QT DISPERSION AND DIPYRIDAMOLE-INDUCED MYOCARDIAL ISCHEMIA

The relationship between QT interval dispersion and dipyridamole-induced, transient myocardial ischemia was assessed in 32 male patients with ischemic heart disease. A standardized, high dose dipyridamole-ECG stress test was used as dipyridamole infusion of 0,56 mg/kg applied i. v. for 4 min followed by 4 min interval of no-dose with E C G and blood pressure monitoring, and in negative test - by a dipyridamole infusion of 0,28mg/kg i. v. for 2 min. Seventeen patients (53%) developed a transient myocardial ischemia with duration of 20 ±7 (4-40) min during the dipyridamole infusion while 15 ones (47%) did not. No regular dynamics and significant differences in the values of total QT interval dispersion and maximum adjacent QT interval dispersion estimated before, during and after the dipyridamole infusion could be established. It was supposed that the severity, duration and time for development of dipyridamole-induced transient myocardial ischemia were not sufficient to generate a dispersion in ventricular repolarization detectable as changes in QT dispersion parameters on surface ECG. The combination of QT dispersion with various non-invasive markers of arrhythmogenic mechanisms could help the estimation of arrhythmogenic risk in the patients with ischemic heart disease

Collective behaviour of partons could be a source of energetic hadrons

We discuss the idea that collective behaviour of the quarks/partons, which has been intensely discussed for the last 40 years in relativistic hadron-nuclear and nuclear-nuclear interactions and confirmed by new data coming from the ultrarelativistic heavy ion collisions, can lead to energetic particle production. Created from hadronization of the quark/parton (or quarks/partons), energetic particles could get the energy of grouped partons from coherent interactions. Therefore, we think that in the centre of some massive stars, a medium with high density, close to Quantum Chromodynamic one could be a source of the super high-energy cosmic rays.Comment: 8 pages, 8 figure

γ-Catenin-Dependent Signals Maintain BCR-ABL1⁺ B Cell Acute Lymphoblastic Leukemia.

The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ-catenin in the initiation and maintenance of BCR-ABL1 <sup>+</sup> B-ALL but not CML. The selectivity was explained by a partial γ-catenin dependence of MYC expression together with the susceptibility of B-ALL, but not CML, to reduced MYC levels. MYC and γ-catenin enabled B-ALL maintenance by augmenting BIRC5 and enforced BIRC5 expression overcame γ-catenin loss. Since γ-catenin was dispensable for normal hematopoiesis, these lineage- and disease-specific features of canonical Wnt signaling identified a potential therapeutic target for the treatment of BCR-ABL1 <sup>+</sup> B-ALL

The 4q12 Amplicon in Malignant Peripheral Nerve Sheath Tumors: Consequences on Gene Expression and Implications for Sunitinib Treatment

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive tumors which originate from Schwann cells and develop in about 10% of neurofibromatosis type 1 (NF1) patients. The five year survival rate is poor and more effective therapies are needed. Sunitinib is a drug targeting receptor tyrosine kinases (RTK) like PDGFRα, c-Kit and VEGFR-2. These genes are structurally related and cluster on chromosomal segment 4q12.) was present in MPNST cell lines suggesting an autocrine loop. We show that VEGF triggered signal transduction via the MAPK pathway, which could be blocked by sunitinib. might serve as predictive markers for efficacy of sunitinib

X Chromosome Inactivation and Differentiation Occur Readily in ES Cells Doubly-Deficient for MacroH2A1 and MacroH2A2

Macrohistones (mH2As) are unusual histone variants found exclusively in vertebrate chromatin. In mice, the H2afy gene encodes two splice variants, mH2A1.1 and mH2A1.2 and a second gene, H2afy2, encodes an additional mH2A2 protein. Both mH2A isoforms have been found enriched on the inactive X chromosome (Xi) in differentiated mammalian female cells, and are incorporated into the chromatin of developmentally-regulated genes. To investigate the functional significance of mH2A isoforms for X chromosome inactivation (XCI), we produced male and female embryonic stem cell (ESC) lines with stably-integrated shRNA constructs that simultaneously target both mH2A1 and mH2A2. Surprisingly, we find that female ESCs deficient for both mH2A1 and mH2A2 readily execute and maintain XCI upon differentiation. Furthermore, male and female mH2A-deficient ESCs proliferate normally under pluripotency culture conditions, and respond to several standard differentiation procedures efficiently. Our results show that XCI can readily proceed with substantially reduced total mH2A content

Structural plasticity of single chromatin fibers revealed by torsional manipulation

Magnetic tweezers are used to study the mechanical response under torsion of single nucleosome arrays reconstituted on tandem repeats of 5S positioning sequences. Regular arrays are extremely resilient and can reversibly accommodate a large amount of supercoiling without much change in length. This behavior is quantitatively described by a molecular model of the chromatin 3-D architecture. In this model, we assume the existence of a dynamic equilibrium between three conformations of the nucleosome, which are determined by the crossing status of the entry/exit DNAs (positive, null or negative). Torsional strain, in displacing that equilibrium, extensively reorganizes the fiber architecture. The model explains a number of long-standing topological questions regarding DNA in chromatin, and may provide the ground to better understand the dynamic binding of most chromatin-associated proteins.Comment: 18 pages, 7 figures, Supplementary information available at http://www.nature.com/nsmb/journal/v13/n5/suppinfo/nsmb1087_S1.htm

Glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study

<p>Abstract</p> <p>Background</p> <p>Cerebral malaria (CM) is associated with high mortality and morbidity caused by a high rate of transient or persistent neurological sequelae. Studies on immunomodulatory and neuroprotective drugs as ancillary treatment in murine CM indicate promising potential. The current study was conducted to evaluate the efficacy of glatiramer acetate (GA), an immunomodulatory drug approved for the treatment of relapsing remitting multiple sclerosis, in preventing the death of C57Bl/6J mice infected with <it>Plasmodium berghei </it>ANKA.</p> <p>Methods and Results</p> <p>GA treatment led to a statistically significant lower risk for developing CM (57.7% versus 84.6%) in treated animals. The drug had no effect on the course of parasitaemia. The mechanism of action seems to be an immunomodulatory effect since lower IFN-gamma levels were observed in treated animals in the early course of the disease (day 4 post-infection) which also led to a lower number of brain sequestered leukocytes in treated animals. No direct neuro-protective effect such as an inhibition of apoptosis or reduction of micro-bleedings in the brain was found.</p> <p>Conclusion</p> <p>These findings support the important role of the host immune response in the pathophysiology of murine CM and might lead to the development of new adjunctive treatment strategies.</p

Packet Forwarding Algorithms in a Line Network

Abstract. We initiate a competitive analysis of packet forwarding poli-cies for maximum and average flow in a line network. We show that the policies Earliest Arrival and Furthest-To-Go are scalable, but not con-stant competitive, for maximum flow. We show that there is no constant competitive algorithm for average flow.