State-of-the-art report childlessness in Europe

In the last decades, European societies have experienced changes in the postponement of the age of having a first child, shrinking family size, and increased (in)voluntary childlessness. This report provides a review of the state-of-the-art research in relation to one of the central research goals of Working Package 4: to examine the rise, determinants and societal consequences of childlessness by different perspectives. The report provides an overview of the central macro-level determinants of childlessness among women and men firstly from a quantitative perspective examining trends, relevant determinants and measures. We will then outline the central micro-level determinants of childlessness among women, men and couples by examining core characteristics of childless individuals such as higher education or marital disruption. We then turn to an overview of anthropological and qualitative examinations of the determinants of childlessness and the psychological, social and socio-political consequences of childlessness. A reflection on potential data sources to study childlessness and a discussion on research gaps are offered in the concluding chapters

Role of Interaction and Nucleoside Diphosphate Kinase B in Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Function by cAMP-Dependent Protein Kinase A

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate kinase B (NDPK-B, NM23-H2) forms a functional complex with CFTR. In airway epithelia forskolin/IBMX significantly increases NDPK-B co-localisation with CFTR whereas PKA inhibitors attenuate complex formation. Furthermore, an NDPK-B derived peptide (but not its NDPK-A equivalent) disrupts the NDPK-B/CFTR complex in vitro (19-mers comprising amino acids 36-54 from NDPK-B or NDPK-A). Overlay (Far-Western) and Surface Plasmon Resonance (SPR) analysis both demonstrate that NDPK-B binds CFTR within its first nucleotide binding domain (NBD1, CFTR amino acids 351-727). Analysis of chloride currents reflective of CFTR or outwardly rectifying chloride channels (ORCC, DIDS-sensitive) showed that the 19-mer NDPK-B peptide (but not its NDPK-A equivalent) reduced both chloride conductances. Additionally, the NDPK-B (but not NDPK-A) peptide also attenuated acetylcholine-induced intestinal short circuit currents. In silico analysis of the NBD1/NDPK-B complex reveals an extended interaction surface between the two proteins. This binding zone is also target of the 19-mer NDPK-B peptide, thus confirming its capability to disrupt NDPK-B/CFTR complex. We propose that NDPK-B forms part of the complex that controls chloride currents in epithelia

Validity and reliability of fitbit flex for step count, moderate to vigorous physical activity and activity energy expenditure

Objectives: To examine the validity and reliability of the Fitbit Flex against direct observation for measuring steps in the laboratory and against the Actigraph for step counts in free-living conditions and for moderate-to-vigorous physical activity (MVPA) and activity energy expenditure (AEE) overall. Methods: Twenty-five adults (12 females, 13 males) wore a Fitbit Flex and an Actigraph GT3X+ during a laboratory based protocol (including walking, incline walking, running and stepping) and free-living conditions during a single day period to examine measurement of steps, AEE and MVPA. Twenty-four of the participants attended a second session using the same protocol. Results: Intraclass correlations (ICC) for test-retest reliability of the Fitbit Flex were strong for walking (ICC = 0.57), moderate for stair stepping (ICC = 0.34), and weak for incline walking (ICC = 0.22) and jogging (ICC = 0.26). The Fitbit significantly undercounted walking steps in the laboratory (absolute proportional difference: 21.2%, 95%CI 13.0-29.4%), but it was more accurate, despite slightly over counting, for both jogging (6.4%, 95%CI 3.7-9.0%) and stair stepping (15.5%, 95%CI 10.1-20.9%). The Fitbit had higher coefficients of variation (Cv) for step counts compared to direct observation and the Actigraph. In free-living conditions, the average MVPA minutes were lower in the Fitbit (35.4 minutes) compared to the Actigraph (54.6 minutes), but AEE was greater from the Fitbit (808.1 calories) versus the Actigraph (538.9 calories). The coefficients of variation were similar for AEE for the Actigraph (Cv = 36.0) and Fitbit (Cv = 35.0), but lower in the Actigraph (Cv = 25.5) for MVPA against the Fitbit (Cv = 32.7). Conclusion: The Fitbit Flex has moderate validity for measuring physical activity relative to direct observation and the Actigraph. Test-rest reliability of the Fitbit was dependant on activity type and had greater variation between sessions compared to the Actigraph. Physical activity surveillance studies using the Fitbit Flex should consider the potential effect of measurement reactivity and undercounting of steps

The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension

Human WIPI β-propellers function as PI3P effectors in autophagy, with WIPI4 and WIPI3 being able to link autophagy control by AMPK and TORC1 to the formation of autophagosomes. WIPI1, instead, assists WIPI2 in efficiently recruiting the ATG16L1 complex at the nascent autophagosome, which in turn promotes lipidation of LC3/GABARAP and autophagosome maturation. However, the specific role of WIPI1 and its regulation are unknown. Here, we discovered the ABL-ERK-MYC signalling axis controlling WIPI1. As a result of this signalling, MYC binds to the WIPI1 promoter and represses WIPI1 gene expression. When ABL-ERK-MYC signalling is counteracted, increased WIPI1 gene expression enhances the formation of autophagic membranes capable of migrating through tunnelling nanotubes to neighbouring cells with low autophagic activity. ABL-regulated WIPI1 function is relevant to lifespan control, as ABL deficiency in C. elegans increased gene expression of the WIPI1 orthologue ATG-18 and prolonged lifespan in a manner dependent on ATG-18. We propose that WIPI1 acts as an enhancer of autophagy that is physiologically relevant for regulating the level of autophagic activity over the lifespan

Salmonella Strains Isolated from Galápagos Iguanas Show Spatial Structuring of Serovar and Genomic Diversity

It is thought that dispersal limitation primarily structures host-associated bacterial populations because host distributions inherently limit transmission opportunities. However, enteric bacteria may disperse great distances during food-borne outbreaks. It is unclear if such rapid long-distance dispersal events happen regularly in natural systems or if these events represent an anthropogenic exception. We characterized Salmonella enterica isolates from the feces of free-living Galápagos land and marine iguanas from five sites on four islands using serotyping and genomic fingerprinting. Each site hosted unique and nearly exclusive serovar assemblages. Genomic fingerprint analysis offered a more complex model of S. enterica biogeography, with evidence of both unique strain pools and of spatial population structuring along a geographic gradient. These findings suggest that even relatively generalist enteric bacteria may be strongly dispersal limited in a natural system with strong barriers, such as oceanic divides. Yet, these differing results seen on two typing methods also suggests that genomic variation is less dispersal limited, allowing for different ecological processes to shape biogeographical patterns of the core and flexible portions of this bacterial species' genome

Epigenetic mechanisms in virus-induced tumorigenesis

About 15–20% of human cancers worldwide have viral etiology. Emerging data clearly indicate that several human DNA and RNA viruses, such as human papillomavirus, Epstein–Barr virus, Kaposi’s sarcoma-associated herpesvirus, hepatitis B virus, hepatitis C virus, and human T-cell lymphotropic virus, contribute to cancer development. Human tumor-associated viruses have evolved multiple molecular mechanisms to disrupt specific cellular pathways to facilitate aberrant replication. Although oncogenic viruses belong to different families, their strategies in human cancer development show many similarities and involve viral-encoded oncoproteins targeting the key cellular proteins that regulate cell growth. Recent studies show that virus and host interactions also occur at the epigenetic level. In this review, we summarize the published information related to the interactions between viral proteins and epigenetic machinery which lead to alterations in the epigenetic landscape of the cell contributing to carcinogenesis