Repeated exposure to eucalyptus wood smoke alters pulmonary gene and metabolic profiles in male Long-Evans rats.

Exposure to wildfire smoke is associated with both acute and chronic cardiopulmonary illnesses, which are of special concern for wildland firefighters who experience repeated exposure to wood smoke. It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at two concentrations, low (11.0 ± 1.89 mg/m3) and high (23.7 ± 0.077 mg/m3), over a 2-week period. Whole body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24 hours after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3,446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only one gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 (EIF2) stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters.

Making History in 1 h: How Sex, Aging, Technology, and Elevation Affect the Cycling Hour Record.

PURPOSE: The purpose of this article was to analyze more than a century of cycling hour records (CHR) to examine the effects of sex, age, and altitude on cycling performance. Our hypotheses were that men's performance (distance) would exceed those of women by more than 10% but would decline at similar rates with aging and that altitude would have a small benefit, which might reach a maximum. METHODS: Data were cultivated from the Facebook World Hour Record Discussion Group's crowd-sourced database of more than 600-known-hour records and verified through extensive online research and/or personal communication. Regression and statistical modeling were produced using STATA v15.0. R2 values were used to ascertain model quality, with four distinct models being produced for comparisons. Alpha was set at 0.05 significance for all tests. RESULTS: R2 values ranged from 65% to 74.9%. Women's distances were 10.8% shorter ( P < 0.001) than those of men, but the difference was narrower than either the historical elite women's difference of 14.2% or the 2022 record difference of 13.3%. Age-related decline modeling indicates performance declines significantly past age 40 yr at a rate of 1.08% per year. Altitude had a significant ( P < 0.001) marginal improvement up to 1000 m before declining. The marginal benefits of altitude were small, but this is consistent with the finding benefits reach a maximum at a moderate altitude with "benefits" becoming ambiguous starting at ~1000 m. Technological advancement was estimated to be a small but significant ( P < 0.001) improvement of ~0.18% per year. CONCLUSIONS: Across decades of CHR data in well-trained endurance cyclists, men are only ~11% faster, and this difference remains stable until at least age 80 yr. CHR attempts greater than 500 m likely offer at best a small advantage. Despite small year-on-year improvements, the CHR has likely improved more than 10 km because of technological advancements.

Differential transcriptomic alterations in nasal versus lung tissue of acrolein-exposed rats.

Introduction: Acrolein is a significant component of anthropogenic and wildfire emissions, as well as cigarette smoke. Although acrolein primarily deposits in the upper respiratory tract upon inhalation, patterns of site-specific injury in nasal versus pulmonary tissues are not well characterized. This assessment is critical in the design of in vitro and in vivo studies performed for assessing health risk of irritant air pollutants. Methods: In this study, male and female Wistar-Kyoto rats were exposed nose-only to air or acrolein. Rats in the acrolein exposure group were exposed to incremental concentrations of acrolein (0, 0.1, 0.316, 1 ppm) for the first 30 min, followed by a 3.5 h exposure at 3.16 ppm. In the first cohort of male and female rats, nasal and bronchoalveolar lavage fluids were analyzed for markers of inflammation, and in a second cohort of males, nasal airway and left lung tissues were used for mRNA sequencing. Results: Protein leakage in nasal airways of acrolein-exposed rats was similar in both sexes; however, inflammatory cells and cytokine increases were more pronounced in males when compared to females. No consistent changes were noted in bronchoalveolar lavage fluid of males or females except for increases in total cells and IL-6. Acrolein-exposed male rats had 452 differentially expressed genes (DEGs) in nasal tissue versus only 95 in the lung. Pathway analysis of DEGs in the nose indicated acute phase response signaling, Nrf2-mediated oxidative stress, unfolded protein response, and other inflammatory pathways, whereas in the lung, xenobiotic metabolism pathways were changed. Genes associated with glucocorticoid and GPCR signaling were also changed in the nose but not in the lung. Discussion: These data provide insights into inhaled acrolein-mediated sex-specific injury/inflammation in the nasal and pulmonary airways. The transcriptional response in the nose reflects acrolein-induced acute oxidative and cytokine signaling changes, which might have implications for upper airway inflammatory disease susceptibility.

Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction.

