VP30.01: Cell‐free DNA screening for 22q11.2DS by targeted method based on microarray quantitation in the average risk population: results from a single European laboratory

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A multidisciplinary approach to study the reproductive biology of wild prawns

This work aims to provide deeper knowledge on reproductive biology of P. kerathurus in a multidisciplinary way. Upon 789 examined females, 285 were found inseminated. The logistic equation enabled to estimate the size at first maturity at 30.7 mm CL for female. The Gono-Somatic Index (GSI) showed a pronounced seasonality, ranged from 0.80 ± 0.34 to 11.24 ± 5.72. Histological analysis highlighted five stages of ovarian development. Gonadal fatty acids analysis performed with gas chromatograph evidenced a pronounced seasonal variation; total lipids varied from 1.7% dry weight (dw) in Winter, to 7.2% dw in Summer. For the first time, a chemometric approach (Principal Component Analysis) was applied to relate GSI with total lipid content and fatty acid composition of gonads. The first two components (PC1 and PC2) showed that seasonality explained about 84% of the variability of all data set. In particular, in the period February-May, lipids were characterized by high PUFAs content, that were probably utilized during embryogenesis as energy source and as constituent of the cell membranes. During the summer season, gonads accumulated saturated FAs, that will be used during embryogenesis and early larval stages, while in the cold season total lipids decreased drastically and the gonad reached a quiescent state

Prenatal maternal plasma DNA screening for cystic fibrosis: A computer modelling study of screening performance.

Background: Prenatal cystic fibrosis (CF) screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity) is 70% (100% of those detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal screening based on parental carrier testing. Conclusions: Compared with current screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study.The author(s) declared that no grants were involved in supporting this work

Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like

Hair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear. Two members of the myosin-III family, MYO3A and MYO3B, are thought to regulate stereocilia length by transporting cargos that control actin polymerization at stereocilia tips. We show that eliminating espin-1 (ESPN-1), an isoform of ESPN and a myosin-III cargo, dramatically alters the slope of the stereocilia staircase in a subset of hair cells. Furthermore, we show that espin-like (ESPNL), primarily present in developing stereocilia, is also a myosin-III cargo and is essential for normal hearing. ESPN-1 and ESPNL each bind MYO3A and MYO3B, but differentially influence how the two motors function. Consequently, functional properties of different motor-cargo combinations differentially affect molecular transport and the length of actin protrusions. This mechanism is used by hair cells to establish the required range of stereocilia lengths within a single cell

Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like

Hair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear. Two members of the myosin-III family, MYO3A and MYO3B, are thought to regulate stereocilia length by transporting cargos that control actin polymerization at stereocilia tips. We show that eliminating espin-1 (ESPN-1), an isoform of ESPN and a myosin-III cargo, dramatically alters the slope of the stereocilia staircase in a subset of hair cells. Furthermore, we show that espin-like (ESPNL), primarily present in developing stereocilia, is also a myosin-III cargo and is essential for normal hearing. ESPN-1 and ESPNL each bind MYO3A and MYO3B, but differentially influence how the two motors function. Consequently, functional properties of different motor-cargo combinations differentially affect molecular transport and the length of actin protrusions. This mechanism is used by hair cells to establish the required range of stereocilia lengths within a single cell

Stereocilia-staircase spacing is influenced by myosin III motors and their cargos espin-1 and espin-like

Hair cells tightly control the dimensions of their stereocilia, which are actin-rich protrusions with graded heights that mediate mechanotransduction in the inner ear. Two members of the myosin-III family, MYO3A and MYO3B, are thought to regulate stereocilia length by transporting cargos that control actin polymerization at stereocilia tips. We show that eliminating espin-1 (ESPN-1), an isoform of ESPN and a myosin-III cargo, dramatically alters the slope of the stereocilia staircase in a subset of hair cells. Furthermore, we show that espin-like (ESPNL), primarily present in developing stereocilia, is also a myosin-III cargo and is essential for normal hearing. ESPN-1 and ESPNL each bind MYO3A and MYO3B, but differentially influence how the two motors function. Consequently, functional properties of different motor-cargo combinations differentially affect molecular transport and the length of actin protrusions. This mechanism is used by hair cells to establish the required range of stereocilia lengths within a single cell

Isolation of single circulating trophoblasts from maternal circulation for noninvasive fetal copy number variant profiling

