Lead toxicity and genetics in Flint, MI

It has been well established that lead poisoning, as defined by the CDC as blood lead levels (BLLs) at or above 5 μg/dl, can lead to long-term neurotoxic effects in children and requires immediate treatment. As such, the CDC has long recommended clinicians’ assess to all patients for lead exposure and test BLLs for all at-risk patients. Furthermore, it is increasingly recognised that there is no safe level of lead for children due to the irreversible lifelong detrimental effects of lead exposure.2,3 Since the disaster of lead contaminated drinking water in Flint, MI has been uncovered, action has been taken to test children for lead poisoning. However, when children are tested and results show that lead levels are below the 5 μg/dl criteria no further follow-up is conducted with these children, as they are deemed ‘healthy’. This practice is problematic, given that other studies have shown that blood lead levels, even at rates lower than the poison range can be detrimental to a child’s health. The estimated population of Flint is ~99,002, with about 27% of the residents categorised as children under the age of 18 years. Therefore, more than ~26,730 children, of whom 60% are African Americans (N=16,038), have been exposed to environmental lead in the drinking water.National Institute of Nursing Research (U.S.) (Grant NR013520

Functional variants of DOG1 control seed chilling responses and variation in seasonal life-history strategies in Arabidopsis thaliana.

The seasonal timing of seed germination determines a plant's realized environmental niche, and is important for adaptation to climate. The timing of seasonal germination depends on patterns of seed dormancy release or induction by cold and interacts with flowering-time variation to construct different seasonal life histories. To characterize the genetic basis and climatic associations of natural variation in seed chilling responses and associated life-history syndromes, we selected 559 fully sequenced accessions of the model annual species Arabidopsis thaliana from across a wide climate range and scored each for seed germination across a range of 13 cold stratification treatments, as well as the timing of flowering and senescence. Germination strategies varied continuously along 2 major axes: 1) Overall germination fraction and 2) induction vs. release of dormancy by cold. Natural variation in seed responses to chilling was correlated with flowering time and senescence to create a range of seasonal life-history syndromes. Genome-wide association identified several loci associated with natural variation in seed chilling responses, including a known functional polymorphism in the self-binding domain of the candidate gene DOG1. A phylogeny of DOG1 haplotypes revealed ancient divergence of these functional variants associated with periods of Pleistocene climate change, and Gradient Forest analysis showed that allele turnover of candidate SNPs was significantly associated with climate gradients. These results provide evidence that A. thaliana's germination niche and correlated life-history syndromes are shaped by past climate cycles, as well as local adaptation to contemporary climate

A perspective for sequencing familial hypercholesterolaemia in African Americans

African Americans suffer disproportionately from poor cardiovascular health outcomes despite similar proportions of African Americans and Americans of European ancestry experiencing elevated cholesterol levels. Some of the variation in cardiovascular outcomes is due to confounding effects of other risk factors, such as hypertension and genetic influence. However, genetic variants found to contribute to variation in serum cholesterol levels in populations of European ancestry are less likely to replicate in populations of African ancestry. To date, there has been limited follow-up on variant discrepancies or on identifying variants that exist in populations of African ancestry. African and African-American populations have the highest levels of genetic heterogeneity, which is a factor that must be considered when evaluating genetic variants in the burgeoning era of personalised medicine. Many of the large published studies identifying genetic variants associated with disease risk have evaluated populations of mostly European ancestry and estimated risk in other populations based on these findings. The purpose of this paper is to provide a perspective, using familial hypercholesterolaemia as an exemplar, that studies evaluating genetic variation focused within minority populations are necessary to identify factors that contribute to disparities in health outcomes and realise the full utility of personalised medicine

Circadian Alterations Increase with Progression in a Patient-Derived Cell Culture Model of Breast Cancer

Circadian rhythm disruption can elicit the development of various diseases, including breast cancer. While studies have used cell lines to study correlations between altered circadian rhythms and cancer, these models have different genetic backgrounds and do not mirror the changes that occur with disease development. Isogenic cell models can recapitulate changes across cancer progression. Hence, in this study, a patient-derived breast cancer model, the 21T series, was used to evaluate changes to circadian oscillations of core clock protein transcription as cells progress from normal to malignant states. Three cell lines were used: H16N2 (normal breast epithelium), 21PT (atypical ductal hyperplasia), and 21MT-1 (invasive metastatic carcinoma). The cancerous cells are both HER2+. We assessed the transcriptional profiles of two core clock proteins, BMAL1 and PER2, which represent a positive and negative component of the molecular oscillator. In the normal H16N2 cells, both genes possessed rhythmic mRNA oscillations with close to standard periods and phases. However, in the cancerous cells, consistent changes were observed: both genes had periods that deviated farther from normal and did not have an anti-phase relationship. In the future, mechanistic studies should be undertaken to determine the oncogenic changes responsible for the circadian alterations found

