Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

Velocity variations in the uppermost mantle beneath the southern Sierra Nevada and Walker Lane

We model Pn waveforms from two earthquakes in the southwestern United States (Mammoth Lakes, California, and western Nevada) to determine a velocity model of the crustal and mantle structure beneath the southern Sierra Nevada and Walker Lane. We derive a one-dimensional velocity model that includes a smooth crust-mantle transition east of Death Valley and extending south into the eastern Mojave desert. West of Death Valley and toward the Sierra Nevada a low-velocity mantle (V_p = 7.6 km/s) directly below the crust indicates the lithosphere is absent. At the base of this low-velocity structure (at 75–100 km depth) the P wave velocity jumps discontinuously to V_p 8.0 km/s. The area of low velocity is bounded by the Garlock Fault to the south and the Sierra Nevada to the west, but we cannot resolve its northern extent. However, on the basis of teleseismic travel times we postulate that the anomaly terminates at about 38°N. The presence of a low-velocity, upper mantle anomaly in this area agrees with geochemical research on xenoliths from the southern Sierras and recent studies of receiver functions, refraction profiles, tomography, and gravity. However, the velocity discontinuity at 75–100 km is a new discovery and may represent the top of the once present, now unaccounted for and possibly sunken Sierra Nevada lithosphere

Public and Private Sector HRD Differences

The purpose of this study is to examine literature on the differences between the public and private sector with respect to human resource development (HRD). This study will define HRD in addition to exploring various published theories on sector differences. The study will address the importance of values, in addition to, specific sector differences. This study will specifically explore any theoretical, human resource management (HRM), organizational development (OD), organizational commitment, wage or motivational differences between the public and private sector. This study is valuable because it will reveal and define some of the public and private sector differences with respect to human resources. This study, in part, helps to answer the question about what is HRD and how is it defined

Analysis of satellite gravity and bathymetry data over Ninety-East Ridge: Variation in the compensation mechanism and implication for emplacement process

International audienceWe investigate the mode of compensation, emplacement history and deep density structure of the Ninety-East Ridge (Indian Ocean) using spectral analyses and forward modeling of satellite gravity and bathymetry data. We find that the northern (0–10°N) and the southern (20–30°S) parts of the ridge are flexurally compensated with an effective elastic thickness >15 km, whereas the central part (0–20°S) is locally compensated. Furthermore, we find that for a part of central block (10–20°S, over Osborn Knoll) the compensation depth is unreasonably very high (30–40 km). Therefore we favor a model with subsurface loading and interpret this to be due to underplating of mafic material at the base of the crust, a hypothesis that is supported by seismic results and direct modeling of gravity data along some profiles. These results suggest that the northern and southern parts of Ninety-East Ridge were emplaced off to a ridge axis compared to the central one, which might have been emplaced on or near a spreading center. Locally compensated large topography, thick underplated crust in the central part (near Osborn Knoll), might result from an interaction of a hot spot with the extinct Wharton spreading ridge

Re-reading between the lines: a re-evaluation of the pragmatic implications of minimization within police interrogations

Past research has suggested that minimization (i.e., downplaying the moral or psychological seriousness of the crime) pragmatically implies that a suspect will receive a more lenient sentence in exchange for information and this is not mitigated by a leniency warning. Across four studies (Ns = 187, 124, 236, 241), participants read a case overview involving a break and enter, a suspect-interview transcript and then answered questions regarding various perceptions of the interview and potential subsequent judicial process. We manipulated (1) the perspective taken by participants in the follow-up questions (Self v. Other) and (2) the language and placement of the leniency warning. Results indicated that minimization only implies leniency when an imagine-other perspective is used; however, this effect can be successfully negated if a leniency warning is provided directly to the suspect. We also conducted a fifth study as a first step to begin assessing the pragmatic implications of minimization within in-person interviews. Participants (N = 49) either carried out a mock-crime or they did not (Guilty v. Innocent). Next they underwent an interview in which minimization was either applied or it was not (Minimization: Present v. Absent), and a leniency warning was provided or it was not (Warning: Present v. Absent). Results indicated that guilt significantly influenced perceptions regarding sentencing expectations if they confessed, but Minimization and a Warning did not. The implications of our findings in regards to the impact of minimization within police interviews are discussed

Identification of novel CD8+ T cell epitopes in human herpesvirus 6B U11 and U90

Human herpesvirus 6B (HHV6B) infects over 90% of the population, and normally establishes a latent infection, where episodes of reactivation are asymptomatic. However, in immunocompromised patients HHV6B reactivation is associated with high morbidity and mortality. Cellular immunotherapy has been utilised against other herpesvirus in immunocompromised settings. However, limited information on the immune response against HHV6B has hampered the development of immunotherapy for HHV6B-driven disease. In this study we have analysed the cellular immune response against four HHV6B antigens in a panel of 30 healthy donors. We show that the base-line level of T cell reactivity in peripheral blood is very low to undetectable. A short-term reactivation step enabled expansion of T cell responses, and all donors responded to at least 1 antigen, but more commonly 3 or 4. A hierarchy of immunogenicity was determined with antigens U90 and U54 being co-dominant, followed by U11 and U39. Putative CD8+ T cell epitopes were mapped to U90 and U11, predicted to be presented in the context of HLA-A1, A29, B39 and C6. T cells reactive against these novel epitopes were able to recognise virus-infected cells. Our data is supportive of the application and on-going development of T cell immunotherapy against HHV6B-driven disease in the immunocompromised host

Human cytomegalovirus infection of langerhans-type dendritic cells does not require the presence of the gH/gL/UL128-131A complex and is blocked after nuclear deposition of viral genomes in immature cells

Human cytomegalovirus (CMV) enters its host via the oral and genital mucosae. Langerhans-type dendritic cells (LC) are the most abundant innate immune cells at these sites, where they constitute a first line of defense against a variety of pathogens. We previously showed that immature LC (iLC) are remarkably resistant to CMV infection, while mature LC (mLC) are more permissive, particularly when exposed to clinical-strain-like strains of CMV, which display a pentameric complex consisting of the viral glycoproteins gH, gL, UL128, UL130, and UL131A on their envelope. This complex was recently shown to be required for the infection of immature monocyte-derived dendritic cells. We thus sought to establish if the presence of this complex is also necessary for virion penetration of LC and if defects in entry might be the source of iLC resistance to CMV. Here we report that the efficiency of LC infection is reduced, but not completely abolished, in the absence of the pentameric complex. While virion penetration and nuclear deposition of viral genomes are not impaired in iLC, the transcription of the viral immediate early genes UL122 and UL123 and of the delayed early gene UL50 is substantially lower than that in mLC. Together, these data show that the UL128, UL130, and UL131A proteins are dispensable for CMV entry into LC and that progression of the viral cycle in iLC is restricted at the step of viral gene expression