461 research outputs found

    The Role of PAX5 in ALL

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    Ab-initio self-energy corrections in systems with metallic screening

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    The calculation of self-energy corrections to the electron bands of a metal requires the evaluation of the intraband contribution to the polarizability in the small-q limit. When neglected, as in standard GW codes for semiconductors and insulators, a spurious gap opens at the Fermi energy. Systematic methods to include intraband contributions to the polarizability exist, but require a computationally intensive Fermi-surface integration. We propose a numerically cheap and stable method, based on a fit of the power expansion of the polarizability in the small-q region. We test it on the homogeneous electron gas and on real metals such as sodium and aluminum.Comment: revtex, 14 pages including 5 eps figures v2: few fixe

    Monitoring of minimal residual disease in leukemia, advantages and pitfalls.

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    The term 'minimal residual disease' (MRD) defines the level of disease detectable in patients in clinical remission during therapy, below the detection limit of conventional methods. Very sensitive methods can be used, able to identify one leukemic cell out of 10,000 normal lymphocytes. In vivo measurements of leukemia cytoreduction reflect the combined effect of clinical and biological variables, thus providing direct information on the effectiveness of treatment in each patient. Thus, these methods can potentially be used for tailoring treatment and personalize the cure. Although MRD studies are becoming an integral part of the modern management of patients with leukemia, several parameters are critical for the application and interpretation of MRD studies, including therapeutic context, timing of sampling, target genes and sensitivity of the polymerase chain reaction (PCR) assay, inter-laboratory standardization (particularly relevant in multicenter studies), selection of patients, retrospective or prospective nature of the study. Methodologies and pitfalls as well as results of clinical uses of MRD will be reviewed in this article by selecting significant examples of its clinical impact in the management of patients with leukemia

    Atomistic study of the structural and electronic properties of a-Si:H/c-Si interfaces

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    Producción CientíficaWe investigate the structural and electronic properties of the interface between hydrogenated amorphous silicon (a-Si:H) and crystalline silicon (c-Si) by combining tight-binding molecular dynamics and DFT ab initio electronic structure calculations. We focus on the c-Si(100)(1×1)/a-Si:H, c-Si(100)(2×1)/a-Si:H and c-Si(111)/a-Si:H interfaces, due to their technological relevance. The analysis of atomic rearrangements induced at the interface by the interaction between H and Si allowed us to identify the relevant steps that lead to the transformation from c-Si(100)(1×1)/a-Si:H to c-Si(100)(2×1)/a-Si:H. The interface electronic structure is found to be characterized by spatially localized mid-gap states. Through them we have identified the relevant atomic structures responsible for the interface defect states, namely: dangling-bonds, H bridges, and strained bonds. Our analysis contributes to a better understanding of the role of such defects in c-Si/a-Si:H interfaces.Ministerio de Ciencia e Innovación (Proyect TEC2011-27701

    Different Roles of α- and β-Branch Xanthophylls in Photosystem Assembly and Photoprotection

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    Xanthophylls (oxygenated carotenoids) are essential components of the plant photosynthetic apparatus, where they act in photosystem assembly, light harvesting, and photoprotection. Nevertheless, the specific function of individual xanthophyll species awaits complete elucidation. In this work, we analyze the photosynthetic phenotypes of two newly isolated Arabidopsis mutants in carotenoid biosynthesis containing exclusively alpha-branch (chy1chy2lut5) or beta-branch (chy1chy2lut2) xanthophylls. Both mutants show complete lack of qE, the rapidly reversible component of nonphotochemical quenching, and high levels of photoinhibition and lipid peroxidation under photooxidative stress. Both mutants are much more photosensitive than npq1lut2, which contains high levels of viola- and neoxanthin and a higher stoichiometry of light-harvesting proteins with respect to photosystem II core complexes, suggesting that the content in light-harvesting complexes plays an important role in photoprotection. In addition, chy1chy2lut5, which has lutein as the only xanthophyll, shows unprecedented photosensitivity even in low light conditions, reduced electron transport rate, enhanced photobleaching of isolated LHCII complexes, and a selective loss of CP26 with respect to chy1chy2lut2, highlighting a specific role of beta-branch xanthophylls in photoprotection and in qE mechanism. The stronger photosystem II photoinhibition of both mutants correlates with the higher rate of singlet oxygen production from thylakoids and isolated light-harvesting complexes, whereas carotenoid composition of photosystem II core complex was not influential. In depth analysis of the mutant phenotypes suggests that alpha-branch (lutein) and beta-branch (zeaxanthin, violaxanthin, and neoxanthin) xanthophylls have distinct and complementary roles in antenna protein assembly and in the mechanisms of photoprotection

