Quantifying engineered nanomaterial toxicity: comparison of common cytotoxicity and gene expression measurements

BACKGROUND: When evaluating the toxicity of engineered nanomaterials (ENMS) it is important to use multiple bioassays based on different mechanisms of action. In this regard we evaluated the use of gene expression and common cytotoxicity measurements using as test materials, two selected nanoparticles with known differences in toxicity, 5 nm mercaptoundecanoic acid (MUA)-capped InP and CdSe quantum dots (QDs). We tested the effects of these QDs at concentrations ranging from 0.5 to 160 µg/mL on cultured normal human bronchial epithelial (NHBE) cells using four common cytotoxicity assays: the dichlorofluorescein assay for reactive oxygen species (ROS), the lactate dehydrogenase assay for membrane viability (LDH), the mitochondrial dehydrogenase assay for mitochondrial function, and the Comet assay for DNA strand breaks. RESULTS: The cytotoxicity assays showed similar trends when exposed to nanoparticles for 24 h at 80 µg/mL with a threefold increase in ROS with exposure to CdSe QDs compared to an insignificant change in ROS levels after exposure to InP QDs, a twofold increase in the LDH necrosis assay in NHBE cells with exposure to CdSe QDs compared to a 50% decrease for InP QDs, a 60% decrease in the mitochondrial function assay upon exposure to CdSe QDs compared to a minimal increase in the case of InP and significant DNA strand breaks after exposure to CdSe QDs compared to no significant DNA strand breaks with InP. High-throughput quantitative real-time polymerase chain reaction (qRT-PCR) data for cells exposed for 6 h at a concentration of 80 µg/mL were consistent with the cytotoxicity assays showing major differences in DNA damage, DNA repair and mitochondrial function gene regulatory responses to the CdSe and InP QDs. The BRCA2, CYP1A1, CYP1B1, CDK1, SFN and VEGFA genes were observed to be upregulated specifically from increased CdSe exposure and suggests their possible utility as biomarkers for toxicity. CONCLUSIONS: This study can serve as a model for comparing traditional cytotoxicity assays and gene expression measurements and to determine candidate biomarkers for assessing the biocompatibility of ENMs.1R01GM84702-01 - National Institute of General Medical Science

Bandgap Engineering of Indium Phosphide-Based Core/Shell Heterostructures Through Shell Composition and Thickness

The large bulk bandgap (1.35 eV) and Bohr radius (~10 nm) of InP semiconductor nanocrystals provides bandgap tunability over a wide spectral range, providing superior color tuning compared to that of CdSe quantum dots. In this paper, the dependence of the bandgap, photoluminescence emission, and exciton radiative lifetime of core/shell quantum dot heterostructures has been investigated using colloidal InP core nanocrystals with multiple diameters (1.5, 2.5, and 3.7 nm). The shell thickness and composition dependence of the bandgap for type-I and type-II heterostructures was observed by coating the InP core with ZnS, ZnSe, CdS, or CdSe through one to ten iterations of a successive ion layer adsorption and reaction (SILAR)-based shell deposition. The empirical results are compared to bandgap energy predictions made with effective mass modeling. Photoluminescence emission colors have been successfully tuned throughout the visible and into the near infrared (NIR) wavelength ranges for type-I and type-II heterostructures, respectively. Based on sizing data from transmission electron microscopy (TEM), it is observed that at the same particle diameter, average radiative lifetimes can differ as much as 20-fold across different shell compositions due to the relative positions of valence and conduction bands. In this direct comparison of InP/ZnS, InP/ZnSe, InP/CdS, and InP/CdSe core/shell heterostructures, we clearly delineate the impact of core size, shell composition, and shell thickness on the resulting optical properties. Specifically, Zn-based shells yield type-I structures that are color tuned through core size, while the Cd-based shells yield type-II particles that emit in the NIR regardless of the starting core size if several layers of CdS(e) have been successfully deposited. Particles with thicker CdS(e) shells exhibit longer photoluminescence lifetimes, while little shell-thickness dependence is observed for the Zn-based shells. Taken together, these InP-based heterostructures demonstrate the extent to which we are able to precisely tailor the material properties of core/shell particles using core/shell dimensions and composition as variables

