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Irg1 is an enzyme that generates itaconate, a metabolite that plays a key role in the regulation of inflammatory responses. Previous studies have implicated Irg1 as an important mediator in preventing excessive inflammation and tissue damage in Mycobacterium tuberculosis ( Mtb ) infection. Here, we investigated the pattern recognition receptors and signaling pathways by which Mtb triggers Irg1 gene expression by comparing the responses of control and genetically deficient BMDMs. Using this approach, we demonstrated partial roles for TLR-2 (but not TLR-4 or -9), MyD88 and NFκB signaling in Irg1 induction by Mtb bacilli. In addition, drug inhibition studies revealed major requirements for phagocytosis and endosomal acidification in Irg1 expression triggered by Mtb but not LPS or PAM3CSK4. Importantly, the Mtb -induced Irg1 response was highly dependent on the presence of the bacterial ESX-1 secretion system, as well as host STING and Type I IFN receptor (IFNAR) signaling with Type II IFN (IFN-γ) signaling playing only a minimal role. Based on these findings we hypothesize that Mtb induces Irg1 expression in macrophages via the combination of two independent triggers both dependent on bacterial phagocytosis: 1) a major signal stimulated by phagocytized Mtb products released by an ESX-1-dependent mechanism into the cytosol where they activate the STING pathway leading to Type I-IFN production, and 2) a secondary TLR-2, MyD88 and NFκB dependent signal that enhances Irg1 production independently of Type I IFN induction.

The interplay between (Mtb) and humans is multifactorial. The susceptibility/resistance profile and the establishment of clinical tuberculosis (TB) still remains elusive. The gain-of-function variant rs10754558 in the gene (found in 30% of the world population) confers protection against the development of TB, indicating a prominent role played by NLRP3 inflammasome against Mtb. Through genotype-guided assays and various Mtb strains (BCG, H37Rv, Beijing-1471, MP287/03), we demonstrate that Mtb strains activate inflammasome according to the NLRP3/IL-1ß or NLRC4/IL18 preferential axis. and enetic variants contribute to the presentation of TB. For the first time, we have shown that loss-of-function variants in significantly contribute to the development of extra-pulmonary TB. The analysis of inflammasome activation in a cohort of TB patients and their \"household contacts\" (CNT) revealed that plasma IL-1ß/IFN-α ratio lets us distinguish patients from Mtb-exposed-but-healthy individuals from an endemic region. Moreover, NLRP3 inflammasome seemed \"exhausted\" in TB patients compared to CNT, indicating a more efficient activation of inflammasome in resistant individuals. These findings suggest that inflammasome genetics as well as virulence-dependent level of inflammasome activation contribute to the onset of a susceptible/resistant profile among Mtb-exposed individuals.

Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, a transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. We found that BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion in Mtb-infected mice increased glutathione levels and Gpx4 expression that inhibit lipid peroxidation. Bach1 −/− macrophages exhibited increased resistance to Mtb-induced cell death, while Mtb-infected Bach1-deficient mice displayed reduced bacterial loads, pulmonary necrosis and lipid peroxidation concurrent with increased survival. Single-cell RNA-seq analysis of lungs from Mtb-infected Bach1 −/− mice revealed an enrichment of genes associated with ferroptosis suppression. Bach1 depletion in Mtb-infected B6.Sst1 S mice that display human-like necrotic lung pathology also markedly reduced necrosis and increased host resistance. These findings identify Bach1 as a key regulator of cellular and tissue necrosis and host resistance in Mtb infection. The host transcription factor, Bach1, promotes Mycobacterium tuberculosis pathogenesis by inhibiting protective glutathione metabolism and antioxidant responses that prevent ferroptosis.

