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Although vaccines have reduced the burden of COVID-19, their efficacy in helminth infection-endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal roundworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4 + and CD8 + T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA-vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared with animals immunized without Hpb infection. Helminth-mediated suppression of spike protein-specific CD8 + T cell responses occurred independently of signal transducer and activator of transcription 6 (STAT6) signaling, whereas blockade of interleukin-10 (IL-10) rescued vaccine-induced CD8 + T cell responses. Together, these data show that, in mice, intestinal helminth infection impaired vaccine-induced T cell responses through an IL-10 pathway, which compromised protection against antigenically drifted SARS-CoV-2 variants.

Purpose of Review: Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies., Recent Findings: During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials., Summary: Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8 + memory T cells develop at the location of infection: tissue-resident memory T cells (T RM ). CD8 + T-cell responses are associated with type-1 infections and type-1 regulatory T cells (T REG ) are important for CD8 + T-cell development, however, if CD8 + T RM cells develop under other infection types and require immune type-specific T REG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8 + T RM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching T REG population contributing transforming growth factor-β. Nevertheless, type-1 T REG cells remain the most important population for T RM cell development. Once established, T RM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8 + T RM cells., (© 2023. Springer Nature Limited.)

Despite the considerable morbidity and mortality of yellow fever virus (YFV) infections in Brazil, our understanding of disease outbreaks is hampered by limited viral genomic data. Here, through a combination of phylogenetic and epidemiological models, we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modeling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centers in the Southeast. Phylodynamic analysis unraveled the circulation of three distinct lineages and provided proof of the directionality of a known spatial corridor that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with eco-epidemiology can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.

Background: Efforts to modulate the function of tumor-associated myeloid cell are underway to overcome the challenges in immunotherapy and find a cure. One potential therapeutic target is integrin CD11b, which can be used to modulate the myeloid-derived cells and induce tumor-reactive T-cell responses. However, CD11b can bind to multiple different ligands, leading to various myeloid cell functions such as adhesion, migration, phagocytosis, and proliferation. This has created a major challenge in understanding how CD11b converts the differences in the receptor-ligand binding into subsequent signaling responses and using this information for therapeutic development., Methods: This study aimed to investigate the antitumor effect of a carbohydrate ligand, named BG34-200, which modulates the CD11b + cells. We have applied peptide microarrays, multiparameter FACS (fluorescence-activated cell analysis) analysis, cellular/molecular immunological technology, advanced microscopic imaging, and transgenic mouse models of solid cancers, to study the interaction between BG34-200 carbohydrate ligand and CD11b protein and the resulting immunological changes in the context of solid cancers, including osteosarcoma, advanced melanoma, and pancreatic ductal adenocarcinoma (PDAC)., Results: Our results show that BG34-200 can bind directly to the activated CD11b on its I (or A) domain, at previously unreported peptide residues, in a multisite and multivalent manner. This engagement significantly impacts the biological function of tumor-associated inflammatory monocytes (TAIMs) in osteosarcoma, advanced melanoma, and PDAC backgrounds. Importantly, we observed that the BG34-200-CD11b engagement triggered endocytosis of the binding complexes in TAIMs, which induced intracellular F-actin cytoskeletal rearrangement, effective phagocytosis, and intrinsic ICAM-1 (intercellular adhesion molecule I) clustering. These structural biological changes resulted in the differentiation in TAIMs into monocyte-derived dendritic cells, which play a crucial role in T-cell activation in the tumor microenvironment., Conclusions: Our research has advanced the current understanding of the molecular basis of CD11b activation in solid cancers, revealing how it converts the differences in BG34 carbohydrate ligands into immune signaling responses. These findings could pave the way for the development of safe and novel BG34-200-based therapies that modulate myeloid-derived cell functions, thereby enhancing immunotherapy for solid cancers., Competing Interests: Competing interests: None declared, (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the impact of impaired pulmonary function on patient-centered outcomes after hospital discharge due to severe COVID-19 in patients without preexisting respiratory disease., Methods: This is an ongoing prospective cohort study evaluating patients (> 18 years of age) 2-6 months after hospital discharge due to severe COVID-19. Respiratory symptoms, health-related quality of life, lung function, and the six-minute walk test were assessed. A restrictive ventilatory defect was defined as TLC below the lower limit of normal, as assessed by plethysmography. Chest CT scans performed during hospitalization were scored for the presence and extent of parenchymal abnormalities., Results: At a mean follow-up of 17.2 ± 5.9 weeks after the diagnosis of COVID-19, 120 patients were assessed. Of those, 23 (19.2%) reported preexisting chronic respiratory diseases and presented with worse lung function and exertional dyspnea at the follow-up visit in comparison with their counterparts. When we excluded the 23 patients with preexisting respiratory disease plus another 2 patients without lung volume measurements, a restrictive ventilatory defect was observed in 42/95 patients (44%). This subgroup of patients (52.4% of whom were male; mean age, 53.9 ± 11.3 years) showed reduced resting gas exchange efficiency (DLCO), increased daily-life dyspnea, increased exertional dyspnea and oxygen desaturation, and reduced health-related quality of life in comparison with those without reduced TLC (50.9% of whom were male; mean age, 58.4 ± 11.3 years). Intensive care need and higher chest CT scores were associated with a subsequent restrictive ventilatory defect., Conclusions: The presence of a restrictive ventilatory defect approximately 4 months after severe COVID-19 in patients without prior respiratory comorbidities implies worse clinical outcomes.

