No abstract

IntroductionHuman cytomegalovirus (CMV) is a widespread ␤-herpes virus that infects more than half of the Western population. Primary infection induces a life-long latent infection in the immunocompetent host with asymptomatic episodes of viral replication, which are controlled by a vigorous immune response. CMV infection is responsible for increased morbidity and mortality after allogeneic stem cell transplantation (SCT) as either CMV reactivation in CMV-seropositive patients or primary infection in CMV-seronegative patients receiving grafts from seropositive donors. Several studies have demonstrated a significant decline in a overall survival in human leukocyte antigen-identical sibling transplantations or in unrelated transplantations where either the donor or the patient was CMV-seropositive. 1,2 The central mechanism controlling CMV infection is mediated by antigen-specific CD8 ϩ cytotoxic and CD4 ϩ ␣␤ T lymphocytes and natural killer (NK) cells. [3][4][5] CMV-specific CD3 ϩ CD8 ϩ CD28 Ϫ CD57 ϩ ␣␤ T cells are regarded as the principle effector cells controlling CMV reactivation. 6,7 Both humoral and cellular immunity is involved in protective immune responses to CMV reactivation and CMV resolution. 8 Recent interest has focused on ␥␦ T cells and their role in immune responses during CMV infection. ␥␦ T cells are often termed the "unconventional" T cells and represent a minor population of circulating T cells (Ͻ 5%) in humans but are present in large numbers in epithelial tissues. [9][10][11][12][13] In contrast to ␣␤ T cells, which recognize peptides bound to major histocompatibility complex (MHC) class I or class II molecules, most ␥␦ T cells lack surface expression of CD4 or CD8 and display a non-MHC-restricted recognition. 14,15 There are 2 major subsets of ␥␦ T cells present in human peripheral blood: a subset of ␥␦ T cells expressing a T-cell receptor (TCR) encoded by the V␦2 and V␥9 gene segments, which accounts for 50% to 90% of ␥␦ T cells in adult peripheral blood and a minor V␦1 subset more frequent at mucosal epithelium sites, such as skin and the intestine. An additional small subset of V␦3 ␥␦ T cells is also present in peripheral blood but represents a minor population of less than 0.1% of CD3 ϩ T cells. The ␥␦ T cells recognize ligands that are not seen by ␣␤ T cells and provide additional means by which the immune system can maintain local immunosurveillance with immediate tumor defense, selective recognition of viral antigens, and bacterial metabolites. 12,14 V␦1 ␥␦ T cells recognize ligands for an activating receptor NKG2D, such as MHC class I-related chain A (MICA and MICB) stress-induced antigens expressed on epithelial tumor cells, some leukemias, lymphomas, and the UL16-binding proteins. [16][17][18][19][20][21][22][23][24] V␦2 ␥␦ T cells recognize low molecular weight nonpeptidic phosphoantigens, particularly intermediates of the nonmevalonate pathway of bacterial isoprenoid biosynthesis 25 or isopenthenyl pyrophosphate and aminobiphosphonates in eukaryotic cells. 26 Recent studies have...

Depression and anxiety are prevalent in children with rheumatologic diseases, including juvenile idiopathic arthritis (JIA). However, prevalence rates and the relationship with disease outcomes, including quality of life are conflicting in the early literature. To review the current literature, determine gaps in our knowledge, and identify areas in need of further investigation, we conducted a systematic review of studies examining depression and anxiety symptoms among children with JIA and the impact these symptoms may have on disease outcomes and quality of life. Six electronic databases were searched up until January 2019. Of 799 potential articles, 60 articles were included with the main focus on 28 articles from 2009 to 2019, to concentrate on the most current evidence. We found that JIA patients experience symptoms of depression and anxiety similar to other childhood chronic diseases and at higher rates than in healthy children. Patients who experience these symptoms have worse quality of life, with some evidence pointing to depression and anxiety symptoms having a greater impact on quality of life than other disease features, such as active joint count. Family members of JIA patients experience high rates of anxiety and depression symptoms which may impact their child's mental health and pain symptoms related to JIA. Conflicting reports of associations between depression/anxiety symptoms and disease features/disease outcomes and a paucity of longitudinal studies investigating the impact of treatment on mental health symptoms indicate areas in need of further research to effectively identify patients at greatest risk of depression and anxiety and to better understand how to treat and prevent these symptoms in youth with JIA. Family mental health should also be considered in investigations concerning mental health and disease outcomes of children with JIA.

The family of the Nine amino acid Transactivation Domain, 9aaTAD family, comprises currently over 40 members. The 9aaTAD domains are universally recognized by the transcriptional machinery from yeast to man. We had identified the 9aaTAD domains in the p53, Msn2, Pdr1 and B42 activators by our prediction algorithm. In this study, their competence to activate transcription as small peptides was proven. Not surprisingly, we elicited immense 9aaTAD divergence in hundreds of identified orthologs and numerous examples of the 9aaTAD species' convergence. We found unforeseen similarity of the mammalian p53 with yeast Gal4 9aaTAD domains. Furthermore, we identified artificial 9aaTAD domains generated accidentally by others. From an evolutionary perspective, the observed easiness to generate 9aaTAD transactivation domains indicates the natural advantage for spontaneous generation of transcription factors from DNA binding precursors.