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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
NASA NTRS2016

Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. We aimed to elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis, we performed global postnatal deletion of Atg12 using tamoxifen-inducible Cre. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. qPCR revealed increased expression of pro-osteoclastogenic cytokines in bone and marrow respectively in male iKOs compared to controls. Microcomputed tomography revealed decreased cortical bone volume, cortical thickness and periosteal perimeter consistent with bone loss; and a longer primary spongiosa in male Atg12 iKOs display compared to male controls. Histology showed that compared to male controls, male iKOs had a profound increase in chondrocyte column length of the growth plate with hyper-expansion of both proliferating and hypertrophic zones. Taken together, these findings indicate that autophagy plays an important role in the maintenance of bone structural integrity by mediating the production of pro-osteoclastogenic signals and regulating chondrocyte proliferation and differentiation.

Atg12↗
NASA NTRS2016

Consequences of Prenatal Stress on Appetite Control and the Energy Expenditure Pathway

Established research has illustrated that moderate exposure to stress in the womb influences both adult phonotype and genotype for several physiological pathways, especially in males. Proposed explanations include adaptions made by the fetus resulting from a limited supply of nutrients, referred to as the thrifty phenotype. In this study, we examine this fetal programming effect on the appetite control and energy expenditure pathways in prenatally stressed adult male offspring. Subjects were male rats born from time-mated female rats exposed to unpredictable, variable prenatal stress (UVPS) throughout gestation. An analysis of the adult male rat offspring genetic expression of epididymal fat pads and the plasma concentrations of hormones involved in appetite control and energy expenditure pathways showed a significantly diminished expression of leptin and adiponectin compared to unstressed controls. Leptin and adiponectin are both major hormones involved in the appetite control and energy expenditure pathways, with leptin regulating energy balance due to its function as an inhibitor of hunger, and adiponectin modulating glucose levels and fatty acid breakdown. We observed higher leptin concentrations within the prenatally stressed male plasma, and lower expression of leptin (OB) and adiponectin (ADIPOQ) genes from the epididymal fat pads. We suggest that elevated leptin in the plasma elicited a negative feedback effect on OB expression levels, decreasing their quantification compared to control animals. Further analysis will include plasma quantification of insulin and glucose, as well as expression of ghrelin, a peptide which acts on the central nervous system and the bodys perception of hunger.

appetite control↗
DOE OSTI2020

Repatriated Desert Bighorn Sheep Population on the Nevada National Security Site

Ecological studies have been conducted on the Nevada National Security Site (NNSS) since the 1960s. Desert bighorn sheep (Ovis canadensis nelsoni) were considered rare visitors on the NNSS, with only 9 recorded observations between 1963 and 2009, all of which were males. Females and young were not documented definitively until winter 2011, when several were killed by a radio-collared female mountain lion (Puma concolor). Following these observations, we initiated a study of desert bighorn sheep on the NNSS to better understand their movements/interactions with other populations, prevalence of disease, population size, origin, radionuclide burdens and potential radiological dose to humans that may consume harvested animals away from the NNSS. We captured and radio-collared 6 sheep (2 females, 4 males) in November 2015, and 15 (7 females, 8 males) in November 2016. We sampled blood for genetic and disease testing and collected nasal swabs for respiratory disease testing. Sheep from the NNSS spent most of their time around Shoshone Mountain, Fortymile Canyon, and Yucca Mountain but also moved to Bare Mountain, Thirsty Canyon, and Black Mountain. Females greatly expanded their core and overall home ranges during spring, whereas males expanded their home ranges during summer. Of 18 sheep sampled for disease, 12 showed an immune response to Mycoplasma ovipneumoniae, and 5 had the bacteria present. Genetic testing revealed that the ancestry of NNSS sheep is from the Bare Mountain (1991-1995, within 24 km of our study area), Specter Range (1990-1995, within 32 km of our study area), and Stonewall Mountain (1975-1983, within 72 km of our study area) reintroduced populations. Radionuclide burden in NNSS sheep was minimal with no significant difference from sheep captured on the Nevada Test and Training Range and northern Nevada. One marked adult male was legally harvested off the NNSS north of Bare Mountain. Finally, this recently colonized reproducing population of sheep on the NNSS warrants further monitoring, protection, and inclusion in resource management plans.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Imaging of transgender patients: expected findings and complications of gender reassignment therapy