Genome Sequencing Technologies and Nursing

Background Advances in DNA sequencing technology have resulted in an abundance of personalized data with challenging clinical utility and meaning for clinicians. This wealth of data has potential to dramatically impact the quality of healthcare. Nurses are at the focal point in educating patients regarding relevant healthcare needs; therefore, an understanding of sequencing technology and utilizing these data are critical. Aim The objective of this study was to explicate the role of nurses and nurse scientists as integral members of healthcare teams in improving understanding of DNA sequencing data and translational genomics for patients. Approach A history of the nurse role in newborn screening is used as an exemplar. Discussion This study serves as an exemplar on how genome sequencing has been utilized in nursing science and incorporates linkages of other omics approaches used by nurses that are included in this special issue. This special issue showcased nurse scientists conducting multi-omic research from various methods, including targeted candidate genes, pharmacogenomics, proteomics, epigenomics, and the microbiome. From this vantage point, we provide an overview of the roles of nurse scientists in genome sequencing research and provide recommendations for the best utilization of nurses and nurse scientists related to genome sequencing

Improving Parenting to Promote School Readiness: A Preliminary Evaluation of the Books Can…© Public Library Program

The present study examines associations between parents’ involvement in an enhanced storytime program and parenting knowledge and efficacy for supporting their child’s socioemotional development and book reading. Books Can…© was developed by a public library to teach parents important child development information and strategies for supporting their child’s socioemotional learning. Parents and their young children participated in a 6-week interactive program that included book reading, songs, interactive activities, and parenting tips. Parents (n =119) completed questionnaires both prior to and after participating in the program. Multilevel general linear models compared responses to survey items before and after the program, indicating significant increases in parent knowledge, attitudes, and reading behavior by the end of the program. This study provides preliminary support documenting the benefits of the Books Can…© program. Moreover, results highlight public libraries and enhanced storytime programs as meaningful settings for promoting family involvement in children’s early learning

Gas leakage and distribution characteristics of methyl bromide and sulfuryl fluoride during fumigations in a pilot flour mill

The half-loss time (HLT) is used as an indicator to quantify gas leakage rates during methyl bromide (MB) and sulfuryl fluoride (SF) fumigations. Comparisons of HLTs between three MB and three SF fumigations were quantified in the Hal Ross pilot flour mill, Department of Grain Science and Industry, Kansas State University, USA. The sealing quality or gas tightness of the mill before each fumigation was verified by a pressurization test. Fumigant concentrations during the six fumigations were monitored continuously at 30 locations among the five mill floors during the 24 h fumigation period. A weather station on the mill roof monitored barometric pressure, wind speed and direction, temperature, and relative humidity. A data logger on each mill floor recorded temperature and relative humidity. The pressurization test showed that the relationship between airflow rate and building static pressure varied among the fumigations despite the same areas being sealed by two separate fumigation service providers due to environmental conditions not being identical among the fumigations. Concentrations of both fumigants within the mill ranged from 2 to 7 g/m³ . The observed HLTs for the MB and SF fumigations were in the range of 3.61 to 28.64 h and 9.97 to 31.65 h, respectively, and were inversely related only to wind speeds during fumigation and not any other environmental conditions recorded. In our study, the fumigant leakage rate was found to be predominantly a function of wind speed rather than inherent gas characteristics of MB and SF

Helicobacter pylori Lipopolysaccharide Is Synthesized via a Novel Pathway with an Evolutionary Connection to Protein N-Glycosylation

