotic diseases in the world and endemic in the Caribbean Islands. Bovine leptospirosis is an important reproductive disease. Globally, cattle are recognized as a reservoir host for L. borgpetersenii serovar Hardjo, which is transmitted via urine, semen, and uterine discharges, and can result in abortion and poor reproductive performance. The dairy industry in Puerto Rico comprises up to 25% of agriculture-related income and is historically the most financially important agricultural commodity on the island. In this study, we report the isolation of two different pathogenic Leptospira species, from two different serogroups, from urine samples collected from dairy cows in Puerto Rico: L. borgpetersenii serogroup Sejroe serovar Hardjo and L. santarosai serogroup Pyrogenes. Recovered isolates were classified using whole-genome sequencing, serotyping with reference antisera and monoclonal antibodies, and immunoblotting. These results demonstrate that dairy herds in Puerto Rico can be concurrently infected with more than one species and serovar of Leptospira, and that bacterin vaccines and serologic diagnostics should account for this when applying intervention and diagnostic strategies.

59 BASIC BIOLOGICAL SCIENCES↗

Identification of Novel Genomic Associations and Gene Candidates for Grain Starch Content in Sorghum

Starch accumulated in the endosperm of cereal grains as reserve energy for germination serves as a staple in human and animal nutrition. Unraveling genetic control for starch metabolism is important for breeding grains with high starch content. In this study, we used a sorghum association panel with 389 individuals and 141,557 single nucleotide polymorphisms (SNPs) to fit linear mixed models (LMM) for identifying genomic regions and potential candidate genes associated with starch content. Three associated genomic regions, one in chromosome (chr) 1 and two novel associations in chr-8, were identified using combination of LMM and Bayesian sparse LMM. All significant SNPs were located within protein coding genes, with SNPs ∼ 52 Mb of chr-8 encoding a Casperian strip membrane protein (CASP)-like protein (Sobic.008G111500) and a heat shock protein (HSP) 90 (Sobic.008G111600) that were highly expressed in reproductive tissues including within the embryo and endosperm. The HSP90 is a potential hub gene with gene network of 75 high-confidence first interactors that is enriched for five biochemical pathways including protein processing. The first interactors of HSP90 also showed high transcript abundance in reproductive tissues. The candidates of this study are likely involved in intricate metabolic pathways and represent candidate gene targets for source-sink activities and drought and heat stress tolerance during grain filling.

genomics↗

Comparison of the Transcriptome Response within the Swine Tracheobronchial Lymphnode Following Infection with PRRSV, PCV-2 or IAV-S.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major respiratory pathogen of swine that has become extremely costly to the swine industry worldwide, often causing losses in production and animal life due to their ease of spread. However, the intracellular changes that occur in pigs following viral respiratory infections are still scantily understood for PRRSV, as well as other viral respiratory infections. The aim of this study was to acquire a better understanding of the PRRS disease by comparing gene expression changes that occur in tracheobronchial lymph nodes (TBLN) of pigs infected with either porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2 (PCV-2), or swine influenza A virus (IAV-S) infections. The study identified and compared gene expression changes in the TBLN of 80 pigs following infection by PRRSV, PCV-2, IAV-S, or sham inoculation. Total RNA was pooled for each group and time-point (1, 3, 6, and 14 dpi) to make 16 libraries—analyses are by Digital Gene Expression Tag Profiling (DGETP). The data underwent standard filtering to generate a list of sequence tag raw counts that were then analyzed using multidimensional and differential expression statistical tests. The results showed that PRRSV, IAV-S and PCV-2 viral infections followed a clinical course in the pigs typical of experimental infection of young pigs with these viruses. Gene expression results echoed this course, as well as uncovered genes related to intersecting and unique host immune responses to the three viruses. By testing and observing the host response to other respiratory viruses, our study has elucidated similarities and differences that can assist in the development of vaccines and therapeutics that shorten or prevent a chronic PRRSV infection.

