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Understanding natural movement patterns and ecological roles of marine megafauna is a research priority best studied in areas with minimal human impact. The spatial distribution patterns specifically for immature turtles at foraging grounds have been highlighted as a research gap for effective management and conservation strategies for sea turtle populations. Capture–mark–recapture (CMR) records (n = 2287) of 1672 immature green (Chelonia mydas) (n = 1158) and hawksbill turtles (Eretmochelys imbricata) (n = 514) from a long-term (1981–2021) in-water CMR program at Aldabra Atoll, Seychelles, were analyzed for 10 sites (0.35–25 km apart). Site fidelity was not correlated with either season or turtle size. Green turtles had lower site fidelity than hawksbill turtles. Green turtles showed avoidance (i.e., opposite of fidelity) of three sites, while hawksbill turtles displayed high fidelity to two sites. Sites displaying non-random behavior (avoidance and/or fidelity) did not share the same benthic habitat types. Results indicate that fidelity can be detected at a fine scale with CMR, but that further exploration into the habitat characteristics of the sites and the ecological roles of both species at the atoll is needed. [ABSTRACT FROM AUTHOR]

Changes in marine ecosystems from human stressors, and concerns over how species will respond to these changes have emphasized the importance of understanding and monitoring crucial demographic parameters for population models. Long-lived, migratory, marine vertebrates such as sea turtles are particularly vulnerable to changes. Life-history parameters like growth-in-body size can be largely influenced by environmental processes which can impact population growth. We analyzed a 40-year (1981–2021) capture-mark-recapture dataset from the protected UNESCO World Heritage Site, Aldabra Atoll, Seychelles, to estimate key population parameters, including body growth, for immature green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata). Curved carapace length (CCL) range was 34.3–110.9 cm (mean ± SD: 51.0 ± 11.4 cm, n = 1191) for green turtles and 28.7–89.4 cm (47.7 ± 14.4 cm, n = 538) for hawksbill turtles. Recapture events, with an 11-month minimum period, revealed a mean annual growth rate of 3.2 ± 1.5 cm year−1 for green turtles (n = 75) and 2.8 ± 1.4 cm year−1 for hawksbill turtles (n = 110). Hawksbill turtles exhibited a non-monotonic growth rate while no significant growth-size relationship was detected for green turtles. Green turtle mean annual growth per 10-cm size class was highest in the larger size classes (50‒69.9 cm). Hawksbill turtle growth rate was highest in the larger size classes (50‒69.9 cm) then declined in the largest size class (70‒79.9 cm). Green turtles and hawksbill turtles may spend > 8 and 18 years, respectively, using Aldabra, Seychelles, as a foraging ground. [ABSTRACT FROM AUTHOR]

The novel coronavirus pandemic continues to cause significant morbidity and mortality around the world. Diverse clinical presentations prompted numerous attempts to predict disease severity to improve care and patient outcomes. Equally important is understanding the mechanisms underlying such divergent disease outcomes. Multivariate modeling was used here to define the most distinctive features that separate COVID-19 from healthy controls and severe from moderate disease. Using discriminant analysis and binary logistic regression models we could distinguish between severe disease, moderate disease, and control with rates of correct classifications ranging from 71 to 100%. The distinction of severe and moderate disease was most reliant on the depletion of natural killer cells and activated class-switched memory B cells, increased frequency of neutrophils, and decreased expression of the activation marker HLA-DR on monocytes in patients with severe disease. An increased frequency of activated class-switched memory B cells and activated neutrophils was seen in moderate compared to severe disease and control. Our results suggest that natural killer cells, activated class-switched memory B cells, and activated neutrophils are important for protection against severe disease. We show that binary logistic regression was superior to discriminant analysis by attaining higher rates of correct classification based on immune profiles. We discuss the utility of these multivariate techniques in biomedical sciences, contrast their mathematical basis and limitations, and propose strategies to overcome such limitations. [ABSTRACT FROM AUTHOR]

