DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring

Background: We examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood. Methods: First, we used cord blood of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip. We performed an epigenome-wide association study for the association between maternal smoking and methylation followed by a mediation analysis of the top signals [false-discovery rate (FDR)<0.05]. We adjusted both analyses for maternal age, education, pre-pregnancy BMI, offspring's sex, gestational age and white blood cell composition. Secondly, in 175 exposed and 1248 unexposed newborns from two independent birth cohorts, we replicated and meta-analysed results of eight cytosine-phosphate-guanine (CpG) sites in the GFI1 gene, which showed the most robust mediation. Finally, we performed functional network and enrichment analysis. Results: We found 35 differentially methylated CpGs (FDR<0.05) in newborns exposed vs unexposed to smoking, of which 23 survived Bonferroni correction (P<1×10-7). These 23 CpGs mapped to eight genes: AHRR, GFI1, MYO1G, CYP1A1, NEUROG1, CNTNAP2, FRMD4A and LRP5. We observed partial confirmation as three of the eight CpGs in GFI1 replicated. These CpGs partly mediated the effect of maternal smoking on birthweight (Sobel P<0.05) in meta-analysis of GECKO and the two replication cohorts. Differential methylation of these three GFI1 CpGs explained 12-19% of the 202 g lower birthweight in smoking mothers. Functional enrichment analysis pointed towards activation of cell-mediated immunity. Conclusions: Maternal smoking during pregnancy was associated with cord blood methylation differences. We observed a potentially mediating role of methylation in the association between maternal smoking during pregnancy and birthweight of the offspring. Functional network analysis suggested a role in activating the immune system

Electric current circuits in astrophysics

Cosmic magnetic structures have in common that they are anchored in a dynamo, that an external driver converts kinetic energy into internal magnetic energy, that this magnetic energy is transported as Poynting fl ux across the magnetically dominated structure, and that the magnetic energy is released in the form of particle acceleration, heating, bulk motion, MHD waves, and radiation. The investigation of the electric current system is particularly illuminating as to the course of events and the physics involved. We demonstrate this for the radio pulsar wind, the solar flare, and terrestrial magnetic storms

Mixed marriages and transnational families in the intercultural context : a case study of African-Spanish couples in Catalonia, Spain

Premi a l'excel·lència investigadora. Àmbit de les Ciències Socials. 2008One of the consequences of international migration and the permanent settlement of immigrants in southern EU countries is the growing number of inter-country marriages and the formation of transnational families. Using both quantitative and qualitative data, this article examines patterns of endogamy and exogamy (i.e. marriage within/outside a particular group or category) among African immigrants in Catalonia, focusing on bi-national Senegalese- and Gambian-Spanish couples. Socio-demographic profiles, transnationality, the dynamics of cultural change or retention, and the formation of transcultural identities are explored. The evidence presented suggests that social-class factors are more important than cultural origins in patterns of endogamy and exogamy, in the dynamics of living together and in the bringing-up of children of mixed unions. Such a conclusion negates culturalists' explanations of endogamy and exogamy while, at the same time, emphasising the role of social actors as active subjects in these processes. I further argue that mixed couples and their offspring deal-to a greater or lesser extent-with multiple localisations and cultural backgrounds (i.e. here and there), rather than experiencing a 'clash between two cultures'. Therefore, it would be a mistake to pretend that multicultural links do not exist and that they cannot be revitalised and functional. The paper starts and ends by addressing the complexities of processes of interculturalism, resisting an interpretation of hybridity and segregation as contradictory or exclusive realities

Optical Light Curves of Supernovae

Photometry is the most easily acquired information about supernovae. The light curves constructed from regular imaging provide signatures not only for the energy input, the radiation escape, the local environment and the progenitor stars, but also for the intervening dust. They are the main tool for the use of supernovae as distance indicators through the determination of the luminosity. The light curve of SN 1987A still is the richest and longest observed example for a core-collapse supernova. Despite the peculiar nature of this object, as explosion of a blue supergiant, it displayed all the characteristics of Type II supernovae. The light curves of Type Ib/c supernovae are more homogeneous, but still display the signatures of explosions in massive stars, among them early interaction with their circumstellar material. Wrinkles in the near-uniform appearance of thermonuclear (Type Ia) supernovae have emerged during the past decade. Subtle differences have been observed especially at near-infrared wavelengths. Interestingly, the light curve shapes appear to correlate with a variety of other characteristics of these supernovae. The construction of bolometric light curves provides the most direct link to theoretical predictions and can yield sorely needed constraints for the models. First steps in this direction have been already made.Comment: To be published in:"Supernovae and Gamma Ray Bursters", Lecture Notes in Physics (http://link.springer.de/series/lnpp

Pharmacologic regimens for knee osteoarthritis prevention: can they be cost-effective?

We sought to determine the target populations and drug efficacy, toxicity, cost, and initiation age thresholds under which a pharmacologic regimen for knee osteoarthritis (OA) prevention could be cost-effective

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Characterization of excitatory amino acid receptors in the mammalian central nervous system

SIGLEAvailable from British Library Document Supply Centre-DSC:D191488 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Robust and Sensitive Nylon Hybridization Membrane Suitable for High-Throughput Robotic Arraying Applications

An important aspect of automated macroarraying is the suitability of the nylon membrane selected on which samples are to be arrayed. PerForma is a positively charged nylon membrane that has been developed specifically for automated macroarraying. Tests using fluorescent hybridization detection methods have shown that immobilized DNA amounts as low as 0.25 pg can be detected and that positive signals are obtainable after 21 stripping cycles. This report describes the improved colony growth, improved handling characteristics, increased hybridization detection sensitivity, and increased stripping and reprobing capability obtained using PerForma