Objectives: Gender dysphoria is defined as a conflict between the biological gender and the gender with which the person identifies. Gender reassignment therapy can alter external sexual features to resemble those of the desired gender and are broadly classified into two types, female to male (FTM) and male to female (MTF). In this paper we describe expected findings and complications of gender reassignment therapy. Methods: Collaborative multi-institutional project supported by Ovarian and Uterine Cancer Disease Focused panel of Society of Abdominal Radiology. Results: Gender dysphoria is defined as a conflict between the biological gender and the gender with which the person identifies. Gender reassignment therapy can alter external sexual features to resemble those of the desired gender and are broadly classified into two types, female to male (FTM) and male to female (MTF). These therapies include hormonal treatment as well as surgical procedures. FTM genital reconstructive therapy includes creation of a neophallus, which can be achieved by metoidioplasty or phalloplasty with mastectomy, along with testosterone administration. MTF gender reassignment surgery includes complete removal of external genitalia with penectomy and orchiectomy, with vaginoplasty, clitoroplasty, labiaplasty, and breast augmentation along with estrogen supplements. Conclusion: Surgical techniques alter the standard anatomy and make imaging interpretation challenging if radiologists are unfamiliar with expected post-operative appearances. It is important to recognize the complications related to surgical and non-surgical treatment of gender dysphoria to avoid interpretation errors. Furthermore, increasing the prevalence of transgender patients requires increased sensitivity when interpreting imaging studies to reduce the potential for misdiagnoses in reporting due to frequently incomplete available clinical history.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Maternal blood metal levels and fetal markers of metabolic function

Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and cord blood adiponectin. • Further work will elucidate the implications of these findings on childhood obesity.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2013

Population of anatomically variable 4D XCAT adult phantoms for imaging research and optimization

Purpose: The authors previously developed the 4D extended cardiac-torso (XCAT) phantom for multimodality imaging research. The XCAT consisted of highly detailed whole-body models for the standard male and female adult, including the cardiac and respiratory motions. In this work, the authors extend the XCAT beyond these reference anatomies by developing a series of anatomically variable 4D XCAT adult phantoms for imaging research, the first library of 4D computational phantoms. Methods: The initial anatomy of each phantom was based on chest-abdomen-pelvis computed tomography data from normal patients obtained from the Duke University database. The major organs and structures for each phantom were segmented from the corresponding data and defined using nonuniform rational B-spline surfaces. To complete the body, the authors manually added on the head, arms, and legs using the original XCAT adult male and female anatomies. The structures were scaled to best match the age and anatomy of the patient. A multichannel large deformation diffeomorphic metric mapping algorithm was then used to calculate the transform from the template XCAT phantom (male or female) to the target patient model. The transform was applied to the template XCAT to fill in any unsegmented structures within the target phantom and to implement the 4D cardiac and respiratory models in the new anatomy. Each new phantom was refined by checking for anatomical accuracy via inspection of the models. Results: Using these methods, the authors created a series of computerized phantoms with thousands of anatomical structures and modeling cardiac and respiratory motions. The database consists of 58 (35 male and 23 female) anatomically variable phantoms in total. Like the original XCAT, these phantoms can be combined with existing simulation packages to simulate realistic imaging data. Each new phantom contains parameterized models for the anatomy and the cardiac and respiratory motions and can, therefore, serve as a jumping point from which to create an unlimited number of 3D and 4D variations for imaging research. Conclusions: A population of phantoms that includes a range of anatomical variations representative of the public at large is needed to more closely mimic a clinical study or trial. The series of anatomically variable phantoms developed in this work provide a valuable resource for investigating 3D and 4D imaging devices and the effects of anatomy and motion in imaging. Combined with Monte Carlo simulation programs, the phantoms also provide a valuable tool to investigate patient-specific dose and image quality, and optimization for adults undergoing imaging procedures.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2002

Sexually dimorphic effects of NMDA receptor antagonism on brain-pituitary-gonad axis development in the platyfish