Acrolein, a respiratory irritant, induces systemic neuroendocrine stress. However, peripheral metabolic effects have not been examined. Male and female WKY rats were exposed to air (0 ppm) or acrolein (3.16 ppm) for 4 h, followed by immediate serum and liver tissue collection. Serum metabolomics in both sexes and liver transcriptomics in males were evaluated to characterize the systemic metabolic response. Of 887 identified metabolites, > 400 differed between sexes at baseline. An acrolein biomarker, 3-hydroxypropyl mercapturic acid, increased 18-fold in males and 33-fold in females, indicating greater metabolic detoxification in females than males. Acrolein exposure changed 174 metabolites in males but only 50 in females. Metabolic process assessment identified higher circulating free-fatty acids, glycerols, and other lipids in male but not female rats exposed to acrolein. In males, acrolein also increased branched-chain amino acids, which was linked with metabolites of nitrogen imbalance within the gut microbiome. The contribution of neuroendocrine stress was evident by increased corticosterone in males but not females. Male liver transcriptomics revealed acrolein-induced over-representation of lipid and protein metabolic processes, and pathway alterations including Sirtuin, insulin-receptor, acute-phase, and glucocorticoid signaling. In sum, acute acrolein inhalation resulted in sex-specific serum metabolomic and liver transcriptomic derangement, which may have connections to chronic metabolic-related diseases.

Differential genomic effects of four nano-sized and one micro-sized CeO2 particles on HepG2 cells.

The objective of this research was to perform a genomics study of five cerium oxide particles, 4 nano and one micrometer-sized particles which have been studied previously by our group with respect to cytotoxicity, biochemistry and metabolomics. Human liver carcinoma HepG2 cells were exposed to between 0.3 to 300 ug/ml of CeO2 particles for 72 hours and then total RNA was harvested. Fatty acid accumulation was observed with W4, X5, Z7 and less with Q but not Y6. The gene expression changes in the fatty acid metabolism genes correlated the fatty acid accumulation we detected in the prior metabolomics study for the CeO2 particles named W4, Y6, Z7 and Q, but not for X5. In particular, the observed genomics effects on fatty acid uptake and fatty acid oxidation offer a possible explanation of why many CeO2 particles increase cellular free fatty acid concentrations in HepG2 cells. The major genomic changes observed in this study were sirtuin, ubiquitination signaling pathways, NRF2-mediated stress response and mitochondrial dysfunction. The sirtuin pathway was affected by many CeO2 particle treatments. Sirtuin signaling itself is sensitive to oxidative stress state of the cells and may be an important contributor in CeO2 particle induced fatty acid accumulation. Ubiquitination pathway regulates many protein functions in the cells, including sirtuin signaling, NRF2 mediated stress, and mitochondrial dysfunction pathways. NRF2-mediated stress response and mitochondrial were reported to be altered in many nanoparticles treated cells. All these pathways may contribute to the fatty acid accumulation in the CeO2 particle treated cells.

Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats.

Air pollutant exposures have been linked to systemic disease; however, the underlying mechanisms between responses of the target tissue and systemic effects are poorly understood. A prototypic inducer of stress, ozone causes respiratory and systemic multiorgan effects through activation of a neuroendocrine stress response. The goal of this study was to assess transcriptomic signatures of multiple tissues and serum metabolomics to understand how neuroendocrine and adrenal-derived stress hormones contribute to multiorgan health outcomes. Male Wistar Kyoto rats (12-13 weeks old) were exposed to filtered air or 0.8 ppm ozone for 4-hours, and blood/tissues were collected immediately post-exposure. Each tissue had distinct expression profiles at baseline. Ozone changed 1,640 genes in lung, 274 in hypothalamus, 2,516 in adrenals, 1,333 in liver, 1,242 in adipose, and 5,102 in muscle (adjusted p-value < 0.1, absolute fold-change > 50%). Serum metabolomic analysis identified 863 metabolites, of which 447 were significantly altered in ozone-exposed rats (adjusted p-value < 0.1, absolute fold change > 20%). A total of 6 genes were differentially expressed in all 6 tissues. Glucocorticoid signaling, hypoxia, and GPCR signaling were commonly changed, but ozone induced tissue-specific changes in oxidative stress, immune processes, and metabolic pathways. Genes upregulated by TNF-mediated NFkB signaling were differentially expressed in all ozone-exposed tissues, but those defining inflammatory response were tissue-specific. Upstream predictor analysis identified common mediators of effects including glucocorticoids, although the specific genes responsible for these predictors varied by tissue. Metabolomic analysis showed major changes in lipids, amino acids, and metabolites linked to the gut microbiome, concordant with transcriptional changes identified through pathway analysis within liver, muscle, and adipose tissues. The distribution of receptors and transcriptional mechanisms underlying the ozone-induced stress response are tissue-specific and involve induction of unique gene networks and metabolic phenotypes, but the shared initiating triggers converge into shared pathway-level responses. This multi-tissue transcriptomic analysis, combined with circulating metabolomic assessment, allows characterization of the systemic inhaled pollutant-induced stress response.