The immunopathological mechanisms driving the development of severe COVID-19 remain poorly defined. Here, we utilize a rhesus macaque model of acute SARS-CoV-2 infection to delineate perturbations in the innate immune system. SARS-CoV-2 initiates a rapid infiltration of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and a significant increase of blood CD14 - CD16 + monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generate a longitudinal scRNA-Seq dataset of airway cells, and map these subsets to corresponding populations in the human lung. SARS-CoV-2 infection elicits a rapid recruitment of two macrophage subsets: CD163 + MRC1 - , and TREM2 + populations that are the predominant source of inflammatory cytokines. Treatment with baricitinib (Olumiant®), a JAK1/2 inhibitor is effective in eliminating the influx of non-alveolar macrophages, with a reduction of inflammatory cytokines. This study delineates the major lung macrophage subsets driving airway inflammation during SARS-CoV-2 infection., (© 2023. The Author(s).)

Background & Objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level., Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated., Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO 2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO 2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate., Interpretation & Conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Ophiocordyceps australis (Ascomycota, Hypocreales, Ophiocordycipitaceae) is a classic entomopathogenic fungus that parasitizes ants (Hymenoptera, Ponerinae, Ponerini). Nonetheless, according to our results, this fungal species also exhibits a complete set of genes coding for plant cell wall degrading Carbohydrate-Active enZymes (CAZymes), enabling a full endophytic stage and, consequently, its dual ability to both parasitize insects and live inside plant tissue. The main objective of our study was the sequencing and full characterization of the genome of the fungal strain of O. australis (CCMB661) and its predicted secretome. The assembled genome had a total length of 30.31 Mb, N50 of 92.624 bp, GC content of 46.36%, and 8,043 protein-coding genes, 175 of which encoded CAZymes. In addition, the primary genes encoding proteins and critical enzymes during the infection process and those responsible for the host-pathogen interaction have been identified, including proteases (Pr1, Pr4), aminopeptidases, chitinases (Cht2), adhesins, lectins, lipases, and behavioral manipulators, such as enterotoxins, Protein Tyrosine Phosphatases (PTPs), and Glycoside Hydrolases (GHs). Our findings indicate that the presence of genes coding for Mad2 and GHs in O. australis may facilitate the infection process in plants, suggesting interkingdom colonization. Furthermore, our study elucidated the pathogenicity mechanisms for this Ophiocordyceps species, which still is scarcely studied.