Miller↗

Comprehensive Genome-Wide Natural Variation and Expression Analysis of Tubby-like Proteins Gene Family in Brachypodium distachyon

The Tubby-like proteins (TLPs) gene family is a group of transcription factors found in both animals and plants. In this study, we identified twelve B. distachyon TLPs, divided into six groups based on conserved domains and evolutionary relationships. We predicted cis-regulatory elements involved in light, hormone, and biotic and abiotic stresses. The expression patterns in response to light and hormones revealed that BdTLP3, 4, 7, and 14 are involved in light responses, and BdTLP1 is involved in ABA responses. Furthermore, BdTLP2, 7, 9, and 13 are expressed throughout vegetative and reproductive stages, whereas BdTLP1, 3, 5, and 14 are expressed at germinating grains and early vegetative development, and BdTLP4, 6, 8, and 10 are expressed at the early reproduction stage. The natural variation in the eleven most diverged B. distachyon lines revealed high conservation levels of BdTLP1-6 to high variation in BdTLP7-14 proteins. Based on diversifying selection, we identified amino acids in BdTLP1, 3, 8, and 13, potentially substantially affecting protein functions. This analysis provided valuable information for further functional studies to understand the regulation, pathways involved, and mechanism of BdTLPs.

Plant Sciences↗

Proteases Shape the Chlamydomonas Secretome: Comparison to Classical Neuropeptide Processing Machinery

The recent identification of catalytically active peptidylglycine α-amidating monooxygenase (PAM) in Chlamydomonas reinhardtii, a unicellular green alga, suggested the presence of a PAM-like gene and peptidergic signaling in the last eukaryotic common ancestor (LECA). We identified prototypical neuropeptide precursors and essential peptide processing enzymes (subtilisin-like prohormone convertases and carboxypeptidase B-like enzymes) in the C. reinhardtii genome. Reasoning that sexual reproduction by C. reinhardtii requires extensive communication between cells, we used mass spectrometry to identify proteins recovered from the soluble secretome of mating gametes, and searched for evidence that the putative peptidergic processing enzymes were functional. After fractionation by SDS-PAGE, signal peptide-containing proteins that remained intact, and those that had been subjected to cleavage, were identified. The C. reinhardtii mating secretome contained multiple matrix metalloproteinases, cysteine endopeptidases, and serine carboxypeptidases, along with one subtilisin-like proteinase. Published transcriptomic studies support a role for these proteases in sexual reproduction. Multiple extracellular matrix proteins (ECM) were identified in the secretome. Several pherophorins, ECM glycoproteins homologous to the Volvox sex-inducing pheromone, were present; most contained typical peptide processing sites, and many had been cleaved, generating stable N- or C-terminal fragments. Our data suggest that subtilisin endoproteases and matrix metalloproteinases similar to those important in vertebrate peptidergic and growth factor signaling play an important role in stage transitions during the life cycle of C. reinhardtii.