The N-methyl-D-aspartate glutamate receptor (NMDAR) is found in hypothalamic nuclei involved in the regulation of reproduction in several species of mammals and fishes. NMDAR is believed to affect reproductive development and function by regulating gonadotropin releasing hormone (GnRH)-producing cells. These pathways are likely to be sexually dimorphic, as are several other neurotransmitter systems involved in reproductive function. In this report, male and female platyfish received intraperitoneal injections of 0, 5, 10, 20, 40 or 60 microg/g body wt. of the non-competitive NMDAR antagonist MK-801. Injections began at 6 weeks of age and continued thrice weekly until control animals reached puberty, as evidenced by anal fin maturation. The percent of pubescent animals was significantly affected by sex and treatment, with fewer MK-801-injected females in puberty than control females at each dose (P<0.001), and fewer pubescent females than males at 10, 20 and 40 microg/g (P<0.05). There were no MK-801-related effects in males. Histological analyses revealed typical immature gonads and pituitary glands in treated females, and typical mature morphology in control females and all males. Immunocytochemical distribution of the R1 subunit of the NMDAR within the brain-pituitary-gonad (BPG) axis was limited to GnRH-containing brain cells in all animals; however, NMDAR1 distribution was in an immature pattern in treated females and a mature pattern in all others. Neural concentrations of GnRH were unaffected by MK-801 treatment in both sexes. These data suggest that in the platyfish, NMDAR influence on reproductive development is sexually dimorphic and occurs at, or above, the level of GnRH-containing cells of the BPG axis.

Non-NASA Center↗
DOE OSTI2015

Evaluate an impact of incident alpha particle and gamma ray on human blood components: A comparison study

An impact of alpha and gamma irradiation on human blood components have been evaluated and compared for healthy blood samples (male and females). Irradiation dose and time of irradiation calibrated and considered as a main comparison factors. Density of blood components measured for each in vitro irradiation before and after irradiation for males and females. Survey radiation dosimeter (Inspector Exp) and nuclear track detectors type CR-39 used to evaluate exposure dose rate and incident density of alpha particles, respectively. Experiment results verified that the irradiation of blood makes ionizing of blood components, either alpha or gamma irradiation dose, and the impacts of ionizing radiation were relativity for WBC, RBC, and PLT. Limited irradiation doses of 1-5 μSv/hr considered as a low radiation dose of alpha and gamma radiation sources ({sup 226}Ra, and {sup 137}Cs). Density of alpha particles accumulated on the blood surface was 34 (alpha particle/cm{sup 2}) for selected dose of incident alpha particle. Optimum value of irradiation dose and time of irradiation were 5 μSv/hr and 4 second for males and females. On the other hands, the values of irradiation dose and time of irradiation were 2.1 μSv/hr and 2 second for males and females for gamma irradiation. Thus, present results demonstrated that densities of RBC and WBC cells are capable of inducing reproduction in vitro for both type of irradiation. (authors)

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2023

Variance in offspring sex ratio and maternal allocation in a highly invasive mammal

Abstract Skewed sex ratios at birth are widely reported in wild populations, however, the extent to which parents are able to modulate the sex ratio of offspring to maximize their own fitness remains unclear. This is particularly true for highly polytocous species as maximizing fitness may include trade‐offs between sex ratio and the size and number of offspring in litters. In such cases, it may be adaptive for mothers to adjust both the number of offspring per litter and offspring sex to maximize individual fitness. Investigating maternal sex allocation in wild pigs ( Sus scrofa ) under stochastic environmental conditions, we predicted that under favorable conditions, high‐quality mothers (larger and older) would produce male‐biased litters and invest more in producing larger litters with more males. We also predicted sex ratio would vary relative to litter size, with a male‐bias among smaller litters. We found evidence that increasing wild boar ancestry, maternal age and condition, and resource availability may weakly contribute to male‐biased sex ratio, however, unknown factors not measured in this study are assumed to be more influential. High‐quality mothers allocated more resources to litter production, but this relationship was driven by adjustment of litter size, not sex ratio. There was no relationship between sex ratio and litter size. Collectively, our results emphasized that adjustment of litter size appeared to be the primary reproductive characteristic manipulated in wild pigs to increase fitness rather than adjustment of offspring sex ratio.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Age at Release, Size, and Maturation Status Influence Residualism in Hatchery Steelhead