We investigated whether a set of phylogeographical tracked emergent events of Orthocoronavirinae were related to developed, urban and polluted environments worldwide. We explored coronavirus records in response to climate (rainfall parameters), population density, CO 2 emission, Human Developmental Index (HDI) and deforestation. We contrasted environmental characteristics from regions with spillovers or encounters of wild Orthocoronavirinae against adjacent areas having best-preserved conditions. We used all complete sequenced CoVs genomes deposited in NCBI and GISAID databases until January 2021. Except for Deltacoronavirus, concentrated in Hong Kong and in birds, the other three genera were scattered all over the planet, beyond the original distribution of the subfamily, and found in humans, mammals, fishes and birds, wild or domestic. Spillovers and presence in wild animals were only reported in developed/densely populated places. We found significantly more occurrences reported in places with higher HDI, CO 2 emission, or population density, along with more rainfall and more accentuated seasonality. Orthocoronavirinae occurred in areas with significantly higher human populations, CO 2 emissions and deforestation rates than in adjacent locations. Intermediately disturbed ecosystems seemed more vulnerable for Orthocoronavirinae emergence than forested regions in frontiers of deforestation. Sadly, people experiencing poverty in an intensely consumerist society are the most vulnerable., (© 2022 Society for Applied Microbiology and John Wiley & Sons Ltd.)

In the last decade a large outbreak of Yellow Fever (YF) has been observed in Brazilian Atlantic Forest region, traditionally a non-endemic area. In this scenario, the role of wild mammal species as YF reservoirs can be questioned, especially the hematophagous bat, Desmodus rotundus. So, the objective of this study was to analyze molecularly the presence of the YF virus (YFV) in hematophagous bats during a YF outbreak in Brazil. Twenty-one samples were collected from seven adult male hematophagous bats D. rotundus. As YFV is considered a viscerotropic and neurotropic virus, samples of liver, kidney and brain were collected and molecularly analyzed using the RT qPCR technique. The animals were captured according to ethical protocols during a YF outbreak in Brazil in 2017, from a region of the Brazilian Atlantic Forest. The results revealed that the analyzed tissue samples were not infected with the YFV. The negative results for this bat species allow us to infer that other animals may be reservoirs of this virus in this ecosystem and they probably have not been identified yet. Therefore, health surveillance actions are essential to monitor the role of wild animals in the YF dissemination in Brazilian Atlantic Forest and alert to the possibility of new geographic amplification of areas where YF occurs. This research encourages the new search about the role of wild animals on YFV transmission and reinforces the importance of epidemiological surveillance in the transmission of human infectious diseases., Competing Interests: Conflict of interest statement On behalf of all authors, the corresponding author states that there are no conflicts of interest or funding related to this study., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Current climate change is disrupting biotic interactions and eroding biodiversity worldwide. However, species sensitive to aridity, high temperatures, and climate variability might find shelter in microclimatic refuges, such as leaf rolls built by arthropods. To explore how the importance of leaf shelters for terrestrial arthropods changes with latitude, elevation, and climate, we conducted a distributed experiment comparing arthropods in leaf rolls versus control leaves across 52 sites along an 11,790 km latitudinal gradient. We then probed the impact of short- versus long-term climatic impacts on roll use, by comparing the relative impact of conditions during the experiment versus average, baseline conditions at the site. Leaf shelters supported larger organisms and higher arthropod biomass and species diversity than non-rolled control leaves. However, the magnitude of the leaf rolls' effect differed between long- and short-term climate conditions, metrics (species richness, biomass, and body size), and trophic groups (predators vs. herbivores). The effect of leaf rolls on predator richness was influenced only by baseline climate, increasing in magnitude in regions experiencing increased long-term aridity, regardless of latitude, elevation, and weather during the experiment. This suggests that shelter use by predators may be innate, and thus, driven by natural selection. In contrast, the effect of leaf rolls on predator biomass and predator body size decreased with increasing temperature, and increased with increasing precipitation, respectively, during the experiment. The magnitude of shelter usage by herbivores increased with the abundance of predators and decreased with increasing temperature during the experiment. Taken together, these results highlight that leaf roll use may have both proximal and ultimate causes. Projected increases in climate variability and aridity are, therefore, likely to increase the importance of biotic refugia in mitigating the effects of climate change on species persistence., (© 2022 John Wiley & Sons Ltd.)

