Primary osteoporosis is an age-related disease characterized by an imbalance in bone homeostasis. While the resorptive aspect of the disease has been studied intensely, less is known about the ...anabolic part of the syndrome or presumptive deficiencies in bone regeneration. Multipotent mesenchymal stem cells (MSC) are the primary source of osteogenic regeneration. In the present study we aimed to unravel whether MSC biology is directly involved in the pathophysiology of the disease and therefore performed microarray analyses of hMSC of elderly patients (79-94 years old) suffering from osteoporosis (hMSC-OP). In comparison to age-matched controls we detected profound changes in the transcriptome in hMSC-OP, e.g. enhanced mRNA expression of known osteoporosis-associated genes (LRP5, RUNX2, COL1A1) and of genes involved in osteoclastogenesis (CSF1, PTH1R), but most notably of genes coding for inhibitors of WNT and BMP signaling, such as Sclerostin and MAB21L2. These candidate genes indicate intrinsic deficiencies in self-renewal and differentiation potential in osteoporotic stem cells. We also compared both hMSC-OP and non-osteoporotic hMSC-old of elderly donors to hMSC of ∼30 years younger donors and found that the transcriptional changes acquired between the sixth and the ninth decade of life differed widely between osteoporotic and non-osteoporotic stem cells. In addition, we compared the osteoporotic transcriptome to long term-cultivated, senescent hMSC and detected some signs for pre-senescence in hMSC-OP.Our results suggest that in primary osteoporosis the transcriptomes of hMSC populations show distinct signatures and little overlap with non-osteoporotic aging, although we detected some hints for senescence-associated changes. While there are remarkable inter-individual variations as expected for polygenetic diseases, we could identify many susceptibility genes for osteoporosis known from genetic studies. We also found new candidates, e.g. MAB21L2, a novel repressor of BMP-induced transcription. Such transcriptional changes may reflect epigenetic changes, which are part of a specific osteoporosis-associated aging process.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this paper is to propose a method for dealing with the problem of mesh deformation (or mesh evolution) in the context of free and moving boundary problems, in three space dimensions. The ...method consists in combining two different numerical parameterizations of domains: on the one hand, domains are equipped with a computational tetrahedral mesh, and on the other hand, they are represented as the negative subdomains of ‘level set’ functions. We then consistently switch from one description to the other, depending on their respective convenience with respect to the operations to be performed. Among other things, doing so implies to be able to get a computational mesh from an implicitly-defined domain. This in turns relies on an algorithm for handling three-dimensional domain remeshing (that is, remeshing at the same time both surface and volume parts of a given tetrahedral mesh). Applications are considered in the fields of mesh generation, shape optimization, and computational fluid dynamics.
In natural conditions, mycorrhizal fungi are surrounded by complex microbial communities, which modulate the mycorrhizal symbiosis. Here, the focus is on the so-called 'mycorrhiza helper bacteria' ...(MHB). This concept is revisited, and the distinction is made between the helper bacteria, which assist mycorrhiza formation, and those that interact positively with the functioning of the symbiosis. After considering some examples of MHB from the literature, the ecological and evolutionary implications of the relationships of MHB with mycorrhizal fungi are discussed. The question of the specificity of the MHB effect is addressed, and an assessment is made of progress in understanding the mechanisms of the MHB effect, which has been made possible through the development of genomics. Finally, clear evidence is presented suggesting that some MHB promote the functioning of the mycorrhizal symbiosis. This is illustrated for three critical functions of practical significance: nutrient mobilization from soil minerals, fixation of atmospheric nitrogen, and protection of plants against root pathogens. The review concludes with discussion of future research priorities regarding the potentially very fruitful concept of MHB.
In this article, we discuss an approach for geometry and topology optimization of structures which benefits from an accurate description of shapes at each stage of the iterative process–by means of a ...mesh amenable for mechanical analyses–while retaining the whole versatility of the level set method when it comes to accounting for their evolution. The key ingredients of this method are two operators for switching from a meshed representation of a domain to an implicit one, and conversely; this notably brings into play an algorithm for generating the signed distance function to an arbitrary discrete domain, and a mesh generation algorithm for implicitly-defined geometries.