Effect of Sedentary and Physical Activities on Children’s Food Choice

International Journal of Exercise Science 10(5): 702-712, 2017. Childhood obesity is a growing public health concern. Research has shown sedentary behavior (SB) increases children’s unhealthy food consumption, while physical activity (PA) decreases caloric intake and increases energy expenditure. The purpose of this study was to examine child snack choice following a bout of active, SB, and a mix of SB and active (SB-A). Participants included a volunteer sample of children (n=24) ranging from 9-13 years of age. A within-subjects simple experimental design was used, and children participated in three conditions: active, SB, and SB-A. After each condition, the children were asked to choose one snack from two healthy and two unhealthy options. The children were randomized into one of the six possible condition sequences (4 children per group) based on when they enrolled in the study. Data were analyzed in SPSS (v21) using the Friedman, Wilcoxon Signed-Rank, and Kruskal-Wallis tests. There was not a statistically significant difference in the overall model comparing the three conditions on snack choice (p=0.15). Overweight/obese children were significantly more likely than normal weight children to choose a healthier snack option after the active condition (p=0.02). There was no difference between boys and girls for snack choice following the active (p\u3e0.05), SB (p\u3e0.05), and SB-A (p\u3e0.05). Our overall findings suggest SB and active had no effect on children’s snack choice. Promoting PA to children who are overweight/obese could lead to decreased energy intake and increased energy expenditure combating the obesity epidemic

Ligands and media impact interactions between engineered nanomaterials and clay minerals

The exponential growth in technologies incorporating engineered nanomaterials (ENMs) requires plans to handle waste ENM disposal and accidental environmental release throughout the material life cycle. These scenarios motivate efforts to quantify and model ENM interactions with diverse background particles and solubilized chemical species in a variety of environmental systems. In this study, quantum dot (QD) nanoparticles and clay minerals were mixed in a range of water chemistries in order to develop simple assays to predict aggregation trends. CdSe QDs were used as a model ENM functionalized with either negatively charged or zwitterionic small molecule ligand coatings, while clays were chosen as an environmentally relevant sorbent given their potential as an economical water treatment technology and ubiquitous presence in nature. In our unbuffered experimental systems, clay type impacted pH, which resulted in a change in zwitterionic ligand speciation that favored aggregation with kaolinite more than with montmorillonite. With kaolinite, the zwitterionic ligand-coated QD exhibited greater than ten times the relative attachment efficiency for QD-clay heteroaggregation compared to the negatively charged ligand coated QD. Under some conditions, particle oxidative dissolution and dynamic sorption of ions and QDs to surfaces complicated the interpretation of the removal kinetics. This work demonstrates that QDs stabilized by small molecule ligands and electrostatic surface charges are highly sensitive to changes in water chemistry in complex media. Natural environments enable rapid dynamic physicochemical changes that will influence the fate and mobility of ENMs, as seen by the differential adsorption of water-soluble QDs to our clay media.Accepted manuscrip

Respiratory temperature responses of tropical conifers differ with leaf morphology