Interleukin-10 (IL-10) is an immunosuppressive cytokine that signals through STAT3 to regulate T follicular helper (Tfh) cell differentiation and germinal center formation. In SIV-infected macaques, levels of IL-10 in plasma and lymph nodes (LNs) were induced by infection and not normalized with antiretroviral therapy (ART). During chronic infection, plasma IL-10 and transcriptomic signatures of IL-10 signaling were correlated with the cell-associated SIV-DNA content within LN CD4+ memory subsets, including Tfh cells, and predicted the frequency of CD4+ Tfh cells and their cell-associated SIV-DNA content during ART, respectively. In ART-treated rhesus macaques, cells harboring SIV-DNA by DNAscope were preferentially found in the LN B cell follicle in proximity to IL-10. Finally, we demonstrated that the in vivo neutralization of soluble IL-10 in ART-treated, SIV-infected macaques reduced B cell follicle maintenance and, by extension, LN memory CD4+ T cells, including Tfh cells and those expressing PD-1 and CTLA-4. Thus, these data support a role for IL-10 in maintaining a pool of target cells in lymphoid tissue that serve as a niche for viral persistence. Targeting IL-10 signaling to impair CD4+ T cell survival and improve antiviral immune responses may represent a novel approach to limit viral persistence in ART-suppressed people living with HIV.

Despite advances in antiretroviral therapy, chronic immune activation continues to be observed among individuals with well-controlled HIV viral loads, and is associated with non-AIDS defining morbidities among people living with HIV. Alcohol use disorder impacts a significant proportion of individuals living with HIV, and alcohol exposure is known to damage the intestinal epithelium which may increase translocation of pathogens and their molecular products, driving systemic immune activation and dysregulation. The aim of this study was to determine if adults living with HIV with well-controlled viral loads, who also suffer from alcohol use disorder with and without hepatitis C virus co-infection (n=23), exhibit evidence of advanced systemic immune activation, intestinal damage, and microbial translocation, as compared to adults living with HIV who are not exposed to chronic alcohol or other substances of abuse (n=29). The impact of a 1-month intervention to treat alcohol-use disorder was also examined. Alcohol-use disorder was associated with evidence of advanced innate immune activation, alterations in monocyte phenotype including increased expression of Toll-like receptor 4, increased burden of stimulatory ligands for Toll-like receptor 4, and alterations in plasma cytokine signature, most notably elevations in soluble CD40 ligand and transforming growth factor beta. Alcohol-associated immune activation was more pronounced among individuals with hepatitis C virus co-infection. Although the 1-month intervention to treat alcohol use disorder did not result in significant reductions in the interrogated indicators of immune activation, our findings suggest that chronic alcohol exposure is a major modifiable risk factor for chronic immune activation and dysregulation among people-living with HIV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TW declared a shared affiliation with the authors RPS and SR to the handling editor at the time of review., (Copyright © 2022 Underwood, Park, Uebelhoer, Gu, Kunkel, Korthuis, Cook, Sekaly, Ribeiro and Lancioni.)

Type I IFNs (TI-IFNs) drive immune effector functions during acute viral infections and regulate cell cycling and systemic metabolism. That said, chronic TI-IFN signaling in the context of HIV infection treated with antiretroviral therapy (ART) also facilitates viral persistence, in part by promoting immunosuppressive responses and CD8+ T cell exhaustion. To determine whether inhibition of IFN-α might provide benefit in the setting of chronic, ART-treated SIV infection of rhesus macaques, we administered an anti-IFN-α antibody followed by an analytical treatment interruption (ATI). IFN-α blockade was well-tolerated and associated with lower expression of TI-IFN-inducible genes (including those that are antiviral) and reduced tissue viral DNA (vDNA). The reduction in vDNA was further accompanied by higher innate proinflammatory plasma cytokines, expression of monocyte activation genes, IL-12-induced effector CD8+ T cell genes, increased heme/metabolic activity, and lower plasma TGF-β levels. Upon ATI, SIV-infected, ART-suppressed nonhuman primates treated with anti-IFN-α displayed lower levels of weight loss and improved erythroid function relative to untreated controls. Overall, these data demonstrated that IFN-α blockade during ART-treated SIV infection was safe and associated with the induction of immune/erythroid pathways that reduced viral persistence during ART while mitigating the weight loss and anemia that typically ensue after ART interruption.

