CONSIDERATIONS ON THE ISSUE OF COMBINED INJURIES

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FURTHER ON THE PROBLEM OF REGIONAL ENTERITIS

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DIABETIC ANGIOPATHY - SURGICAL PROBLEMS AND POSSIBILITIES

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OPERATIONS COMBINED WITH VAGOTOMY IN THE TREATMENT OF DUODENAL ULCER

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Magnetization Reversal by Electric-Field Decoupling of Magnetic and Ferroelectric Domains Walls in Multiferroic-Based Heterostructures

We demonstrate that the magnetization of a ferromagnet in contact with an antiferromagnetic multiferroic (LuMnO3) can be speedily reversed by electric field pulsing, and the sign of the magnetic exchange bias can switch and recover isothermally. As LuMnO3 is not ferroelastic, our data conclusively show that this switching is not mediated by strain effects but is a unique electric-field driven decoupling of the ferroelectric and ferromagnetic domains walls. Their distinct dynamics are essential for the observed magnetic switching

Metal-to-insulator transition and magnetic ordering in CaRu_{1-x}Cu_xO_3

CaRuO_3 is perovskite with an orthorhombic distortion and is believed to be close to magnetic ordering. Magnetic studies of single crystal and polycrystalline CaRu_{1-x}Cu_xO_3 (0\le x \le 15 at.%Cu) reveal that spin-glass-like transition develops for x\le 7 at.%Cu and obtained value for effective magnetic moment p_{eff}=3.55 mu_B for x=5 at.% Cu, single crystal, indicates presence of Ru^{5+}. At higher Cu concentrations more complex magnetic behaviors are observed. Electrical resistivity measured on polycrystalline samples shows metal-to-insulator transition (MIT) at 51 K for only 2 at.% Cu. Charge compensation, which is assumed to be present upon Cu^{2+/3+} substitution, induces appearance of Ru^{5+} and/or creation of oxygen vacancies in crystal structure. Since the observed changes in physical properties are completely attributable to the charge compensation, they cannot be related to behaviors of pure compound where no such mechanism is present. This study provides the criterion for "good" chemical probes for studying Ru-based perovskites.Comment: 12 pages, 7 figure

Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability

Collisions between the DNA replication machinery and co-transcriptional R-loops can impede DNA synthesis and are a major source of genomic instability in cancer cells. How cancer cells deal with R-loops to proliferate is poorly understood. Here we show that the ATP-dependent chromatin remodelling INO80 complex promotes resolution of R-loops to prevent replication-associated DNA damage in cancer cells. Depletion of INO80 in prostate cancer PC3 cells leads to increased R-loops. Overexpression of the RNA:DNA endonuclease RNAse H1 rescues the DNA synthesis defects and suppresses DNA damage caused by INO80 depletion. R-loops co-localize with and promote recruitment of INO80 to chromatin. Artificial tethering of INO80 to a LacO locus enabled turnover of R-loops in cis. Finally, counteracting R-loops by INO80 promotes proliferation and averts DNA damage-induced death in cancer cells. Our work suggests that INO80-dependent resolution of R-loops promotes DNA replication in the presence of transcription, thus enabling unlimited proliferation in cancers

Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity.

DNA double-strand breaks (DSBs) are perhaps the most toxic of all DNA lesions, with defects in the DNA-damage response to DSBs being associated with various human diseases. Although it is known that DSB repair pathways are tightly regulated by ubiquitylation, we do not yet have a comprehensive understanding of how deubiquitylating enzymes (DUBs) function in DSB responses. Here, by carrying out a multidimensional screening strategy for human DUBs, we identify several with hitherto unknown links to DSB repair, the G2/M DNA-damage checkpoint and genome-integrity maintenance. Phylogenetic analyses reveal functional clustering within certain DUB subgroups, suggesting evolutionally conserved functions and/or related modes of action. Furthermore, we establish that the DUB UCHL5 regulates DSB resection and repair by homologous recombination through protecting its interactor, NFRKB, from degradation. Collectively, our findings extend the list of DUBs promoting the maintenance of genome integrity, and highlight their potential as therapeutic targets for cancer.This is the author's accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ncb302

A genome-wide IR-induced RAD51 foci RNAi screen identifies CDC73 involved in chromatin remodeling for DNA repair

To identify new regulators of homologous recombination repair, we carried out a genome-wide short-interfering RNA screen combined with ionizing irradiation using RAD51 foci formation as readout. All candidates were confirmed by independent short-interfering RNAs and validated in secondary assays like recombination repair activity and RPA foci formation. Network analysis of the top modifiers identified gene clusters involved in recombination repair as well as components of the ribosome, the proteasome and the spliceosome, which are known to be required for effective DNA repair. We identified and characterized the RNA polymerase II-associated protein CDC73/Parafibromin as a new player in recombination repair and show that it is critical for genomic stability. CDC73 interacts with components of the SCF/Cullin and INO80/NuA4 chromatin-remodeling complexes to promote Histone ubiquitination. Our findings indicate that CDC73 is involved in local chromatin decondensation at sites of DNA damage to promote DNA repair. This function of CDC73 is related to but independent of its role in transcriptional elongation