59 BASIC BIOLOGICAL SCIENCES↗

A Suite of Mechanistic Epidemiological Decision Support Tools

Objective: We will demonstrate tools that allow mechanistic contraints on disease progression and epidemic spread to play off against interventions, mitigation, and control measures. The fundamental mechanisms of disease progression and epidemic spread provide important constraints on interpreting changing epidemic cases counts with time and geography in the context of on-going interventions, mitigations, and controls. Models such as these that account for the effects of human actions can also allow evaluation of the importance of categories of epidemic and disease controls. Introduction: We present the EpiEarly, EpiGrid, and EpiCast tools for mechanistically-based biological decision support. The range of tools covers coarse-, medium-, and fine-grained models. The coarse-grained, aggregated time-series only data tool (EpiEarly) provides a statistic quantifying epidemic growth potential and associated uncertainties. The medium grained, geographically-resolved model (EpiGrid) is based on differential equation type simulations of disease and epidemic progression in the presence of various human interventions geared toward understanding the role of infection control, early vs. late diagnosis, vaccination, etc. in outbreak control. A fine-grained hybrid-agent epidemic model (EpiCast) with diurnal agent travel and contagion allows the analysis of the importance of contact-networks, travel, and detailed intervention strategies for the control of outbreaks and epidemics. Methods: We use three types of methods for simulation and analysis. They are: (1) Bayesian and regression methods allowing estimation of the basic reproductive number from case-count data; (2) ordinary-differential equation integration with modifications to account for discreteness of disease spread when case counts are small (we include space- and time-dependent effects); and (3) methods that hybridize agent-based travel, mixing, and disease progression with nested-mass action contagion (i.e. not fully agent-based). From the perspective of decision support, the crucial feature of mechanistic infectious epidemiological models is a way to capture the human interventions that determine epidemic outcome. Categorizing types of mitigation into those that change the force of infection, and those that branch disease progression allows a common framework that can be extended from medium-grained models through fine-grained. Our canonical example is our EpiGrid tool which allows for the modulation of the force of infection (i.e. contagion) with time (and potentially space), the vaccination of a susceptible population in a geographically-targeted manner, movement controls, and branching our disease progression model to account for early- vs. late-intervention during host disease progression.ResultsWe will present analysis of diseases that exemplify the various aspects of analysis in support of outbreak and epidemic control. Human and animal diseases relevant to this demonstration include rinderpest, avian influenza, and measles. We will begin with EpiEarly’s estimate of epidemic potential using aggregated time-dependent case-count data. The key observation for EpiEarly is that under a wide range of situations a disease's reproductive number should be generalized to a distribution of possibilities to account for inherent randomness and other factors (including the variability of a disease contact network). We will then continue with a demonstration of EpiGrid’s capabilities for understanding and modelling the role of interventions including contagion control (the force of infection), treatment (changing disease progression and infectiousness depending on treatment), vaccination, culling, and movement controls. We will briefly touch on the capabilities of EpiCast for more detailed analysis of specific intervention strategies. Conclusions: We will demonstrate examples where modeling either contributed or plausibly would contribute to informing epidemic and outbreak control constrained by the possibilities of the underlying epidemic and disease dynamics.

Geospatial↗

Eccentric preformative molt in the spotted Towhee

Examination of wing-feather molt often provides information essential for aging birds in the hand (Mulvihill 1993, pyle 1997b, 2008). Correctly aging birds is important for understanding the causal relationships between age-class survival rates and population changes (DeSante et al. 2005). For example, correctly aging birds facilitates understanding of climate effects on reproduction better than merely moni- toring population numbers because reproduction varies widely with annual weather patterns (DeSante and O’grady 2000). Age-class information can also provide a clear measure of habitat quality without confounding effects such as population sources and sinks (Van horne 1983) or misleading habitat-quality information based on relative abundance or population size (pulliam 1988). Changes in bird populations often lag changes in the survival rate of an age class, while environmental changes often affect one age class immediately or after a short lag (Temple and Wiens 1989)

54 ENVIRONMENTAL SCIENCES↗

A ``Tail" of Two Cities: Fatality-based Modeling of COVID-19 Evolution in New York City and Cook County, IL

