2,590 research outputs found

    Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases

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    Background: Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells have mostly assessed a small number of presumptive canine induced pluripotent stem cell (iPSC) lines for generic pluripotency attributes. However, why canine cell reprogramming remains extremely inefficient is poorly understood. Methods: To better characterize the initial steps of pluripotency induction in canine somatic cells, we optimized an experimental system where canine fetal fibroblasts (cFFs) are transduced with the Yamanaka reprogramming factors by Sendai virus vectors. We use quantitative PCR arrays to measure the expression of 80 target genes at various stages of canine cell reprogramming. We ask how cFF reprogramming is influenced by small molecules affecting the epigenomic modification 5-hydroxymethylcytosine, specifically L-ascorbic acid and retinoic acid (AA/RA). Results: We found that the expression and catalytic output of a class of 2-oxoglutarate-dependent (2-OG) hydroxylases, known as ten-eleven translocation (TET) enzymes, can be modulated in canine cells treated with AA/RA. We further show that AA/RA treatment induces TET1 expression and facilitates early canine reprogramming, evidenced by upregulation of epithelial and pluripotency markers. Using a chemical inhibitor of 2-OG hydroxylases, we demonstrate that 2-OG hydroxylase activity regulates the expression of a subset of genes involved in mesenchymal-to-epithelial transition (MET) and pluripotency in early canine reprogramming. We identify a set of transcription factors depleted in maturing reprogramming intermediates compared to pluripotent canine embryonic stem cells. Conclusions: Our findings highlight 2-OG hydroxylases have evolutionarily conserved and divergent functions regulating the early reprogramming of canine somatic cells and show reprogramming conditions can be rationally optimized for the generation of maturing canine iPSC

    Phytotherapy for the treatment of Glioblastoma: a review

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    Background: Phytotherapy; the study of extracts of natural origin in the treatment of disease, has scarcely been applied in the management of GBM. A body of literature exists studying in-vitro, the use of natural extracts against GBM cells. Given persisting poor prognoses, we evaluated, through systematic literature-review the therapeutic potential of naturally sourced extracts in-vivo. Methods: Using OVID, MEDLINE and EMBASE databases were searched with compound search term. Abstracts and full-texts were double-screened by independent reviewers. Results: Nine hundred and eighty-seven articles, excluding duplicated were screened, leading to the inclusion of 14. Amongst murine studies, Ashwagandha, Coptis Chinensis and Fructus Ligustri Lucidi in unprocessed forms, produced significant reductions in tumour volume. Amongst human studies, Perrilyl alcohol, derived from Lavender, reduced angiogenic cytokines in 31% of subjects, halted 6 month disease progression in 48.2% of subjects, and improved mean survival by 4.9 months in separate studies, respectively. Conclusion: Although cursory, current trends in literature demonstrate the value of inhaled Lavender extract in the treatment of GBM, offering tangible clinical benefit to patients receiving conventional treatments. Furthermore, the administration of 8, discrete extracts in mice to produce significant responses in survival and tumour volume, suggest there is further scope for study. Although additional safety tests are required, currently, phytotherapeutics are the crossover to clinical translation, and additional trials are warranted to expound upon thus far promising results

    Confining and hoop stresses in ring-confined thin-walled concrete-filled steel tube columns

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    Concrete-filled steel tube (CFST) columns are now widely adopted in many structures due to the superior behaviour provided by composite action. However, this composite action is limited because of the different dilation properties of the constitutive materials at the early elastic stage. Furthermore, due to inelastic outward buckling of the steel tube, CFST columns may suffer serious degradation of the steel confinement. To overcome these problems, external confinement in the form of rings has been recently studied, and test results have shown that such provision can improve the strength, elastic stiffness, ductility and interface bonding of CFST columns. In the work reported in this paper, as a continuation of a previous study of ring-confined CFST columns, ten concrete-filled thin-walled steel tubes were fabricated and tested under uniaxial compression. The main parameters examined were the concrete cylinder strength, the steel tube thickness and the ring spacing. The test results show that external rings are highly effective in improving the uniaxial behaviour of CFST columns. Based on the experimental hoop–axial strain relationships and Prandtl–Reuss theory for the steel tube, the true structural behaviour of unconfined and ring-confined CFST columns, such as the steel–concrete interface bonding condition, the behaviour of the steel tube and core concrete as well as the confining mechanisms, were explored

    Strutural Damage Induced by Pyritic Shale

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    The Evangelical Hospital located in Lewisburg, Pennsylvania has experienced distress in the form of cracked floor slabs and displaced structural steel due to swelling of the underlying fill material and natural bedrock formation. The bedrock consisted of black, pyritic, calcareous shale from the Marcellus Formation of the Hamilton Group (Devonian Age). The fill materials beneath the cracked concrete floor slabs consisted of the weathered shale fragments from this formation. Although mitigating the structural distress has been attempted, the building continued to experience problems relating to the swelling of the underlying bedrock materials. The expansion of the shale could be attributed to the oxidation of the pyrite, which produced sulfuric acid. The sulfuric acid, in turn, reacted with the calcium carbonate (calcite) in the shale partings producing the mineral gypsum. Since gypsum has approximately twice the molar volume of calcite, the result is an expansion or swelling of the shale. Various laboratory tests were conducted on the shale in an attempt to simulate the swelling processes. The failures and successes of the laboratory testing have given new directions for additional research to further educate Geotechnical Engineers unfamiliar with the expansive nature of pyritic shale

