Expression of Epsin3 and its interaction with Notch signalling in oral epithelial dysplasia and oral squamous cell carcinoma.

Background: Most oral squamous cell carcinoma patients present with late-stage disease. Early detection of the disease is considered to be the most effective way of improving patient outcomes. Several biomarkers have been identified as indicators of oral cancer development and progression; however, none have been translated into clinical practice.

Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study: A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments.

STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts.

Effect of Physical Exercise and Genetic Background on Glucose Homeostasis and Liver/Muscle Proteomes in Mice.

We compared the parameters related to glucose homeostasis, and liver and muscle proteomes in fluorosis-susceptible (A/J; S) and fluorosis-resistant (129P3/J; R) mice in response to fluoride (F) exposure and exercise. Ninety male mice (45 R-mice and 45 S-mice) were randomized into three groups: (SI; RI) No-F, No-Exercise, (SII; RII) 50 ppm F, No-Exercise, (SIII; RIII) 50 ppm F, Exercise. Overall, mean F concentrations in the plasma and femur were significantly higher in R-mice compared with S-mice.

Biomarkers for the Assessment of Exposure to Fluoride in Adults.

To monitor deficient or excessive intakes of biologically available fluoride (F), various biological samples have been tested for use as biomarkers of human exposure to F. Most such studies have concerned children and often have only involved measurement of F in 1 or 2 types of sample. The present study investigated the relationships of F concentrations in biomarkers of F exposure; including plasma, saliva, hair, finger- and toenails, and daily urinary F excretion (UFE) with the total daily F intake (TDFI) of adults.

Biomarkers for the Assessment of Fluoride Exposure in Children.

Due to practical difficulties in quantifying fluoride exposure, the ability of various biomarkers to predict exposure has been investigated previously. However, the results are inadequate for validation of their application and usefulness. This study aimed to investigate the association between contemporary/recent biomarkers of fluoride exposure and total daily fluoride intake (TDFI) of children with large differences in fluoride exposure through drinking water.

Chapter 11: Nutrigenomics and Oral Health.

The advent of the "genomic era" has allowed for nutrigenomics studies to be carried out, which aim to reveal whether there are interactions between the food we consume and our genetic make-up. In turn this information will provide the scientific basis for improved public health messages related to nutrition and diet. With the availability of high throughput, inexpensive and sometime "bed-side" technology, studies into the effect of diet on the aetiology of common oral diseases and oral conditions could now be easily carried out.

A Pilot Study to Assess Feasibility of Lay Representation in Dental School Admissions Interviews.

Regulatory bodies in the dental profession often include members of the public as a way to ensure that patient interests are represented. With student selection for admission to dental school being a multifaceted, highly competitive process, this study was motivated by curiosity about the value of involving members of the public in the admissions process. At Newcastle University School of Dental Sciences, UK, semi-structured selection interviews conducted by two members of the faculty staff are part of the process.

The presence and response to Zn of ZnT family mRNAs in human dental pulp.

Zinc (Zn) is distributed throughout the body and within cells by saturable processes mediated by the transport proteins of the ZnT (SLC30) and ZIP (SLC39) families. The two families function in opposite directions. ZnT transporters mediate cellular zinc efflux or intracellular sequestration.

Fluoride retention in infants living in fluoridated and non-fluoridated areas: effects of weaning.

Limited knowledge is available on total fluoride exposure, excretion and retention in infants, despite the first year of human life being the critical period for dental development and risk of dental fluorosis. This study investigated total daily fluoride intake (TDFI), excretion (TDFE) and retention (TDFR) in infants living in fluoridated and non-fluoridated water areas at pre- and post-weaning stages of development. Healthy infants, aged 0-12 months, were recruited and their TDFI (mg/kg body weight (BW) per d), from diet and toothpaste ingestion, was assessed over a 3-d period using a dietary diary and tooth-brushing questionnaire.

Comparison of total ionic strength adjustment buffers III and IV in the measurement of fluoride concentration of teas.