I describe $SIR$ modeling of the COVID-19 pandemic in two U.S. urban environments, New York City (NYC) and Cook County, IL, from onset through the month of June, 2020. Since testing was not widespread early in the pandemic in the U.S., I do not use data on confirmed cases and rely solely on public fatality data to estimate model parameters. Fits to the first 20 days of data determine a degenerate combination of the basic reproduction number, $R_0$, and the mean time to removal from the infectious population, $\gamma^{-1}$, with $\gamma (R_0-1) = 0.25 (0.21)$ inverse days for NYC (Cook County). Equivalently, the initial doubling time was $t_d = 2.8 (3.4)$ days for NYC (Cook). The early fatality data suggest that both locations had infections in early February. I model the mitigation measures implemented in mid-March in both locations (distancing, quarantine, isolation, etc) via a time-dependent reproduction number $R_t$ that declines monotonically from $R_0$ to a sma ller asymptotic value, with a parameterized functional form. The timing (mid-March) and duration (several days) of the transitions in $R_t$ appear well determined by the data. However, the fatality data determine only a degenerate combination of the parameters $R_0$, the percentage reduction in social contact due to mitigation measures, $X$, and the infection fatality rate (IFR), $f$. With flat priors, based on simulations the NYC model parameters have 95.45\% credible intervals of $R_0 = 3.0-5.4$, $X= 80-99.9\%$ and $f=2-6\%$, with $5-13\%$ of the population asymptotically infected. A strong external prior indicating a lower value of $f$ or of $\gamma^{-1}$ would imply lower values of $R_0$ and $X$ and higher percentage infection of the population. For Cook County, the evolution was qualitatively different: after mitigation measures were implemented, the daily fatality counts reached a plateau for about a month before tailing off. This is consistent with an $SIR$ model that exhibits ``critical slowing-down", in which $R_t$ plateaus ! at a value just above unity. For Cook County, the 95.45\% credible intervals for the model parameters are much broader and shifted downward, $R_0=1.4-4.7$, $X=26-54\%$, and $f=0.1-0.6\%$ with $15-88\%$ of the population asymptotically infected. Despite the apparently lower efficacy of its social contact reduction measures, Cook County has had significantly fewer fatalities per population than NYC, $D_\infty/N=100$ vs. 270 per 100,000. In the model, this is attributed to the lower inferred IFR for Cook; an external prior pointing to similar values of the IFR for the two locations would instead chalk up the difference in $D/N$ to differences in the relative growth rate of the disease. I derive a model-dependent threshold, $X^{crit}_e$, for `safe' re-opening, that is, for easing of contact reduction that would not trigger a second wave; for NYC, the models predict that increasing social contact by more than 20\% from post-mitigation levels will lead to renewed spread, while for Cook County the threshold value is very uncertain, given the parameter degeneracies. The timing of 2nd-wave growth will depend on the amplitude of contact increase relative to $X^{crit}_e$ and on the asymptotic growth rate, and the impact in terms of fatalities will depend on the parameter $f$.

Frieman, Joshua↗

Modifying flowering time in maize

The present invention provides compositions and methods for modulating the reproductive transition in plants, such as grasses (e.g., maize). In particular, the invention provides methods for enhancing agronomic properties in plants by modulating expression of GRMZM2G171650 (zmm22) or homologs thereof. Modulation of expression of one or more additional genes which affect reproductive transition such as zagl1, in conjunction with such modulation of expression is also contemplated. Nucleic acid constructs for down-regulation of GRMZM2G171650 are also contemplated, as are transgenic plants, and products produced therefrom, that demonstrate altered development such as extended flowering time and display associated phenotypes such as enhanced yield of vegetative biomass, improved digestibility, and increased disease resistance. Plants described herein may be used, for example, as improved forage or feed crops or in biofuel production.

Kaeppler, Shawn↗

Toward the Neutrino Discovery Platform: An Auditable, Uncertainty-Bearing Toolchain for MINERvA Open-Data Cross-Section Analysis