The Relationship Between Metabolic Comorbidities and Post-surgical Weight Loss Outcomes in Adolescents Undergoing Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Little is known about the relationship between metabolic factors and weight loss success in adolescents undergoing bariatric surgery. METHODS: The objective of this study was to assess if baseline metabolic characteristics associate with weight loss in adolescents undergoing laparoscopic sleeve gastrectomy. A retrospective study was conducted in a comprehensive adolescent bariatric surgery center of 151 subjects (34 male, 117 female). Anthropometric measurements and metabolic factors including blood pressure, fasting glucose, HbA1c, Metabolic Syndrome (MeS), liver function, triglycerides, and waist circumference were collected at one pre-surgical visit, and at 6 and/or 12 months post-laparoscopic sleeve gastrectomy. Weight loss was compared between subjects with normal or abnormal baseline metabolic factors. Absolute BMI change was used to measure successful weight loss. RESULTS: Higher baseline systolic blood pressure (SBP) was associated with greater weight loss as measured by body mass index (BMI) change and BMI standard deviation score (BMI-SDS) change at 6 and 12 months. Those patients in the 6-month follow up group with an abnormal hemoglobin A1C (HbA1c) at baseline had significantly more weight loss as measured by BMI-SDS. None of the other parameters, including fasting glucose, Metabolic Syndrome (MeS), liver function, triglycerides and waist circumference showed a predictive relationship. DISCUSSION/CONCLUSION: Elevated SBP and HbA1c in adolescents with morbid obesity may reflect a population more likely to achieve successful weight loss, and thus, may be a good target for bariatric surgery, specifically laparoscopic sleeve gastrectomy, as an intervention for severe obesity. An assessment of behavioral differences in patients with and without elevated BP and HbA1c might explain the mechanism for the improved weight loss.

Staying and Returning dynamics of young children's attention.

In this paper, we decompose selective sustained attending behavior into components of continuous attention maintenance and attentional transitions and study how each of these components develops in young children. Our results in two experiments suggest that changes in children's ability to return attention to a target locus after distraction ("Returning") play a crucial role in the development of selective sustained attention between the ages of 3.5-6 years, perhaps to a greater extent than changes in the ability to continuously maintain attention on the target ("Staying"). We further distinguish Returning from the behavior of transitioning attention away from task (i.e., becoming distracted) and investigate the relative contributions of bottom-up and top-down factors on these different types of attentional transitions. Overall, these results (a) suggest the importance of understanding the cognitive process of transitioning attention for understanding selective sustained attention and its development, (b) provide an empirical paradigm within which to study this process, and (c) begin to characterize basic features of this process, namely its development and its relative dependence on top-down and bottom-up influences on attention. RESEARCH HIGHLIGHTS: Young children exhibited an endogenously ability, Returning, to preferentially transition attention to task-relevant information over task-irrelevant information. Selective sustained attention and its development were decomposed into Returning and Staying, or task-selective attention maintenance, using novel eye-tracking-based measures. Returning improved between the ages of 3.5-6 years, to a greater extent than Staying. Improvements in Returning supported improvements in selective sustained attention between these ages.

Mild allergic airways responses to an environmental mixture increase cardiovascular risk in rats.

