516 research outputs found
Family functioning guidelines for the care of people with spina bifida
Research supports a resilience-disruption model of family functioning in families with a child with spina bifida. Guidelines are warranted to both minimize disruption to the family system and maximize family resilience and adaptation to multiple spina bifida-related and normative stressors. This article discusses the spina bifida family functioning guidelines from the 2018 Spina Bifida Association’s Fourth Edition of the Guidelines for the Care of People with Spina Bifida, and reviews evidence-based directions with the intention of helping individuals with spina bifida achieve optimal mental health throughout their lifespan. Guidelines address clinical questions pertaining to the impact of having a child with spina bifida on family functioning, resilience and vulnerability factors, parenting behaviors that may facilitate adaptive child outcomes, and appropriate interventions or approaches to promote family functioning. Gaps in the research and future directions are discussed
The presence of extracellular matrix degrading metalloproteinases during fetal development of the intervertebral disc
Matrix metalloproteinases (MMPs) regulate connective tissue architecture and cell migration through extracellular matrix (ECM) degradation and are associated with both physiological and pathological processes. Although they are known to play a role in skeletal development, little is known about the role of MMPs in intervertebral disc (IVD) development. Sixteen fetal human lumbar spine segments, obtained at autopsy, were compared with five normal, non-fetal L4–L5 IVDs. Intensity and/or localization of immunohistochemical staining for MMP-1, -2, -3 and -14 were evaluated by three independent observers. MMP-2 production and activation was quantified by gelatin zymography. MMP-1 and -14 were abundantly present in the nucleus pulposus (NP) and notochordal (NC) cells of the fetal IVDs. In non-fetal IVDs, MMP-1 and -14 staining was significantly less intense (p = 0.001 and p < 0.001, respectively). MMP-3 was found in almost the entire IVD with no significant difference from non-fetal IVDs. MMP-2 staining in the NC and NP cells of the fetal IVD was moderate, but weak in the non-fetal IVD. Gelatin zymography showed a negative correlation of age with MMP-2 activity (p < 0.001). MMP-14 immunostaining correlated positively with MMP-2 activity (p = 0.001). For the first time, the presence of MMP-1, -2, -3 and -14 in the fetal human IVD is shown and the high levels of MMP-1, -2 and -14 suggest a role in the development of the IVD. In particular, the gradual decrease in MMP-2 activation during gestation pinpoints this enzyme as key player in fetal development, possibly through activation by MMP-1 and -14
Altered Bone Mechanics, Architecture and Composition in the Skeleton of TIMP-3-Deficient Mice
The r-Process Pattern of a Bright, Highly r-Process-Enhanced, Metal-Poor Halo Star at [Fe/H] ~ -2
A high-resolution spectroscopic analysis is presented for a new highly
r-process-enhanced ([Eu/Fe] = 1.27, [Ba/Eu] = -0.65), very metal-poor ([Fe/H] =
-2.09), retrograde halo star, RAVE J153830.9-180424, discovered as part of the
R-Process Alliance survey. At V = 10.86, this is the brightest and most
metal-rich r-II star known in the Milky Way halo. Its brightness enables
high-S/N detections of a wide variety of chemical species that are mostly
created by the r-process, including some infrequently detected lines from
elements like Ru, Pd, Ag, Tm, Yb, Lu, Hf, and Th, with upper limits on Pb and
U. This is the most complete r-process census in a very metal-poor r-II star.
J1538-1804 shows no signs of s-process contamination, based on its low [Ba/Eu]
and [Pb/Fe]. As with many other r-process-enhanced stars, J1538-1804's
r-process pattern matches that of the Sun for elements between the first,
second, and third peaks, and does not exhibit an actinide boost.
Cosmo-chronometric age-dating reveals the r-process material to be quite old.
