The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.

The amyloid-β peptide or Aβ is the key player in the amyloid-cascade hypothesis of Alzheimer's disease. Aβ appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer's disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of Aβ peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of Aβ-induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair Aβ-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA-mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when Aβ increase and RA decrease probably lead to a pathological state

Findings in multidetector computed tomography in the diagnosis of hepatocellular carcinoma in patients with cirrhosis and correlation with pathology of liver explants

Objetivos: Describir el comportamiento imagenológico del hepatocarcinoma en pacientes con cirrosis utilizando la tomografía computada multidetector (TCMD) dinámica y correlacionar los hallazgos con el grado histológico de los tumores. Materiales y métodos: Estudio retrospectivo, observacional y descriptivo, donde se evaluaron 51 nódulos de 32 pacientes trasplantados de hígado con diagnóstico de cirrosis. La anatomía patológica del explante fue utilizada como referencia y los nódulos con histología de hepatocarcinoma fueron analizados retrospectivamente en las tomografías computadas efectuadas antes del trasplante. Las tomografías se llevaron a cabo con técnica dinámica, evaluando las características más frecuentes reportadas en la literatura: realce arterial, lavado del realce, cápsula y vasos arteriales intratumorales. Resultados: Cuarenta y seis de 51 (90%) tumores mostraron realce arterial. De estos 46 tumores, 39 (85%) mostraron lavado del realce en la fase portal y/o tardía. De los 51, 5 (10%) fueron hipovasculares, 22 (43%) presentaron cápsula y 12 (24%) mostraron vasos arteriales intratumorales. La combinación de hallazgos más frecuente fue la asociación de realce arterial y lavado del realce en la fase portal-tardía (39/51 tumores: 76%), y el grado histológico más usual fue el II en 35 tumores (69%). Se hallaron asociaciones estadísticamente significativas entre el grado histológico de los tumores y los comportamientos imagenológicos realce arterial e hipovascular. Conclusión: En nuestra población, el hallazgo tomográfico de realce arterial con lavado del realce en tiempo portal y/o tardío fue observado en la mayoría de los tumores. Esto coincide con publicaciones anteriores y contribuye a fortalecer el valor de estos criterios para el diagnóstico del hepatocarcinoma.Objectives: To describe the imagenological behavior of hepatocellular carcinoma in cirrhotic patients using a dynamic multidetector computed tomography (MDCT) technique, and correlate these À ndings with histological tumor grades. Materials and methods: A retrospective, descriptive observational study was conducted to evaluate 51 nodules in 32 liver transplant patients diagnosed with liver cirrhosis. The pathology of liver explants was used as a reference. Nodules with hepatocellular carcinoma histopathology were retrospectively analyzed by computed tomography scans performed pre-transplant. Using a dynamic multidetector computed tomography technique, we evaluated the most common imagenological behavior reported in the literature: arterial enhancement, washout, capsule, and intratumoral arterial vessels. Results: Forty-six of 51 (90%) tumors showed arterial enhancement. Of the 46 tumors with arterial enhancement, 39 (85%) had washout in portal-late phase. Five of 51 (10%) were hypovascular. Twenty-two of 51 (43%) had capsule and 12 of 51 (24%) showed intratumoral arterial vessels. The more frequent image combination was the combination of arterial enhancement and washout (39 of 51 tumors or 76%). The most frequent histological grade was II (35 of 51 tumors or 69%). Statistically signiÀ cant relationships were found between histological grade tumors and imagenological behavior: arterial enhancement and hypovascular. Conclusion: In our population, arterial enhancement with washout in portal-late phases was observed in most of the tumors. Our results are consistent with previously reported studies, demonstrating the high reliability of this imaging pattern for the diagnosis of hepatocellular carcinoma.Fil: Haberman, D. Fundación Favaloro; ArgentinaFil: Castignola, M. Fundación Favaloro; ArgentinaFil: Mela, M. Fundación Favaloro; ArgentinaFil: Paladini, H. Fundación Favaloro; ArgentinaFil: Santilli, J. P. Fundación Favaloro; ArgentinaFil: Gruz, F. Fundación Favaloro; ArgentinaFil: Gondolesi, Gabriel Eduardo. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

