Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity

Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and VLA-4 amongst B cells are found on MBCs. In vivo blockade of VLA-4 alone or in combination with LFA-1, but not LFA-1 alone, causes a release of MBCs from the spleen into the blood stream. In humans, we find that in peripheral blood, spleens, and tonsils from healthy donors the highest expression levels of the integrins LFA-1 and VLA-4 are also found on MBCs. Consistent with this, we found MBCs to have a higher capacity to adhere to ICAM-1 and VCAM-1 than naïve B cells. In patients with the autoimmune disease rheumatoid arthritis, it is the MBCs that have the highest levels of LFA-1 and VLA-4; moreover, compared with healthy donors, naïve B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active αL subunit can be induced on B cells from healthy donors by exposure to the integrin ligands. Thus, our findings establish the selective use of the integrins LFA-1 and VLA-4 in the localization and adhesion of MBCs in both mice and humans

CamTrapAsia: a dataset of tropical forest vertebrate communities from 239 camera trapping studies

Information on tropical Asian vertebrates has traditionally been sparse, particularly when it comes to cryptic species inhabiting the dense forests of the region. Vertebrate populations are declining globally due to land-use change and hunting, the latter frequently referred as “defaunation.” This is especially true in tropical Asia where there is extensive land-use change and high human densities. Robust monitoring requires that large volumes of vertebrate population data be made available for use by the scientific and applied communities. Camera traps have emerged as an effective, non-invasive, widespread, and common approach to surveying vertebrates in their natural habitats. However, camera-derived datasets remain scattered across a wide array of sources, including published scientific literature, gray literature, and unpublished works, making it challenging for researchers to harness the full potential of cameras for ecology, conservation, and management. In response, we collated and standardized observations from 239 camera trap studies conducted in tropical Asia. There were 278,260 independent records of 371 distinct species, comprising 232 mammals, 132 birds, and seven reptiles. The total trapping effort accumulated in this data paper consisted of 876,606 trap nights, distributed among Indonesia, Singapore, Malaysia, Bhutan, Thailand, Myanmar, Cambodia, Laos, Vietnam, Nepal, and far eastern India. The relatively standardized deployment methods in the region provide a consistent, reliable, and rich count data set relative to other large-scale pressence-only data sets, such as the Global Biodiversity Information Facility (GBIF) or citizen science repositories (e.g., iNaturalist), and is thus most similar to eBird. To facilitate the use of these data, we also provide mammalian species trait information and 13 environmental covariates calculated at three spatial scales around the camera survey centroids (within 10-, 20-, and 30-km buffers). We will update the dataset to include broader coverage of temperate Asia and add newer surveys and covariates as they become available. This dataset unlocks immense opportunities for single-species ecological or conservation studies as well as applied ecology, community ecology, and macroecology investigations. The data are fully available to the public for utilization and research. Please cite this data paper when utilizing the data

A Toll-Like Receptor 2 Pathway Regulates the Ppargc1a/b Metabolic Co-Activators in Mice with Staphylococcal aureus Sepsis

Activation of the host antibacterial defenses by the toll-like receptors (TLR) also selectively activates energy-sensing and metabolic pathways, but the mechanisms are poorly understood. This includes the metabolic and mitochondrial biogenesis master co-activators, Ppargc1a (PGC-1α) and Ppargc1b (PGC-1β) in Staphylococcus aureus (S. aureus) sepsis. The expression of these genes in the liver is markedly attenuated inTLR2−/− mice and markedly accentuated in TLR4−/− mice compared with wild type (WT) mice. We sought to explain this difference by using specific TLR-pathway knockout mice to test the hypothesis that these co-activator genes are directly regulated through TLR2 signaling. By comparing their responses to S. aureus with WT mice, we found that MyD88-deficient and MAL-deficient mice expressed hepatic Ppargc1a and Ppargc1b normally, but that neither gene was activated in TRAM-deficient mice. Ppargc1a/b activation did not require NF-kβ, but did require an interferon response factor (IRF), because neither gene was activated in IRF-3/7 double-knockout mice in sepsis, but both were activated normally in Unc93b1-deficient (3d) mice. Nuclear IRF-7 levels in TLR2−/− and TLR4−/− mice decreased and increased respectively post-inoculation and IRF-7 DNA-binding at the Ppargc1a promoter was demonstrated by chromatin immunoprecipitation. Also, a TLR2-TLR4-TRAM native hepatic protein complex was detected by immunoprecipitation within 6 h of S. aureus inoculation that could support MyD88-independent signaling to Ppargc1a/b. Overall, these findings disclose a novel MyD88-independent pathway in S. aureus sepsis that links TLR2 and TLR4 signaling in innate immunity to Ppargc1a/b gene regulation in a critical metabolic organ, the liver, by means of TRAM, TRIF, and IRF-7

