Prenatal ultrasound and postmortem histologic evaluation of tooth germs: an observational, transversal study

Introduction: Hypodontia is the most frequent developmental anomaly of the orofacial complex, and its detection in prenatal ultrasound may indicate the presence of congenital malformations, genetic syndromes and chromosomal abnormalities.To date, only a few studies have evaluated the histological relationship of human tooth germs identified by two-dimensional (2D) ultrasonography. In order to analyze whether two-dimensional ultrasonography of tooth germs may be successfully used for identifying genetic syndromes, prenatal ultrasound images of fetal tooth germs obtained from a Portuguese population sample were compared with histological images obtained from fetal autopsies.Methods: Observational, descriptive, transversal study. The study protocol followed the ethical principles outlined by the Helsinki Declaration and was approved by the Ethics Committee of the School of Dental Medicine, University of Porto (FMDUP, Porto, Portugal) and of the Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/EPE, Porto, Portugal) as well as by the CGC Genetics Embryofetal Pathology Laboratory. Eighty-five fetuses examined by prenatal ultrasound screening from May 2011 to August 2012 had an indication for autopsy following spontaneous fetal death or medical termination of pregnancy. Of the 85 fetuses, 37 (43.5%) were randomly selected for tooth germ evaluation by routine histopathological analysis. Fetuses who were up to 30 weeks of gestation, and whose histological pieces were not representative of all maxillary tooth germs was excluded. Twenty four fetus between the 13th and 30th weeks of gestation fulfilled the parameters to autopsy.Results: Twenty four fetuses were submitted to histological evaluation and were determined the exact number, morphology, and mineralization of their tooth germs. All tooth germs were identifiable with ultrasonography as early as the 13th week of gestation. Of the fetuses autopsied, 41.7% had hypodontia (29.1% maxillary hypodontia and 20.9% mandibular hypodontia).Conclusions: This results indicateinfo:eu-repo/semantics/publishedVersio

Genome-wide association for major depression through age at onset stratification

BACKGROUND: Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. METHODS: Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer’s disease, and coronary artery disease. RESULTS: We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11–1.21, p = 5.2 × 10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. CONCLUSIONS: We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder

The Virtual-Spine Platform—Acquiring, visualizing, and analyzing individual sitting behavior

Back pain is a serious medical problem especially for those people sitting over long periods during their daily work. Here we present a system to help users monitoring and examining their sitting behavior. The Virtual-Spine Platform (VSP) is an integrated system consisting of a real-time body position monitoring module and a data visualization module to provide individualized, immediate, and accurate sitting behavior support. It provides a comprehensive spine movement analysis as well as accumulated data visualization to demonstrate behavior patterns within a certain period. The two modules are discussed in detail focusing on the design of the VSP system with adequate capacity for continuous monitoring and a web-based interactive data analysis method to visualize and compare the sitting behavior of different persons. The data was collected in an experiment with a small group of subjects. Using this method, the behavior of five subjects was evaluated over a working day, enabling inferences and suggestions for sitting improvements. The results from the accumulated data module were used to elucidate the basic function of body position recognition of the VSP. Finally, an expert user study was conducted to evaluate VSP and support future developments

Astrocytes grown in Alvetex® 3 dimensional scaffolds retain a non-reactive phenotype

yesProtocols which permit the extraction of primary astrocytes from either embryonic or postnatal mice are well established however astrocytes in culture are different to those in the mature CNS. Three dimensional (3D) cultures, using a variety of scaffolds may enable better phenotypic properties to be developed in culture. We present data from embryonic (E15) and postnatal (P4) murine primary cortical astrocytes grown on coated coverslips or a 3D polystyrene scaffold, Alvetex. Growth of both embryonic and postnatal primary astrocytes in the 3D scaffold changed astrocyte morphology to a mature, protoplasmic phenotype. Embryonic-derived astrocytes in 3D expressed markers of mature astrocytes, namely the glutamate transporter GLT-1 with low levels of the chondroitin sulphate proteoglycans, NG2 and SMC3. Embroynic astrocytes derived in 3D show lower levels of markers of reactive astrocytes, namely GFAP and mRNA levels of LCN2, PTX3, Serpina3n and Cx43. Postnatal-derived astrocytes show few protein changes between 2D and 3D conditions. Our data shows that Alvetex is a suitable scaffold for growth of astrocytes, and with appropriate choice of cells allows the maintenance of astrocytes with the properties of mature cells and a non-reactive phenotype.BBSR

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)&gt;5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P&lt;5 × 10-8).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways

Space- and time-resolved investigation on diffusion kinetics of human skin following macromolecule delivery by microneedle arrays

Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development of these devices is dependent on understanding the macro-molecular diffusion properties of skin. We hypothesised that diffusion varied according to specific skin layers. Using three different molecular weights of rhodamine dextran (RD) (MW of 70, 500 and 2000 kDa) relevant to the vaccine and therapeutic scales, we deposited molecules to a range of depths (0–300 µm) in ex vivo human skin using the Nanopatch device. We observed significant dissipation of RD as diffusion with 70 and 500 kDa within the 30 min timeframe, which varied with MW and skin layer. Using multiphoton microscopy, image analysis and a Fick’s law analysis with 2D cartesian and axisymmetric cylindrical coordinates, we reported experimental trends of epidermal and dermal diffusivity values ranging from 1–8 µm2 s-1 to 1–20 µm2 s-1 respectively, with a significant decrease in the dermal-epidermal junction of 0.7–3 µm2 s-1. In breaching the stratum corneum (SC) and dermal-epidermal junction barriers, we have demonstrated practical application, delivery and targeting of macromolecules to both epidermal and dermal antigen presenting cells, providing a sound knowledge base for future development of skin-targeting clinical technologies in humans

Production and Characterization of Antifungal Compounds Produced by Lactobacillus plantarum IMAU10014

Lactobacillus plantarum IMAU10014 was isolated from koumiss that produces a broad spectrum of antifungal compounds, all of which were active against plant pathogenic fungi in an agar plate assay. Two major antifungal compounds were extracted from the cell-free supernatant broth of L. plantarum IMAU10014. 3-phenyllactic acid and Benzeneacetic acid, 2-propenyl ester were carried out by HPLC, LC-MS, GC-MS, NMR analysis. It is the first report that lactic acid bacteria produce antifungal Benzeneacetic acid, 2-propenyl ester. Of these, the antifungal products also have a broad spectrum of antifungal activity, namely against Botrytis cinerea, Glomerella cingulate, Phytophthora drechsleri Tucker, Penicillium citrinum, Penicillium digitatum and Fusarium oxysporum, which was identified by the overlay and well-diffusion assay. F. oxysporum, P. citrinum and P. drechsleri Tucker were the most sensitive among molds