Interactions of thrombospondins with α4β1 integrin and CD47 differentially modulate T cell behavior

Thrombospondin (TSP)-1 has been reported to modulate T cell behavior both positively and negatively. We found that these opposing responses arise from interactions of TSP1 with two different T cell receptors. The integrin α4β1 recognizes an LDVP sequence in the NH2-terminal domain of TSP1 and was required for stimulation of T cell adhesion, chemotaxis, and matrix metalloproteinase gene expression by TSP1. Recognition of TSP1 by T cells depended on the activation state of α4β1 integrin, and TSP1 inhibited interaction of activated α4β1 integrin on T cells with its counter receptor vascular cell adhesion molecule-1. The α4β1 integrin recognition site is conserved in TSP2. A recombinant piece of TSP2 containing this sequence replicated the α4β1 integrin–dependent activities of TSP1. The β1 integrin recognition sites in TSP1, however, were neither necessary nor sufficient for inhibition of T cell proliferation and T cell antigen receptor signaling by TSP1. A second TSP1 receptor, CD47, was not required for some stimulatory responses to TSP1 but played a significant role in its T cell antigen receptor antagonist and antiproliferative activities. Modulating the relative expression or function of these two TSP receptors could therefore alter the direction or magnitude of T cell responses to TSPs

A New Endemic Focus of Chagas Disease in the Northern Region of Veraguas Province, Western Half Panama, Central America

Background: Chagas disease was originally reported in Panama in 1931. Currently, the best knowledge of this zoonosis is restricted to studies done in historically endemic regions. However, little is known about the distribution and epidemiology of Chagas disease in other rural areas of the country. Methods and Findings: A cross-sectional descriptive study was carried out between May 2005 – July 2008 in four rural communities of the Santa Fe District, Veraguas Province. The study included an entomologic search to collect triatomines, bloodmeal type identification and infection rate with trypanosomes in collected vectors using a dot- blot and PCR analysis, genotyping of circulating Trypanosoma cruzi (mini-exon gene PCR analysis) and the detection of chagasic antibodies among inhabitants. The vector Rhodnius pallescens was more frequently found in La Culaca and El Pantano communities (788 specimens), where it was a sporadic household visitor. These triatomines presented darker coloration and larger sizescompared with typical specimens collected in Central Panama. Triatoma dimidiata was more common in Sabaneta de El Macho (162 specimens). In one small sub-region (El Macho), 60 % of the houses were colonized by this vector. Of the examined R. pallescens, 54.7.0 % (88/161) had fed on Didelphis marsupialis, and 24.6 % (34/138) of T. dimidiata specimens collected inside houses were positive for human blood. R. pallescens presented an infection index with T. cruzi of 17.7 % (24/ 136), with T. rangeli of 12.5 % (17/136) and 50.7 % (69/136) were mixed infections. In 117 T. dimidiata domestic specimens th

Antiretroviral therapy duration and immunometabolic state determine efficacy of ex vivo dendritic cell-based treatment restoring functional HIV-specific CD8+ T cells in people living with HIV.