    Thermal emission spectroscopy of the middle atmosphere

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    The general objective of this research is to obtain, via remote sensing, simultaneous measurements of the vertical distributions of stratospheric temperature, ozone, and trace constituents that participate in the catalytic destruction of ozone (NO(sub y): NO, NO2, NO3, HNO3, ClONO2, N2O5, HNO4; Cl(sub x): HOCl), and the source gases for the catalytic cycles (H2O, CH4, N2O, CF2Cl2, CFCl3, CCl4, CH3Cl, CHF2Cl, etc.). Data are collected during a complete diurnal cycle in order to test our present understanding of ozone chemistry and its associate catalytic cycles. The instrumentation employed is an emission-mode, balloon-borne, liquid-nitrogen-cooled Michelson interferometer-spectrometer (SIRIS), covering the mid-infrared range with a spectral resolution of 0.020 cm(exp -1). Cryogenic cooling combined with the use of extrinsic silicon photoconductor detectors allows the detection of weak emission features of stratospheric gaseous species. Vertical distributions of these species are inferred from scans of the thermal emission of the limb in a sequence of elevation angles. The fourth SIRIS balloon flight was carried out from Palestine, Texas on September 15-16, 1986 with 9 hours of nighttime data (40 km). High quality data with spectral resolution 0.022 cm(exp -1), were obtained for numerous limb sequences. Fifteen stratospheric species have been identified to date from this flight: five species from the NO(sub y) family (HNO3, NO2, NO, ClONO2, N2O5), plus CO2, O3, H2O, N2O, CH4, CCl3F, CCl2F2, CHF2Cl, CF4, and CCl4. The nighttime values of N2O5, ClONO2, and total odd nitrogen have been measured for the first time, and compared to model results. Analysis of the diurnal variation of N2O5 within the 1984 and 1986 data sets, and of the 1984 ClONO2 measurements, were presented in the literature. The demonstrated ability of SIRIS to measure all the major NO(sub y) species, and therefore to determine the partitioning of the nitrogen family over a continuous diurnal cycle, is a powerful tool in the verification and improvement of photochemical modeling

    Tall Fescue Expressed Sequence Tag and Simple Sequence Repeats: Important Resources for Grass Species

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    Expressed sequence tag (EST) databases have been growing exponentially. The simple sequence repeat (SSR) has become one of the most useful molecular marker systems in plant breeding and is widely used in cultivar fingerprinting, genetic diversity assessment, molecular mapping and marker-assisted selection. ESTs are a potential source for SSRs. The EST-SSR markers are of high quality and have versatile applications in molecular breeding (Bughrara et al., 2003; Saha et al., 2004 a, b, c). Here, we present an overview of our efforts to develop SSRs from tall fescue ESTs and their application for the genetic improvement of forage and turf grass species

    Tibial Plateau Fracture Following Low Energy Fall in the Rocky Mountains

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    Tibial plateau fractures are debilitating injuries. They can occurin younger individuals who sustain a high energy trauma or, withincreasing age, lesser degrees of trauma and underlying bone pathology such as osteoporosis, metabolic bone disease, and malignancy.1Outside these cases, tibial plateau fractures are relatively uncommon.However, these fractures can occur in healthy patients who have sustained direct trauma to the knee.Fractures of the tibial plateau often are classified according to theSchatzker or AO classification systems.2,3 These systems evaluate theinvolvement of both the medial and lateral plateaus, degree of comminution, extension into the joint, and displacement (both articularsurfaces and the relationship of the diaphysis to the metaphysis).Most tibial plateau fractures occur in the lateral aspect of the tibialplateau.1 The increased frequency of lateral fractures is due to themedial tibial plateau being able to resist higher weight-bearing loaddue to the presence of more cancellous bone. More importantly, thelateral plateau has more articular surface exposed during extensioncompared to the medial plateau, which increases likelihood of injury.4The standard of care for most displaced tibial plateau fracturesis surgical management with open reduction and internal fixation(ORIF).5 Conservative management, such as leg bracing, is an optionfor fractures that are nondisplaced or in patients too fragile for surgical intervention. In the senior population, a total knee arthroplasty(TKA) is a less common option. Tibial plateau fractures, particularlymedial tibial plateau fractures, caused by direct trauma in the elderly,non-osteoporotic population are uncommon.We present the case of an active male without overt risk for severefracture (10-year fracture risk of 10% via FRAX score) who wasworking to repair a trail in the Rocky Mountains. While other injurieswere more likely given the mechanism of injury and patient risk, thiscase highlighted the importance of considering tibial plateau fracture,even in atypical settings without significant risk. Improved awarenessof this mechanism of injury will lead to more accurate diagnosis andgreater post-injury management
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