Repair of gaps opposite lesions by homologous recombination in mammalian cells

Damages in the DNA template inhibit the progression of replication, which may cause single-stranded gaps. Such situations can be tolerated by translesion DNA synthesis (TLS), or by homology-dependent repair (HDR), which is based on transfer or copying of the missing information from the replicated sister chromatid. Whereas it is well established that TLS plays an important role in DNA damage tolerance in mammalian cells, it is unknown whether HDR operates in this process. Using a newly developed plasmid-based assay that distinguishes between the three mechanisms of DNA damage tolerance, we found that mammalian cells can efficiently utilize HDR to repair DNA gaps opposite an abasic site or benzo[a]pyrene adduct. The majority of these events occurred by a physical strand transfer (homologous recombination repair; HRR), rather than a template switch mechanism. Furthermore, cells deficient in either the human RAD51 recombination protein or NBS1, but not Rad18, exhibited decreased gap repair through HDR, indicating a role for these proteins in DNA damage tolerance. To our knowledge, this is the first direct evidence of gap-lesion repair via HDR in mammalian cells, providing further molecular insight into the potential activity of HDR in overcoming replication obstacles and maintaining genome stability

Interaction between Coastal and Oceanic Ecosystems of the Western and Central Pacific Ocean through Predator-Prey Relationship Studies

The Western and Central Pacific Ocean sustains the highest tuna production in the world. This province is also characterized by many islands and a complex bathymetry that induces specific current circulation patterns with the potential to create a high degree of interaction between coastal and oceanic ecosystems. Based on a large dataset of oceanic predator stomach contents, our study used generalized linear models to explore the coastal-oceanic system interaction by analyzing predator-prey relationship. We show that reef organisms are a frequent prey of oceanic predators. Predator species such as albacore (Thunnus alalunga) and yellowfin tuna (Thunnus albacares) frequently consume reef prey with higher probability of consumption closer to land and in the western part of the Pacific Ocean. For surface-caught-predators consuming reef prey, this prey type represents about one third of the diet of predators smaller than 50 cm. The proportion decreases with increasing fish size. For predators caught at depth and consuming reef prey, the proportion varies with predator species but generally represents less than 10%. The annual consumption of reef prey by the yellowfin tuna population was estimated at 0.8±0.40CV million tonnes or 2.17×1012±0.40CV individuals. This represents 6.1%±0.17CV in weight of their diet. Our analyses identify some of the patterns of coastal-oceanic ecosystem interactions at a large scale and provides an estimate of annual consumption of reef prey by oceanic predators

AN OPEN SYSTEMS MODEL: MAINSTREAMING EXCEPTIONAL AND BILINGUAL ELEMENTARY EDUCATION CHILDREN CONCEPTUALIZED ALONG A PIAGETIAN DEVELOPMENTAL CONTINUUM.

Abstract not availabl

Multivalent Group A Streptococcal Vaccine Elicits Bactericidal Antibodies against Variant M Subtypes

Group A streptococci cause a wide spectrum of clinical illness. One of several strategies for vaccine prevention of these infections is based on the type-specific M protein epitopes. A multivalent M protein-based vaccine containing type-specific determinants from 26 different M serotypes is now in clinical trials. Recent epidemiologic studies have shown that, within some serotypes, the amino-terminal M protein sequence may show natural variation, giving rise to subtypes. This raises the possibility that vaccine-induced antibodies against the parent type may not be as effective in promoting bactericidal killing of variant subtypes. In the present study we used rabbit antisera against the 26-valent M protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci, which were represented by multiple subtypes. We show that the vaccine antibodies effectively promoted in vitro bactericidal activity despite the fact that the M proteins contained naturally occurring variant sequences in the regions corresponding to the vaccine sequence. Our results show that the variant M proteins generally do not result in significant differences in opsonization promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that a multivalent M protein vaccine may not permit variant subtypes of group A streptococci to escape in a highly immunized population