ObjectiveTo develop a multi-step workflow for the isolation of circulating extravillous trophoblasts (cEVTs) by describing the key steps enabling a semi-automated process, including a proprietary algorithm for fetal cell origin genetic confirmation and copy number variant (CNV) detection. MethodsDetermination of the limit of detection (LoD) for submicroscopic CNV was performed by serial experiments with genomic DNA and single cells from Coriell cell line biobank with known imbalances of different sizes. A pregnancy population of 372 women was prospectively enrolled and blindly analyzed to evaluate the current workflow. ResultsAn LoD of 800 Kb was demonstrated with Coriell cell lines. This level of resolution was confirmed in the clinical cohort with the identification of a pathogenic CNV of 800 Kb, also detected by chromosomal microarray. The mean number of recovered cEVTs was 3.5 cells per sample with a significant reverse linear trend between gestational age and cEVT recovery rate and number of recovered cEVTs. In twin pregnanices, evaluation of zygosity, fetal sex and copy number profiling was performed in each individual cell. ConclusionOur semi-automated methodology for the isolation and single-cell analysis of cEVTS supports the feasibility of a cell-based noninvasive prenatal test for fetal genomic profiling. © 2022 A. Menarini Biomarkers Singapore Pte Ltd. Prenatal Diagnosis published by John Wiley & Sons Ltd

The Seascape of Demersal Fish Nursery Areas in the North Mediterranean Sea, a First Step Towards the Implementation of Spatial Planning for Trawl Fisheries

The identification of nursery grounds and other essential fish habitats of exploited stocks is a key requirement for the development of spatial conservation planning aimed at reducing the adverse impact of fishing on the exploited populations and ecosystems. The reduction in juvenile mortality is particularly relevant in the Mediterranean and is considered as one of the main prerequisites for the future sustainability of trawl fisheries. The distribution of nursery areas of 11 important commercial species of demersal fish and shellfish was analysed in the European Union Mediterranean waters using time series of bottom trawl survey data with the aim of identifying the most persistent recruitment areas. A high interspecific spatial overlap between nursery areas was mainly found along the shelf break of many different sectors of the Northern Mediterranean indicating a high potential for the implementation of conservation measures. Overlap of the nursery grounds with existing spatial fisheries management measures and trawl fisheries restricted areas was also investigated. Spatial analyses revealed considerable variation depending on species and associated habitat/depth preferences with increased protection seen in coastal nurseries and minimal protection seen for deeper nurseries (e.g. Parapenaeus longirostris 6%). This is partly attributed to existing environmental policy instruments (e.g. Habitats Directive and Mediterranean Regulation EC 1967/2006) aiming at minimising impacts on coastal priority habitats such as seagrass, coralligenous and maerl beds. The new knowledge on the distribution and persistence of demersal nurseries provided in this study can support the application of spatial conservation measures, such as the designation of no-take Marine Protected Areas in EU Mediterranean waters and their inclusion in a conservation network. The establishment of no-take zones will be consistent with the objectives of the Common Fisheries Policy applying the ecosystem approach to fisheries management and with the requirements of the Marine Strategy Framework Directive to maintain or achieve seafloor integrity and good environmental status.Versión del editor4,411

Impact of DNA methylation on trophoblast function

The influence of epigenetics is evident in many fields of medicine today. This is also true in placentology, where versatile epigenetic mechanisms that regulate expression of genes have shown to have important influence on trophoblast implantation and placentation. Such gene regulation can be established in different ways and on different molecular levels, the most common being the DNA methylation. DNA methylation has been shown today as an important predictive component in assessing clinical prognosis of certain malignant tumors; in addition, it opens up new possibilities for non-invasive prenatal diagnosis utilizing cell-free fetal DNA methods. By using a well known demethylating agent 5-azacytidine in pregnant rat model, we have been able to change gene expression and, consequently, the processes of trophoblast differentiation and placental development. In this review, we describe how changes in gene methylation effect trophoblast development and placentation and offer our perspective on use of trophoblast epigenetic research for better understanding of not only placenta development but cancer cell growth and invasion as well

Neural correlates of socio-emotional perception in 22q11.2 deletion syndrome.

BACKGROUND: Social impairments are described as a common feature of the 22q11.2 deletion syndrome (22q11DS). However, the neural correlates underlying these impairments are largely unknown in this population. In this study, we investigated neural substrates of socio-emotional perception. METHODS: We used event-related functional magnetic resonance imaging (fMRI) to explore neural activity in individuals with 22q11DS and healthy controls during the visualization of stimuli varying in social (social or non-social) or emotional (positive or negative valence) content. RESULTS: Neural hyporesponsiveness in regions of the default mode network (inferior parietal lobule, precuneus, posterior and anterior cingulate cortex and frontal regions) in response to social versus non-social images was found in the 22q11DS population compared to controls. A similar pattern of activation for positive and negative emotional processing was observed in the two groups. No correlation between neural activation and social functioning was observed in patients with the 22q11DS. Finally, no social × valence interaction impairment was found in patients. CONCLUSIONS: Our results indicate atypical neural correlates of social perception in 22q11DS that appear to be independent of valence processing. Abnormalities in the social perception network may lead to social impairments observed in 22q11DS individuals