K0s K0s Final State in Two-Photon Collisions and Implications for Glueballs

The K0s K0s final state in two-photon collisions is studied with the L3 detector at LEP. The mass spectrum is dominated by the formation of the f_2'(1525) tensor meson in the helicity-two state with a two-photon width times the branching ratio into K Kbar of 76 +- 6 +- 11 eV. A clear signal for the formation of the f_J(1710) is observed and it is found to be dominated by the spin-two helicity-two state. No resonance is observed in the mass region around 2.2 GeV and an upper limit of 1.4 eV at 95% C.L. is derived for the two-photon width times the branching ratio into K0s K0s for the glueball candidate xi(2230)

A nucleotide binding rectification Brownian ratchet model for translocation of Y-family DNA polymerases

Y-family DNA polymerases are characterized by low-fidelity synthesis on undamaged DNA and ability to catalyze translesion synthesis over the damaged DNA. Their translocation along the DNA template is an important event during processive DNA synthesis. In this work we present a Brownian ratchet model for this translocation, where the directed translocation is rectified by the nucleotide binding to the polymerase. Using the model, different features of the available structures for Dpo4, Dbh and polymerase ι in binary and ternary forms can be easily explained. Other dynamic properties of the Y-family polymerases such as the fast translocation event upon dNTP binding for Dpo4 and the considerable variations of the processivity among the polymerases can also be well explained by using the model. In addition, some predicted results of the DNA synthesis rate versus the external force acting on Dpo4 and Dbh polymerases are presented. Moreover, we compare the effect of the external force on the DNA synthesis rate of the Y-family polymerase with that of the replicative DNA polymerase

Hallazgos en tomografía computada multidetector en el diagnóstico del carcinoma hepatocelular en pacientes con cirrosis y su correlación con la anatomía patológica del explante hepático

Objetivos: Describir el comportamiento imagenológico del hepatocarcinoma en pacientes con cirrosis utilizando la tomografía computada multidetector (TCMD) dinámica y correlacionar los hallazgos con el grado histológico de los tumores. Materiales y métodos: Estudio retrospectivo, observacional y descriptivo, donde se evaluaron 51 nódulos de 32 pacientes trasplantados de hígado con diagnóstico de cirrosis. La anatomía patológica del explante fue utilizada como referencia y los nódulos con histología de hepatocarcinoma fueron analizados retrospectivamente en las tomografías computadas efectuadas antes del trasplante. Las tomografías se llevaron a cabo con técnica dinámica, evaluando las características más frecuentes reportadas en la literatura: realce arterial, lavado del realce, cápsula y vasos arteriales intratumorales. Resultados: Cuarenta y seis de 51 (90%) tumores mostraron realce arterial. De estos 46 tumores, 39 (85%) mostraron lavado del realce en la fase portal y/o tardía. De los 51, 5 (10%) fueron hipovasculares, 22 (43%) presentaron cápsula y 12 (24%) mostraron vasos arteriales intratumorales. La combinación de hallazgos más frecuente fue la asociación de realce arterial y lavado del realce en la fase portal-tardía (39/51 tumores: 76%), y el grado histológico más usual fue el II en 35 tumores (69%). Se hallaron asociaciones estadísticamente significativas entre el grado histológico de los tumores y los comportamientos imagenológicos realce arterial e hipovascular. Conclusión: En nuestra población, el hallazgo tomográfico de realce arterial con lavado del realce en tiempo portal y/o tardío fue observado en la mayoría de los tumores. Esto coincide con publicaciones anteriores y contribuye a fortalecer el valor de estos criterios para el diagnóstico del hepatocarcinoma