Lipopolysaccharide (LPS) is a major component on the surface of Gram negative bacteria and is composed of lipid A-core and the O antigen polysaccharide. O polysaccharides of the gastric pathogen Helicobacter pylori contain Lewis antigens, mimicking glycan structures produced by human cells. The interaction of Lewis antigens with human dendritic cells induces a modulation of the immune response, contributing to the H. pylori virulence. The amount and position of Lewis antigens in the LPS varies among H. pylori isolates, indicating an adaptation to the host. In contrast to most bacteria, the genes for H. pylori O antigen biosynthesis are spread throughout the chromosome, which likely contributed to the fact that the LPS assembly pathway remained uncharacterized. In this study, two enzymes typically involved in LPS biosynthesis were found encoded in the H. pylori genome; the initiating glycosyltransferase WecA, and the O antigen ligase WaaL. Fluorescence microscopy and analysis of LPS from H. pylori mutants revealed that WecA and WaaL are involved in LPS production. Activity of WecA was additionally demonstrated with complementation experiments in Escherichia coli. WaaL ligase activity was shown in vitro. Analysis of the H. pylori genome failed to detect a flippase typically involved in O antigen synthesis. Instead, we identified a homolog of a flippase involved in protein N-glycosylation in other bacteria, although this pathway is not present in H. pylori. This flippase named Wzk was essential for O antigen display in H. pylori and was able to transport various glycans in E. coli. Whereas the O antigen mutants showed normal swimming motility and injection of the toxin CagA into host cells, the uptake of DNA seemed to be affected. We conclude that H. pylori uses a novel LPS biosynthetic pathway, evolutionarily connected to bacterial protein N-glycosylation

Nobiletin Affects Circadian Rhythms and Oncogenic Characteristics in a Cell-Dependent Manner

The natural product nobiletin is a small molecule, widely studied with regard to its therapeutic effects, including in cancer cell lines and tumors. Recently, nobiletin has also been shown to affect circadian rhythms via their enhancement, resulting in protection against metabolic syndrome. We hypothesized that nobiletin’s anti-oncogenic effects, such as prevention of cell migration and formation of anchorage independent colonies, are correspondingly accompanied by modulation of circadian rhythms. Concurrently, we wished to determine whether the circadian and anti-oncogenic effects of nobiletin differed across cancer cell lines. In this study, we assessed nobiletin’s circadian and therapeutic characteristics to ascertain whether these effects depend on cell line, which here also varied in terms of baseline circadian rhythmicity. Three cell culture models where nobiletin’s effects on cell proliferation and migration have been studied previously were evaluated: U2OS (bone osteosarcoma), which possesses robust circadian rhythms; MCF7 (breast adenocarcinoma), which has weak circadian rhythms; and MDA-MB-231 (breast adenocarcinoma), which is arrhythmic. We found that circadian, migration, and proliferative effects following nobiletin treatment were subtle in the U2OS and MCF7 cells. On the other hand, changes were clear in MDA-MB-231s, where nobiletin rescued rhythmicity and substantially reduced oncogenic features, specifically two-dimensional cell motility and anchorage-independent growth. Based on these results and those previously described, we posit that the effects of nobiletin are indeed cell-type dependent, and that a positive correlation may exist between nobiletin’s circadian and therapeutic effects

Chronic and episodic interpersonal stress as statistically unique predictors of depression in two samples of emerging adults.

Few studies comprehensively evaluate which types of life stress are most strongly associated with depressive episode onsets, over and above other forms of stress, and comparisons between acute and chronic stress are particularly lacking. Past research implicates major (moderate to severe) stressful life events (SLEs), and to a lesser extent, interpersonal forms of stress; research conflicts on whether dependent or independent SLEs are more potent, but theory favors dependent SLEs. The present study used 5 years of annual diagnostic and life stress interviews of chronic stress and SLEs from 2 separate samples (Sample 1 N = 432; Sample 2 N = 146) transitioning into emerging adulthood; 1 sample also collected early adversity interviews. Multivariate analyses simultaneously examined multiple forms of life stress to test hypotheses that all major SLEs, then particularly interpersonal forms of stress, and then dependent SLEs would contribute unique variance to major depressive episode (MDE) onsets. Person-month survival analysis consistently implicated chronic interpersonal stress and major interpersonal SLEs as statistically unique predictors of risk for MDE onset. In addition, follow-up analyses demonstrated temporal precedence for chronic stress; tested differences by gender; showed that recent chronic stress mediates the relationship between adolescent adversity and later MDE onsets; and revealed interactions of several forms of stress with socioeconomic status (SES). Specifically, as SES declined, there was an increasing role for noninterpersonal chronic stress and noninterpersonal major SLEs, coupled with a decreasing role for interpersonal chronic stress. Implications for future etiological research were discussed