The Role of NKG2D in Vitiligo

Vitiligo is an acquired multifactorial disease that affects melanocytes and results in skin depigmentation. In this review, we examine the role of cells stress and self-reactive T cells responses. Given the canonical and non-canonical functions of NKG2D, such as authenticating stressed target and enhance TCR signaling, we examine how melanocyte stress leads to the expression of ligands that are recognized by the activating receptor NKG2D, and how its signaling results in the turning of T cells against self (melanocyte suicide by proxy). We also discuss how this initiation phase is followed by T cell perpetuation, as NKG2D signaling results in self-sustained long-lasting T cells, with improved cytolytic properties

Sex Steroids Induce Apoptosis of CD8⁺CD4⁺ Double-Positive Thymocytes via TNF-α

T cell production by the thymus, thymic size, cellularity and output all decrease drastically after puberty. Among the candidates that may mediate this decrease are the sex steroids: Hypersecretion or pharmacological administration of these hormones has long been known to induce thymic hypocellularity, and their depletion yields thymic hypercellularity. Here we show that a typical sex steroid, testosterone, specifically targets CD8⁺CD4⁺ double-positive (DP) thymocytes for apoptosis via TNF-α Anti-TNF-α monoclonal antibodies abrogated testosterone-induced DP apoptosis, and TNF-a⁻^/⁻DP thymocytes were largely resistant to testosterone-mediated apoptosis in vivo. Testosterone accomplishes this effect by up-regulating TNF-α production and by simultaneously sensitizing DP thymocytes to TNF-α. Thus, TNF-α is the critical mediator of sex steroid-induced apoptosis in thymocytes, and its manipulation should provide a point of intervention to modulate T cell production in sex hormone disorders

Concomitant Tumor Immunity to a Poorly Immunogenic Melanoma Is Prevented by Regulatory T Cells

Concomitant tumor immunity describes immune responses in a host with a progressive tumor that rejects the same tumor at a remote site. In this work, concomitant tumor immunity was investigated in mice bearing poorly immunogenic B16 melanoma. Progression of B16 tumors did not spontaneously elicit concomitant immunity. However, depletion of CD4+ T cells in tumor-bearing mice resulted in CD8+ T cell–mediated rejection of challenge tumors given on day 6. Concomitant immunity was also elicited by treatment with cyclophosphamide or DTA-1 monoclonal antibody against the glucocorticoid-induced tumor necrosis factor receptor. Immunity elicited by B16 melanoma cross-reacted with a distinct syngeneic melanoma, but not with nonmelanoma tumors. Furthermore, CD8+ T cells from mice with concomitant immunity specifically responded to major histocompatibility complex class I–restricted epitopes of two melanocyte differentiation antigens. RAG1−/− mice adoptively transferred with CD8+ and CD4+ T cells lacking the CD4+CD25+ compartment mounted robust concomitant immunity, which was suppressed by readdition of CD4+CD25+ cells. Naturally occurring CD4+CD25+ T cells efficiently suppressed concomitant immunity mediated by previously activated CD8+ T cells, demonstrating that precursor regulatory T cells in naive hosts give rise to effective suppressors. These results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor

