Search Results (8)

Prenatal exposure to metals can influence fetal programming via DNA methylation and has been linked to adverse birth outcomes and long-term consequences. Epigenetic clocks estimate the biological age of a given tissue based on DNA methylation and are potential health biomarkers. This study leveraged the Extremely Low Gestational Age Newborn (ELGAN) study (n = 265) to evaluate associations between umbilical cord tissue concentrations of 11 metals as single exposures as well as mixtures in relation to (1) placental epigenetic gestational age acceleration (eGAA) and the (2) methylation status of the Robust Placental Clock (RPC) CpGs. Linear mixed effect regression models were stratified by infant sex. Both copper (Cu) and manganese (Mn) were significantly associated with a decelerated placental eGA of −0.98 (95% confidence interval (CI): −1.89, −0.07) and −0.90 weeks (95% CI: −1.78, −0.01), respectively, in male infants. Cu and Mn levels were also associated with methylation at RPC CpGs within genes related to processes including energy homeostasis and inflammatory response in placenta. Overall, these findings suggest that prenatal exposures to Cu and Mn impact placental eGAA in a sex-dependent manner in ELGANs, and future work could examine eGAA as a potential mechanism mediating in utero metal exposures and later life consequences. Full article

Cherry eye is the common name for prolapse of the nictitans gland, a tear-producing gland situated under the third eyelid of dogs. Cherry eye is characterized by a red fleshy protuberance in the corner of the eye, resembling a cherry. This protrusion is a displacement of the normal gland of the third eyelid, thought to be caused by a defect in the connective tissue that secures the gland in place. Options for treatment may include anti-inflammatory medications in mild cases, but surgical replacement of the gland is usually indicated. Cherry eye is most often seen in dogs under the age of two years, with certain breeds having a higher incidence, suggesting a potential genetic association. Integration of panel genetic testing into routine clinical practice allows for the generation of large numbers of genotyped individuals paired with clinical records and enables the investigation of common disorders using a genome-wide association study (GWAS) approach at scale. In this investigation, several thousand cases and controls for cherry eye in both purebred dogs and mixed breeds are used for a large-scale GWAS, revealing a single peak of genome-wide significance on canine chromosome 18, directly at the location of the previously identified FGF4 insertion known to cause chondrodysplasia in several breeds. Full article

This review paper covers a topic of significant importance in micro- and nano-systems development and manufacturing, specifically the residual stresses in deposited thin-film material layers and methods to control or mitigate their impact on device behavior. A residual stress is defined as the presence of a state of stress in a thin-film material layer without any externally applied forces wherein the residual stress can be compressive or tensile. While many material properties of deposited thin-film layers are dependent on the specific processing conditions, the residual stress often exhibits the most variability. It is not uncommon for residual stresses in deposited thin-film layers to vary over extremely large ranges of values (100% percent or more) and even exhibit changes in the sign of the stress state. Residual stresses in deposited layers are known to be highly dependent on a number of factors including: processing conditions used during the deposition; type of material system (thin-films and substrate materials); and other processing steps performed after the thin-film layer has been deposited, particularly those involving exposure to elevated temperatures. The origins of residual stress can involve a number of complex and interrelated factors. As a consequence, there is still no generally applicable theory to predict residual stresses in thin-films. Hence, device designers usually do not have sufficient information about the residual stresses values when they perform the device design. Obviously, this is a far less than ideal situation. The impact of this is micro- and nano-systems device development takes longer, is considerably more expensive, and presents higher risk levels. The outline of this paper is as follows: a discussion of the origins of residual stresses in deposited thin-film layers is given, followed by an example demonstrating the impact on device behavior. This is followed by a review of thin-film deposition methods outlining the process parameters known to affect the resultant residual stress in the deposited layers. Then, a review of the reported methods used to measure residual stresses in thin-films are described. A review of some of the literature to illustrate the level of variations in residual stresses depending on processing conditions is then provided. Methods which can be used to control the stresses and mitigate the impact of residual stresses in micro- and nano-systems device design and fabrication are then covered, followed by some recent development of interest. Full article

This study examines the influence of prescribed and prognostic aerosol model configurations on the formation of tropical cyclones (TCs) in the North Atlantic Ocean in Community Atmosphere Model version 5 (CAM5). The impact of aerosol parameterization is examined by investigating storm track density, genesis density, potential intensity, and genesis potential index. This work shows that both CAM5 configurations simulate reduced storm frequency when compared to observations and that differences in TC climatology between the model configurations can be explained by differences in the large-scale environment. The analysis shows that simulation with the prognostic aerosol parameterization scheme reasonably captures the observed interannual variability in tropical cyclones and aerosols (i.e., dust) in the North Atlantic, while simulation with the prescribed configuration (climatology) is less favorable. The correlation between dust and TCs in observations (i.e., reanalysis and satellite datasets) is shown to be negative, and this relationship was also found for the prognostic aerosol configuration despite an overall decrease in the frequency of TCs. This indicates that, to accurately replicate certain aspects of TC interannual variability, the aerosol configuration within CAM5 needs to account for the appropriate dust variability. Full article