1. Photosynthetic traits suggest that shade tolerance may explain the contrasting success of two conifer taxa, Podocarpaceae and Pinaceae, in tropical forests. Needle-leaved species from Pinus (Pinaceae) are generally absent from tropi- cal forests, whereas Pinus krempfii, a flat-leaved pine, and numerous flat-leaved Podocarpaceae are abundant. Respiration (R) traits may provide additional insight into the drivers of the contrasting success of needle- and flat-leaved conifers in tropical forests. 2. We measured the short-term respiratory temperature (RT) response between 10 and 50°C and foliar morphological traits of three needle- and seven flat-leaved conifer species coexisting in a tropical montane forest in the Central Highlands of Vietnam containing notable conifer diversity. We fit a lognormal polynomial model to each RT curve and extracted the following three parameters: a (basal R), and b and c (together describing the shape of the response). 3. Needle-leaved species (Pinus kesiya, Pinus dalatensis and Dacrydium elatum) had higher rates of area-based R at 25°C (R25-area) as well as higher area-based mod- elled basal respiration (a) than flat-leaved species (P. krempfii, Podocarpus neriifolius, Dacrycarpus imbricatus, Nageia nana, Taxus wallichiana, Keteeleria evelyniana and Fokienia hodginsii). No significant differences were found between needle- and flat-leaved species in mass-based R25 (R25-mass) or in the shape of the RT response (b and c); however, interspecific differences in R25-mass, R at nighttime temperature extremes (R4.1 and R20.6) and leaf traits were apparent. 4. Differences in R25-area and a suggest that needle-leaved foliage may be more en- ergetically costly to maintain than flat-leaved foliage, providing new insight and additional support for the hypothesis that shade tolerance is an important driver of Podocarpaceae success and Pinaceae absence in the majority of tropical forests. 5. Interspecific differences in R25-mass and leaf traits highlight that varying ecological strategies are employed by conifers to coexist and survive in the Central Highland

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

An Integrated Approach for the Analysis of Biological Pathways using Mixed Models

Gene class, ontology, or pathway testing analysis has become increasingly popular in microarray data analysis. Such approaches allow the integration of gene annotation databases, such as Gene Ontology and KEGG Pathway, to formally test for subtle but coordinated changes at a system level. Higher power in gene class testing is gained by combining weak signals from a number of individual genes in each pathway. We propose an alternative approach for gene-class testing based on mixed models, a class of statistical models that

Evaluation and implications of natural product use in preoperative patients: a retrospective review

<p>Abstract</p> <p>Background</p> <p>Medication Reconciliation and Medication Safety are two themes emphasized in a variety of healthcare organizations. As a result, health care facilities have established methods for obtaining a patient's medication history. However, these methods may vary among institutions or even among the health care professionals in a single institution, and studies have shown that patients are reluctant to disclose their complementary and alternative medicine use to any health care professional. This lack of disclosure is important in surgical patients because of potential herbal interactions with medications and drugs used during the surgical procedure; and the potential for adverse reactions including effects on coagulation, blood pressure, sedation, electrolytes or diuresis. Therefore, the objectives of this study are to identify patterns of natural product use, to identify potential complications among patients scheduled for surgery, to improve existing medication reconciliation efforts, and to develop discontinuation guidelines for the use of these products prior to surgery.</p> <p>Methods</p> <p>A retrospective review of surgery patients presenting to the Anesthesia Preoperative Evaluation Clinic (APEC) at the University of Kansas Hospital was conducted to identify the prevalence of natural product use. The following data was collected: patient age; gender; allergy information; date of medication history; number of days prior to surgery; source of medication history; credentials of person obtaining the history; number and name of prescription medications, over-the-counter medications and natural products; and natural product dosage. Following the collection of data and analysis of the most common natural products used, possible complications and interactions were identified, and a protocol regarding the pre-operative use of natural products was developed and implemented.</p> <p>Results</p> <p>Approximately one-fourth of patients seen in the APEC indicated the use of natural products. Patients taking natural products were significantly older, were more likely to undergo cardiac or chest surgery, and were more likely to be taking more prescription and non-prescription medications (all p < 0.001).</p> <p>Conclusion</p> <p>Based on the results of this study, it is concluded that there is a need for established guidelines regarding discontinuation of selected natural products prior to surgery and further education is needed concerning the perioperative implications of natural products.</p

Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by ∼2 logs between weeks 2–32 (P ≤ 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8+ T cells in this control. Furthermore, transient depletion of peripheral CD8+ lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I–restricted CD8+ T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8+ T cell responses can control replication of heterologous challenge viruses