This article is composed of three independent commentaries about the state of Integrated, Coordinated, Open, Networked (ICON) principles in the American Geophysical Union Biogeosciences section, and discussion on the opportunities and challenges of adopting them. Each commentary focuses on a different topic: (a) Global collaboration, technology transfer, and application (Section 2), (b) Community engagement, community science, education, and stakeholder involvement (Section 3), and (c) Field, experimental, remote sensing, and real‐time data research and application (Section 4). We discuss needs and strategies for implementing ICON and outline short‐ and long‐term goals. The inclusion of global data and international community engagement are key to tackling grand challenges in biogeosciences. Although recent technological advances and growing open‐access information across the world have enabled global collaborations to some extent, several barriers, ranging from technical to organizational to cultural, have remained in advancing interoperability and tangible scientific progress in biogeosciences. Overcoming these hurdles is necessary to address pressing large‐scale research questions and applications in the biogeosciences, where ICON principles are essential. Here, we list several opportunities for ICON, including coordinated experimentation and field observations across global sites, that are ripe for implementation in biogeosciences as a means to scientific advancements and social progress. Plain Language Summary Biogeosciences is an interdisciplinary field that requires multiscale global data and concerted international community efforts to tackle grand challenges. However, several technical, institutional, and cultural hurdles have remained as major roadblocks toward scientific progress, hindering seamless global data acquisition and international community engagement. To bring a paradigm shift in biogeosciences, there is a need to implement integrated, coordinated, open, and networked efforts, collectively known as the Integrated, Coordinated, Open, Networked (ICON) principles. In this article, we present three related commentaries about the state of ICON, discuss needs to reduce geographical bias in data for enhancing scientific progress, and identify action items. Action items are primarily people‐centric and include but are not limited to: longer‐term funding priorities to institutionalize capacity and reduce entry costs, engagement of local stakeholders across the globe, incentivization of collaborations, and development of training and workshops for capacity building. Key Points Biogeosciences needs Integrated, Coordinated, Open, Networked (ICON) principles to address multiscale global problems and reduce geographical bias in scientific progress Much potential exists for emphasizing people‐centric capacity building, involving relevant stakeholders within an ICON framework Globally coordinated experimental and field data provide challenges and opportunities for scientific advancement in biogeosciences

Amazonian Dark Earths (ADEs) are unusually fertile soils characterised by elevated concentrations of microscopic charcoal particles, which confer their distinctive colouration. Frequent occurrences of pre-Columbian artefacts at ADE sites led to their ubiquitous classification as Anthrosols (soils of anthropic origin). However, it remains unclear how indigenous peoples created areas of high fertility in one of the most nutrient-impoverished environments on Earth. Here, we report new data from a well-studied ADE site in the Brazilian Amazon, which compel us to reconsider its anthropic origin. The amounts of phosphorus and calcium—two of the least abundant macronutrients in the region—are orders of magnitude higher in ADE profiles than in the surrounding soil. The elevated levels of phosphorus and calcium, which are often interpreted as evidence of human activity at other sites, correlate spatially with trace elements that indicate exogenous mineral sources rather than in situ deposition. Stable isotope ratios of neodymium, strontium, and radiocarbon activity of microcharcoal particles also indicate exogenous inputs from alluvial deposition of carbon and mineral elements to ADE profiles,  beginning several thousands of years before the earliest evidence of soil management for plant cultivation in the region. Our data suggest that indigenous peoples harnessed natural processes of landscape formation, which led to the unique properties of ADEs, but were not responsible for their genesis. If corroborated elsewhere, this hypothesis would transform our understanding of human influence in Amazonia, opening new frontiers for the sustainable use of tropical landscapes going forward. Amazonian Dark Earth is soil that has had mysteriously high fertility since ancient times, despite the fact that surrounding soils have very low nutrients. Here the authors’ use of isotope reconstructions indicate that these soils predate human settlement and could have alluvial and burning origins.

The incidence of cancer cases is increasing worldwide, and chemotherapy is often necessary as part of the treatment for many of these cases. Nature-based interventions have been shown to offer potential benefits for human well-being. Objective: This study aims to investigate the outcome of nature images on clinical symptom management related to chemotherapy. Methods: A randomized clinical trial was conducted in an outpatient cancer unit of a private hospital in Brazil, with 173 participants over the age of 18 who were undergoing chemotherapy and had signed an informed consent form. The intervention consisted of the presentation of a 12-min video featuring nature images categorized under the themes of Tranquility, Beauty, Emotions Up, or Miscellany. Images were sourced from the e-Nature Positive Emotions Photography Database (e-NatPOEM), a publicly available collection of affectively rated images. Sociodemographic and clinical data, as well as the participants’ connection to nature, were investigated. The Positive Affect/Negative Affect Scale (PANAS) and the Edmonton Symptom Assessment System (ESAS) were applied pre- and post-intervention. Results: Data showed very strong evidence of a reduction in negative affect for the intervention group (p < 0.001) and moderate evidence for the control group (p = 0.034). There was also a significant reduction in the intervention group for pain (p < 0.001), tiredness (p = 0.002), sadness (p < 0.001), anxiety (p < 0.001), and appetite (p = 0.001). The Beauty video had the best performance, while the Tranquility video showed no significant improvement in any of the symptoms evaluated. These findings suggest that images of nature may be a valuable tool to help control clinical and psychological symptoms in cancer patients undergoing chemotherapy.

