Comparison of abacavir-specific effector and proliferating functions of CD8 T cells in abacavir-treated HIV-1 patients

Susceptibility to abacavir hypersensitivity (ABH) in HIV-1-positive patients is strongly linked to the carriage of HLA-B*57:01 and the potential mechanism includes drug-specific activation of cytokine producing CD8 T cells exclusively in individuals carrying HLA-B*57:01. Here, we report a detailed characterization of abacavir-induced functional response of CD8 T cells in HLA-B*57:01^pos individuals. Peripheral blood mononuclear cells (PBMNCs) from HLA-B*57:01^posABH^pos and HLA-B*57:01^negABH^neg individuals were stimulated with abacavir. Multicolor flow cytometry was performed to assess the cytokine (IFNγ) production and degranulation (CD107a expression) after 6–18 hr culture and to enumerate proliferating CD4/CD8 T cells by culturing carboxyfluorescein diacetate succinimidyl ester-loaded PBMNCs for 7 days. CD8 T cells from HLA-B*57:01^posABH^pos individuals were multifunctional: proliferating, IFNγ producing, degranulating (CD107a^pos), and both degranulating and IFNγ producing (CD107a^posIFNγ^pos). Degranulating CD8 T cells in general and both degranulating and IFNγ producing CD8 T cells in particular dominated abacavir-specific immune response. All functional responses were partially blocked by addition of HLA-B*57:01-reactive Bw4 mAb, but not by non-HLA-B*57:01-reactive Bw6 mAb. In conclusion, the study demonstrates that abacavir-specific CD8 T-cell-restricted immune response in HLA-B*57:01^posABH^pos HIV-1 patients has multiple effector and proliferating functions, where the primary effector response appears to be the release of cytolytic granules. The findings have implications for immunotherapy of HLA-related drug hypersensitivities.     

Validation of a laser driven plasma X-ray microfocus source for high resolution radiography imaging

Hard X-ray radiation with high brightness and high fluxes is nowadays available on the fourth generation of synchrotrons and X-FELs, but the large size and complexity of these sources makes its use difficult for widespread applications. New table top X-ray sources driven by ultrashort high power lasers offer a compelling route to expand the availability of hard X-ray sources. They can be used for advanced imaging techniques, due to its small source size and spatial coherence. We present in this paper the validation of a compact laser-driven X-ray microfocus source for high-resolution radiography imaging. This novel device was built at the Laser Laboratory for Acceleration and Applications (L2A2) at the University of Santiago de Compostela. This paper describes the laser-plasma X-ray source with improved stability and characterize some of its properties. We demonstrate the high-contrast and resolution of the images obtained with this source by using masks with well known geometries, and detailed analysis by using the modulation transfer function. Finally, we discuss the properties of this source in comparison to other compact microfocus X-ray sources.     

Assessing the climate change effects on the distribution pattern of the Azerbaijan Mountain Newt (Neurergus crocatus)

Climate change is a grave danger for humans and a looming threat to Earth's biodiversity in the twenty-first century. Assessing the vulnerability of species to climate change is critical for practical conservation efforts. Due to their limited dispersal ability, amphibians are one of the most vulnerable groups of vertebrates to climate change. Among them, the species that inhabit mountains suffer a tremendous amount of climate change-induced pressures. We, therefore, adopted the Azerbaijan Mountain Newt (Neurergus crocatus), which currently inhabits Northwest Iran, North Iraq, and Southeast Turkey, as a case study for assessing the effects of climate change on the distribution patterns of mountain amphibians. By applying the species distribution models (SDMs) in this study, we tried to hindcast the species distribution area in the past and illustrate the impacts of climate change on its distribution in the present and future (the 2050s and 2070s) climate conditions. Also, the patch metrics have been deployed for identifying habitat fragmentation. Our results indicate a more than 50% rise in the species’ current suitable habitats compared to its glacial refugia. The suitable habitat is expected to gradually decrease in RCP 2.6 and RCP 8.5. Among the three countries in which the species occurs, its distribution overlaps with protected areas only in Iraq. The number of habitat patches will grow and reach approximately 20 to 60 patches by 2070 and the average area of the patches will decrease throughout this time. Aside from the numerous threats that endanger the species, climate change puts the long-term existence of Azerbaijan Newt in jeopardy. The results of this study stress the urgent need for taking extreme measures on the species management and conserving its remnant habitat patches.     

HUMF13A01 in autochthonous Basques and in genetically related populations

A population gentics study was carried out on 678 Basque individuals using the short tandem repeat HUMF13A01. Thirteen different alleles were detected. This population is in Hardy-Weinberg equilibrium. The singularity of the Basque population’s HUMF13A01 allele frequencies is displayed in the European context, through some genetic similarities are shown, especially with some neighbouring and culturally related populations, and with other populations with which Basques may have shared ancient common roots, such as the Sardinians.