Recent epidemiological findings link asthma to adverse cardiovascular responses. Yet, the precise cardiovascular impacts of asthma have been challenging to disentangle from the potential cardiovascular effects caused by asthma medication. The purpose of this study was to determine the impacts of allergic airways disease alone on cardiovascular function in an experimental model. Female Wistar rats were intranasally sensitized and then challenged once per week for 5 weeks with saline vehicle or a mixture of environmental allergens (ragweed, house dust mite, and Aspergillus fumigatus). Ventilatory and cardiovascular function, measured using double-chamber plethysmography and implantable blood pressure (BP) telemetry and cardiovascular ultrasound, respectively, were assessed before sensitization and after single and final allergen challenge. Responses to a single 0.5 ppm ozone exposure and to the cardiac arrhythmogenic agent aconitine were also assessed after final challenge. A single allergen challenge in sensitized rats increased tidal volume and specific airways resistance in response to provocation with methacholine and increased bronchoalveolar lavage fluid (BALF) eosinophils, neutrophils, lymphocytes, cytokines interleukin (IL)-4, IL-5, IL-10, IL-1ß, tumor necrosis factor-α, and keratinocyte chemoattract-growth-related oncogene characteristic of allergic airways responses. Lung responses after final allergen challenge in sensitized rats were diminished, although ozone exposure increased BALF IL-6, IL-13, IL-1 ß, and interferon-γ and modified ventilatory responses only in the allergen group. Final allergen challenge also increased systolic and mean arterial BP, stroke volume, cardiac output, end-diastolic volume, sensitivity to aconitine-induced cardiac arrhythmia, and cardiac gene expression with lesser effects after a single challenge. These findings demonstrate that allergic airways responses may increase cardiovascular risk in part by altering BP and myocardial function and by causing cardiac electrical instability.

Intratracheal instillation of respirable particulate matter elicits neuroendocrine activation.

OBJECTIVE: Inhalation of ozone activates central sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal stress axes. While airway neural networks are known to communicate noxious stimuli to higher brain centers, it is not known to what extent responses generated from pulmonary airways contribute to neuroendocrine activation. MATERIALS AND METHODS: Unlike inhalational exposures that involve the entire respiratory tract, we employed intratracheal (IT) instillations to expose only pulmonary airways to either soluble metal-rich residual oil fly ash (ROFA) or compressor-generated diesel exhaust particles (C-DEP). Male Wistar-Kyoto rats (12-13 weeks) were IT instilled with either saline, C-DEP or ROFA (5 mg/kg) and necropsied at 4 or 24 hr to assess temporal effects. RESULTS: IT-instillation of particulate matter (PM) induced hyperglycemia as early as 30-min and glucose intolerance when measured at 2 hr post-exposure. We observed PM- and time-specific effects on markers of pulmonary injury/inflammation (ROFA>C-DEP; 24 hr>4hr) as corroborated by increases in lavage fluid injury markers, neutrophils (ROFA>C-DEP), and lymphocytes (ROFA). Increases in lavage fluid pro-inflammatory cytokines differed between C-DEP and ROFA in that C-DEP caused larger increases in TNF-α whereas ROFA caused larger increases in IL-6. No increases in circulating cytokines occurred. At 4 hr, PM impacts on neuroendocrine activation were observed through depletion of circulating leukocytes, increases in adrenaline (ROFA), and decreases in thyroid-stimulating-hormone, T3, prolactin, luteinizing-hormone, and testosterone. C-DEP and ROFA both increased lung expression of genes involved in acute stress and inflammatory processes. Moreover, small increases occurred in hypothalamic Fkbp5, a glucocorticoid-sensitive gene. CONCLUSION: Respiratory alterations differed between C-DEP and ROFA, with ROFA inducing greater overall lung injury/inflammation; however, both PM induced a similar degree of neuroendocrine activation. These findings demonstrate neuroendocrine activation after pulmonary-only PM exposure, and suggest the involvement of pituitary- and adrenal-derived hormones.

A Literature Review on the Effects of Exergames on Executive Function in Youth.