Chronic HIV infection causes persistent low-grade inflammation that induces premature aging of the immune system including senescence of memory and effector CD8 T cells. To uncover the reasons of gradually diminished potency of CD8 T cells from people living with HIV, here we expose the T cells to planar lipid bilayers containing ligands for T-cell receptor and a T-cell integrins and analyze the cellular morphology, dynamics of synaptic interface formation and patterns of the cellular degranulation. We find a large fraction of phenotypically naive T cells from chronically infected people are capable to form mature synapse with focused degranulation, a signature of a differentiated T cells. Further, differentiation of aberrant naive T cells may lead to the development of anomalous effector T cells undermining their capacity to control HIV and other pathogens that could be contained otherwise. HIV infection over time is thought to result in premature aging and aberrant immune responses including the induction of immunological senescence. Here the authors show altered formation of immune synapses by naive CD8+ T cells and dysregulated synapse functioning at late differentiated stages in people living with HIV. [ABSTRACT FROM AUTHOR]

Around the world, declines in the mean size of nesting sea turtles have been reported with concerns of a concomitant decrease in the reproductive output of populations. Here, we explore this possibility using long-term observations of green turtles (Chelonia mydas) at Aldabra Atoll, Seychelles. Based on > 4500 individual measurements over 21 years (1996–2016), we found the curved carapace length of nesting females declined by about 0.64 cm per decade, from 111.43 to 110.08 cm. For 391 individuals that were measured more than once with measurement interval of 2.8–19 years apart, the mean growth rate was 0.14 cm year−1. Comparisons between the size of adult females and males were based on 23 and 14 weight measurements, 107 and 33 carapace length measurements and 103 and 33 carapace width measurements, respectively, taken during 1981–1983. Adult females were larger than males, with the sexual dimorphism index, i.e. the ratio of size of the larger sex to the smaller, being 1.09 and 1.10 for carapace length and width, respectively, and 1.25 for weight. Smaller females tended to lay fewer eggs per clutch but the decrease in female mean size was accompanied by increases in numbers of turtles nesting annually, such that the estimated total numbers of eggs per year increased from 1.3 million to 2.0 million between 1996 and 2016. Therefore, a decrease in mean size of nesting females has not compromised egg production for this population. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) is not curative due to the persistence of a reservoir of HIV-infected cells, particularly in tissues such as lymph nodes, with the potential to cause viral rebound after treatment cessation. In this study, fingolimod (FTY720), a lysophospholipid sphingosine-1-phosphate receptor modulator is administered to SIV-infected rhesus macaques at initiation of ART to block the egress from lymphoid tissues of natural killer and T-cells, thereby promoting proximity between cytolytic cells and infected CD4+ T-cells. When compared with the ART-only controls, FTY720 treatment during the initial weeks of ART induces a profound lymphopenia and increases frequencies of CD8+ T-cells expressing perforin in lymph nodes, but not their killing capacity; FTY720 also increases frequencies of cytolytic NK cells in lymph nodes. This increase of cytolytic cells, however, does not limit measures of viral persistence during ART, including intact proviral genomes. After ART interruption, a subset of animals that initially receives FTY720 displays a modest delay in viral rebound, with reduced plasma viremia and frequencies of infected T follicular helper cells. Further research is needed to optimize the potential utility of FTY720 when coupled with strategies that boost the antiviral function of T-cells in lymphoid tissues. Although antiretroviral therapy (ART) is able to successfully suppress plasma viremia in most people living with HIV, ART withdrawal typically results in viral replication and rebound. Authors investigate the effect, in terms of delay in viral replication, and immune cell dynamics in lymphoid tissue, of fingolimod (FTY720) administration at the time of ART initiation in SIV-infected rhesus macaques. [ABSTRACT FROM AUTHOR]