The Neutrino Discovery Platform (NDP) aims to accelerate DUNE-era science by making the neutrino program's existing datasets analyzable through fast, reproducible, and auditable workflows. We report a working version of two of its layers, data curation and agentic orchestration, built and tested end to end on MINERvA open data. The guiding lesson throughout is that a cross section is a measurement, and not just a plotted shape, only if it carries a defensible systematic-uncertainty budget, a trustworthy unfolding, and a reproducible record. Using a single medium-energy playlist pair from the MINERvA open-data release (about $2.05\times10^{17}$ protons on target of data), we first reproduced the shapes of two published charged-current inclusive $\nu_\mu$ measurements through a complete extraction ladder: selection, background subtraction, D'Agostini unfolding, efficiency correction, and flux normalization. These shape-level reproductions ran and tracked the published results, but they lacked the systematic-uncertainty machinery that defines a MINERvA cross section. To supply it, we vendored and built the MINERvA Analysis Toolkit and developed a many-universe systematic-uncertainty tool that produces a portable covariance artifact, a parallel event-loop runner, and a per-run auditability harness. Validated against a published covariance release, the toolchain reproduces the released statistical, flux, and muon-energy-scale terms and shows that they account for roughly 63\% of the total variance, with the remainder unreleased. Using this same infrastructure, we then performed a measurement of our own design, the hadronic recoil-energy distribution of low-energy ($E_\nu<2.5$~GeV) charged-current inclusive events, and found data/simulation shape agreement of $\chi^2/\mathrm{ndf}=1.26$. Together these results show that the platform supports original physics and not only reproductions.

Breaux, Auto [Tulane U. (main)]↗

Adaptive changes in sexual behavior in the high–risk population in response to human monkeypox transmission in Canada can help control the outbreak: Insights from a two–group, two–route epidemic model

Monkeypox, a zoonotic disease, is emerging as a potential sexually transmitted infection/disease, with underlying transmission mechanisms still unclear. We devised a risk-structured, compartmental model, incorporating sexual behavior dynamics. We compared different strategies targeting the high-risk population: a scenario of control policies geared toward the use of condoms and/or sexual abstinence (robust control strategy) with risk compensation behavior change, and a scenario of control strategies with behavior change in response to the doubling rate (adaptive control strategy). Monkeypox's basic reproduction number is 1.464, 0.0066, and 1.461 in the high-risk, low-risk, and total populations, respectively, with the high-risk group being the major driver of monkeypox spread. Policies imposing condom use or sexual abstinence need to achieve a 35% minimum compliance rate to stop further transmission, while a combination of both can curb the spread with 10% compliance to abstinence and 25% to condom use. With risk compensation, the only option is to impose sexual abstinence by at least 35%. Adaptive control is more effective than robust control where the daily sexual contact number is reduced proportionally and remains constant thereafter, shortening the time to epidemic peak, lowering its size, facilitating disease attenuation, and playing a key role in controlling the current outbreak.

60 APPLIED LIFE SCIENCES↗

Upregulated expression of Nogo-A and NgR in an experimental model of focal microgyria regulates the migration, proliferation and self-renewal of subventricular zone neural progenitors

Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5–75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed by treatment of NgR antagonist peptide NEP1-40. In vitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation. - Highlights: • NFL model is an accurate experimental reproduction of focal microgyria of FCD. • The increase of the Nogo-A Levels occurs in response to freeze-induced focal lesioning. • Nogo-A/NgR may play a critical role for in the pathologic progression of FCD. • Nogo-A is associated with the migration, proliferation and self-renewal of SVZ-NPCs.

60 APPLIED LIFE SCIENCES↗

Bisphenol A-elicited miR-146a-5p impairs murine testicular steroidogenesis through negative regulation of Mta3 signaling

