Menthol and related compounds in waterpipe products.

Introduction: The addition of cooling substances, such as menthol, might be attractive for youth to start smoking waterpipe by reducing the harshness of the smoke, thereby facilitating inhalation. These compounds simultaneously increase the addictiveness of tobacco and related products by stimulating nicotine uptake. Some menthol-like compounds also increase attractiveness by imparting a menthol/mint flavor.

Activation of Human Monocytes by Colloidal Aluminum Salts.

Subunit vaccines often contain colloidal aluminum salt-based adjuvants to activate the innate immune system. These aluminum salts consist of micrometer-sized aggregates. It is well-known that particle size affects the adjuvant effect of particulate adjuvants.

Meta-Analysis of Pulmonary Transcriptomes from Differently Primed Mice Identifies Molecular Signatures to Differentiate Immune Responses following Challenge.

Respiratory infection with leads to severe effects in the lungs. The resulting immunity and also immunization with pertussis vaccines protect against disease, but the induced type of immunity and longevity of the response are distinct. In this study the effects of priming, by either vaccination or infection, on a subsequent pathogen encounter were studied.

Metabolic profiling of presymptomatic Huntington's disease sheep reveals novel biomarkers.

The pronounced cachexia (unexplained wasting) seen in Huntington's disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach.

Identification of flavour additives in tobacco products to develop a flavour library.

Objectives: This study combines chemical analysis and flavour descriptions of flavour additives used in tobacco products, and provides a starting point to build an extensive library of flavour components, useful for product surveillance.

Methods: Headspace gas chromatography-mass spectrometry (GC-MS) was used to compare 22 commercially available tobacco products (cigarettes and roll-your-own) expected to have a characterising flavour and 6 commercially available products not expected to have a characterising flavour with 5 reference products (natural tobacco leaves and research cigarettes containing no flavour additives). The flavour components naturally present in the reference products were excluded from components present in commercially available products containing flavour additives.

Proteome Analysis Is a Valuable Tool to Monitor Antigen Expression during Upstream Processing of Whole-Cell Pertussis Vaccines.

Physicochemical and immunochemical assays were applied to substantiate the relation between upstream processing and the quality of whole-cell pertussis vaccines. Bordetella pertussis bacteria were cultured on a chemically defined medium using a continuous cultivation process in stirred tank reactors to obtain uniform protein expression. Continuous culture favors the consistent production of proteins known as virulence factors.

Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine.

The demand for improved pertussis vaccines is urgent due to the resurgence of whooping cough. A deeper understanding of the mode of action of pertussis vaccines is required to achieve this improvement. The vaccine-induced effects of a candidate outer membrane vesicle vaccine (omvPV) and a classical protective but reactogenic whole cell vaccine (wPV) were comprehensively compared in mice.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions.

Immunological Signatures after Bordetella pertussis Infection Demonstrate Importance of Pulmonary Innate Immune Cells.

Effective immunity against Bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. Natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. We applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotected mice and protected mice with infection-induced immunity, around a B.

An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome.

Anatomical and functional brain abnormalities begin during fetal life in Down syndrome (DS). We hypothesize that novel prenatal treatments can be identified by targeting signaling pathways that are consistently perturbed in cell types/tissues obtained from human fetuses with DS and mouse embryos. We analyzed transcriptome data from fetuses with trisomy 21, age and sex-matched euploid controls, and embryonic day 15.

Transcriptome signature for dampened Th2 dominance in acellular pertussis vaccine-induced CD4(+) T cell responses through TLR4 ligation.

Current acellular pertussis (aP) vaccines promote a T helper 2 (Th2)-dominated response, while Th1/Th17 cells are protective. As our previous study showed, after adding a non-toxic TLR4 ligand, LpxL1, to the aP vaccine in mice, the Bordetella pertussis-specific Th2 response is decreased and Th1/Th17 responses are increased as measured at the cytokine protein level. However, how this shift in Th response by LpxL1 addition is regulated at the gene expression level remains unclear.

Absence of Prenatal Forebrain Defects in the Dp(16)1Yey/+ Mouse Model of Down Syndrome.

Studies in humans with Down syndrome (DS) show that alterations in fetal brain development are followed by postnatal deficits in neuronal numbers, synaptic plasticity, and cognitive and motor function. This same progression is replicated in several mouse models of DS. Dp(16)1Yey/+ (hereafter called Dp16) is a recently developed mouse model of DS in which the entire region of mouse chromosome 16 that is homologous to human chromosome 21 has been triplicated.

Males are from Mars, and females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity.

Background: Maternal obesity is associated with adverse neurodevelopmental outcomes in children, including autism spectrum disorders, developmental delay, and attention-deficit hyperactivity disorder. The underlying mechanisms remain unclear. We previously identified second-trimester amniotic fluid and term cord blood gene expression patterns suggesting dysregulated brain development in fetuses of obese compared with lean women.

Classification of Cholestatic and Necrotic Hepatotoxicants Using Transcriptomics on Human Precision-Cut Liver Slices.