ESTUDIOS QUÍMICOS DE AMBROSIA CUMANENSIS KUNTH EN PANAMÁ

Ambrosia cumanesis K (Asteraceae), known as Altamisa, is an aromatic species widely distributed throughout the country. Its use is associated with the treatment of kidney, anti-inflammatory, antiparasitic and laxative disorders. The chemical characterization of the aqueous and ethanolic extracts of the leaves of A. cumanesis K. was carried out, as well as of its essential oil, in order to evaluate its biological activity. Phytochemical screening tests were carried out to identify secondary metabolites, chromatographic methods were used for the purification of plant extracts and the identification of the main compounds was carried out by IR and NMR spectroscopy, and by CG-MS for the essential oil. The chemical analysis of the ethanolic extracts of the fresh leaves of Ambrosia cumanensis Kunth has led to the identification of alkaloids, terpenes and flavonoids as the major secondary metabolites. The extraction and purification of the extracts led to the isolation of three (3) known compounds, psilostachyn A, psilostachyn C and camphor. The analysis of the chemical composition of the essential oil of this plant has led to the identification of 25 compounds and the possible correlation between the composition variability and the seasonality. The microbiological activity of the ethanolic extracts and the essential oil was evaluated by inhibition halo, showing selective antimicrobial activity for the essential oil. This is the first report of chemical studies on Ambrosia cumanensis Kunth in Panama.Ambrosia cumanesis K (Asteraceae), conocida como Altamisa, es una especie aromática distribuida ampliamente en el país. Se ha asociado su uso al tratamiento de afecciones renales, como antiinflamatorio, antiparasitario y purgante, por lo que se realizó la caracterización química de los extractos acuosos y etanólicos de las hojas de A. cumanesis K., así como de su aceite esencial, con el fin de evaluar su actividad biológica. Se llevaron a cabo pruebas de tamizaje fitoquímico para identificación de metabolitos secundarios, se emplearon métodos cromatográficos para la purificación de los extractos vegetales y la identificación de los compuestos principales se realizó por espectroscopía IR y de RMN, y por CG-MS para el caso del aceite esencial. El análisis químico de los extractos etanólicos de las hojas frescas de A. cumanensis Kunth llevó a la identificación de alcaloides, terpenos y flavonoides como los metabolitos secundarios mayoritarios. La extracción y purificación de los extractos llevó al aislamiento de tres (3) compuestos conocidos, psilostachina A, psilostachina C y alcanfor. El análisis de la composición química del aceite esencial de esta planta ha producido la identificación de 25 compuestos, y mostró que la composición puede variar dependiendo de la estacionalidad. La actividad microbiológica de los extractos etanólicos y del aceite esencial fue evaluada por halo de inhibición, mostrando actividad antimicrobiana selectiva para el aceite esencial. Este es el primer reporte de estudios químicos sobre Ambrosia cumanensis Kunth en Panamá

Differing patterns of selection and geospatial genetic diversity within two leading Plasmodium vivax candidate vaccine antigens

Although Plasmodium vivax is a leading cause of malaria around the world, only a handful of vivax antigens are being studied for vaccine development. Here, we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens--Plasmodium vivax merozoite surface protein 1 (pvmsp-1) and Plasmodium vivax circumsporozoite protein (pvcsp). Using scalable next-generation sequencing, we deep-sequenced amplicons of the 42 kDa region of pvmsp-1 (n = 44) and the complete gene of pvcsp (n = 47) from Cambodian isolates. These sequences were then compared with global parasite populations obtained from GenBank. Using a combination of statistical and phylogenetic methods to assess for selection and population structure, we found strong evidence of balancing selection in the 42 kDa region of pvmsp-1, which varied significantly over the length of the gene, consistent with immune-mediated selection. In pvcsp, the highly variable central repeat region also showed patterns consistent with immune selection, which were lacking outside the repeat. The patterns of selection seen in both genes differed from their P. falciparum orthologs. In addition, we found that, similar to merozoite antigens from P. falciparum malaria, genetic diversity of pvmsp-1 sequences showed no geographic clustering, while the non-merozoite antigen, pvcsp, showed strong geographic clustering. These findings suggest that while immune selection may act on both vivax vaccine candidate antigens, the geographic distribution of genetic variability differs greatly between these two genes. The selective forces driving this diversification could lead to antigen escape and vaccine failure. Better understanding the geographic distribution of genetic variability in vaccine candidate antigens will be key to designing and implementing efficacious vaccines

Amazon tree dominance across forest strata

The forests of Amazonia are among the most biodiverse plant communities on Earth. Given the immediate threats posed by climate and land-use change, an improved understanding of how this extraordinary biodiversity is spatially organized is urgently required to develop effective conservation strategies. Most Amazonian tree species are extremely rare but a few are common across the region. Indeed, just 227 ‘hyperdominant’ species account for >50% of all individuals >10 cm diameter at 1.3 m in height. Yet, the degree to which the phenomenon of hyperdominance is sensitive to tree size, the extent to which the composition of dominant species changes with size class and how evolutionary history constrains tree hyperdominance, all remain unknown. Here, we use a large floristic dataset to show that, while hyperdominance is a universal phenomenon across forest strata, different species dominate the forest understory, midstory and canopy. We further find that, although species belonging to a range of phylogenetically dispersed lineages have become hyperdominant in small size classes, hyperdominants in large size classes are restricted to a few lineages. Our results demonstrate that it is essential to consider all forest strata to understand regional patterns of dominance and composition in Amazonia. More generally, through the lens of 654 hyperdominant species, we outline a tractable pathway for understanding the functioning of half of Amazonian forests across vertical strata and geographical locations