This robust main r-process pattern is a necessary constraint for r-process
formation scenarios (of particular interest in light of the recent neutron star
merger, GW 170817), and has important consequences for the origins of r-II
stars. Additional r-I and r-II stars will be reported by the R-Process Alliance
in the near future.Comment: Accepted for publication in ApJ letter
uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion
The uptake and lysosomal degradation of collagen by fibroblasts constitute a major pathway in the turnover of connective tissue. However, the molecular mechanisms governing this pathway are poorly understood. Here, we show that the urokinase plasminogen activator receptor–associated protein (uPARAP)/Endo180, a novel mesenchymally expressed member of the macrophage mannose receptor family of endocytic receptors, is a key player in this process. Fibroblasts from mice with a targeted deletion in the uPARAP/Endo180 gene displayed a near to complete abrogation of collagen endocytosis. Furthermore, these cells had diminished initial adhesion to a range of different collagens, as well as impaired migration on fibrillar collagen. These studies identify a central function of uPARAP/Endo180 in cellular collagen interactions
Fibroblast-derived MT1-MMP promotes tumor progression in vitro and in vivo
BACKGROUND: Identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. Multiple matrix metalloproteases (MMPs) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas (HNSCCs), but the relative importance of these enzymes and the cell source is the subject of controversy. METHODS: The invasive potential of HNSCC tumor cells were assessed in vitro atop type I collagen gels in coculture with wild-type (WT), MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts. A floor of mouth mouse model of HNSCC was used to assess in vivo growth after co-injection of FaDu tumor cells with MMP null fibroblasts. RESULTS: Here we report changes in tumor phenotype when FaDu HNSCCs cells are cocultured with WT, MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts in vitro and in vivo. WT, MMP-2 null and MMP-9 null fibroblasts, but not MT1-MMP null fibroblasts, spontaneously invaded into type I collagen gels. WT fibroblasts stimulated FaDu tumor cell invasion in coculture. This invasive phenotype was unaffected by combination with MMP-9 null fibroblasts, reduced with MMP-2 null fibroblasts (50%) and abrogated in MT1-MMP null fibroblasts. Co-injection of FaDu tumor cells with fibroblasts in an orthotopic oral cavity SCID mouse model demonstrated a reduction of tumor volume using MMP-9 and MMP-2 null fibroblasts (48% and 49%, respectively) compared to WT fibroblasts. Consistent with in vitro studies, MT1-MMP null fibroblasts when co-injected with FaDu cells resulted in a 90% reduction in tumor volume compared to FaDu cells injected with WT fibroblasts. CONCLUSION: These data suggest a role for fibroblast-derived MMP-2 and MT1-MMP in HNSCC tumor invasion in vitro and tumor growth in vivo
The R-Process Alliance: The Peculiar Chemical Abundance Pattern of RAVE J183013.5-455510
We report on the spectroscopic analysis of RAVE J183013.5-455510, an
extremely metal-poor star, highly enhanced in CNO, and with discernible
contributions from the rapid neutron-capture process. There is no evidence of
binarity for this object. At [Fe/H]=-3.57, this is one of the lowest
metallicity stars currently observed, with 18 measured abundances of
neutron-capture elements. The presence of Ba, La, and Ce abundances above the
Solar System r-process predictions suggest that there must have been a
non-standard source of r-process elements operating at such low metallicities.
One plausible explanation is that this enhancement originates from material
ejected at unusually fast velocities in a neutron star merger event. We also
explore the possibility that the neutron-capture elements were produced during
the evolution and explosion of a rotating massive star. In addition, based on
comparisons with yields from zero-metallicity faint supernova, we speculate
that RAVE J1830-4555 was formed from a gas cloud pre-enriched by both
progenitor types. From analysis based on Gaia DR2 measurements, we show that
this star has orbital properties similar to the Galactic metal-weak thick-disk
stellar population.Comment: Accepted for publication in Ap
Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo
Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages
Reciprocal Associations between Parenting Challenges and Parents' Personality Development in Young and Middle Adulthood
Having children affects many aspects of people's lives. However, it remains unclear to what degree the challenges that come along with having children are associated with parents' personality development. We addressed this question in two studies by investigating the relationship between parenting challenges and personality development in mothers of newborns (Study 1, N = 556) and the reciprocal associations between (mastering) parenting challenges and personality development in parents of adolescents (Study 2, N = 548 mothers and 460 fathers). In Study 1, we found the stress of having a newborn baby to be associated with declines in maternal Agreeableness, Conscientiousness, and Emotional Stability. Parenting challenges were also related to personality development in parents of adolescent children in Study 2, with parent–child conflict being reciprocally associated with decreases in Conscientiousness and Emotional Stability. Mastering parenting challenges in the form of high parenting self-efficacy, on the other hand, was found to be associated with increases in Agreeableness, Conscientiousness, and Emotional Stability, and vice versa. In sum, our results suggest that mastering the challenges associated with the social role of parenthood is one of the mechanisms underlying personality development in young and middle adulthood
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Parent-child interactions and adolescent anxiety: a systematic review
Parental behaviours have been implicated in the development and maintenance of anxiety in children and young people; however the degree to which findings apply to adolescents specifically remains unclear. We conducted a systematic review of studies examining the evidence for an association between parental behaviours and adolescent anxiety. Twenty two studies were identified. The results of this systematic review provide fairly consistent preliminary evidence for an association between anxiety and perceived parental control and anxious rearing in adolescence. The findings relating to an association between adolescent anxiety and perceived parental rejection and lack of warmth are somewhat less consistent. Methodological shortcomings in the studies mean that these results should be interpreted with caution. Future research should be conducted using observational and experimental design with adolescents from referred, clinical populations to help identify the critical parental processes and clarify the direction of effects
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