Exergames (video games that promote cognitive and physical activity simultaneously) benefit executive function in elderly populations. It has been suggested that exergames may induce larger effects than cognitive or exercise training alone, but few reviews have synthesized the causal factors of exergames on executive function from experimental research with youth. This review investigates (1) the various types of exergames and associated comparison conditions (2) the executive function outcome assessments commonly utilized in exergame research with youth (3) the efficacy of exergames by evaluating experimental studies that compared exergaming to cognitive, exercise, and passive control conditions inclusive of effect sizes and (4) the potential mechanisms underlying the changes in executive function induced from exergames. Eligible outcome data were available from 607 participants across ten studies, with the age of participants ranging from 4-21 (Mage=10.46). The findings indicate that exergames improve aspects of executive function from both acute and chronic studies. Despite the high variability of exergame contexts, dosage, populations, and outcome assessments, improvements in executive function comparing exergaming to passive control conditions were exhibited across all studies. While there is evidence of exergaming demonstrating advantages over passive control conditions, evidence is mixed when comparing exergaming to sedentary cognitive and exercise comparison conditions. Potential sources of these mixed results and future directions to address current gaps in the field are identified. As video game and technology use grows exponentially and concerns of childhood sedentary behavior and play deprivation increase, evidence-based practices that promote both physical and cognitive activity are needed.

Longitudinal investigation of executive function development employing task-based, teacher reports, and fNIRS multimethodology in 4- to 5-year-old children.

Increased focus on resting-state functional connectivity (rsFC) and the use and accessibility of functional near-infrared spectroscopy (fNIRS) have advanced knowledge on the interconnected nature of neural substrates underlying executive function (EF) development in adults and clinical populations. Less is known about the relationship between rsFC and developmental changes in EF during preschool years in typically developing children, a gap the present study addresses employing task-based assessment, teacher reports, and fNIRS multimethodology. This preregistered study contributes to our understanding of the neural basis of EF development longitudinally with 41 children ages 4-5. Changes in prefrontal cortex (PFC) rsFC utilizing fNIRS, EF measured with a common task-based assessment (Day-Night task), and teacher reports of behavior (BRIEF-P) were monitored over multiple timepoints: Initial Assessment, 72 h follow-up, 1 Month Follow-up, and 4 Month Follow-up. Measures of rsFC were strongly correlated 72 h apart, providing evidence of high rsFC measurement reliability using fNIRS with preschool-aged children. PFC rsFC was positively correlated with performance on task-based and report-based EF assessments. Children's PFC functional connectivity at rest uniquely predicted later EF, controlling for verbal IQ, age, and sex. Functional connectivity at rest using fNIRS may potentially show the rapid changes in EF development in young children, not only neurophysiologically, but also as a correlate of task-based EF performance and ecologically-relevant teacher reports of EF in a classroom context.

Dietary Practices during Pregnancy in a Marshallese Community: A Mixed Methods Analysis.

Dietary practices during pregnancy play a pivotal role in the health of women and their children and set the foundation for long-term health. Marshallese women have disproportionally higher rates of maternal and infant health disparities, yet little is known about the dietary practices during their pregnancy. The purpose of this study was to identify dietary practices during pregnancy among Marshallese women. From March 2019 to March 2020, a purposive sample of 33 pregnant Marshallese participants participated in a mixed methods study. Two primary themes emerged: (1) traditional beliefs about a healthy diet during pregnancy; and (2) dietary change during pregnancy. Within the first theme, four subthemes emerged: (1) should eat; (2) should not eat; (3) challenges to traditional diet; and (4) spiritual dietary customs during pregnancy. Within the second theme, three subthemes emerged: (1) a healthy diet for my baby; (2) autonomy and diet; and (3) sugar-sweetened beverages. The transition in discourse from traditional customs of dietary practices to an individualistic discourse highlights that acculturation is a complex process that should be included in maternal health education and interventions. Findings from this study provide insight into potential considerations for future interventions aiming to improve maternal and child health outcomes among Marshallese.

Adrenal Stress Hormone Regulation of Hepatic Homeostatic Function After an Acute Ozone Exposure in Wistar-Kyoto Male Rats.

