The authors present a similarity-based model of induction and categorization in young children (SINC). The model suggests that (a). linguistic labels contribute to the perceived similarity of compared entities and (b). categorization and induction are a function of similarity computed over perceptual information and linguistic labels. The model also predicts young children's similarity judgment, induction, and categorization performance under different stimuli and task conditions. Predictions of the model were tested and confirmed in 6 experiments, in which 4- to 5-year-olds performed similarity judgment, induction, and categorization tasks using artificial and real labels (Experiments 1-4) and recognition memory tasks (Experiments 5A and 5B). Results corroborate the similarity-based account of young children's induction and categorization, and they support both qualitative and quantitative predictions of the model.

DNA double-strand breaks (DSBs) represent an important radiation-induced lesion and impaired DSB repair provides the best available correlation with radiosensitivity. Physical techniques for monitoring DSB repair require high, non-physiological doses and cannot reliably detect subtle defects. One outcome from extensive research into the DNA damage response is the observation that H2AX, a variant form of the histone H2A, undergoes extensive phosphorylation at the DSB, creating gammaH2AX foci that can be visualized by immunofluorescence. There is a close correlation between gammaH2AX foci and DSB numbers and between the rate of foci loss and DSB repair, providing a sensitive assay to monitor DSB repair in individual cells using physiological doses. However, gammaH2AX formation can occur at single-stranded DNA regions which arise during replication or repair and thus does not solely correlate with DSB formation. Here, we present and discuss evidence that following exposure to ionizing radiation, gammaH2AX foci analysis can provide a sensitive monitor of DSB formation and repair and describe techniques to optimize the analysis. We discuss the limitations and benefits of the technique, enabling the procedure to be optimally exploited but not misused.

PARP-3 is a member of the ADP-ribosyl transferase superfamily of unknown function. We show that PARP-3 is stimulated by DNA double-strand breaks (DSBs) in vitro and functions in the same pathway as the poly (ADP-ribose)-binding protein APLF to accelerate chromosomal DNA DSB repair. We implicate PARP-3 in the accumulation of APLF at DSBs and demonstrate that APLF promotes the retention of XRCC4/DNA ligase IV complex in chromatin, suggesting that PARP-3 and APLF accelerate DNA ligation during nonhomologous end-joining (NHEJ). Consistent with this, we show that class switch recombination in Aplf(-/-) B cells is biased toward microhomology-mediated end-joining, a pathway that operates in the absence of XRCC4/DNA ligase IV, and that the requirement for PARP-3 and APLF for NHEJ is circumvented by overexpression of XRCC4/DNA ligase IV. These data identify molecular roles for PARP-3 and APLF in chromosomal DNA double-strand break repair reactions.

Single-strand breaks are the commonest lesions arising in cells, and defects in their repair are implicated in neurodegenerative disease. One of the earliest events during single-strand break repair (SSBR) is the rapid synthesis of poly(ADP-ribose) (PAR) by poly(ADP-ribose) polymerase (PARP), followed by its rapid degradation by poly(ADP-ribose) glycohydrolase (PARG). While the synthesis of poly(ADP-ribose) is important for rapid rates of chromosomal SSBR, the relative importance of poly(ADP-ribose) polymerase 1 (PARP-1) and PARP-2 and of the subsequent degradation of PAR by PARG is unclear. Here we have quantified SSBR rates in human A549 cells depleted of PARP-1, PARP-2, and PARG, both separately and in combination. We report that whereas PARP-1 is critical for rapid global rates of SSBR in human A549 cells, depletion of PARP-2 has only a minor impact, even in the presence of depleted levels of PARP-1. Moreover, we identify PARG as a novel and critical component of SSBR that accelerates this process in concert with PARP-1.Single-strand breaks (SSBs) are the commonest type of lesion arising in cells and can arise from direct attack of deoxyribose, as abortive intermediates of topoisomerase 1 activity, or as normal intermediates of base excision repair. One of the earliest responses to DNA strand breakage is the induction of poly(ADP-ribose) (PAR) synthesis (reviewed in references 17 and 35). Poly(ADP-ribose) polymerase 1 (PARP-1) is an abundant and stable component of chromatin and is the major source of PAR synthesis following DNA strand breakage (27,40). PARP-1 rapidly binds to and is activated by DNA singleand double-strand breaks, resulting in covalent modification of itself and to a lesser extent other target proteins with long chains of PAR (4,5,15,41,42). The binding and activity of PARP-1 at DNA breaks are very transient because the ribosylated enzyme dissociates from DNA through charge repulsion (24, 60). Subsequently, a second DNA damage-activated PARP was identified in human cells and was called PARP-2 (1, 30). PARP-2 has 18-fold lower activity than PARP-1 but can support up to 25% of normal levels of DNA damage-induced PAR synthesis in the absence of PARP-1 (1, 49). While PARP-1 is the primary source of global PAR synthesis following DNA strand breakage, it is possible that PARP-2 fulfils an overlapping or backup role. In support of this, mice lacking either PARP-1 or PARP-2 are viable, but mice lacking both enzymes are not (38). The presence of high levels of PAR in cells following DNA strand breakage is very transient because the polymer is rapidly degraded by poly(ADP-ribose) glycohydrolase (PARG). Consequently, proteins that become ribosylated following DNA strand breakage are rapidly converted back to their unmodified form (16,32,56,60). PARG is composed of a 110-kDa nuclear form and at least two cytoplasmic isoforms of 99 kDa and 103 kDa, each of which most likely arises from the same primary transcript (34, 39).Despite their central roles in PAR metabolism, the relative importance of PARP-1, ...

A large body of evidence supports the importance of focused attention for encoding and task performance. Yet young children with immature regulation of focused attention are often placed in elementary-school classrooms containing many displays that are not relevant to ongoing instruction. We investigated whether such displays can affect children's ability to maintain focused attention during instruction and to learn the lesson content. We placed kindergarten children in a laboratory classroom for six introductory science lessons, and we experimentally manipulated the visual environment in the classroom. Children were more distracted by the visual environment, spent more time off task, and demonstrated smaller learning gains when the walls were highly decorated than when the decorations were removed.