Abstract Steelhead Oncorhynchus mykiss that fail to emigrate seaward after release from hatcheries, commonly referred to as “residuals,” can have negative impacts on natural populations ranging from competition and predation to interbreeding with returning anadromous adults. We investigated how age at release, size, and maturation status influenced the rate of residual production in hatchery summer-run steelhead released from the Winthrop National Fish Hatchery (Methow River, Washington) between 2010 and 2015. Migration data from 21,598 individuals implanted with PIT tags identified 1,783 residual steelhead expressing two distinct phenotypes: immature male and female parr; and precociously mature males. We found that age at release significantly affected the predominant residual phenotype. Age-1 steelhead residuals (S1 rearing strategy) were dominated by smaller parr of both sexes (fish < 146 mm FL), while age-2 residuals (S2 rearing strategy) were dominated by mature males, although both phenotypes were present in both S1 and S2 residual groups. Collections of residual steelhead in the Methow River indicated that parr phenotype residuals grew as well as natural-origin juvenile O. mykiss, suggesting potential competition for food resources and habitat. Detections of PIT tags within the Methow River basin indicated that precocious male residuals may overlap both spatially and temporally with previously documented spawning anadromous adults, posing a potential genetic management risk. Both residual phenotypes had poor overwinter survival, and only 1 of the 1,783 residual fish eventually returned to the Methow River as an anadromous adult. We conclude that the ecological and genetic consequences of residual steelhead far outweigh their potential contribution to anadromous production, and measures should be taken to reduce their production by changing hatchery rearing practices.

Tatara, Christopher P.↗
DOE OSTI2019

Effects of Chronic Metal Exposure on the Morphology of Beetles Species Representing Different Ecological Niches

To test effects of metal contamination on beetles morphology, specimens from species representing herbivores (Strophosoma capitatum), carnivores (Carabus arcensis and C. violaceus) and detritivores (Anoplotrupes stercorosus) were collected from an area polluted with zinc, lead and cadmium and from a control site. Both the length and width of elytra and pronotum were compared. Females of all species from the polluted area were smaller than those from the control site with the average difference of 2.7% (range 0.7%–6%). In contrast, males responded less consistently among species: A. stercorosus showed lower size of elytra and pronotum at the polluted area, while in C. arcensis only the elytra length and pronotum width were smaller. C. violaceus males exhibited smaller elytra length and pronotum length and width at the polluted area. In contrast, no differences between the two sites were found for S. capitatum males. Sex differences may originate from different energy investment strategies in females and males related to the reproduction needs. Even if the observed differences in body size were small, the smaller body size in females of all studied species, irrespectively of the guild, is striking and may indicate on lower fitness of a range of species inhabiting metal polluted areas.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2026

Endurance exercise elicits temporal and sexual dimorphic multi-omics remodeling of liver metabolism revealed by MoTrPAC

The mechanisms by which exercise modulate liver metabolism, a central regulator of systemic metabolism, are poorly understood. Leveraging data from MoTrPAC, we analyzed liver adaptations across 1, 2, 4, and 8 weeks of exercise in male and female rats using multi-omic approaches. Female livers displayed a progressive increase in oxidative phosphorylation (OXPHOS) complexes (at the protein level), while male livers showed an increase in acetylation of OXPHOS, TCA cycle, and fatty acid oxidation enzymes. Exercise also enhanced liver cholesterol and bile acid synthesis, reducing liver lipid metabolites in males after 8 weeks of exercise. Male rats had higher fecal cholesterol and cholic acid levels, indicating a sex-specific mechanism of lipid excretion with exercise. Moreover, 8 weeks of training reduced markers related to hepatic stellate cell activation and fibrosis in both sexes. This study highlights the sexual dimorphic and temporal molecular signatures by which exercise modulates liver metabolism to provide hepatoprotective effects.

