An integrated map of structural variation in 2,504 human genomes

Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association. © 2015 Macmillan Publishers Limited. All rights reserved

Dietary patterns of breastfeeding mothers and human milk composition : Data from the italian MEDIDIET study

(1) Background: Several studies have reported associations between maternal diet in terms of single foods or nutrients and human milk compounds, while the overall role of maternal diet and related dietary patterns has rarely been investigated. (2) Methods: Between 2012 and 2014, we enrolled 300 healthy Italian mothers, who exclusively breastfed their infant. During a hospital visit at 6 weeks postpartum, a sample of freshly expressed foremilk was collected and information on maternal dietary habits in the postpartum period was obtained through an intervieweradministered food frequency questionnaire. We applied principal component factor analysis to selected nutrients in order to identify maternal dietary patterns, and assessed correlations in human milk macronutrients and fatty acids across levels of dietary patterns. (3) Results: Five dietary patterns were identified, named “Vitamins, minerals and fibre”, “Proteins and fatty acids with legs”, “Fatty acids with fins”, “Fatty acids with leaves”, “Starch and vegetable proteins”. These dietary patterns were correlated with some milk components, namely fatty acids, and in particular ω-3 and its subcomponents. (4) Conclusions: This study showed that overall maternal dietary habits during breastfeeding may influence human milk composition, suggesting the importance of adequate maternal nutrition during lactation not only for the mother herself but also to provide the infant with milk containing adequate amount and quality of nutrients for a balanced nutrition

Teaching Robust Argumentation Informed by the Nature of Science to Support Social Justice. Experiences from Two Projects in Lower Secondary Schools in Norway

Under embargo until: 2022-09-09This chapter suggests a set of design principles for science curricula that will enable students to produce evidence-based arguments expressing views related to their own interests. It is based on the assumption that the ability to construct evidence-based arguments strengthens students’ ability to promote their own views in the interest of social justice. This is of special importance for students not enculturated into such argumentation through their upbringing. To promote one’s own views in a debate means to critique others’ arguments, and especially to ensure one’s own arguments are resistent to criticism. Insight into the nature of science includes insights in how to construct sound arguments based on facts and research results. The discussion of design principles is based on an analysis of two science projects in two lower secondary schools in Norway (Grade 8). In the first project, students produced scientific claims based on evidence from their own practical experiments. In the second project, the students developed and applied a method for estimating energy use and carbon dioxide (CO2) emissions. The students used their findings to construct arguments related to local transport plans. The analysis focuses on challenges and successes in scaffolding students at different competence levels to successfully produce evidence-based arguments.acceptedVersio

Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour

<p>Abstract</p> <p>Background</p> <p>Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters.</p> <p>Methods</p> <p>The validation assay was performed in a different set of 8 patients with colorectal cancer (CRC) by means quantitative reverse-transcriptase polymerase chain reaction analysis. The differential RNA expression profiles of three CRC cell lines before and after 5-aza-2'-deoxycytidine treatment were compared to identify the hypermethylated genes. The DNA methylation status of these genes was evaluated by means of bisulphite genomic sequencing and methylation-specific polymerase chain reaction (MSP) in the 3 cell lines and in tumour tissues from 30 patients with CRC.</p> <p>Results</p> <p>Data from our previous genome search have received confirmation in the new set of 8 patients with CRC. In this validation set six genes showed a high induction after drug treatment in at least two of three CRC cell lines. Among them, the N-myc downstream-regulated gene 2 (<it>NDRG2) </it>promoter was found methylated in all CRC cell lines. <it>NDRG2 </it>hypermethylation was also detected in 8 out of 30 (27%) primary CRC tissues and was significantly associated with advanced AJCC stage IV. Normal colon tissues were not methylated.</p> <p>Conclusion</p> <p>The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage.</p

With or without ν\nu? Hunting for the seed of the matter-antimatter asymmetry

The matter-antimatter asymmetry underlines the incompleteness of the current understanding of particle physics. Neutrinoless double-beta ($0\nu \beta\beta$) decay may help explain this asymmetry, while unveiling the Majorana nature of the neutrino. The CUORE experiment searches for $0\nu \beta\beta$ decay of $^{130}$Te using a tonne-scale cryogenic calorimeter operated at milli-kelvin temperatures. We report no evidence for $0\nu \beta\beta$ decay and place a lower limit on the half-life of T$_{1/2}$ $>$ 3.8 $\times$ 10$^{25}$ years (90% C.I.) with over 2 tonne$\cdot$year TeO$_2$ exposure. The tools and techniques developed for this result and the 5 year stable operation of nearly 1000 detectors demonstrate the infrastructure for a next-generation experiment capable of searching for $0\nu \beta\beta$ decay across multiple isotopes