Ozone-induced lung injury, inflammation, and pulmonary/hypothalamus gene expression changes are diminished in adrenalectomized (AD) rats. Acute ozone exposure induces metabolic alterations concomitant with increases in epinephrine and corticosterone. We hypothesized that adrenal hormones are responsible for observed hepatic ozone effects, and in AD rats, these changes would be diminished. In total, 5-7 days after sham (SH) or AD surgeries, male Wistar-Kyoto rats were exposed to air or 0.8-ppm ozone for 4 h. Serum samples were analyzed for metabolites and liver for transcriptional changes immediately post-exposure. Ozone increased circulating triglycerides, cholesterol, free fatty-acids, and leptin in SH but not AD rats. Ozone-induced inhibition of glucose-mediated insulin release was absent in AD rats. Unlike diminution of ozone-induced hypothalamus and lung mRNA expression changes, AD in air-exposed rats (AD-air/SH-air) caused differential hepatic expression of ∼1000 genes. Likewise, ozone in AD rats caused differential expression of ∼1000 genes (AD-ozone/AD-air). Ozone-induced hepatic changes in SH rats reflected enrichment for pathways involving metabolic processes, including acetyl-CoA biosynthesis, TCA cycle, and sirtuins. Upstream predictor analysis identified similarity to responses produced by glucocorticoids and pathways involving forskolin. These changes were absent in AD rats exposed to ozone. However, ozone caused unique changes in AD liver mRNA reflecting activation of synaptogenesis, neurovascular coupling, neuroinflammation, and insulin signaling with inhibition of senescence pathways. In these rats, upstream predictor analysis identified numerous microRNAs likely involved in glucocorticoid insufficiency. These data demonstrate the critical role of adrenal stress hormones in ozone-induced hepatic homeostasis and necessitate further research elucidating their role in propagating environmentally driven diseases.

Effect of Repeated Exposure to the Visual Environment on Young Children's Attention.

Prior research suggests that visual features of the classroom environment (e.g., charts and posters) are potential sources of distraction hindering children's ability to maintain attention to instructional activities and reducing learning gains in a laboratory classroom. However, prior research only examined short-term exposure to elements of classroom décor, and it remains unknown whether children habituate to the visual environment with repeated exposure. In study 1, we explored experimentally the possibility that children may habituate to the visual environment if the visual displays are static. We measured kindergarten children's patterns of attention allocation in a decorated classroom environment over a 2-week period and compared the percentage of time children spent off-task to a baseline condition in which the classroom environment was streamlined (i.e., charts, posters, and manipulatives were removed). The findings indicate that with more prolonged exposure to a static visual environment, partial habitation effects were observed: Attention to the environment declined at the end of the exposure period compared to the beginning of the study; however, the environment remained a significant source of off-task behavior even after 2 weeks of exposure. In study 2, we extend this work by conducting a longitudinal observation of six primary classrooms in which we measured children's patterns of attention allocation in real classrooms for 15 weeks to investigate whether increasing familiarity with the classroom décor would influence attention toward the visual environment. No evidence of habituation was observed in genuine classrooms in study 2. Potential implications for classroom design and future directions are discussed.

Research at a Distance: Replicating Semantic Differentiation Effects Using Remote Data Collection With Children Participants.

Remote data collection procedures can strengthen developmental science by addressing current limitations to in-person data collection and helping recruit more diverse and larger samples of participants. Thus, remote data collection opens an opportunity for more equitable and more replicable developmental science. However, it remains an open question whether remote data collection procedures with children participants produce results comparable to those obtained using in-person data collection. This knowledge is critical to integrate results across studies using different data collection procedures. We developed novel web-based versions of two tasks that have been used in prior work with 4-6-year-old children and recruited children who were participating in a virtual enrichment program. We report the first successful remote replication of two key experimental effects that speak to the emergence of structured semantic representations (N = 52) and their role in inferential reasoning (N = 40). We discuss the implications of these findings for using remote data collection with children participants, for maintaining research collaborations with community settings, and for strengthening methodological practices in developmental science.

Effects of Silver Nanoparticles and Silver Nitrate on mRNA and microRNA Expression in Human Hepatocellular Carcinoma Cells (HepG2).

