The ␤ clamp is an essential replication sliding clamp required for processive DNA synthesis. The ␤ clamp is also critical for several additional aspects of DNA metabolism, including DNA mismatch repair (MMR). The dnaN5 allele of Bacillus subtilis encodes a mutant form of ␤ clamp containing the G73R substitution. Cells with the dnaN5 allele are temperature sensitive for growth due to a defect in DNA replication at 49°C, and they show an increase in mutation frequency caused by a partial defect in MMR at permissive temperatures. We selected for intragenic suppressors of dnaN5 that rescued viability at 49°C to determine if the DNA replication defect could be separated from the MMR defect. We isolated three intragenic suppressors of dnaN5 that restored growth at the nonpermissive temperature while maintaining an increase in mutation frequency. All three dnaN alleles encoded the G73R substitution along with one of three novel missense mutations. The missense mutations isolated were S22P, S181G, and E346K. Of these, S181G and E346K are located near the hydrophobic cleft of the ␤ clamp, a common site occupied by proteins that bind the ␤ clamp. Using several methods, we show that the increase in mutation frequency resulting from each dnaN allele is linked to a defect in MMR. Moreover, we found that S181G and E346K allowed growth at elevated temperatures and did not have an appreciable effect on mutation frequency when separated from G73R. Thus, we found that specific residue changes in the B. subtilis ␤ clamp separate the role of the ␤ clamp in DNA replication from its role in MMR.Replication sliding clamps are essential cellular proteins imparting a spectacular degree of processivity to DNA polymerases during genome replication (24,(39)(40)(41). Encoded by the dnaN gene, the ␤ clamp is a highly conserved bacterial sliding clamp found in virtually all eubacterial species (reviewed in reference 7). The ␤ clamp is a head-to-tail, ringshaped homodimer that encircles double-stranded DNA (1, 39). In eukaryotes and archaea, the analog of the ␤ clamp is proliferating cell nuclear antigen (PCNA) (15,28,40,41). Eukaryotic PCNA is a ring-shaped homotrimer that also acts to encircle DNA, increasing the processivity of the replicative DNA polymerases (40,41). Although the primary structures of the ␤ clamp and PCNA are not conserved, the tertiary structures of these proteins are very similar, demonstrating structural conservation among bacterial, archaeal, and eukaryotic replication sliding clamps (28, 39-41; reviewed in reference 6).The function of the ␤ clamp is not limited to its well-defined role in genome replication. The Escherichia coli ␤ clamp binds Hda, which also binds the replication initiation protein DnaA, regulating the active form of DnaA complexed with ATP (19,37,43). This allows the ␤ clamp to regulate replication initiation through the amount of available DnaA-ATP. In Bacillus subtilis, the ␤ clamp binds YabA, a negative regulator of DNA replication initiation (12,29,52). It has also been suggested that the B. subt...

Context: Previous studies have linked posttraumatic emotional numbing symptoms in US combat veterans with an adverse impact in multiple important life domains.Objectives: We updated and evaluated the evidence examining the psychosocial impact of combat-related emotional numbing, including ethnoracial and gender differences. Method:We reviewed 1,209 articles published betwen January 2012 and 2018 and selected 24 studies for inclusion. We assessed the overall study quality as fair using a national quality assessment tool. Results: Studies found emotional numbing to wield adverse effects in the areas of symptom nonimprovement, mental health difficulties, increased service utilization, poor relationship functioning, reduced quality of life, substance use disorders, suicidality, and aggression/violence. We also found evidence of ethnoracial and gender differences in veterans' posttraumatic stress disorder-related emotional numbing symptoms. Conclusion: Clinicians should incorporate findings on emotional numbing into assessment, treatment planning, and monitoring, to improve treatment retention and psychosocial outcomes. Implications for ethnoracial and gender differences require further exploration. K E Y W O R D S emotional numbing, military, posttraumatic stress disorder, systematic review, veteran J. Clin. Psychol. 2019;75:644-663. wileyonlinelibrary.com/journal/jclp 644 |

A strong commitment to undergraduate teaching will improve the attractiveness of psychiatry as a career. This must include exposure of students to teachers who mentor practice patterns attuned to provincial mental health reforms, since government initiatives alone, developed to promote desired transitions in psychiatric care, will not influence training program choice.

No abstract

High state densities in the band gap of the SiC-SiO 2 interface significantly reduce the channel mobilities in SiC-based high-temperature/high-power microelectronics. Investigations of the nature of the interface defects are thus of great importance. While several possible defects including very small carbon clusters with up to four carbon atoms have been identified by first-principles theory, larger carbon clusters as possible defects have attracted less attention. Here, we report first-principles quantum-mechanical calculations for two larger carbon clusters, the C 10 ring and the C 20 fullerence, at the SiC-SiO 2 interface. We find that both carbon clusters introduce significant states in the band gap. The states extend over the entire band gap with higher densities in the upper half of the gap, thus accounting for some of the interface trap densities observed experimentally.