Comparison of Human Memory CD8 T Cell Responses to Adenoviral Early and Late Proteins in Peripheral Blood and Lymphoid Tissue

Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16–24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients

Aggregatibacter actinomycetemcomitans Omp29 Is Associated with Bacterial Entry to Gingival Epithelial Cells by F-Actin Rearrangement

The onset and progressive pathogenesis of periodontal disease is thought to be initiated by the entry of Aggregatibacter actinomycetemcomitans (Aa) into periodontal tissue, especially gingival epithelium. Nonetheless, the mechanism underlying such bacterial entry remains to be clarified. Therefore, this study aimed to investigate the possible role of Aa outer membrane protein 29 kD (Omp29), a homologue of E. coli OmpA, in promoting bacterial entry into gingival epithelial cells. To accomplish this, Omp29 expression vector was incorporated in an OmpA-deficient mutant of E. coli. Omp29+/OmpA− E. coli demonstrated 22-fold higher entry into human gingival epithelial line cells (OBA9) than Omp29−/OmpA− E. coli. While the entry of Aa and Omp29+/OmpA− E. coli into OBA9 cells were inhibited by anti-Omp29 antibody, their adherence to OBA9 cells was not inhibited. Stimulation of OBA9 cells with purified Omp29 increased the phosphorylation of focal adhesion kinase (FAK), a pivotal cell-signaling molecule that can up-regulate actin rearrangement. Furthermore, Omp29 increased the formation of F-actin in OBA9 cells. The internalization of Omp29-coated beads and the entry of Aa into OBA9 were partially inhibited by treatment with PI3-kinase inhibitor (Wortmannin) and Rho GTPases inhibitor (EDIN), both known to convey FAK-signaling to actin-rearrangement. These results suggest that Omp29 is associated with the entry of Aa into gingival epithelial cells by up-regulating F-actin rearrangement via the FAK signaling pathway

VASP: A Volumetric Analysis of Surface Properties Yields Insights into Protein-Ligand Binding Specificity

Many algorithms that compare protein structures can reveal similarities that suggest related biological functions, even at great evolutionary distances. Proteins with related function often exhibit differences in binding specificity, but few algorithms identify structural variations that effect specificity. To address this problem, we describe the Volumetric Analysis of Surface Properties (VASP), a novel volumetric analysis tool for the comparison of binding sites in aligned protein structures. VASP uses solid volumes to represent protein shape and the shape of surface cavities, clefts and tunnels that are defined with other methods. Our approach, inspired by techniques from constructive solid geometry, enables the isolation of volumetrically conserved and variable regions within three dimensionally superposed volumes. We applied VASP to compute a comparative volumetric analysis of the ligand binding sites formed by members of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains and the serine proteases. Within both families, VASP isolated individual amino acids that create structural differences between ligand binding cavities that are known to influence differences in binding specificity. Also, VASP isolated cavity subregions that differ between ligand binding cavities which are essential for differences in binding specificity. As such, VASP should prove a valuable tool in the study of protein-ligand binding specificity

Editors’ Introduction: An Overview of the Educational Administration and Leadership Curriculum: Traditions of Islamic Educational Administration and Leadership in Higher Education

This chapter provides an overview of several topics relevant to constructing an approach to teaching educational administration and leadership in Muslim countries. First, it places the topic in the context of the changing nature and critiques of the field that argue for a greater internationalisation to both resist some of the negative aspects of globalisation and to represent countries’ traditions in the professional curriculum. Then, it identifies literature that presents the underlying principles and values of Islamic education that guide curriculum and pedagogy and shape its administration and leadership including the Qur’an and Sunnah and the classical educational literature which focuses on aims, values and goals of education as well as character development upon which a ‘good’ society is built. This is followed by a section on the Islamic administration and leadership traditions that are relevant to education, including the values of educational organisations and how they should be administered, identifying literature on the distinctive Islamic traditions of leadership and administrator education and training as it applies to education from the establishment of Islam and early classical scholars and senior administrators in the medieval period who laid a strong foundation for a highly sophisticated preparation and practice of administration in philosophical writings and the Mirrors of Princes writings, and subsequent authors who have built upon it up to the contemporary period. The final section provides an overview of the chapters in this collection

Distribution patterns of riodinid butterflies (Lepidoptera: Riodinidae) from southern Brazil

Background: The aim of this study was to synthesize the knowledge of Riodinidae butterflies (Lepidoptera: Papilionoidea) in Rio Grande do Sul state (RS), southern Brazil, evaluating the role of climatic, topographic, and vegetational variables on the observed patterns of occurrence and distribution of these butterflies in the Pampa and Atlantic Forest biomes. The records of riodinid butterflies in RS were collected from published studies and the examination of museum collections in Brazil. Results: A total of 97 taxa of Riodinidae were recorded, distributed in 92 municipalities. The NMDS analysis and the Constrained Analysis of Principal Coordinates grouped the municipalities according to the phytogeographic regions and biomes - Pampa and Atlantic Forest domains - in which the species records were made. Distance from the ocean, precipitation and temperature were the environmental variables which most contributed to explain the distribution patterns of these butterflies. The multivariate Mantel correlogram suggests that over short distances, the composition of species shows significant levels of spatial autocorrelation, and as geographic distance increases, these levels tend to present negative values. Conclusions: The results suggest that the observed distribution pattern of Riodinidae in the different biomes and phytogeographic regions in the extreme southern Brazil could be explained by climatic, environmental variables and geographic distance

NATURAL HISTORY, NEW RECORDS, AND NOTES ON THE CONSERVATION STATUS OF CYANOPHRYS BERTHA (JONES) (LEPIDOPTERA: LYCAENIDAE)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The natural history of the potentially threatened hairstreak butterfly Cyanophrys bertha (Jones) is discussed, and the morphology of its penultimate and last instar larvae and pupa are described and illustrated. New distribution records from southern Brazil are provided. Based on morphological and ecological traits of immatures and adults, the conservation status of this species is discussed and compared with other sympatric Eumaeini.11215460Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [140183/2006-0, 478787/2001-4

Aneurysmal SAH: cognitive outcome and structural damage after clipping or coiling.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) and surgical clipping of intracranial aneurysms are associated with substantial morbidity and mortality. OBJECTIVE: To compare cognitive outcome and structural damage in patients with aneurysmal SAH treated with surgical clipping or endovascular coiling. METHODS: Forty case-matched pairs of patients with aneurysmal SAH treated by surgical clipping or endovascular coiling were prospectively assessed by use of a battery of cognitive tests. Twenty-three case-matched pairs underwent MRI 1 year after the procedure. Matching was based on grade of SAH on admission, location of aneurysm, age, and premorbid IQ. RESULTS: Both groups were impaired in all cognitive domains when compared with age-matched healthy control subjects. Comparison of cognitive outcome between the two groups indicated an overall trend toward a poorer cognitive outcome in the surgical group, which achieved significance in four tests. MRI showed focal encephalomalacia exclusively in the surgical group. This group also had a significantly higher incidence of single or multiple small infarcts within the vascular territory of the aneurysm, but both groups had similar incidence of large infarcts and global ischemic damage. CONCLUSION: Endovascular treatment may cause less structural brain damage than surgery and have a more favorable cognitive outcome. However, cognitive outcome appears to be dictated primarily by the complications of SAH