In order to understand toxicity of nano silver, human hepatocellular carcinoma (HepG2) cells were treated either with silver nitrate (AgNO3) or with nano silver capped with glutathione (Ag-S) at various concentration. Differentially expressed genelists for mRNA and microRNA were obtained through Illumina RNA sequencing and DEseq data analyses. Both treatments showed non-linear dose response relationships for mRNA and microRNA. Gene expression analysis showed signaling pathways common to both nano Ag-S and AgNO3, such as cell cycle regulation, DNA damage response and cancer related pathways. But, nano Ag-S caused signaling pathway changes that were not altered by AgNO3 such as NRF2-mediated oxidative stress response inflammation, cell membrane signaling, and cell proliferation. Nano Ag-S also affected p53 signaling, survival, apoptosis, tissue repair, lipid synthesis, angiogenesis, liver fibrosis and tumor development. Several of the pathways affected by nano Ag-S are hypothesized as major contributors to nanotoxicity. MicroRNA target filter analysis revealed additional affected pathways that were not reflected in the mRNA expression response alone, including DNA damage signaling, genomic stability, ROS, cell cycle, ubiquitination, DNA methylation, cell proliferation and fibrosis for AgNO3; and cell cycle regulation, P53 signaling, cell proliferation, survival, apoptosis, tissue repair and so on for nano Ag-S. These pathways may be mediated by microRNA repression of protein translation.Our study clearly showed that the addition of microRNA profiling increased the numbers of signaling pathways discovered that affected by the treatments on HepG2 cells and gave US a better picture of the effects of these reagents in the cells.

The Emergence of Richly Organized Semantic Knowledge from Simple Statistics: A Synthetic Review.

As adults, we draw upon our ample knowledge about the world to support such vital cognitive feats as using language, reasoning, retrieving knowledge relevant to our current goals, planning for the future, adapting to unexpected events, and navigating through the environment. Our knowledge readily supports these feats because it is not merely a collection of stored facts, but rather functions as an organized, semantic network of concepts connected by meaningful relations. How do the relations that fundamentally organize semantic concepts emerge with development? Here, we cast a spotlight on a potentially powerful but often overlooked driver of semantic organization: Rich statistical regularities that are ubiquitous in both language and visual input. In this synthetic review, we show that a driving role for statistical regularities is convergently supported by evidence from diverse fields, including computational modeling, statistical learning, and semantic development. Finally, we identify a number of key avenues of future research into how statistical regularities may drive the development of semantic organization.

Effects of Copper Nanoparticles on mRNA and Small RNA Expression in Human Hepatocellular Carcinoma (HepG2) Cells.

With the advancement of nanotechnology, nanoparticles are widely used in many different industrial processes and consumer products. Copper nanoparticles (Cu NPs) are among the most toxic nanomaterials. We investigated Cu NPs toxicity in Human Hepatocellular carcinoma (HepG2) cells by examining signaling pathways, and microRNA/mRNA interactions. We compared the effects of exposures to Cu NPs at various concentrations and CuCl2 was used as a control. The number of differentially expressed mRNA did not follow a linear dose-response relationship for either Cu NPs or CuCl2 treatments. The most significantly altered genes and pathways by Cu NPs exposure were NRF2 (nuclear factor erythroid 2 related factor 2)-mediated oxidative stress response, protein ubiquitination, Tumor protein p53 (p53), phase I and II metabolizing enzymes, antioxidant proteins and phase III detoxifying gene pathways.Messenger RNA-microRNA interaction from MicroRNA Target Filter Analyses revealed more signaling pathways altered in Cu NPs treated samples than transcriptomics alone, including cell proliferation, DNA methylation, endoplasmic reticulum (ER) stress, apoptosis, autophagy, reactive oxygen species, inflammation, tumorigenesis, extracellular matrix/angiogenesis and protein synthesis. In contrast, in the control (CuCl2) treated samples showed mostly changes in inflammation mainly through regulation of the Nuclear Factor Kappa-light-chain-enhancer of Activated B-cells (NFκB). Further, some RNA based parameters that showed promise as biomarkers of Cu NPs exposure including both well and lesser known genes: heme oxygenase 1 (HMOX1), heat shock protein, c-Fos proto-oncogene, DNA methyltransferases, and glutamate-cysteine ligase modifier subunit (GCLM, part of the glutathione synthesis pathway). The differences in signaling pathways altered by the Cu NPs and CuCl2 treatments suggest that the effects of the Cu NPs were not the results of nanomaterial dissolution to soluble copper ions.