Kelty, Taylor↗
DOE OSTI2015

Infant sex-specific placental cadmium and DNA methylation associations

Background: Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. Objectives: Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. Methods: We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10). Results: Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males. Conclusions: Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these findings. Such investigations may further our understanding of epigenetic mechanisms underlying maternal Cd burden with suboptimal fetal growth associations. - Highlights: • We examine sex-specific placental-Cd and -genome-wide DNA methylation associations. • In females, associated sites were at/near genes involved in cell damage response. • In males, associated sites were at/near angiogenesis and organ development genes. • Our study supports infant sex-specific placental Cd-DNA methylation associations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Maternal and paternal serum concentrations of persistent organic pollutants and the secondary sex ratio: A population-based preconception cohort study

Highlights: • Recent declines in the SSR in some countries may be attributed to exposure to POPs. • Maternal PCB 128 and paternal HCB were associated with a female excess. • Maternal mirex and paternal PCB 128 and p,p′-DDE were associated with a male excess. • These findings await corroboration given the exploratory design of this study. Recent declines in the secondary sex ratio (SSR), defined as the ratio of males to females at birth, in some industrialized countries may be attributed to exposure to environmental toxicants such as persistent organic pollutants (POPs). This study aimed to evaluate the association of couples’ preconception exposure to POPs with the SSR. The study cohort comprised 235 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and prospectively followed through delivery of a singleton birth. Upon enrollment, couples’ serum concentrations (ng/g) were measured for 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, and 36 polychlorinated biphenyls (PCBs). Birth outcome data including infant sex were collected upon delivery. Modified Poisson regression models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of a male birth for each chemical. Of the 56 POPs examined, maternal PCB 128 and paternal hexachlorobenzene were significantly associated with a female excess (RRs, 0.75 [95% CI, 0.60–0.94] and 0.81 [95% CI, 0.68–0.97] per 1 SD increase in log-transformed serum chemical concentrations, respectively), whereas maternal mirex and paternal PCB 128 and p,p′-dichlorodiphenyldichloroethylene were significantly associated with a male excess (RR range, 1.10–1.22 per 1 SD increase in log-transformed serum chemical concentrations). After adjusting for multiple comparisons, only maternal mirex remained significantly associated with the SSR. This exploratory study on multiple classes of POPs demonstrated no conclusive evidence on the association between parental preconception exposure to POPs and the SSR.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Persistent organic pollutants, skull size and bone density of polar bears (Ursus maritimus) from East Greenland 1892–2015 and Svalbard 1964–2004

Highlights: • Density in East Greenland males decreased over time. • Size in East Greenland females tented to decrease over time. • Size was highest in Svalbard polar bears. • Density was positive correlated to POPs. • Environmental changes and POPs may affect bone density and size. We investigated skull size (condylobasal length; CBL) and bone mineral density (BMD) in polar bears (Ursus maritimus) from East Greenland (n = 307) and Svalbard (n = 173) sampled during the period 1892–2015 in East Greenland and 1964–2004 at Svalbard. Adult males from East Greenland showed a continuous decrease in BMD from 1892 to 2015 (linear regression: p < 0.01) indicating that adult male skulls collected in the early pre-pollution period had the highest BMD. A similar decrease in BMD over time was not found for the East Greenland adult females. However, there was a non-significant trend that the skull size of adult East Greenland females was negatively correlated with collection year 1892–2015 (linear regression: p = 0.06). No temporal change was found for BMD or skull size in Svalbard polar bears (ANOVA: all p > 0.05) nor was there any significant difference in BMD between Svalbard and East Greenland subpopulations. Skull size was larger in polar bears from Svalbard than from East Greenland (two-way ANOVA: p = 0.003). T-scores reflecting risk of osteoporosis showed that adult males from both East Greenland and Svalbard are at risk of developing osteopenia. Finally, when correcting for age and sex, BMD in East Greenland polar bears increased with increasing concentrations of persistent organic pollutants (POPs) i.e. ΣPCB (polychlorinated biphenyls), ΣHCH (hexachlorohexane), HCB (hexachlorobenzene) and ΣPBDE (polybrominated diphenyl ethers) while skull size increased with ΣHCH concentrations all in the period 1999–2014 (multiple linear regression: all p < 0.05, n = 175). The results suggest that environmental changes over time, including exposure to POPs, may affect bone density and size of polar bears.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Effects of biometrics, location and persistent organic pollutants on blood clinical-chemical parameters in polar bears (Ursus maritimus) from Svalbard, Norway

