DNA-Dependent Protein Kinase Inhibits AID-Induced Antibody Gene Conversion

Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(D)J regions, subsequent excision of the deaminated bases by uracil-DNA glycosylase, or by mismatch repair, leads to further point mutation or gene conversion, depending on the species. In Ig S regions, nicking at the abasic sites produced by AID and uracil-DNA glycosylases results in staggered double-strand breaks, whose repair by nonhomologous end joining mediates Ig class switching. We have tested whether nonhomologous end joining also plays a role in V(D)J hypermutation using chicken DT40 cells deficient for Ku70 or the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inactivation of the Ku70 or DNA-PKcs genes in DT40 cells elevated the rate of AID-induced gene conversion as much as 5-fold. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion

Religion, Belonging, and Social Mobility in Civil Rights Era Birmingham, Alabama

This project narrates the story of Greek-Americans' reactions to the historic civil rights movement in perhaps its most important nerve centers, Birmingham, Alabama. In 1960 Archbishop Iakovos placed in that racial hotbed a young priest named Father Soterios “Sam” Gouvellis, who served the Holy Trinity-Holy Cross Greek Orthodox Church during the most volatile years of the black freedom struggle. Father Sam joined the ad hoc ministerial group whose letter to Martin Luther King Jr. spawned the famous Letter from Birmingham Jail. Gouvellis became involved with the black freedom struggle in Birmingham and eventually marched with King and Archbishop Iakovos in Selma. This project will tell the story of how Gouvellis and his congregation negotiated the mysteries of evangelical religion in the Bible Belt and the enigmas of race in the Jim Crow South. This article distills the argument of what will be the only biography of Gouvellis and one of a very few studies of religion, race, and Greek ethnicity in the American South

Brief, parent-led, transdiagnostic cognitive-behavioral teletherapy for youth with emotional problems related to the COVID-19 pandemic

•Implemented CBT for youth with emotional problems during the COVID-19 pandemic.•Program consisted of a six-session, parent-led, transdiagnostic telehealth protocol.•Parent-related anxiety, depression, stress, anger, family relationships, and COVID-19-related distress improved.•62% of families who completed the program were classified as responders.•Parents reported high satisfaction with the program. The COVID-19 pandemic has led to increased stress, anxiety, and depression in children. A six-session, parent-led, transdiagnostic, cognitive-behavioral teletherapy program was adapted from an established protocol to help youth aged between 5 and 13 years manage emotional problems during the pandemic. One-hundred twenty-nine parents of youth struggling with emotional problems during the COVID-19 pandemic participated in the program. Parents reported on their children's psychosocial functioning before and after treatment using validated assessments. They also reported on treatment satisfaction. Clinician-rated global improvement was assessed at each session to determine clinically significant treatment response. Significant improvements in parent proxy-reported anxiety (d = 0.56), depression (d = 0.69), stress (d = 0.61), anger (d = 0.69), family relationships (d = 0.32), and COVID-19-related distress (d = 1.08) were found, with 62% of participants who completed the program being classified as treatment responders. Parents reported high levels of satisfaction with the program. This study was limited by use of primarily parent-report assessments and a lack of a control group. Brief, parent-led, transdiagnostic cognitive-behavioral teletherapy appeared to be an effective way to help youth cope with the pandemic and may be a scalable framework in response to large-scale mental health crises