Family policy and child well-being: The case of Montenegro in the European perspective

Family policies and family support measures have been identified as having major implications for child well-being, particularly through their role in influencing parental and family resources, circumstances and behaviour. The official approach to family policies focuses on opportunities for families to balance their work and family duties and care for their children. This paper analyses the type of policies available in Montenegro compared to the European Union. Potentially, Montenegro will become an EU member state, thus it is important to take a look at Montenegrin practice, as children should have equal life chances and protection of their well-being. Having a solid legal framework per se does not necessarily result in significant positive outcomes, and this paper analyses whether children in Montenegro have the same opportunities for development, in the context of family policies, as their counterparts in the rest of Europe. The focus of the paper will be on the criteria that define family rights and obligations, eligibility, availability and use of family policies in Montenegro. Based on the specific measures and datasets examined, the analysis considers the degree to which a period of family policy investment in Montenegro has been accompanied by improvements in child well-being and family resources, and undertakes comparisons in these regards with EU-wide family policy and child well-being trends. The paper uses a welfare state theoretical approach, with the focus on social investment and relevant data on children’s well-being obtained from the Eurostat, the OECD and the official national statistics

Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.

Detection of cytosolic DNA is a central element of the innate immunity system against viral infection. The Ku heterodimer, a component of the NHEJ pathway of DNA repair in the nucleus, functions as DNA sensor that detects dsDNA of viruses that replicate in the cytoplasm. Vaccinia virus expresses two proteins, C4 and C16, that inactivate DNA sensing and enhance virulence. The structural basis for this is unknown. Here we determine the structure of the C16 - Ku complex using cryoEM. Ku binds dsDNA by a preformed ring but C16 sterically blocks this access route, abrogating binding to a dsDNA end and its insertion into DNA-PK, thereby averting signalling into the downstream innate immunity system. C4 replicates these activities using a domain with 54% identity to C16. Our results reveal how vaccinia virus subverts the capacity of Ku to recognize viral DNA

Collective effects in spin-crossover chains with exchange interaction

The collective properties of spin-crossover chains are studied. Spin-crossover compounds contain ions with a low-spin ground state and low lying high-spin excited states and are of interest for molecular memory applications. Some of them naturally form one-dimensional chains. Elastic interaction and Ising exchange interaction are taken into account. The transfer-matrix approach is used to calculate the partition function, the fraction of ions in the high-spin state, the magnetization, susceptibility, etc., exactly. The high-spin-low-spin degree of freedom leads to collective effects not present in simple spin chains. The ground-state phase diagram is mapped out and compared to the case with Heisenberg exchange interaction. The various phases give rise to characteristic behavior at nonzero temperatures, including sharp crossovers between low- and high-temperature regimes. A Curie-Weiss law for the susceptibility is derived and the paramagnetic Curie temperature is calculated. Possible experiments to determine the exchange coupling are discussed.Comment: 9 pages, 13 color figures, published versio

Spin dynamics in molecular ring nanomagnets: Significant effect of acoustic phonons and magnetic anisotropies

The nuclear spin-lattice relaxation rate 1/T_1_ is calculated for magnetic ring clusters by fully diagonalizing their microscopic spin Hamiltonians. Whether the nearest-neighbor exchange interaction J is ferromagnetic or antiferromagnetic, 1/T_1_ versus temperature T in ring nanomagnets may be peaked at around k_B_T=|J| provided the lifetime broadening of discrete energy levels is in proportion to T^3^. Experimental findings for ferromagnetic and antiferromagnetic Cu^II^ rings are reproduced with crucial contributions of magnetic anisotropies as well as acoustic phonons.Comment: 5 pages with 5 figures embedded, to be published in J. Phys. Soc. Jpn. 75, No. 10 (2006

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses

Validation platform implementation description - D5.2

This deliverable describes different test-beds for the validation of the architecture, algorithms and protocols for the operator governed opportunistic networking as defined in the OneFIT Project. Further on, this deliverable provides a description of the implementation of the OneFIT cognitive management systems CSCI and CMON as well as the C4MS protocol. Also, implementation of the blocks supporting the OneFIT system (JRRM, CCM, DSONPM, and DSM) is described. This document also describes the implementation of the OneFIT scenarios for opportunistic coverage extension, opportunistic capacity extension, infrastructure supported ad-hoc networking and device-to-device communication as well as opportunistic resource aggregation in the backhaul network

Repair at Single Targeted DNA Double-Strand Breaks in Pluripotent and Differentiated Human Cells

Differences in ex vivo cell culture conditions can drastically affect stem cell physiology. We sought to establish an assay for measuring the effects of chemical, environmental, and genetic manipulations on the precision of repair at a single DNA double-strand break (DSB) in pluripotent and somatic human cells. DSBs in mammalian cells are primarily repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). For the most part, previous studies of DSB repair in human cells have utilized nonspecific clastogens like ionizing radiation, which are highly nonphysiologic, or assayed repair at randomly integrated reporters. Measuring repair after random integration is potentially confounded by locus-specific effects on the efficiency and precision of repair. We show that the frequency of HR at a single DSB differs up to 20-fold between otherwise isogenic human embryonic stem cells (hESCs) based on the site of the DSB within the genome. To overcome locus-specific effects on DSB repair, we used zinc finger nucleases to efficiently target a DSB repair reporter to a safe-harbor locus in hESCs and a panel of somatic human cell lines. We demonstrate that repair at a targeted DSB is highly precise in hESCs, compared to either the somatic human cells or murine embryonic stem cells. Differentiation of hESCs harboring the targeted reporter into astrocytes reduces both the efficiency and precision of repair. Thus, the phenotype of repair at a single DSB can differ based on either the site of damage within the genome or the stage of cellular differentiation. Our approach to single DSB analysis has broad utility for defining the effects of genetic and environmental modifications on repair precision in pluripotent cells and their differentiated progeny

Whole genome sequence analysis of the TALLYHO/Jng mouse

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes. Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing runs. Genome-wide, we found approximately 4.31 million homozygous single nucleotide polymorphisms (SNPs) and 1.10 million homozygous small insertions and deletions (indels) of which 98,899 SNPs and 163,720 indels were unique to the TH strain compared to 28 previously sequenced inbred mouse strains. In order to identify potentially clinically-relevant genes, we intersected our list of SNP and indel variants with human orthologous genes in which variants were associated in GWAS studies with obesity, diabetes, and metabolic syndrome, and with genes previously shown to confer a monogenic obesity phenotype in humans, and found several candidate variants that could be functionally tested using TH mice. Further, we filtered our list of variants to those occurring in an obesity quantitative trait locus, tabw2, identified in TH mice and found a missense polymorphism in the Cidec gene and characterized this variant’s effect on protein function. Conclusions: We generated a complete catalog of variants in TH mice using the data from whole genome sequencing. Our findings will facilitate the identification of causal variants that underlie metabolic diseases in TH mice and will enable identification of candidate susceptibility genes for complex human obesity and type 2 diabetes

Results analysis and validation - D5.3

This deliverable describes the validation processes followed to assess the performance of the algorithms and protocols for the operator governed opportunistic networking as defined in the OneFIT Project. Therefore, this document includes the description of the set-up of the different validation platforms, the design of the test plans for each one of them, and the analysis of the results obtained from the tests. A per-scenario approach rather than a per-platform approach has been followed, so an additional analysis has been performed, gathering the results related to each scenario, in order to validate the premises stated to each one of them. The OneFIT concept has been therefore validated for all foreseen business scenarios