This paper reviews the recent advances in reaction-ion etching (RIE) for application in high-aspect-ratio microfabrication. High-aspect-ratio etching of materials used in micro- and nanofabrication has become a very important enabling technology particularly for bulk micromachining applications, but increasingly also for mainstream integrated circuit technology such as three-dimensional multi-functional systems integration. The characteristics of traditional RIE allow for high levels of anisotropy compared to competing technologies, which is important in microsystems device fabrication for a number of reasons, primarily because it allows the resultant device dimensions to be more accurately and precisely controlled. This directly leads to a reduction in development costs as well as improved production yields. Nevertheless, traditional RIE was limited to moderate etch depths (e.g., a few microns). More recent developments in newer RIE methods and equipment have enabled considerably deeper etches and higher aspect ratios compared to traditional RIE methods and have revolutionized bulk micromachining technologies. The most widely known of these technologies is called the inductively-coupled plasma (ICP) deep reactive ion etching (DRIE) and this has become a mainstay for development and production of silicon-based micro- and nano-machined devices. This paper will review deep high-aspect-ratio reactive ion etching technologies for silicon, fused silica (quartz), glass, silicon carbide, compound semiconductors and piezoelectric materials. Full article

The increased global use of pyrethroids raises concern for non-target aquatic species. Bifenthrin, among the most predominantly detected pyrethroids in the environment, is frequently measured in water samples above concentrations reported to induce neuroendocrine and neurotoxic effects to several threatened and endangered fish species, such as the Chinook salmon and steelhead trout. To better characterize the neurotoxic effect of bifenthrin to salmonids, rainbow trout were treated with environmentally relevant concentrations of bifenthrin (15 and 30 ng/L) for two weeks and assessed for changes in transcriptomic profiles and histopathological alterations. The top bioinformatic pathways predicted to be impaired in bifenthrin-exposed trout were involved in gonadotropin releasing hormone signaling, the dysregulation of iron homeostasis, reduced extracellular matrix stability and adhesion, and cell death. Subsequent histopathological analysis showed a significant increase in TUNEL positive cells in the cerebellum and optic tectum of bifenthrin-treated trout, relative to controls (p < 0.05). These findings suggest that low, ng/L concentrations of bifenthrin are capable of dysregulating proper neuroendocrine function, impair the structural integrity of the extracellular matrix and cell signaling pathways in the brain, and induce apoptosis in neurons of juvenile salmonids following bifenthrin treatment, which is consistent with metabolomic profiles demonstrating a common target and mechanism. Full article

Ontogenetic shifts in venom occur in many snakes but establishing their nature as gradual or discrete processes required additional study. We profiled shifts in venom expression from the neonate to adult sizes of two rattlesnake species, the eastern diamondback and the timber rattlesnake. We used serial sampling and venom chromatographic profiling to test if ontogenetic change occurs gradually or discretely. We found evidence for gradual shifts in overall venom composition in six of eight snakes, which sometimes spanned more than two years. Most chromatographic peaks shift gradually, but one quarter shift in a discrete fashion. Analysis of published diet data showed gradual shifts in overall diet composition across the range of body sizes attained by our eight study animals, while the shifts in abundance of different prey classes varied in form from gradual to discrete. Testosterone concentrations were correlated with the change in venom protein composition, but the relationship is not strong enough to suggest causation. Venom research employing simple juvenile versus adult size thresholds may be failing to account for continuous variation in venom composition lifespan. Our results imply that venom shifts represent adaptive matches to dietary shifts and highlight venom for studies of alternative gene regulatory mechanisms. Full article

Estrogen-receptor-negative breast cancer (BCER−) is mainly treated with chemotherapeutics. Leptin signaling can influence BCER− progression, but its effects on patient survival and chemoresistance are not well understood. We hypothesize that leptin signaling decreases the survival of BCER− patients by, in part, inducing the expression of chemoresistance-related genes. The correlation of expression of leptin receptor (OBR), leptin-targeted genes (CDK8, NANOG, and RBP-Jk), and breast cancer (BC) patient survival was determined from The Cancer Genome Atlas (TCGA) mRNA data. Leptin-induced expression of proliferation and chemoresistance-related molecules was investigated in triple-negative BC (TNBC) cells that respond differently to chemotherapeutics. Leptin-induced gene expression in TNBC was analyzed by RNA-Seq. The specificity of leptin effects was assessed using OBR inhibitors (shRNA and peptides). The results show that OBR and leptin-targeted gene expression are associated with lower survival of BCER− patients. Importantly, the co-expression of these genes was also associated with chemotherapy failure. Leptin signaling increased the expression of tumorigenesis and chemoresistance-related genes (ABCB1, WNT4, ADHFE1, TBC1D3, LL22NC03, RDH5, and ITGB3) and impaired chemotherapeutic effects in TNBC cells. OBR inhibition re-sensitized TNBC to chemotherapeutics. In conclusion, the co-expression of OBR and leptin-targeted genes may be used as a predictor of survival and drug resistance of BCER− patients. Targeting OBR signaling could improve chemotherapeutic efficacy. Full article