Human toxicity screening is an important stage in the development of safe drug candidates. Hepatotoxicity is one of the major reasons for the withdrawal of drugs from the market because the liver is the major organ involved in drug metabolism, and it can generate toxic metabolites. There is a need to screen molecules for drug-induced hepatotoxicity in humans at an earlier stage.

Zebrafish embryos as a screen for DNA methylation modifications after compound exposure.

Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds.

Development of an in vitro test to identify respiratory sensitizers in bronchial epithelial cells using gene expression profiling.

Chemicals that induce asthma at the workplace are substances of concern. At present, there are no widely accepted methods to identify respiratory sensitizers, and classification of these substances is based on human occupational data. Several studies have contributed to understanding the mechanisms involved in respiratory sensitization, although uncertainties remain.

Diurnal Variation of Hormonal and Lipid Biomarkers in a Molecular Epidemiology-Like Setting.

Introduction: Many molecular epidemiology studies focusing on high prevalent diseases, such as metabolic disorders and cancer, investigate metabolic and hormonal markers. In general, sampling for these markers can occur at any time-point during the day or after an overnight fast. However, environmental factors, such as light exposure and food intake might affect the levels of these markers, since they provide input for the internal time-keeping system.

Chronically Alternating Light Cycles Increase Breast Cancer Risk in Mice.

Although epidemiological studies in shift workers and flight attendants have associated chronic circadian rhythm disturbance (CRD) with increased breast cancer risk, causal evidence for this association is lacking. Several scenarios have been proposed to contribute to the shift work-cancer connection: (1) internal desynchronization, (2) light at night (resulting in melatonin suppression), (3) sleep disruption, (4) lifestyle disturbances, and (5) decreased vitamin D levels due to lack of sunlight. The confounders inherent in human field studies are less problematic in animal studies, which are therefore a good approach to assess the causal relation between circadian disturbance and cancer.

First-Trimester Serum Acylcarnitine Levels to Predict Preeclampsia: A Metabolomics Approach.

Objective: To expand the search for preeclampsia (PE) metabolomics biomarkers through the analysis of acylcarnitines in first-trimester maternal serum.

Methods: This was a nested case-control study using serum from pregnant women, drawn between 8 and 14 weeks of gestational age. Metabolites were measured using an UPLC-MS/MS based method.

Comparison of gene expression regulation in mouse- and human embryonic stem cell assays during neural differentiation and in response to valproic acid exposure.

Embryonic stem cell tests (EST) are considered promising alternative assays for developmental toxicity testing. Classical mouse derived assays (mEST) are being replaced by human derived assays (hEST), in view of their relevance for human hazard assessment. We have compared mouse and human neural ESTn assays for neurodevelopmental toxicity as to regulation of gene expression during cell differentiation in both assays.

Immunoproteomic Profiling of Bordetella pertussis Outer Membrane Vesicle Vaccine Reveals Broad and Balanced Humoral Immunogenicity.

The current resurgence of whooping cough is alarming, and improved pertussis vaccines are thought to offer a solution. Outer membrane vesicle vaccines (omvPV) are potential vaccine candidates, but omvPV-induced humoral responses have not yet been characterized in detail. The purpose of this study was to determine the antigen composition of omvPV and to elucidate the immunogenicity of the individual antigens.

Biomarkers for circadian rhythm disruption independent of time of day.

Frequent shift work causes disruption of the circadian rhythm and might on the long-term result in increased health risk. Current biomarkers evaluating the presence of circadian rhythm disturbance (CRD), including melatonin, cortisol and body temperature, require 24-hr ("around the clock") measurements, which is tedious. Therefore, these markers are not eligible to be used in large-scale (human) studies.

Predictive performance of a seven-plex antibody array in prenatal screening for Down Syndrome.

We evaluated the use of multiplex antibody array methodology for simultaneous measurement of serum protein markers for first trimester screening of Down Syndrome (DS) and other pregnancy outcomes such as preeclampsia. For this purpose, we constructed an antibody array for indirect ("sandwich") measurement of seven serum proteins: pregnancy-associated plasma protein-A (PAPP-A), free beta subunit of human chorionic gonadotropin (fβ-hCG), alpha-fetoprotein (AFP), angiopoietin-like 3 (ANGPTL3), epidermal growth factor (EGF), insulin-like growth factor 2 (IGFII), and superoxide dismutase 1 (SOD1). This array was tested using 170 DS cases and 510 matched controls drawn during the 8th-13th weeks of pregnancy.

Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.

Differentiating pluripotent stem cells in vitro have proven useful for the study of developmental toxicity. Here, we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC)-based neurodevelopmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to noncytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), antiepileptic drugs known to cause neurodevelopmental toxicity.

The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje mouse model of Down syndrome.

Human fetuses with Down syndrome demonstrate abnormal brain growth and reduced neurogenesis. Despite the prenatal onset of the phenotype, most therapeutic trials have been conducted in adults. Here, we present evidence for fetal brain molecular and neonatal behavioral alterations in the Ts1Cje mouse model of Down syndrome.