Physical interactions between MCM and Rad51 facilitate replication fork lesion bypass and ssDNA gap filling by non-recombinogenic functions

The minichromosome maintenance (MCM) helicase physically interacts with the recombination proteins Rad51 and Rad52 from yeast to human cells. We show, in Saccharomyces cerevisiae, that these interactions occur within a nuclease-insoluble scaffold enriched in replication/repair factors. Rad51 accumulates in a MCM- and DNA-binding-independent manner and interacts with MCMhelicases located outside of the replication origins and forks. MCM, Rad51, and Rad52 accumulate in this scaffold in G1 and are released during the S phase. In the presence of replication-blocking lesions, Cdc7 prevents their release from the scaffold, thus maintaining the interactions. We identify a rad51 mutant that is impaired in its ability to bind to MCM but not to the scaffold. This mutant is proficient in recombination but partially defective in single-stranded DNA (ssDNA) gap filling and replication fork progression through damaged DNA. Therefore, cells accumulate MCM/Rad51/Rad52 complexes at specific nuclear scaffolds in G1 to assist stressed forks through non-recombinogenic functions.Cancer Signaling networks and Molecular Therapeutic

Excitation spectrum and high-energy plasmons in single-layer and multilayer graphene

Contains fulltext : 91789.pdf (preprint version ) (Open Access

Genetic analysis of tuna populations, <i>Thunnus thynnus thynnus</i> and <i>T. alalunga</i>

The genetic population structures of Atlantic northern bluefin tuna (Thunnus thynnus thynnus) and albacore (T. alalunga) were examined using allozyme analysis. A total of 822 Atlantic northern bluefin tuna from 18 different samples (16 Mediterranean, 1 East Atlantic, 1 West Atlantic) and 188 albacore from 5 samples (4 Mediterranean, 1 East Atlantic) were surveyed for genetic variation in 37 loci. Polymorphism and heterozygosity reveal a moderate level of genetic variability, with only two highly polymorphic loci in both Atlantic northern bluefin tuna (FH* and SOD-1*) and albacore (GPI-3* and XDH*). The level of population differentiation found for Atlantic northern bluefin tuna and albacore fits the pattern that has generally been observed in tunas, with genetic differences on a broad rather than a more local scale. For Atlantic northern bluefin tuna, no spatial or temporal genetic heterogeneity was observed within the Mediterranean Sea or between the East Atlantic and Mediterranean, indicating the existence of a single genetic grouping on the eastern side of the Atlantic Ocean. Very limited genetic differentiation was found between West Atlantic and East Atlantic/Mediterranean northern bluefin tuna, mainly due to an inversion of SOD-1* allele frequencies. Regarding albacore, no genetic heterogeneity was observed within the Mediterranean Sea or between Mediterranean and Azores samples, suggesting the existence of a single gene pool in this area

Caring and the welfare state in the 1990s

New series: The implications of the 1992 social policySIGLEGBUnited Kingdo

Electronic structure of monolayer antimonene nanoribbons under out-of-plane and transverse bias

Contains fulltext : 198627pub.pdf (publisher's version ) (Open Access)7 p

Evolución en niños con falla intestinal en un hospital de referencia en Medellín, Colombia

Antecedentes: Los pacientes con falla intestinal son incapaces de mantener una adecuada nutrición e hidratación debido a una reducción en el área intestinal funcional. La implementación de diferentes estrategias tiene el potencial de beneficiar a estos pacientes en términos de favorecer la autonomía intestinal, aumentar la calidad de vida y elevar la supervivencia. Objetivos: Describir las características clínicas de niños con falla intestinal, así como la evolución en términos de autonomía intestinal y supervivencia. Materiales y métodos: Estudio retrospectivo en el que se evaluó a 33 pacientes pediátricos con falla intestinal, hospitalizados entre diciembre del 2005 y diciembre del 2013 en una institución de alta especialidad. Se describieron las características de los pacientes al ingreso hospitalario, se estimó la probabilidad de lograr la autonomía intestinal y se calculó la tasa de supervivencia. Resultados: La mediana de edad al momento de ingresar al hospital fue 2 meses (rango intercuartílico [RIC]: 1-4 meses) y el 54.5% de los pacientes fueron de sexo masculino. El 69.7% de los casos lograron la autonomía intestinal con una mediana de tiempo de 148 días (RIC: 63-431 días), la cual disminuyó a 63 días cuando los pacientes tenían presencia de válvula ileocecal. La supervivencia fue del 91% durante una mediana se seguimiento de 281días (RIC: 161-772 días). Conclusiones: El manejo médico de los pacientes con falla intestinal es complejo. El soporte nutricional y la monitorización continua son de vital importancia y la morbimortalidad a largo plazo depende del reconocimiento y manejo precoz de las complicaciones asociadas