The Obesity-Associated Polymorphisms FTO rs9939609 and MC4R rs17782313 and Endometrial Cancer Risk in Non-Hispanic White Women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis

The global abundance of tree palms

Aim Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change. Location Tropical and subtropical moist forests. Time period Current. Major taxa studied Palms (Arecaceae). Methods We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure. Results On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work. Conclusions Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests

An estimate of the number of tropical tree species

The high species richness of tropical forests has long been recognized, yet there remains substantial uncertainty regarding the actual number of tropical tree species. Using a pantropical tree inventory database from closed canopy forests, consisting of 657,630 trees belonging to 11,371 species, we use a fitted value of Fisher’s alpha and an approximate pantropical stem total to estimate the minimum number of tropical forest tree species to fall between ∼40,000 and ∼53,000, i.e. at the high end of previous estimates. Contrary to common assumption, the Indo-Pacific region was found to be as species-rich as the Neotropics, with both regions having a minimum of ∼19,000–25,000 tree species. Continental Africa is relatively depauperate with a minimum of ∼4,500–6,000 tree species. Very few species are shared among the African, American, and the Indo-Pacific regions. We provide a methodological framework for estimating species richness in trees that may help refine species richness estimates of tree-dependent taxa

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe

CamTrapAsia: A dataset of tropical forest vertebrate communities from 239 camera trapping studies

Information on tropical Asian vertebrates has traditionally been sparse, particularly when it comes to cryptic species inhabiting the dense forests of the region. Vertebrate populations are declining globally due to land‐use change and hunting, the latter frequently referred as “defaunation.” This is especially true in tropical Asia where there is extensive land‐use change and high human densities. Robust monitoring requires that large volumes of vertebrate population data be made available for use by the scientific and applied communities. Camera traps have emerged as an effective, non‐invasive, widespread, and common approach to surveying vertebrates in their natural habitats. However, camera‐derived datasets remain scattered across a wide array of sources, including published scientific literature, gray literature, and unpublished works, making it challenging for researchers to harness the full potential of cameras for ecology, conservation, and management. In response, we collated and standardized observations from 239 camera trap studies conducted in tropical Asia. There were 278,260 independent records of 371 distinct species, comprising 232 mammals, 132 birds, and seven reptiles. The total trapping effort accumulated in this data paper consisted of 876,606 trap nights, distributed among Indonesia, Singapore, Malaysia, Bhutan, Thailand, Myanmar, Cambodia, Laos, Vietnam, Nepal, and far eastern India. The relatively standardized deployment methods in the region provide a consistent, reliable, and rich count data set relative to other large‐scale pressence‐only data sets, such as the Global Biodiversity Information Facility (GBIF) or citizen science repositories (e.g., iNaturalist), and is thus most similar to eBird. To facilitate the use of these data, we also provide mammalian species trait information and 13 environmental covariates calculated at three spatial scales around the camera survey centroids (within 10‐, 20‐, and 30‐km buffers). We will update the dataset to include broader coverage of temperate Asia and add newer surveys and covariates as they become available. This dataset unlocks immense opportunities for single‐species ecological or conservation studies as well as applied ecology, community ecology, and macroecology investigations. The data are fully available to the public for utilization and research. Please cite this data paper when utilizing the data