3,948 research outputs found

    EZH2, HIF-1, and their inhibitors: An overview on pediatric cancers

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    During the past decades, several discoveries have established the role of epigenetic modifications and cellularmicroenvironment in tumor growth and progression. One of the main representatives concerning epigenetic modification is the polycomb group (PcG). It is composed of different highly conserved epigenetic effector proteins preserving, through several post-translational modifications of histones, the silenced state of the genes implicated in a wide range of central biological events such as development, stem cell formation, and tumor progression. Proteins of the PcG can be divided in polycomb repressive complexes (PRCs): PRC1 and PRC2. In particular, enhancer of zeste homolog 2 (EZH2), the catalytic core subunit of PRC2, acts as an epigenetic silencer ofmany tumor suppressor genes through the trimethylation of lysine 27 on histone H3, an essential binding site for DNA methyl transferases and histone deacetylases. A growing number of data suggests that overexpression of EZH2 associates with progression and poor outcome in a large number of cancer cases. Hypoxia inducible factor (HIF) is an important transcription factor involved in modulating cellular response to the microenvironment by promoting and regulating tumor development such as angiogenesis, inflammation, metabolic reprogramming, invasion, and metastatic fate. The HIF complex is represented by different subunits (α and β) acting together and promoting the expression of vascular endothelial growth factor (VEGF), hexokinase II (HKII), receptor for advanced glycation end products (RAGE), carbonic anhydrase (CA), etc., after binding to the hypoxia-response element (HRE) binding site on the DNA. In this review, we will try to connect these two players by detailing the following: (i) the activity and influence of these two important regulators of cancer progression in particular for what concerns pediatric tumors, (ii) the possible correlation between them, and (iii) the feasibility and efficiency to contrast them using several inhibitors

    Supergravity and matrix theory do not disagree on multi-graviton scattering

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    We compare the amplitudes for the long-distance scattering of three gravitons in eleven dimensional supergravity and matrix theory at finite N. We show that the leading supergravity term arises from loop contributions to the matrix theory effective action that are not required to vanish by supersymmetry. We evaluate in detail one type of diagram---the setting sun with only massive propagators---reproducing the supergravity behavior.Comment: 10 pages, 1 eps figure, it requires JHEP.cl

    Many-body correlations and coupling in benzene-dithiol junctions

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    Most theoretical studies of nanoscale transport in molecular junctions rely on the combination of the Landauer formalism with Kohn-Sham density functional theory (DFT) using standard local and semilocal functionals to approximate exchange and correlation effects. In many cases, the resulting conductance is overestimated with respect to experiments. Recent works have demonstrated that this discrepancy may be reduced when including many-body corrections on top of DFT. Here we study benzene-dithiol (BDT) gold junctions and analyze the effect of many-body perturbation theory (MBPT) on the calculation of the conductance with respect to different bonding geometries. We find that the many-body corrections to the conductance strongly depend on the metal-molecule coupling strength. In the BDT junction with the lowest coupling, many-body corrections reduce the overestimation on the conductance to a factor two, improving the agreement with experiments. In contrast, in the strongest coupling cases, many-body corrections on the conductance are found to be sensibly smaller and standard DFT reveals a valid approach.Comment: 9 pages, 4 figure

    Reducing visual stimulations in european hares (Lepus europaeus Pallas) captured for translocation

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    Stress may be an important variable affecting the survival of the captured hares, for this reason the Authors studied the effect of the use of a blindfolding hood applied to the hares immediately after net trapping. A total of 119 hares were captured by coursing with 3-4 dogs (greyhounds or lurchers) in no hunting areas of Tuscany. Immediately after net trapping 38 hares were blindfolded with a hood and 81 were normally handled to the wooden darkened capture- boxes without blinding their eyes (control). From all the hares a sample of blood was collected within 1-2 min by the auricular vein. Blood samples were analyzed for haemocromocytometry and metabolic profile determination. Data were analyzed by ANOVA. Sub-clinically stressed hares were discriminated from nonstressed hares by the use of the discriminant function based on CK, AST and glucose and the differences were tested by chi2c Results showed that body temperature, heart and respiratory rates, glucose, cholesterol, CK, AST, ALT, BUN, total protein and some haemocromo-cytometric parameters were significantly higher in captured hares without blindfold. The incidence of subclinically stressed hares was 26% in the hares equipped with the blindfold and 81% in the hares without blindfold (chi2c=32.98, P<0.0001) (presence of subclinical stress discriminated by the use of a discriminant function based on CPK, AST and glucose). For this reason the procedures designed for the translocation of the hares could take advantage by the use of a blindfold which should be applied to the hares immediately after their trapping

    Treatment of a Femur Nonunion with Microsurgical Corticoperiosteal Pedicled Flap from the Medial Femoral Condyle

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    Introduction.Te vascularized corticoperiosteal fap is harvested from the medial femoral condyle and it is nourished by the articular branch of the descending genicular artery and the superomedial genicular artery. Tis fap is usually harvested as a free fap for the reconstruction of bone defects at forearm, distal radius, carpus, hand, and recently at lower limb too. Case Report. A 50-year-old Caucasian man referred to our department for hypertrophic nonunion of the distal femur, refractory to the conservative treatments. Te frst surgical choice was the revision of the nail and the bone reconstruction with a corticoperiosteal pedicled fap from the medial femoral condyle. We considered union to have occurred 3.5 months afer surgery when radiographs showed bridging of at least three of the four bony cortices and clinically the patient was able to walk with full weight bearing without any pain. At the last follow-up (25 months), the patient was completely satisfed with the procedure. Discussion. Te corticoperiosteal fap allows a faster healing of fractures with a minimal morbidity at the donor site. We suggest that the corticoperiosteal pedicled fap graf is a reliable and efective treatment for distal femur nonunion

    Captive rearing technologies and survival of pheasants (Phasianus colchicus L.) after release

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    Studies have repeatedly emphasized the limited survival of pheasants reared using traditional methods compared to the wild one. For this reason we performed a field trial to compare survival rates, home ranges and habitat uses of pheasants artificial hatched and reared (traditional method) with pheasants artificial hatched and reared by fostering mothers (hens). A total of 117 artificially hatched pheasants, 57 artificially brooded after hatch and 60 brooded by fostering hens, were equipped with a radio necklace tag or a poncho tag. Both groups were localized two-three times a week after their release in the wild. The survival rates of the brooded-by-hen pheasants showed an improvement of survival rates, either poncho or radio tagged (P<0.05), 90.0% vs 57.1% and 35.0% vs 21.1%, respectively. The average maximum dispersion was 390 and 426 m and the home range were 12.0 and 11.6 ha in artificially brooded and brooded-by-hen pheasants, respectively. The land use showed that the woods were less represented than the available in the home range of every pheasant. For this reason the woods can be reduced in the agricultural areas interspersed with natural Mediterranean vegetation
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