The Kepler mission has recently announced the discovery of Kepler-10 b, the smallest exoplanet discovered to date and the first rocky planet found by the spacecraft. A second, 45 day period ...transit-like signal present in the photometry from the first eight months of data could not be confirmed as being caused by a planet at the time of that announcement. Here we apply the light curve modeling technique known as BLENDER to explore the possibility that the signal might be due to an astrophysical false positive (blend). To aid in this analysis we report the observation of two transits with the Spitzer Space Telescope at 4.5 Delta *mm. When combined, they yield a transit depth of 344 ? 85 ppm that is consistent with the depth in the Kepler passband (376 ? 9 ppm, ignoring limb darkening), which rules out blends with an eclipsing binary of a significantly different color than the target. Using these observations along with other constraints from high-resolution imaging and spectroscopy, we are able to exclude the vast majority of possible false positives. We assess the likelihood of the remaining blends, and arrive conservatively at a false alarm rate of 1.6 X 10--5 that is small enough to validate the candidate as a planet (designated Kepler-10 c) with a very high level of confidence. The radius of this object is measured to be Rp = 2.227+0.052 --0.057 R {circled plus} (in which the error includes the uncertainty in the stellar properties), but currently available radial-velocity measurements only place an upper limit on its mass of about 20 M {circled plus}. Kepler-10 c represents another example (with Kepler-9 d and Kepler-11 g) of statistical 'validation' of a transiting exoplanet, as opposed to the usual 'confirmation' that can take place when the Doppler signal is detected or transit timing variations are measured. It is anticipated that many of Kepler's smaller candidates will receive a similar treatment since dynamical confirmation may be difficult or impractical with the sensitivity of current instrumentation.
Genetics of aging bone Adams, Douglas J.; Rowe, David W.; Ackert-Bicknell, Cheryl L.
Mammalian Genome,
08/2016, Letnik:
27, Številka:
7-8
Journal Article, Book Review
Recenzirano
Odprti dostop
With aging, the skeleton experiences a number of changes, which include reductions in mass and changes in matrix composition, leading to fragility and ultimately an increase of fracture risk. A ...number of aspects of bone physiology are controlled by genetic factors, including peak bone mass, bone shape, and composition; however, forward genetic studies in humans have largely concentrated on clinically available measures such as bone mineral density (BMD). Forward genetic studies in rodents have also heavily focused on BMD; however, investigations of direct measures of bone strength, size, and shape have also been conducted. Overwhelmingly, these studies of the genetics of bone strength have identified loci that modulate strength via influencing bone size, and may not impact the matrix material properties of bone. Many of the rodent forward genetic studies lacked sufficient mapping resolution for candidate gene identification; however, newer studies using genetic mapping populations such as Advanced Intercrosses and the Collaborative Cross appear to have overcome this issue and show promise for future studies. The majority of the genetic mapping studies conducted to date have focused on younger animals and thus an understanding of the genetic control of age-related bone loss represents a key gap in knowledge.
Transition education should be grounded in quality research. To do so, educators need information on which practices are effective for teaching students with disabilities transition-related skills. ...The purpose of this systematic literature review was to identify evidence-based and research-based practices in secondary special education and transition for students with disabilities. This systematic review resulted in the identification of nine secondary transition evidence-based practices and 22 research-based practices across more than 45 different transition-related skills. The range of effects for each of the secondary transition evidence-based and research-based practices identified are also included. Limitations and implications for future research, policy, and practice are discussed.
In adult mammals, the bone marrow microenvironment is defined by close interactions between cells derived from mesenchymal progenitors and cells derived from hematopoietic progenitors. The influence ...that one population of cells has over the other has been a matter of intense study since it was established that hematopoietic stem cells (HSCs) require support of stromal elements to engraft, self‐renew, and progress towards lineage commitment. Within the stromal components, cells of the osteoblastic lineage have the ability to interact with HSCs, and it has been proposed that they could be one of the main cell types responsible for the generation and maintenance of hematopoietic niches. Possible molecular mechanisms involved in the interaction between osteoblastic and hematopoietic cells have been described. However, understanding the relative importance of each one of them, their production by defined cells, and their kinetics of appearance have been limited by the lack of in vivo models allowing the physical and/or temporal dissection of the components of the osteoblastic lineage. Here, we provide a summary of the evidence that have established the importance of osteoblasts in hematopoiesis, and we propose new experimental strategies that could help to define the nature of these interactions.