    A quadruple mutant of Arabidopsis reveals a β-carotene hydroxylation activity for LUT1/CYP97C1 and a regulatory role of xanthophylls on determination of the PSI/PSII ratio

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    <p>Abstract</p> <p>Background</p> <p>Xanthophylls are oxygenated carotenoids playing an essential role as structural components of the photosynthetic apparatus. Xanthophylls contribute to the assembly and stability of light-harvesting complex, to light absorbance and to photoprotection. The first step in xanthophyll biosynthesis from α- and β-carotene is the hydroxylation of ε- and β-rings, performed by both non-heme iron oxygenases (CHY1, CHY2) and P450 cytochromes (LUT1/CYP97C1, LUT5/CYP97A3). The Arabidopsis triple <it>chy1chy2lut5 </it>mutant is almost completely depleted in β-xanthophylls.</p> <p>Results</p> <p>Here we report on the quadruple <it>chy1chy2lut2lut5 </it>mutant, additionally carrying the <it>lut2 </it>mutation (affecting lycopene ε-cyclase). This genotype lacks lutein and yet it shows a compensatory increase in β-xanthophylls with respect to <it>chy1chy2lut5 </it>mutant. Mutant plants show an even stronger photosensitivity than <it>chy1chy2lut5</it>, a complete lack of qE, the rapidly reversible component of non-photochemical quenching, and a peculiar organization of the pigment binding complexes into thylakoids. Biochemical analysis reveals that the <it>chy1chy2lut2lut5 </it>mutant is depleted in Lhcb subunits and is specifically affected in Photosystem I function, showing a deficiency in PSI-LHCI supercomplexes. Moreover, by analyzing a series of single, double, triple and quadruple Arabidopsis mutants in xanthophyll biosynthesis, we show a hitherto undescribed correlation between xanthophyll levels and the PSI-PSII ratio. The decrease in the xanthophyll/carotenoid ratio causes a proportional decrease in the LHCII and PSI core levels with respect to PSII.</p> <p>Conclusions</p> <p>The physiological and biochemical phenotype of the <it>chy1chy2lut2lut5 </it>mutant shows that (i) LUT1/CYP97C1 protein reveals a major β-carotene hydroxylase activity <it>in vivo </it>when depleted in its preferred substrate α-carotene; (ii) xanthophylls are needed for normal level of Photosystem I and LHCII accumulation.</p

    A case of beta-thalassaemia major resistant to standard treatment

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    We report the case of a 22-year-old woman from Albania, with thalassaemia major, in severe clinical condition who could no longer be transfused due to the occurrence of severe, acute, post-transfusional reactions. After 10 years of treatment, she failed to respond to hydroxyurea. When she received thalidomide, haemoglobin levels increased from 3.7 g/dl to 9 g/dl. Since then, at 22 months of follow-up, the therapy is still effective and well tolerated. The case gives the opportunity to describe the clinical use of thalidomide, and its potential in the management of beta-thalassaemia

    Hepatocyte growth factor receptor c-MET is associated with FAS and when activated enhances drug-induced apoptosis in pediatric B acute lymphoblastic leukemia with TEL-AML1 translocation.