A new coccidian species (Protozoa: Apicomplexa: Isospora) parasitizing the white-shouldered fire-eye Pyriglena leucoptera (Vieillot, 1818) is described in the Parque Nacional do Itatiaia. This park is a protected area in southeastern Brazil with a high degree of vulnerability, representing a “conservation island” of biodiversity. Isospora parnaitatiaiensis n. sp. has oocysts that are ellipsoidal, 23.8 × 19.4 μm, with smooth, bilayered wall, ~1.1 μm thick. Micropyle and oocyst residuum are absent, but one or two polar granules are present. Sporocysts are ellipsoidal, 14.6 × 9.3 μm. The Stieda body is nipple- to knob-like and sub-Stieda body rounded to rectangular. Sporocyst residuum is present, usually as a cluster of numerous granules. Sporozoites are vermiform with two refractile bodies and a nucleus. This is the second isosporoid coccidian described from antbirds (Thamnophilidae).

In the New World, the avian order Psittaciformes comprises 142 species, yet to date only 3 (2%) of the species have been examined for coccidia, and from these only four species of Eimeria Schneider, 1875 have been described. In this study, a new coccidian species (Protozoa: Apicomplexa: Eimeriidae) obtained from the blue-and-yellow macaw Ara ararauna (Linnaeus) is reported from Brazil. Oöcysts of Eimeria ararae n. sp. are ovoidal, measure 28.7 × 20.2 μm and have a smooth, bi-layered wall c. 1.1 μm thick. Both micropyle and oöcyst residuum are absent, but polar granules are present. Sporocysts are ovoidal and measure 17.0 × 8.3 µm, with knob-like, prominent Stieda body and sporocyst residuum is composed of granules; sub-Stieda body is absent. Sporozoites are vermiform with one refractile body and a nucleus. This is the fifth description of an eimerid coccidian infecting a New World psittaciform bird.

The aim of this study was to perform the first molecular genotyping of Giardia duodenalis from goats in Brazil, in order to assess the risk for zoonotic transmission. Samples were collected from two dairy goat farms (Saanen breed) located in the city of Niteroi in the state of Rio de Janeiro, Brazil. Goat faecal samples (n = 58) were collected directly from the rectums of all animals up to one year of age and were subjected to centrifuge-flotation in sugar saturate solution. Nested-PCR and sequencing using β -giardin and tpi gene targets was performed on positive samples. Seventeen out of fifty-eight (29.31%) faecal samples were positive for Giardia duodenalis cysts, all belonging to the same farm. Only eight isolates were successfully sequenced (eight samples for β-giardin and four samples for tpi), all belonging to genotype E. Two types of sequences were identified for each locus within isolates from the current study, which exhibited sequence heterogeneity with variable numbers of single nucleotide polymorphisms. The present study contributes to a better understanding of the molecular epidemiology of this parasite.

Klossiella tejerai Scorza, Torrealba & Dagert, 1957 is a primitive coccidian parasite reported from the New World marsupials Didelphis marsupialis (Linnaeus) and Marmosa demerarae (Thomas). The current work describes K. tejerai from the Brazilian common opossum Didelphis aurita (Wied-Neuwied) in Southeastern Brazil, evidencing the coccidial dispersion across opossums of the same family. The sporocysts recovered from urine samples were ellipsoidal, 20.4 × 12.7 µm, with sporocyst residuum composed of scattered spherules and c. 13 sporozoites per sporocyst, with refractile bodies and nucleus. Macrogametes, microgametes, sporonts, sporoblasts/sporocysts were identified within parasitophorous vacuoles of epithelial cells located near the renal corticomedullary junction. Didelphis marsupialis should not have transmitted K. tejerai to D. aurita because they are not sympatric; however M. demerarae is sympatric with D. marsupialis and D. aurita . Therefore, D. aurita becomes the third host species for K. tejerai in South America.