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

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

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

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

Role of Matrix Metalloproteinase 13 in Both Endochondral and Intramembranous Ossification during Skeletal Regeneration

Extracellular matrix (ECM) remodeling is important during bone development and repair. Because matrix metalloproteinase 13 (MMP13, collagenase-3) plays a role in long bone development, we have examined its role during adult skeletal repair. In this study we find that MMP13 is expressed by hypertrophic chondrocytes and osteoblasts in the fracture callus. We demonstrate that MMP13 is required for proper resorption of hypertrophic cartilage and for normal bone remodeling during non-stabilized fracture healing, which occurs via endochondral ossification. However, no difference in callus strength was detected in the absence of MMP13. Transplant of wild-type bone marrow, which reconstitutes cells only of the hematopoietic lineage, did not rescue the endochondral repair defect, indicating that impaired healing in Mmp13−/− mice is intrinsic to cartilage and bone. Mmp13−/− mice also exhibited altered bone remodeling during healing of stabilized fractures and cortical defects via intramembranous ossification. This indicates that the bone phenotype occurs independently from the cartilage phenotype. Taken together, our findings demonstrate that MMP13 is involved in normal remodeling of bone and cartilage during adult skeletal repair, and that MMP13 may act directly in the initial stages of ECM degradation in these tissues prior to invasion of blood vessels and osteoclasts

Informant discrepancies in assessing child dysfunction relate to dysfunction within mother-child interactions.

We examined whether mother-child discrepancies in perceived child behavior problems relate to dysfunctional interactions between mother and child and stress in the mother. Participants included 239 children (6–16 years old; 58 girls, 181 boys) referred for oppositional, aggressive, and antisocial behavior, and their mothers. Mother-child discrepancies in perceived child behavior problems were related to mother-child conflict. Moreover, maternal stress mediated this relationship. The findings suggest that discrepancies among mother and child evaluations of child functioning are not merely reflections of different perspectives or artifacts of the assessment process, but can form components of conceptual models that can be developed and tested to examine the interrelations among critical domains of child, parent, and family functioning.This work was supported, in part, by a grant from the National Institute of Mental Health (MH67540) awarded to the first author and by grants from the Leon Lowenstein Foundation, the William T. Grant Foundation (98-1872-98), and the National Institute of Mental Health (MH59029) awarded to the second author

Space Telescope and Optical Reverberation Mapping Project. VII. Understanding the Ultraviolet Anomaly in NGC 5548 with X-Ray Spectroscopy

During the Space Telescope and Optical Reverberation Mapping Project observations of NGC 5548, the continuum and emission-line variability became decorrelated during the second half of the six-month-long observing campaign. Here we present Swift and Chandra X-ray spectra of NGC 5548 obtained as part of the campaign. The Swift spectra show that excess flux (relative to a power-law continuum) in the soft X-ray band appears before the start of the anomalous emission-line behavior, peaks during the period of the anomaly, and then declines. This is a model-independent result suggesting that the soft excess is related to the anomaly. We divide the Swift data into on- and off-anomaly spectra to characterize the soft excess via spectral fitting. The cause of the spectral differences is likely due to a change in the intrinsic spectrum rather than to variable obscuration or partial covering. The Chandra spectra have lower signal-to-noise ratios, but are consistent with the Swift data. Our preferred model of the soft excess is emission from an optically thick, warm Comptonizing corona, the effective optical depth of which increases during the anomaly. This model simultaneously explains all three observations: the UV emission-line flux decrease, the soft-excess increase, and the emission-line anomaly