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    Expression of c-MET, the HGF (hepatocyte growth factor) tyrosine kinase receptor, was investigated in pediatric B-acute lymphoblastic leukemia (ALL) patients. c-MET was found to be expressed in normal B cells and in B-ALL patients with the t(12;21) TEL-AML1 translocation, but it is not expressed in the most part of B-ALL without the t(12;21). We also found that c-MET, related to proliferation and protection from apoptosis, is associated with the pro-apoptotic protein FAS in TEL-AML1 B-ALL cells and in normal B lymphocytes. The possible role of this protein complex in drug-induced apoptosis was thus investigated in REH TEL-AML1 B-ALL cell line. REH cells prestimulated with HGF and treated with doxorubicin had shown a higher apoptotic rate than non-HGF-prestimulated ones (p = 0.03). REH cells stimulated with IL-3 and treated with doxorubicin did not undergo apoptosis more than nonstimulated cells, demonstrating that increased proliferation in itself is not directly related to the higher apoptotic sensitivity observed with HGF stimulation. These results indicate that c-MET activation enhances specifically FAS-mediated apoptosis in TEL-AML1 ALL cells and, considering that the c-MET/FAS complex is present only in normal B lymphocytes and in TEL-AML1 leukemias, this implies that it may have an important contribution in cellular homeostasis and in high sensitivity of TEL-AML1 ALL to chemotherapeutic regimens

    Task-oriented exercises improve disability of working patients with surgically-treated proximal humeral fractures. A randomized controlled trial with one-year follow-up

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    Background: General physiotherapy is a common means of rehabilitation after surgery for proximal humeral fracture (PHF). Better-targeted exercises seem worthy of investigation and the aim of this study was to assess the efficacy of a rehabilitation program including task-oriented exercises in improving disability, pain, and quality of life in patients after a PHF. Methods: By means of a randomized controlled trial with one-year follow-up, 70 working patients (mean age of 49 ± 11 years; 41 females), who were selected for open reduction and internal fixation with plates caused by PHF, were randomized to be included in an experimental (n = 35) or control group (n = 35). There was a permuted-block randomization plan, and a list of program codes was previously created; subsequently, an automatic assignment system was used to conceal the allocation. The first group underwent a supervised rehabilitation program of task-oriented exercises based on patients’ specific job activities, and occupational therapy. The second group underwent general physiotherapy, including supervised mobility, strengthening and stretching exercises. Both groups individually followed programs of 60-min session three times per week for 12 weeks in the outpatient setting. The Disability Arm Shoulder Hand questionnaire (DASH; scores range from 0 to 100; primary outcome), a Pain intensity Numerical Rating Scale (scores range 0 to 10; secondary outcomes), and the Short-Form Health Survey (scores range from 0 to 100; secondary outcomes) assessed the interventions. Participants were evaluated before surgery, before and after rehabilitation (primary endpoint), and at the one-year follow-up (secondary endpoint). A linear mixed model analysis for repeated measures was carried out for each outcome measure (p &lt; 0.05). Results: Time, group and time by group showed significant effects for all outcome measures in favour of the experimental group. The DASH and the DASH work achieved clinically important between-group differences of 16.0 points (95% confidence interval [C.I.] 7.3 to 24.7) and 19.7 (95% C.I. 9.0 to 30.5) at follow-up, respectively. The NRS achieved a between-group difference of 2.9 (95% C.I. 1.0 to 3.9) at follow-up. As for SF-36, there were between-group differences ranging from 17.9 to 37.0 at follow-up. Conclusions: A rehabilitation program based on task-oriented exercises was useful in improving disability, pain, and quality of life in working patients after PHFs. Improvements lasted for at least 12 months. Trial registration: On 16/12/2019, the trial was retrospectively registered in the ISRCTN registry with the ID number 17996552
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