Status and prospects of discovery of 0νββ decay with the CUORE detector

In this contribution we present the achievements of the CUORE experiment so far. It is the first tonne-scale bolometric detector and it is in stable data taking since 2018. We reached to collect about 1800 kg×yr of exposure of which more than 1ton×year have been analysed. The CUORE detector is meant to search for the neutrinoless double β decay (0νββ) of the 130Te isotope. This is a beyond Standard Model process which could establish the nature of the neutrino to be Dirac or a Majorana particle. It is an alternative mode of the two-neutrinos double β decay, a rare decay which have been precisely measured by CUORE in the 130Te. We found no evidence of the 0νββ and we set a Bayesian lower limit of 2.2×1025yr on its half-life. The expertise achieved by CUORE set a milestone for any future bolometric detector, including CUPID, which is the planned next generation experiment searching for 0νββ with scintillating bolometers

Adherence to Mediterranean Diet of Breastfeeding Mothers and Fatty Acids Composition of Their Human Milk: Results From the Italian MEDIDIET Study

Background and Aims: The content of fatty acids (FA) in human milk may be influenced by maternal nutrition. We evaluated the role of a Mediterranean diet in influencing the content of FA in human milk among 282 breastfeeding mothers participating in the MEDIDIET study. Materials and Methods: Mediterranean Diet Score (MDS), a composite index, was used to evaluate adherence to the Mediterranean diet. It includes 9 components (i.e., vegetables, fruit, cereals, legumes, monounsaturated to saturated FA ratio – MUFA/SFA, fish, dairy products, meat, and alcohol) and therefore potentially ranges from 0 (no adherence) to 9 (complete adherence) points. None of the mothers obtained the highest score due to the low alcohol consumption in the study population. Mothers were categorized in approximate tertiles of adherence: 0–3 (34.4%), 4 (26.2%), and 5–8 points (39.4%). The mean content of FA across categories of MDS was compared using ANOVA and test for trend. Results: A high adherence of breastfeeding mothers to the Mediterranean diet was associated with lower content of SFA in human milk (42.58 ± 4.36 for MDS = 0–3, 42.58 ± 4.89 for MDS = 4, and 40.92 ± 5.22% of fats for MDS = 5–8 points; p ANOVA and p for trend = 0.02). Conversely, a high adherence was associated with higher content of MUFA in human milk (43.27 ± 4.27 for MDS = 0–3, 43.27 ± 4.47 for MDS = 4, and 45.24 ± 5.22% of fats for MDS = 5–8 points; p ANOVA and p for trend < 0.01), ω-3 FA (1.07 ± 0.25 for MDS = 0–3, 1.22 ± 0.49 for MDS = 4, and 1.31 ± 0.51% of fats for MDS = 5–8 points; p ANOVA and p for trend < 0.01), and the major types of ω-3 FA (i.e., α-linolenic acid – ALA, eicosapentaenoic acid – EPA, docosahexaenoic acid – DHA, docosapentaenoic acid – DPA). These associations were mainly driven by the adherence to the vegetables, MUFA/SFA, fish, and dairy products components of the Mediterranean diet. Conclusion: A high adherence to the Mediterranean diet was associated with human milk showing a lower content of SFA and higher content of MUFA and ω-3 FA, including DHA. The Mediterranean diet may contribute in human milk production with higher content of specific FA which is directly involved in infant’s neural and visual development, as reported by previous studies

A first test of CUPID prototypal light detectors with NTD-Ge sensors in a pulse-tube cryostat

CUPID is a next-generation bolometric experiment aiming at searching for neutrinoless double-beta decay with ~250 kg of isotopic mass of $^{100}$Mo. It will operate at $\sim$10 mK in a cryostat currently hosting a similar-scale bolometric array for the CUORE experiment at the Gran Sasso National Laboratory (Italy). CUPID will be based on large-volume scintillating bolometers consisting of $^{100}$Mo-enriched Li$_2$MoO$_4$ crystals, facing thin Ge-wafer-based bolometric light detectors. In the CUPID design, the detector structure is novel and needs to be validated. In particular, the CUORE cryostat presents a high level of mechanical vibrations due to the use of pulse tubes and the effect of vibrations on the detector performance must be investigated. In this paper we report the first test of the CUPID-design bolometric light detectors with NTD-Ge sensors in a dilution refrigerator equipped with a pulse tube in an above-ground lab. Light detectors are characterized in terms of sensitivity, energy resolution, pulse time constants, and noise power spectrum. Despite the challenging noisy environment due to pulse-tube-induced vibrations, we demonstrate that all the four tested light detectors comply with the CUPID goal in terms of intrinsic energy resolution of 100 eV RMS baseline noise. Indeed, we have measured 70--90 eV RMS for the four devices, which show an excellent reproducibility. We have also obtained outstanding energy resolutions at the 356 keV line from a $^{133}$Ba source with one light detector achieving 0.71(5) keV FWHM, which is -- to our knowledge -- the best ever obtained when compared to $\gamma$ detectors of any technology in this energy range.Comment: Prepared for submission to JINST; 16 pages, 7 figures, and 1 tabl