Dysfunction of CD8+ T cells in people living with HIV-1 (PLWH) receiving anti-retroviral therapy (ART) has restricted the efficacy of dendritic cell (DC)-based immunotherapies against HIV-1. Heterogeneous immune exhaustion and metabolic states of CD8+ T cells might differentially associate with dysfunction. However, specific parameters associated to functional restoration of CD8+ T cells after DC treatment have not been investigated. We studied association of restoration of functional HIV-1-specific CD8+ T cell responses after stimulation with Gag-adjuvant-primed DC with ART duration, exhaustion, metabolic and memory cell subsets profiles. HIV-1-specific CD8+ T cell responses from a larger proportion of PLWH on long-term ART (more than 10 years; LT-ARTp) improved polyfunctionality and capacity to eliminate autologous p24+ infected CD4+ T cells in vitro. In contrast, functional improvement of CD8+ T cells from PLWH on short-term ART (less than a decade; ST-ARTp) after DC treatment was limited. This was associated with lower frequencies of central memory CD8+ T cells, increased co-expression of PD1 and TIGIT and reduced mitochondrial respiration and glycolysis induction upon TCR activation. In contrast, CD8+ T cells from LT-ARTp showed increased frequencies of TIM3+ PD1- cells and preserved induction of glycolysis. Treatment of dysfunctional CD8+ T cells from ST-ARTp with combined anti-PD1 and anti-TIGIT antibodies plus a glycolysis promoting drug restored their ability to eliminate infected CD4+ T cells. Together, our study identifies specific immunometabolic parameters for different PLWH subgroups potentially useful for future personalized DC-based HIV-1 vaccines. NIH (R21AI140930), MINECO/FEDER RETOS (RTI2018-097485-A-I00) and CIBERINF grants.NIH (R21AI140930), MINECO/FEDER RETOS (RTI2018-097485-A-I00) and CIBERINF grants. We would like to thank the NIH AIDS Reagent Pro- gram, Division of AIDS, NIAID, NIH for providing HIV-1 PTE Gag Peptide Pool from NIAID, DAIDS (cat #11057) for the study. We would also like to thank Alvaro Serrano Navarro, for his help on adapting the lin- ear mixed model previously described by Martin- C ofreces N. et al83 to our data. Graphical schematic rep- resentations were created with BioRender.com. EMG was supported by the NIH R21 program (R21AI140930), the Ramón y Cajal Program (RYC2018- 024374-I), the MINECO/FEDER RETOS program (RTI2018-097485-A-I00), by Comunidad de Madrid Talento Program (2017-T1/BMD-5396) and by Gilead becas de investigaci on (GLD19/00168). EMG and IDS are supported by Centro de Investigación Biomédica en Red (CIBERINF) de Enfermedades Infecciosas (CB21/ 13/00107). MCM was supported by NIH R21 program (R21AI140930), “La Caixa Banking Foundation (H20- 00218) and Gilead becas de investigaci on (GLD19/ 00168). MJB is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179), the MINECO/FEDER RETOS program (RTI2018-101082-B-100), and Fundació La Marat o TV3 (201805-10FMTV3). EMG and MJB are both funded by “La Caixa Banking Foundation (H20-00218) and by REDINCOV grant from Fundació La Marat o TV3. FSM was supported by SAF2017-82886-R and PDI-2020- 120412RB-I00 grants from the Ministerio de Ciencia e Innovaci on, and HR17-00016 grant from “La Caixa Banking Foundation. HF was funded by PI21/01583 grant from Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III. MJC was supported by PID2019- 104406RB-I00 from Ministerio de Ciencia e Innovación. ISC was funded by the CM21/00157 Rio- Hortega grant. IT was supported by grant for the pro- motion of research studies master-UAM 2021.S

Ingeniería Forestal y ambiental en medios insulares

Las Islas Canarias a pesar de su reducida extensión y del relativo poco peso específico a nivel mundial, no es ajena a los problemas globales detectados en la conservación de bosques y en la importancia que éstos tienen para obtener beneficios económicos, socioculturales y ambientales. La gestión forestal sostenible es en este sentido esencial para asegurar y compatibilizar los diversos beneficios del bosque. El papel específico de los bosques y su gestión son sin embargo temas aún por conocer en nuestras islas, por lo que el Año Internacional de los Bosques ha representado una oportunidad única para dar a conocer el mundo forestal y acercarlo a nuestra sociedad. El presente libro consta de 25 capítulos donde se ha contemplado la mayoría de los aspectos a tener en cuenta en la planificación y gestión del medio forestal y natural. Desde la historia forestal del archipiélago, hasta el uso y técnicas de manejo de los recursos naturales, incluyendo el agua, la energía en forma de biomasa y la selvicultura

Risk factors associated with Trypanosoma cruziexposure in domestic dogs from a rural community in Panama

Chagas disease, caused by Trypanosoma cruzi infection, is a zoonosis of humans, wild and domestic mammals,including dogs. In Panama, the main T. cruzi vector is Rhodnius pallescens, a triatomine bug whose main naturalhabitat is the royal palm, Attalea butyracea. In this paper, we present results from three T. cruzi serological tests(immunochromatographic dipstick, indirect immunofluorescence and ELISA) performed in 51 dogs from 24 housesin Trinidad de Las Minas, western Panama. We found that nine dogs were seropositive (17.6% prevalence). Dogswere 1.6 times more likely to become T. cruzi seropositive with each year of age and 11.6 times if royal palms wherepresent in the peridomiciliary area of the dog’s household or its two nearest neighbours. Mouse-baited-adhesivetraps were employed to evaluate 12 peridomestic royal palms. All palms were found infested with R. pallescens withan average of 25.50 triatomines captured per palm. Of 35 adult bugs analysed, 88.6% showed protozoa flagellates intheir intestinal contents. In addition, dogs were five times more likely to be infected by the presence of an additionaldomestic animal species in the dog’s peridomiciliary environment. Our results suggest that interventions focused onroyal palms might reduce the exposure to T. cruzi infection

Inducible Nitric Oxide Synthase in Heart Tissue and Nitric Oxide in Serum of Trypanosoma cruzi-Infected Rhesus Monkeys: Association with Heart Injury

Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi, afflicts from 8 to 15 million people in the Latin America. Chronic chagasic cardiomyopathy (CCC) is the most frequent manifestation of Chagas disease. Currently, patient management only mitigates CCC symptoms. The pathogenic factors leading to CCC remain unknown; therefore their comprehension may contribute to develop more efficient therapies. In patients, high nitric oxide (NO) levels have been associated with CCC severity. In T. cruzi-infected mice, NO, mainly produced via inducible nitric oxide synthase (iNOS/NOS2), is proposed to work in parasite control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, infected rhesus monkeys and iNOS/NOS2-deficient mice were used to explore the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. Chronically infected monkeys presented electrical abnormalities, myocarditis and fibrosis, resembling the spectrum of human CCC. Moreover, cardiomyocyte lesion correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue. Our findings support that parasite-driven iNOS/NOS2+ cells accumulation in the cardiac tissue and NO overproduction contribute to cardiomyopathy severity, mainly disturbing the pathway involved in electrical synchrony in T. cruzi infection

Reassessing global change research priorities in mediterranean terrestrial ecosystems : how far have we come and where do we go from here?

Aim: Mediterranean terrestrial ecosystems serve as reference laboratories for the investigation of global change because of their transitional climate, the high spatiotemporal variability of their environmental conditions, a rich and unique biodiversity and a wide range of socio-economic conditions. As scientific development and environmental pressures increase, it is increasingly necessary to evaluate recent progress and to challenge research priorities in the face of global change. - Location: Mediterranean terrestrial ecosystems. - Methods: This article revisits the research priorities proposed in a 1998 assessment. - Results: A new set of research priorities is proposed: (1) to establish the role of the landscape mosaic on fire-spread; (2) to further research the combined effect of different drivers on pest expansion; (3) to address the interaction between drivers of global change and recent forest management practices; (4) to obtain more realistic information on the impacts of global change and ecosystem services; (5) to assess forest mortality events associated with climatic extremes; (6) to focus global change research on identifying and managing vulnerable areas; (7) to use the functional traits concept to study resilience after disturbance; (8) to study the relationship between genotypic and phenotypic diversity as a source of forest resilience; (9) to understand the balance between C storage and water resources; (10) to analyse the interplay between landscape-scale processes and biodiversity conservation; (11) to refine models by including interactions between drivers and socio-economic contexts; (12) to understand forest-atmosphere feedbacks; (13) to represent key mechanisms linking plant hydraulics with landscape hydrology. - Main conclusions:(1) The interactive nature of different global change drivers remains poorly understood. (2) There is a critical need for the rapid development of regional- and global-scale models that are more tightly connected with large-scale experiments, data networks and management practice. (3) More attention should be directed to drought-related forest decline and the current relevance of historical land use

Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi.

Trypanosoma cruzi, a zoonotic kinetoplastid protozoan parasite, is the causative agent of American trypanosomiasis (Chagas disease). Having a very plastic, repetitive and complex genome, the parasite displays a highly diverse repertoire of surface molecules, with pivotal roles in cell invasion, immune evasion and pathogenesis. Before 2016, the complexity of the genomic regions containing these genes impaired the assembly of a genome at chromosomal level, making it impossible to study the structure and function of the several thousand repetitive genes encoding the surface molecules of the parasite. We here describe the genome assembly of the Sylvio X10/1 genome sequence, which since 2016 has been used as a reference genome sequence for T. cruzi clade I (TcI), produced using high coverage PacBio single-molecule sequencing. It was used to analyze deep Illumina sequence data from 34 T. cruzi TcI isolates and clones from different geographic locations, sample sources and clinical outcomes. Resolution of the surface molecule gene distribution showed the unusual duality in the organization of the parasite genome, a synteny of the core genomic region with related protozoa flanked by unique and highly plastic multigene family clusters encoding surface antigens. The presence of abundant interspersed retrotransposons in these multigene family clusters suggests that these elements are involved in a recombination mechanism for the generation of antigenic variation and evasion of the host immune response on these TcI strains. The comparative genomic analysis of the cohort of TcI strains revealed multiple cases of such recombination events involving surface molecule genes and has provided new insights into T. cruzi population structure

Human migration and the spread of malaria parasites to the New World

We examined the mitogenomes of a large global collection of human malaria parasites to explore how and when Plasmodium falciparum and P. vivax entered the Americas. We found evidence of a significant contribution of African and South Asian lineages to present-day New World malaria parasites with additional P. vivax lineages appearing to originate from Melanesia that were putatively carried by the Australasian peoples who contributed genes to Native Americans. Importantly, mitochondrial lineages of the P. vivax-like species P. simium are shared by platyrrhine monkeys and humans in the Atlantic Forest ecosystem, but not across the Amazon, which most likely resulted from one or a few recent human-to-monkey transfers. While enslaved Africans were likely the main carriers of P. falciparum mitochondrial lineages into the Americas after the conquest, additional parasites carried by Australasian peoples in pre-Columbian times may have contributed to the extensive diversity of extant local populations of P. vivax