Aging-dependent functional alterations of mitochondrial DNA (mtDNA) from human fibroblasts transferred into mtDNA-less cells

To investigate the role that aging-dependent accumulation of mitochondrial DNA (mtDNA) mutations plays in the senescence processes, mitochondria from fibroblasts of 21 normal human individuals between 20 weeks (fetal) and 103 years of age were introduced into human mtDNA-less (ρ0) 206 cells by cytoplast × ρ0 cell fusion, and 7-31 transformant clones were isolated from each fusion. A slight cell donor age-dependent decrease in growth rate was detected in the transformants. Using an O2 consumption rate of 1 fmol/min/cell, which was not observed in any transformant among 158 derived from individuals 20 weeks (fetal) to 37 years of age, as a cut-off to identify respiratory-deficient clones, 11 such clones were found among 198 transformants derived from individuals 39-103 years of age. Furthermore, conventional and nonparametric analysis of the respiratory rates of 356 clones revealed a very significant decrease with donor age. In other analyses, a very significant age-dependent decline in the mtDNA content of the clones was observed, without, however, any significant correlation with the decrease in O2 consumption rate in the defective transformants. These observations clearly indicate the occurrence in the fibroblast-derived transformants of two independent, age-related functional alterations of mtDNA, presumably resulting from structural damage to this genome

Stepping Stones Triple P: The theoretical basis and development of an evidence-based positive parenting program for families with a child who has a disability.

Stepping Stones Triple P is the first in a series of programs based on the Triple P – Positive Parenting Program that has been specifically designed for families who have a child with a disability. This paper presents the rationale, theoretical foundations, historical development and distinguishing features of the program. The multi-level intervention adopts a self-regulation framework in consulting with parents that involves the promotion of parental self-sufficiency, selfefficacy, self-management skills, personal agency and problem-solving skills. This paper describes the key program design features, intervention techniques, model of clinical consultation, its clinical applicability, and empirical base. The 10-session individually administered version of the program, known as Standard Stepping Stones Triple P is described and the important role of training, supervision and agency support in disseminating the program is discussed

Behavioral family intervention for children with developmental disabilities and behavioral problems

The outcomes of a randomized clinical trial of a new behavioral family intervention, Stepping Stones Triple P, for preschoolers with developmental and behavior problems are presented. Forty-eight children with developmental disabilities participated, 27 randomly allocated to an intervention group and 20 to a wait-list control group. Parents completed measures of parenting style and stress, and independent observers assessed parent-child interactions. The intervention was associated with fewer child behavior problems reported by mothers and independent observers, improved maternal and paternal parenting style, and decreased maternal stress. All effects were maintained at 6-month follow-up

Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

Extended supersymmetric sigma models in AdS_4 from projective superspace

There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We also develop a novel description of the most general N=2 supersymmetric nonlinear sigma-model in AdS_4 in terms of chiral superfields on three-dimensional N=2 flat superspace without central charge. This superspace naturally originates from a conformally flat realization for the four-dimensional N=2 AdS superspace that makes use of Poincare coordinates for AdS_4. This novel formulation allows us to uncover several interesting geometric results.Comment: 88 pages; v3: typos corrected, version published in JHE

U and Th content in the Central Apennines continental crust: a contribution to the determination of the geo-neutrinos flux at LNGS

The regional contribution to the geo-neutrino signal at Gran Sasso National Laboratory (LNGS) was determined based on a detailed geological, geochemical and geophysical study of the region. U and Th abundances of more than 50 samples representative of the main lithotypes belonging to the Mesozoic and Cenozoic sedimentary cover were analyzed. Sedimentary rocks were grouped into four main "Reservoirs" based on similar paleogeographic conditions and mineralogy. Basement rocks do not outcrop in the area. Thus U and Th in the Upper and Lower Crust of Valsugana and Ivrea-Verbano areas were analyzed. Based on geological and geophysical properties, relative abundances of the various reservoirs were calculated and used to obtain the weighted U and Th abundances for each of the three geological layers (Sedimentary Cover, Upper and Lower Crust). Using the available seismic profile as well as the stratigraphic records from a number of exploration wells, a 3D modelling was developed over an area of 2^{\circ}x2^{\circ} down to the Moho depth, for a total volume of about 1.2x10^6 km^3. This model allowed us to determine the volume of the various geological layers and eventually integrate the Th and U contents of the whole crust beneath LNGS. On this base the local contribution to the geo-neutrino flux (S) was calculated and added to the contribution given by the rest of the world, yielding a Refined Reference Model prediction for the geo-neutrino signal in the Borexino detector at LNGS: S(U) = (28.7 \pm 3.9) TNU and S(Th) = (7.5 \pm 1.0) TNU. An excess over the total flux of about 4 TNU was previously obtained by Mantovani et al. (2004) who calculated, based on general worldwide assumptions, a signal of 40.5 TNU. The considerable thickness of the sedimentary rocks, almost predominantly represented by U- and Th- poor carbonatic rocks in the area near LNGS, is responsible for this difference.Comment: 45 pages, 5 figures, 12 tables; accepted for publication in GC

Six-dimensional Supergravity and Projective Superfields

We propose a superspace formulation of N=(1,0) conformal supergravity in six dimensions. The corresponding superspace constraints are invariant under super-Weyl transformations generated by a real scalar parameter. The known variant Weyl super-multiplet is recovered by coupling the geometry to a super-3-form tensor multiplet. Isotwistor variables are introduced and used to define projective superfields. We formulate a locally supersymmetric and super-Weyl invariant action principle in projective superspace. Some families of dynamical supergravity-matter systems are presented.Comment: 39 pages; v3: some modifications in section 2; equations (2.3), (2.14b), (2.16) and (2.17) correcte

Acceptability and feasibility of peer assisted supervision and support for intervention practitioners: a Q-methodology evaluation

Evidence-based interventions often include quality improvement methods to support fidelity and improve client outcomes. Clinical supervision is promoted as an effective way of developing practitioner confidence and competence in delivery; however, supervision is often inconsistent and embedded in hierarchical line management structures that may limit the opportunity for reflective learning. The Peer Assisted Supervision and Support (PASS) supervision model uses peer relationships to promote the self-regulatory capacity of practitioners to improve intervention delivery. The aim of the present study was to assess the acceptability and feasibility of PASS amongst parenting intervention practitioners. A Q-methodology approach was used to generate data and 30 practitioners volunteered to participate in the study. Data were analyzed and interpreted using standard Q-methodology procedures and by-person factor analysis yielded three factors. There was consensus that PASS was acceptable. Participants shared the view that PASS facilitated an environment of support where negative aspects of interpersonal relationships that might develop in supervision were not evident. Two factors represented the viewpoint that PASS was also a feasible model of supervision. However, the third factor was comprised of practitioners who reported that PASS could be time consuming and difficult to fit into existing work demands. There were differences across the three factors in the extent to which practitioners considered PASS impacted on their intervention delivery. The findings highlight the importance of organizational mechanisms that support practitioner engagement in supervision

Off-shell supergravity-matter couplings in three dimensions

We develop the superspace geometry of N-extended conformal supergravity in three space-time dimensions. General off-shell supergravity-matter couplings are constructed in the cases N=1,2,3,4.Comment: 73 pages; V5: typos in eqs. (3.4b), (3.17) and (4.24) correcte