Highlights: • BCCPs in polar bears may be affected by sex, age, biometrics, lipids and location. • POPs were correlated with HCT and HDL in females, and HCT, GGT, ASAT and CHOL in males. • POPs related biological effects on liver and kidney BCCP values were suggested. • HCT may be used as a simple cost-efficient biomarker of POP exposure in polar bears. • POPs effects on HDL and CHOL may indicate increased risk of cardiovascular disease in polar bears. In the present study, blood clinical-chemical parameters (BCCPs) were analysed in 20 female and 18 male Svalbard polar bears (Ursus maritimus) captured in spring 2007. The aim was to study how age, body condition (BC), biometrics, plasma lipid content and geographical location may confound the relationship between persistent organic pollutants (POPs) including PCBs, HCB, chlordanes, DDTs, HCHs, mirex and OH-PCBs and the concentrations of 12 specific BCCPs (hematocrit [HCT], hemoglobin [HB], aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], γ-glutamyltransferase [GGT], creatine kinase [CK], triglycerides [TG], cholesterol [CHOL], high-density lipoprotein [HDL], creatinine (CREA], urea, potassium (K]), and to investigate if any of these BCCPs may be applied as potential biomarkers for POP exposure in polar bears. Initial PCA and O-PLS modelling showed that age, lipids, BC and geographical location (longitude and latitude) were important parameters explaining BCCPs in females. Following subsequent partial correlation analyses correcting for age and lipids, multiple POPs in females were still significantly correlated with HCT and HDL (all p < 0.05). In males, age, BM, BC and longitude were important parameters explaining BCCPs. Following partial correlation analyses correcting for age, biometrics, lipids and longitude in males, multiple POPs were significantly correlated with HCT, ASAT, GGT and CHOL (all p < 0.05). In conclusion, several confounding parameters has to be taken into account when studying the relations between BCCPs and POPs in polar bears. When correcting for these, in particular HCT may be used as a simple cost-efficient biomarker of POP exposure in polar bears. Furthermore, decreasing HDL concentrations and increasing CHOL concentration with increasing POP concentrations may indicate responses related to increased risk of cardiovascular disease. We therefore suggest to further study POP exposure and lipidome response to increase knowledge of the risk of cardiometabolic syndrome in polar bears.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein

Acrolein is a highly toxic, volatile, unsaturated aldehyde generated during incomplete combustion as in tobacco smoke and indoor fires. Because the transient receptor potential ankyrin 1 (TRPA1) channel mediates tobacco smoke-induced lung injury, we assessed its role in high-level acrolein-induced toxicity in mice. Acrolein (100–275 ppm, 10–30 min) caused upper airway epithelial sloughing, bradypnea and oral gasping, hypothermia, cardiac depression and mortality. Male wild-type mice (WT, C57BL/6; 5–52 weeks) were significantly more sensitive to high-level acrolein than age-matched, female WT mice. Both male and female TRPA1-null mice were more sensitive to acrolein-induced mortality than age- and sex-matched WT mice. Acrolein exposure increased lung weight:body weight ratios and lung albumin and decreased plasma albumin to a greater extent in TRPA1-null than in WT mice. Lung and plasma protein-acrolein adducts were not increased in acrolein-exposed TRPA1-null mice compared with WT mice. To assess TRPA1-dependent protective mechanisms, respiratory parameters were monitored by telemetry. TRPA1-null mice had a slower onset of breathing rate suppression (‘respiratory braking’) than WT mice suggesting TRPA1 mediates this protective response. Surprisingly, WT male mice treated either with a TRPA1 antagonist (HC030031; 200 mg/kg) alone or with combined TRPA1 (100 mg/kg) and TRPV1 (capsazepine, 10 mg/kg) antagonists at 30 min post-acrolein exposure (i.e., “real world” delay in treatment) were significantly protected from acrolein-induced mortality. These data show TRPA1 protects against high-level acrolein-induced toxicity in a sex-dependent manner. Post-exposure TRPA1 antagonism also protected against acrolein-induced mortality attesting to a complex role of TRPA1 in cardiopulmonary injury. - Highlights: • TRPA1 protects mice against toxicity and mortality of inhaled high-level acrolein. • TRPA1 protection against inhaled high-level acrolein is sex-dependent in mice. • Age (5–52 weeks old) was not a determinant of acrolein-induced mortality in mice. • TRPA1 antagonist is protective after inhaled high-level acrolein in male mice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.

54 ENVIRONMENTAL SCIENCES↗