The role of bone morphogenetic proteins (BMPs) in bone healing has been shown in numerous animal models. To date, at least 20 BMPs have been identified, some of which have been shown in vitro to ...stimulate the process of stem cell differentiation into osteoblasts in human and animal models. Having realized the osteoinductive properties of BMPs and having identified their genetic sequences, recombinant gene technology has been used to produce BMPs for clinical application – most commonly, as alternatives or adjuncts in the treatment of cases in which fracture healing is compromised. BMP‐2 and BMP‐7 are approved for clinical use in open fractures of long bones, non‐unions and spinal fusion. However, despite significant evidence of their potential benefit to bone repair and regeneration in animal and preclinical studies, there is, to date, a dearth of convincing clinical trials. The purpose of this paper is to give a brief overview of BMPs and to critically review the clinical data currently available on the use of BMP‐2 and BMP‐7 in fracture healing.
This 14-state study compared mortality rates at hospitals with a level 1 trauma center and hospitals without a trauma center among patients with moderate-to-severe injuries. After adjustment for ...baseline differences in patients' characteristics, the one-year mortality rate was significantly lower at trauma centers than at non–trauma centers (10 percent vs. 14 percent).
This 14-state study compared mortality rates at hospitals with a level 1 trauma center and hospitals without a trauma center among patients with moderate-to-severe injuries. The one-year mortality rate was significantly lower at trauma centers than at non–trauma centers (10 percent vs. 14 percent).
In 1976, the American College of Surgeons Committee on Trauma published criteria for categorizing hospitals according to the resources required to provide various levels of care for traumatic injuries.
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Increasingly, states are using these criteria as a basis for designating trauma centers as part of a regionalized approach to trauma care.
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However, this process has not been uniform. There is substantial variation across states in the number and geographic distribution of trauma centers,
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owing in part to the lack of strong evidence of the effectiveness of trauma centers coupled with high costs of verifying their capabilities.
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The existing evidence . . .
Beneficial interactions between plant roots and rhizosphere microorganisms are pivotal for plant fitness. Nevertheless, the molecular mechanisms controlling the feedback between root architecture and ...microbial community structure remain elusive in maize. Here, we demonstrate that transcriptomic gradients along the longitudinal root axis associate with specific shifts in rhizosphere microbial diversity. Moreover, we have established that root-derived flavones predominantly promote the enrichment of bacteria of the taxa Oxalobacteraceae in the rhizosphere, which in turn promote maize growth and nitrogen acquisition. Genetic experiments demonstrate that LRT1-mediated lateral root development coordinates the interactions of the root system with flavone-dependent Oxalobacteraceae under nitrogen deprivation. In summary, these experiments reveal the genetic basis of the reciprocal interactions between root architecture and the composition and diversity of specific microbial taxa in the rhizosphere resulting in improved plant performance. These findings may open new avenues towards the breeding of high-yielding and nutrient-efficient crops by exploiting their interaction with beneficial soil microorganisms.
Resonant enhancement of spin Seebeck effect (SSE) due to phonons was recently discovered in YFormula: see textFeFormula: see textOFormula: see text (YIG). This effect is explained by hybridization ...between the magnon and phonon dispersions. However, this effect was observed at low temperatures and high magnetic fields, limiting the scope for applications. Here we report observation of phonon-resonant enhancement of SSE at room temperature and low magnetic field. We observe in LuFormula: see textBiFeFormula: see textGaOFormula: see text an enhancement 700% greater than that in a YIG film and at very low magnetic fields around 10Formula: see text T, almost one order of magnitude lower than that of YIG. The result can be explained by the change in the magnon dispersion induced by magnetic compensation due to the presence of non-magnetic ion substitutions. Our study provides a way to tune the magnon response in a crystal by chemical doping, with potential applications for spintronic devices.
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