125 research outputs found
Radiographic, Biomechanical and Histological Characterization of Femoral Fracture Healing in Aged CD-1 Mice
With a gradually increasing elderly population, the treatment of geriatric patients represents
a major challenge for trauma and reconstructive surgery. Although, it is well established that aging
affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we
investigated fracture healing in young adult (3–4 months) and aged (16–18 months) CD-1 mice using
a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical
and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased
callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing
when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly
decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks
after fracture, the analysis showed no significant difference in bending stiffness between the two study
groups. Additional histological analysis showed a delayed endochondral ossification in aged animals
as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a
delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when
compared to young adult animals. However, the overall healing capacity of the fractured femora was
not affected by aging
Profiling microRNA expression in murine bone healing and non-union formation: Role of miR-140 during the early stage of bone healing
Although cellular and molecular mechanisms during the course of bone healing have been
thoroughly investigated, the regulation of gene expression by microRNA during bone regen eration is still poorly understood. We hypothesized that nonunion formation is associated
with different microRNA expression patterns and that target proteins of these microRNAs
are differently expressed in callus tissue of nonunions compared to physiologically healing
bones. In a well-established femoral osteotomy model in CD-1 mice osteotomies were
induced which result either in healing or in nonunion formation. MicroRNA and target protein
expression was evaluated by microarray, quantitative real-time polymerase chain reaction
(qrt-PCR) and Western blot. Microarray analyses demonstrated 44 microRNAs to be rele vant for nonunion formation compared to physiological bone healing. In nonunions qrt-PCR
could validate a higher expression of microRNA-140-3p and microRNA-140-5p. This was
associated with a reduced expression of Dnpep and stromal cell-derived factor (SDF)-1α,
which are both known to be target proteins of microRNA-140 and also to be involved in the
process of bone healing. These data suggest that an increased expression of microRNA 140-3p and microRNA-140-5p markedly contributes to the development of nonunions, most
probably by affecting bone morphogenetic protein (BMP)-2 function during the early stage
of healing due to a reduced SDF-1α expression
Diclofenac, a NSAID, delays fracture healing in aged mice
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic
medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture
healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and
proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of
diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n
= 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicletreated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed
by means of X-ray, biomechanics, micro computed tomography (μCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after
fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further
histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus
remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays
fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as
osteoclast activity and callus remodeling
The Feel-Good Effect at Mega Sport Events - Recommendations for Public and Private Administration Informed by the Experience of the FIFA World Cup 2006
Periodic density functional theory calculations of bulk and the (010) surface of goethite
<p>Abstract</p> <p>Background</p> <p>Goethite is a common and reactive mineral in the environment. The transport of contaminants and anaerobic respiration of microbes are significantly affected by adsorption and reduction reactions involving goethite. An understanding of the mineral-water interface of goethite is critical for determining the molecular-scale mechanisms of adsorption and reduction reactions. In this study, periodic density functional theory (DFT) calculations were performed on the mineral goethite and its (010) surface, using the Vienna <it>Ab Initio </it>Simulation Package (VASP).</p> <p>Results</p> <p>Calculations of the bulk mineral structure accurately reproduced the observed crystal structure and vibrational frequencies, suggesting that this computational methodology was suitable for modeling the goethite-water interface. Energy-minimized structures of bare, hydrated (one H<sub>2</sub>O layer) and solvated (three H<sub>2</sub>O layers) (010) surfaces were calculated for 1 × 1 and 3 × 3 unit cell slabs. A good correlation between the calculated and observed vibrational frequencies was found for the 1 × 1 solvated surface. However, differences between the 1 × 1 and 3 × 3 slab calculations indicated that larger models may be necessary to simulate the relaxation of water at the interface. Comparison of two hydrated surfaces with molecularly and dissociatively adsorbed H<sub>2</sub>O showed a significantly lower potential energy for the former.</p> <p>Conclusion</p> <p>Surface Fe-O and (Fe)O-H bond lengths are reported that may be useful in surface complexation models (SCM) of the goethite (010) surface. These bond lengths were found to change significantly as a function of solvation (i.e., addition of two extra H<sub>2</sub>O layers above the surface), indicating that this parameter should be carefully considered in future SCM studies of metal oxide-water interfaces.</p
The Serotonin 5-HT7Dro Receptor Is Expressed in the Brain of Drosophila, and Is Essential for Normal Courtship and Mating
The 5-HT7 receptor remains one of the less well characterized
serotonin receptors. Although it has been demonstrated to be involved in the
regulation of mood, sleep, and circadian rhythms, as well as relaxation of
vascular smooth muscles in mammals, the precise mechanisms underlying these
functions remain largely unknown. The fruit fly, Drosophila
melanogaster, is an attractive model organism to study
neuropharmacological, molecular, and behavioral processes that are largely
conserved with mammals. Drosophila express a homolog of the mammalian
5-HT7 receptor, as well as homologs for the mammalian
5-HT1A, and 5-HT2, receptors. Each fly receptor
couples to the same effector pathway as their mammalian counterpart and have
been demonstrated to mediate similar behavioral responses. Here, we report on
the expression and function of the 5-HT7Dro receptor in Drosophila.
In the larval central nervous system, expression is detected postsynaptically in
discreet cells and neuronal circuits. In the adult brain there is strong
expression in all large-field R neurons that innervate the ellipsoid body, as
well as in a small group of cells that cluster with the PDF-positive LNvs
neurons that mediate circadian activity. Following both pharmacological and
genetic approaches, we have found that 5-HT7Dro activity is essential
for normal courtship and mating behaviors in the fly, where it appears to
mediate levels of interest in both males and females. This is the first reported
evidence of direct involvement of a particular serotonin receptor subtype in
courtship and mating in the fly
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The Drosophila melanogaster Genetic Reference Panel
A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype–phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype–phenotype mapping using the power of Drosophila genetics
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