The epigenetic effects on expression of non-coding RNAs (e.g. microRNAs) of environmental toxin bisphenol A (BPA) have extended our understanding of the etiology of human reproductive disorders including hypospermatogenesis and androgen deficiency. BPA-induced miR-146a-5p is a potent regulator of endocrine and immune homeostasis, but its role in testis remain unexplored. We show here that in murine testis, miR-146a-5p was exclusively expressed in interstitial Leydig cells (LCs). This expression was significantly induced by BPA exposure. Consequently, the elevated miR-146a-5p exacerbated the deleterious effects of BPA on testicular steroidogenesis. Mechanistically, miR-146a-5p repressed the expression of Mta3, a pivotal chromatin remodeling transcription factor recently involved in controlling the steroidogenic activity, via directly targeting its 3′UTR. This repression thereafter rendered LCs more sensitive to BPA-elicited inhibitory effects. Conversely, ectopic expression of hMTA3 successfully rescued miR-146a-5p-elicited inhibitory effects on testicular steroidogenesis in BPA-challenged LCs. Taken together, the available data provide novel evidence that deregulation of testicular miR-146a-5p/Mta3 cascade mediates, at least in part, the steroidogenic dysfunction caused by BPA exposure.

60 APPLIED LIFE SCIENCES↗

Long-term exposure to wind turbine noise at night and risk for diabetes: A nationwide cohort study

Highlights: • We investigated a cohort of 365,986 Danes living close to wind turbines (WT). • We identified 25,148 cases of diabetes during the period 1996–2002. • Long-term exposure to WT noise was not associated with increased risk of diabetes. • Similar results were seen for indoor night-time noise and across a range of strata. • Results do not support an association between wind turbine noise and diabetes. Focus on renewable energy sources and reduced unit costs has led to increased number of wind turbines (WTs). WT noise (WTN) is reported to be highly annoying at levels from 30 to 35 dB and up, whereas for traffic noise people report to be highly annoyed from 40 to 45 dB and up. This has raised concerns as to whether WTN may increase risk for major diseases, as exposure to traffic noise has consistently been associated with increased risk of cardiovascular disease and diabetes. We identified all Danish dwellings within a radius of 20 WT heights and 25% of all dwellings within 20–40 WT heights from a WT. Using detailed data on WT type and hourly wind data at each WT position and height, we estimated hourly outdoor and low frequency indoor WTN for all dwellings, aggregated as nighttime 1- and 5-year running means. Using nationwide registries, we identified a study population of 614,731 persons living in these dwellings in the period from 1996 to 2012, of whom 25,148 developed diabetes. Data were analysed using Poisson regression with adjustment for individual and area-levels covariates. We found no associations between long-term exposure to WTN during night and diabetes risk, with incidence rate ratios (IRRs) of 0.90 (95% confidence intervals (CI): 0.79–1.02) and 0.92 (95% CI: 0.68–1.24) for 5-year mean nighttime outdoor WTN of 36–42 and ≥ 42 dB, respectively, compared to < 24 dB. For 5-year mean nighttime indoor low frequency WTN of 10–15 and ≥ 15 dB we found IRRs of 0.90 (0.78–1.04) and 0.74 (95% CI: 0.41–1.34), respectively, when compared to and < 5 dB. The lack of association was consistent across strata of sex, distance to major road, validity of noise estimate and WT height. The present study does not support an association between nighttime WTN and higher risk of diabetes. However, there were only few cases in the highest exposure groups and findings need reproduction.

54 ENVIRONMENTAL SCIENCES↗

Urinary phthalate metabolites and environmental phenols in university students in South China