Peptide exchange technologies are essential for the generation of pMHC-multimer libraries used to probe diverse, polyclonal TCR repertoires in various settings. Here, using the molecular chaperone TAPBPR, we develop a robust method for the capture of stable, empty MHC-I molecules comprising murine H2 and human HLA alleles, which can be readily tetramerized and loaded with peptides of choice in a high-throughput manner. Alternatively, catalytic amounts of TAPBPR can be used to exchange placeholder peptides with high affinity peptides of interest. Using the same system, we describe high throughput assays to validate binding of multiple candidate peptides on empty MHC-I/TAPBPR complexes. Combined with tetramer-barcoding via a multi-modal cellular indexing technology, ECCITE-seq, our approach allows a combined analysis of TCR repertoires and other T cell transcription profiles together with their cognate antigen specificities in a single experiment. The new approach allows TCR/pMHC interactions to be interrogated easily at large scale. Peptide-MHC (pMHC) tetramers are important tools for probing T cell repertoire and adaptive immune responses. Here the authors use a molecular chaperone, TAPBPR, to develop a high-throughput, multiplexible platform for pMHC tetramer generation to facilitate simultaneous assessments of T cell repertoire/antigen specificity and transcriptome. [ABSTRACT FROM AUTHOR]

HIV-1-associated neurocognitive disorder (HAND) remains a persistent problem despite antiretroviral therapy (ART), largely a result of continued inflammation in the periphery and the brain and neurotoxin release from activated myeloid cells in the CNS. CD14+CD16+ inflammatory monocytes, expanded in HIV infection, play a central role in the pathogenesis of HAND and have parallels with monocyte-dependent inflammatory mechanisms in atherosclerosis. Statins, through their HMG-CoA reductase inhibitor activity, have pleiotropic immunomodulatory properties that contribute to their benefit in atherosclerosis beyond lipid lowering. Here, we investigated whether statins would modulate the monocyte phenotype and function associated with HIV-1 neuropathogenesis. Treatment ex vivo with simvastatin and atorvastatin reduced the proportion of CD16+ monocytes in peripheral blood mononuclear cells, as well as in purified monocytes, especially CD14++CD16+ 'intermediate' monocytes most closely associated with neurocognitive disease. Statin treatment also markedly reduced expression of CD163, which is also linked to HAND pathogenesis. Finally, simvastatin inhibited production of monocyte chemoattractant protein-1 (MCP-1) and other inflammatory cytokines following LPS stimulation and reduced monocyte chemotaxis in response to MCP-1, a major driver of myeloid cell accumulation in the CNS in HAND. Together, these findings suggest that statin drugs may be useful to prevent or reduce HAND in HIV-1-infected subjects on ART with persistent monocyte activation and inflammation. [ABSTRACT FROM AUTHOR]

HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory receptor, T cell immunoglobulin and ITIM domain (TIGIT), the co-stimulatory receptor CD226 and their ligand PVR are altered in viral infections and cancer. However, the extent to which the TIGIT/CD226/PVR-axis is affected by HIV-infection has not been characterized. Here, we report that TIGIT expression increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T cells, despite early ART. These findings highlight the importance of the TIGIT/CD226/PVR axis as an immune checkpoint barrier that could hinder future 'cure' strategies requiring potent HIV-specific CD8+ T cells. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is an autoimmune disease in which immune cells destroy insulin-producing beta cells. The aetiology of this complex disease is dependent on the interplay of multiple heterogeneous cell types in the pancreatic environment. Here, we provide a single-cell atlas of pancreatic islets of 24 T1D, autoantibody-positive and nondiabetic organ donors across multiple quantitative modalities including ~80,000 cells using single-cell transcriptomics, ~7,000,000 cells using cytometry by time of flight and ~1,000,000 cells using in situ imaging mass cytometry. We develop an advanced integrative analytical strategy to assess pancreatic islets and identify canonical cell types. We show that a subset of exocrine ductal cells acquires a signature of tolerogenic dendritic cells in an apparent attempt at immune suppression in T1D donors. Our multimodal analyses delineate cell types and processes that may contribute to T1D immunopathogenesis and provide an integrative procedure for exploration and discovery of human pancreatic function., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)