Identification of replication-competent HSV-1 Cgal+ strain targets in a mouse model of human hepatocarcinoma xenograft

Recent studies based on animal models have shown the advantages and potential of oncolytic viral therapy using HSV-1 -based replication-competent vectors in the treatment of liver tumors, but little is known about the cellular targets that are modulated during viral infection. In the present work, we have studied the effects of intratumoral injections of HSV-1 Cgal(+) strain in a murine model of human hepatoma xenografts. Viral replication was assessed for more than 1month, leading to a significant reduction of tumor growth rate mediated, in part, by a cyclin B dependent cell proliferation arrest. Early events resulting in this effect were analyzed using a proteomic approach. Protein extracts from xenografted human hepatomas treated with saline or HSV-1 Cgal(+) strain during 24h were compared by 2-D DIGE and differential spots were identified by nanoLC-ESI-MS/MS. Alterations on glutathione S transferase 1 Omega, and ERp29 suggest novel HSV-1 Cgal(+) targets in solid liver tumors. Additionally, ERp29 showed a complex differential isoform pattern upon HSV-1 Cgal(+) infection, suggesting regulatory mechanisms based on post-translational modification events

Identification of replication-competent HSV-1 Cgal+ strain targets in a mouse model of human hepatocarcinoma xenograft

Recent studies based on animal models have shown the advantages and potential of oncolytic viral therapy using HSV-1 -based replication-competent vectors in the treatment of liver tumors, but little is known about the cellular targets that are modulated during viral infection. In the present work, we have studied the effects of intratumoral injections of HSV-1 Cgal(+) strain in a murine model of human hepatoma xenografts. Viral replication was assessed for more than 1month, leading to a significant reduction of tumor growth rate mediated, in part, by a cyclin B dependent cell proliferation arrest. Early events resulting in this effect were analyzed using a proteomic approach. Protein extracts from xenografted human hepatomas treated with saline or HSV-1 Cgal(+) strain during 24h were compared by 2-D DIGE and differential spots were identified by nanoLC-ESI-MS/MS. Alterations on glutathione S transferase 1 Omega, and ERp29 suggest novel HSV-1 Cgal(+) targets in solid liver tumors. Additionally, ERp29 showed a complex differential isoform pattern upon HSV-1 Cgal(+) infection, suggesting regulatory mechanisms based on post-translational modification events

Liquido cefalorraqueano no récem-nascido pré-termo sadio

Estudo da composição do LCR de 54 recém-nascidos prematuros sadios no segundo dia de vida. Os prematuros estudados precediam de gestações sem inter-corrências com parto não-traumático, apresentavam Apgar entre 6 e 9 aos 5 minutos de vida e não apresentavam anormalidades quanto ao exame clínico, neurológico, hematimétrico e gasométrico. Da composição do LCR foram estu-dades a citometria e as concentrações de proteínas totais, glicose, bilirrubina e hemoglobina. As estimativas encontradas permitem aceitar como limites das variações fisiológicas da composição do LCR do RN-PT os seguintes valores: leucócitos até 16 por mm ³; hemácias até 1.280 por mm3; proteínas totais até 300 mg/100 ml; bilirrubina de 10 a 80 µM/l; hemoglobina até 8 µM/l; glicose: cerca de 2/3 da concentração no sangue. Em relação à composição do LCR de 79 recém-nascidos normais a termo, avaliada mediante os mesmos métodos e no mesmo laboratório, são significativamente maiores as concentrações de proteínas totais e de bilirrubina, bem como estar presente a hemoglobina, pigmento não demonstrado no recém-nascido a termo. É discutida a importância da imaturidade da barreira hêmato-liquórica quanto às características do LCR apontadas, considerando-se encontrar-se ela ainda menos diferenciada no recém-nascido prematuro que no recém-nascido a termo