Highlights: • University students in South China might be exposed to higher levels of phthalates than parabens or bisphenol analogues. • Concentrations of target EEDs were relatively low in university students, with higher levels in female than male students. • The usage of PCPs is an important source other than diet to affect the profiles of phthalates and parabens in students. In China, university students have unique lifestyles compared with the rest of the youth population, as they are almost entirely isolated in campuses. The number of university students is large, and since students represent the future of human reproduction, exposure to environmental endocrine disruptors (EEDs) may have a large impact on society. In this study, levels of several EEDs, including phthalate metabolites, parabens, bisphenol A (BPA) and its analogues, triclosan (TCS), and benzophenone-3, were determined in 169 urine samples collected from university students in Guangzhou, South China. In addition, to further understand the potential sources of EEDs in their daily lives, a survey of students’ lifestyles was conducted. Based on the urinary concentrations of EEDs and the survey results, daily exposure doses of target EEDs and their potential sources were investigated. Our results indicated that nine phthalate metabolites, three parabens, and BPA were ubiquitous (detection frequency > 60%) in the urine of university students. The concentrations of total phthalates (median: 99.4 µg L{sup −1}) were orders of magnitude higher than those of total parabens (7.30 µg L{sup −1}) and of other environmental phenols (0.40 µg L{sup −1}). Significantly higher concentrations of phthalates, parabens, and TCS were found in female versus male students, partly due to the higher usage of personal care products (PCPs) by female students (p < 0.05). The estimated daily intakes (EDIs) of phthalates, parabens, BPA, and TCS were 0.46–1.35, 3.29–10.3, 0.007, and 0.67 µg/kg-bw/day, respectively. The EDIs of phthalates and BPA were much lower than those suggested by the European Food Safety guidelines (10, 50, and 50 µg/kg-bw/day for dibutyl phthalate, diethylhexyl phthalate, and BPA, respectively). Our results indicated that university students were widely exposed to EEDs, but at relatively low doses. PCP usage was the main reason for differences in levels of phthalates (especially diethyl phthalate) and parabens between male and female students in South Chinese universities.

54 ENVIRONMENTAL SCIENCES↗

Exposure to tetrachloroethylene-contaminated drinking water and time to pregnancy

Highlights: • Cape Cod residents were exposed to PCE through contaminated drinking water. • Cumulative PCE exposure was not associated with increased risk of infertility. • High PCE exposure around the pregnancy attempt may be associated with infertility. The synthetic solvent tetrachloroethylene (PCE), commonly used in dry cleaning operations, is a human neurotoxicant and carcinogen. However, its effect on reproduction is poorly understood, as prior studies have been limited to small occupational cohorts. We examined the association between PCE exposure from contamination of the public drinking water supply and time-to-pregnancy (TTP) in a cohort of mothers from Cape Cod, Massachusetts.

54 ENVIRONMENTAL SCIENCES↗

Pregnancy exposure to wind turbine noise and adverse birth outcomes: a nationwide cohort study

Highlights: • We identified all Danes exposed to wind turbine noise (WTN) from 1982 to 2013. • We then identified all live born singletons from mothers in this population. • We investigated preterm birth, low birth weight and small for gestational age. • We found no associations between WTN and the adverse birth outcomes. • Few women had high levels of WTN and independent replication is called for. Noise from wind turbines (WTs) is reported as more annoying than traffic noise at similar levels, raising concerns as to whether WT noise (WTN) may negatively affect health, as reported for traffic noise. We aimed to investigate whether residential WTN is associated with adverse birth outcomes. Based on national registries, we identified all Danish dwellings situated within ≤ 20 wt heights radius and a random selection of 25% of dwellings situated within 20–40 wt heights radius of a WT. We identified 135,795 pregnant women living in the dwellings from 1982 to 2013, and collected information on gestational age and birth weight from a national birth registry. Using data on WT type and simulated hourly wind at each WT, we estimated hourly outdoor and low frequency (LF) indoor WTN at the dwellings of the pregnant women and aggregated as mean nighttime WTN during pregnancy. We used logistic regression with adjustment for individual and area-level covariates for the analyses. We did not find evidence suggesting that mean pregnancy or trimester-specific exposure to outdoor or indoor LF WTN were associated with any of the three adverse birth outcomes investigated: preterm birth (n = 13,003), term small for gestational age (n = 12,220) or term low birth weight (n = 1127). However, the number of cases in the highest exposure categories of ≥ 42 dB outdoor WTN or ≥ 15 dB indoor LF WTN were low for all outcomes (n between 0 and 31). The present study does not support an association between nighttime WTN and adverse birth outcomes. However, there were few cases in the high exposure groups and the results call for reproduction.

54 ENVIRONMENTAL SCIENCES↗