Background: Tea is the second most consumed drink in the UK and a primary source of hydration; it is an important source of dietary fluoride (F) for consumers and also abundant in aluminium (Al). Varying ranges of F concentrations in teas have been reported worldwide which may be, in part, due to differences in analytical techniques used to measure this ion.

Aim: The effect of using total ionic adjustment buffers (TISAB) III or IV when measuring F concentration of black teas available in the UK was investigated and compared.

Effect of chronic exercise on fluoride metabolism in fluorosis-susceptible mice exposed to high fluoride.

The present study investigated the effect of chronic exercise on fluoride (F) metabolism in fluorosis-susceptible mice exposed to high-F and explored the relationship between F concentrations in bone and plasma. Thirty male mice were randomised into three groups: Group I (No-F, No-Exercise), Group II (50 ppmF, No-Exercise), Group III (50 ppmF, Exercise). Body weight and physical performance of all mice were measured at baseline and end of experiment.

Prevalence and extent of enamel defects in the permanent teeth of 8-year-old Nigerian children.

Objectives: Enamel formation is a vulnerable developmental process, susceptible to environmental influences such as excessive systemic fluoride (F) exposure and infant/childhood disease. This study determined prevalence and extent of developmental enamel defects (DDE) and dental fluorosis in 8-year-old Nigerians and explored associations with key predictors.

Methods: A sample of 322 healthy 8-year-olds (155 males, 167 females) from primary schools in lower and higher water F areas of (i) rural and (ii) urban parts of Oyo State in south-west Nigeria (n = 4 areas) (in which the mean (SD) F concentration of community water supplies ranged from 0.

Age-related changes in immune function (immune senescence) in caries and periodontal diseases: a systematic review.

Aim: To systematically review the evidence regarding immune senescence in the pathogenesis of periodontitis and dental caries.

Methods: A systematic search of electronic databases utilizing medical subject headings (MeSH terms) supplemented by screening of review articles and other relevant texts was undertaken.

Results: Seventy-three articles were included (43 for periodontitis, 30 for caries).

Effect of topical neuromodulatory medications on oral and skin keratinocytes.

Background: Neuromodulatory medications (NMs), such as amitriptyline, carbamazepine and gabapentin, are used as topical preparations for the management of neuropathic orofacial pain (NOP) and have produced promising preliminary results. The aim of this study was to investigate the effects of three aforementioned NMs on cell lines relevant to the orofacial tissues in vitro as no published studies have examined the effect of these topical NMs.

Methods: Cellular viability was measured using alamarBlue , testing cumulative and specific time point effects of NMs on human skin keratinocytes and oral keratinocytes.

The zinc finger protein ZNF658 regulates the transcription of genes involved in zinc homeostasis and affects ribosome biogenesis through the zinc transcriptional regulatory element.

We previously identified the ZTRE (zinc transcriptional regulatory element) in genes involved in zinc homeostasis and showed that it mediates transcriptional repression in response to zinc. We now report that ZNF658 acts at the ZTRE. ZNF658 was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry of a band excised after electrophoretic mobility shift assay using a ZTRE probe.

Biodentine and mineral trioxide aggregate induce similar cellular responses in a fibroblast cell line.

Introduction: The aim of this study was to assess the cell viability and messenger RNA expression of interleukin (IL)-1α and IL-6 in 3T3 fibroblast cells when in direct contact with Biodentine (Septodont, Saint Maur de Fossés, France) and mineral trioxide aggregate (MTA).

Methods: Biodentine and MTA were coated onto coverslips and allowed to set. An uncoated coverslip and one coated with GC Fuji IX (GC Corporation, Tokyo, Japan) were used as controls.

Nutrigenomics: the role of nutrients in gene expression.

Improved understanding of the mechanism behind periodontal tissue destruction, the potential protective role of nutrients and the advent of modern genomic measurement tools has led to an increased interest in the association between nutrition and periodontal disease. To date, evidence for a direct link between periodontal disease and nutrition has come mainly from large observational cross-sectional studies or very small double-blind randomized supplementation trials, with a large proportion finding no significant association between the nutrient being analyzed and markers of periodontal disease status. The advent of the 'genomic era' has introduced the concept of nutrigenomic studies, which aim to reveal the relationship between nutrition and the genome to provide a scientific basis for improved public health through dietary means.

Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model.

Many neurological conditions are caused by immensely heterogeneous gene mutations. The diagnostic process is often long and complex with most patients undergoing multiple invasive and costly investigations without ever reaching a conclusive molecular diagnosis. The advent of massively parallel, next-generation sequencing promises to revolutionize genetic testing and shorten the 'diagnostic odyssey' for many of these patients.

Altered expression of ZnT10 in Alzheimer's disease brain.

There is an increasing body of evidence suggesting that metal homeostasis is dysregulated in the pathology of Alzheimer's disease (AD). Although expression levels of several transporters belonging the SLC30 family, which comprises predominantly zinc transporters, have been studied in the AD brain, SLC30A10 (ZnT10) has not been studied in this context. To determine if dysregulated expression of ZnT10, which may transport both Zn and Mn, could be a factor that contributes to AD, we investigated if there were differences in ZnT10 mRNA levels in specimens of frontal cortex from AD patients and controls and also if brain tissue from the APP/PS1 transgenic (Tg) mouse model showed abnormal levels of ZnT10 mRNA expression.

Effects of Sirt1 on DNA methylation and expression of genes affected by dietary restriction.

Changes in DNA methylation across the life course may contribute to the ageing process. We hypothesised that some effects of dietary restriction to extend lifespan and/or mitigate against features of ageing result from changes in DNA methylation, so we determined if genes that respond to dietary restriction also show age-related changes in DNA methylation. In support of our hypothesis, the intersection of lists of genes compiled from published sources that (1) were differentially expressed in response to dietary restriction and (2) showed altered methylation with increased age was greater than expected.

Identification of the human zinc transcriptional regulatory element (ZTRE): a palindromic protein-binding DNA sequence responsible for zinc-induced transcriptional repression.

Many genes with crucial roles in zinc homeostasis in mammals respond to fluctuating zinc supply through unknown mechanisms, and uncovering these mechanisms is essential to understanding the process at cellular and systemic levels. We detected zinc-dependent binding of a zinc-induced protein to a specific sequence, the zinc transcriptional regulatory element (ZTRE), in the SLC30A5 (zinc transporter ZnT5) promoter and showed that substitution of the ZTRE abrogated the repression of a reporter gene in response to zinc. We identified the ZTRE in other genes, including (through an unbiased search) the CBWD genes and (through targeted analysis) in multiple members of the SLC30 family, including SLC30A10, which is repressed by zinc.

Efflux function, tissue-specific expression and intracellular trafficking of the Zn transporter ZnT10 indicate roles in adult Zn homeostasis.

Zn is essential to the structure and function of numerous proteins and enzymes so requires tight homeostatic control at both the systemic and cellular level. Two families of Zn transporters - ZIP (SLC39) and ZnT (SLC30) - contribute to Zn homeostasis. There are at least 10 members of the human ZnT family, and the expression profile and regulation of each varies depending on tissue type.

Differential subcellular localization of the splice variants of the zinc transporter ZnT5 is dictated by the different C-terminal regions.

Background: Zinc is emerging as an important intracellular signaling molecule, as well as fulfilling essential structural and catalytic functions through incorporation in a myriad of zinc metalloproteins so it is important to elucidate the molecular mechanisms of zinc homeostasis, including the subcellular localizations of zinc transporters.

Principal Findings: Two splice variants of the human SLC30A5 Zn transporter gene (ZnT5) have been reported in the literature. These variants differ at their N- and C-terminal regions, corresponding with the use of different 5' and 3' exons.

A new direction for manganese homeostasis in bacteria: identification of a novel efflux system in Streptococcus pneumoniae.

The ability to control intracellular levels of transition metals such as Mn(2+), Fe(2+) and Zn(2+) is critical for the virulence of many pathogenic bacteria. In this issue of Molecular Microbiology, Rosch et al. describe the first identification of a Mn(2+) efflux system in bacteria, MntE of Streptococcus pneumoniae, and demonstrate that it is required for virulence in an animal model.