Human and mouse genetic and in vitro evidence has shown that canonical Wnt signaling promotes bone formation, but we found that mice lacking the canonical Wnt antagonist Dickkopf2 (Dkk2) were ...osteopenic. We reaffirmed the finding that canonical Wnt signaling stimulates osteogenesis, including the differentiation from preosteoblasts to osteoblasts, in cultured osteoblast differentiation models, but we also found that canonical Wnts upregulated the expression of Dkk2 in osteoblasts. Although exogenous overexpression of Dkk before the expression of endogenous canonical Wnt (Wnt7b) suppressed osteogenesis in cultures, its expression after peak Wnt7b expression induced a phenotype resembling terminal osteoblast differentiation leading to mineralization. In addition, osteoblasts from Dkk2-null mice were poorly mineralized upon osteogenic induction in cultures, and Dkk2 deficiency led to attenuation of the expression of osteogenic markers, which could be partially reversed by exogenous expression of Dkk2. Taken together with the finding that Dkk2-null mice have increased numbers of osteoids, these data indicate that Dkk2 has a role in late stages of osteoblast differentiation into mineralized matrices. Because expression of another Wnt antagonist, FRP3, differs from Dkk2 expression in rescuing Dkk2 deficiency and regulating osteoblast differentiation, the effects of Dkk2 on terminal osteoblast differentiation may not be entirely mediated by its Wnt signaling antagonistic activity.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have ...been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair.
Clinically relevant human induced pluripotent stem cell (hiPSC) derivatives require efficient protocols to differentiate hiPSCs into specific lineages. Here we developed a fully defined xeno-free ...strategy to direct hiPSCs toward osteoblasts within 21 days. The strategy successfully achieved the osteogenic induction of four independently derived hiPSC lines by a sequential use of combinations of small-molecule inducers. The induction first generated mesodermal cells, which subsequently recapitulated the developmental expression pattern of major osteoblast genes and proteins. Importantly, Col2.3-Cherry hiPSCs subjected to this strategy strongly expressed the cherry fluorescence that has been observed in bone-forming osteoblasts in vivo. Moreover, the protocol combined with a three-dimensional (3D) scaffold was suitable for the generation of a xeno-free 3D osteogenic system. Thus, our strategy offers a platform with significant advantages for bone biology studies and it will also contribute to clinical applications of hiPSCs to skeletal regenerative medicine.
Enzymatically cross-linkable phenol-conjugated glycol chitosan was prepared by reacting glycol chitosan with 3-(4-hydroxyphenyl)propionic acid (HPP). The chemical modification was confirmed by FTIR,
...H-NMR and UV spectroscopy. Glycol chitosan hydrogels (HPP-GC) with or without rhBMP-2 were prepared by the oxidative coupling of the substituted phenol groups in the presence of hydrogen peroxide and horse radish peroxidase. Rheological characterization demonstrated the feasibility of developing hydrogels with varying storage moduli by changing the polymer concentration. The gel presented a microporous structure with pore sizes ranging from 50-350 μm. The good viability of encapsulated 7F2 osteoblasts indicated non-toxicity of the gelation conditions. In vitro release of rhBMP-2 in phosphate buffer solution showed ∼11% release in 360 h. The ability of the hydrogel to maintain the in vivo bioactivity of rhBMP-2 was evaluated in a bilateral critical size calvarial bone defect model in Col3.6 transgenic fluorescent reporter mice. The presence of fluorescent green osteoblast cells with overlying red alizarin complexone and yellow stain indicating osteoclast TRAP activity confirmed active cell-mediated mineralization and remodelling process at the implantation site. The complete closure of the defect site at 4 and 8 weeks post implantation demonstrated the potent osteoinductivity of the rhBMP-2 containing gel.
PDF