Patients with cancers have been severely affected by the COVID-19 pandemic. This is highlighted by the adverse outcomes in cancer patients with COVID-19 as well as by the impact of the COVID-19 pandemic on cancer care. Patients with cancer constitute a heterogeneous population that exhibits distinct mechanisms of immune dysfunction, associated with distinct systemic features of hot (T-cell-inflamed/infiltrated) and cold (Non-T-cell-inflamed and/or infiltrated) tumors. The former show hyper immune activated cells and a highly inflammatory environment while, contrastingly, the latter show the profile of a senescent and/or quiescent immune system. Thus, the evolution of SARS-CoV-2 infection in different types of cancers can show distinct trajectories which could lead to a variety of clinical and pathophysiological outcomes. The altered immunological environment including cytokines that characterizes hot and cold tumors will lead to different mechanisms of immune dysfunction, which will result in downstream effects on the course of SARS-CoV-2 infection. This review will focus on defining the known contributions of soluble pro- and anti-inflammatory mediators on immune function including altered T-cells and B-cells responses and as well on how these factors modulate the expression of SARS-CoV-2 receptor ACE2, TMPRSS2 expression, and lymph node fibrosis in cancer patients. We will propose immune mechanisms that underlie the distinct courses of SARS-CoV-2 infection in cancer patients and impact on the success of immune based therapies that have significantly improved cancer outcomes. Better understanding of the immune mechanisms prevalent in cancer patients that are associated to the outcomes of SARS-CoV-2 infection will help to identify the high-risk cancer patients and develop immune-based approaches to prevent significant adverse outcomes by targeting these pathways., (Copyright © 2021. Published by Elsevier Inc.)

One hundred years after the flu pandemic of 1918, the world faces an outbreak of a new severe acute respiratory syndrome, caused by a novel coronavirus. With a high transmissibility, the pandemic has spread worldwide, creating a scenario of devastation in many countries. By the middle of 2021, about 3% of the world population had been infected and more than 4 million people had died. Different from the H1N1 pandemic, which had a deadly wave and ceased, the new disease is maintained by successive waves, mainly produced by new virus variants and the small number of vaccinated people. In the present work, we create a version of the SIR model using the spatial localization of persons, their movements, and considering social isolation probabilities. We discuss the effects of virus variants, and the role of vaccination rate in the pandemic dynamics. We show that, unless a global vaccination is implemented, we will have continuous waves of infections.

The patterns of insect movement are the cumulate product of many individual decisions and can be shaped by the way morphology and behaviour interacts with landscape structure and composition. Hence, the ongoing process of habitat fragmentation increases the distance among suitable habitats and changes those in such a way that it may favour some movement behaviour. Our study described some biological traits (sex ratio, age structure and individual permanence in a population), as well as the movements of fruit-feeding butterflies along the horizontal dimension (among habitats: forest interior, natural forest transition - ecotone and anthropogenic forest transition - edge) and the vertical dimension (between canopy and understory). We sampled butterflies monthly over 1 year in the Atlantic rainforest, South-eastern Brazil, following a standardized design using bait traps. We found that sex ratio was male biased for five out of the six more abundant species and the age structure showed an increase in recruitment of new individuals in the dry season followed by a noticeable aging of the populations in the wet season. In general, our results revealed an aggregated spatial distribution, in which few individuals travelled long distances while most individuals were recaptured in the same trap, suggesting that all studied habitats currently provide the necessary conditions for the maintenance of butterfly populations, favouring fewer movements and narrow home ranges for both sexes and species. Conservation of a set of heterogeneous habitats it is especially important for the maintenance of sedentary butterflies and of those that move large distances., (© 2021. Sociedade Entomológica do Brasil.)

Tissue changes during embryonic and postnatal development are critical for the success of physiological processes later in mammalian life. Dietary transition from milk to a variety of other food items is one of the factors inducing these changes in mammal species. Blood is utilized as food by only three species of vampire bats among all living mammals. Considering its high protein content, this unique diet is known to induce several metabolic changes, including fasting susceptibility. However, changes in the renal function to meet the excretory needs associated to the blood diet are unknown. Here we aimed at investigating morphological alterations in vampires' kidneys during embryonic and post-natal development in order to better understand the evolutionary adaptations allowing sanguivory. Common vampire bats (Desmodus rotundus) were captured and had their kidneys removed for histological, morphometrical and stereological analysis. Our results showed increased glomerular area and higher glomerular and uriniferous tubules volumetric densities in adults compared to developing bats. These results, together with a higher Renal Somatic Index and a thicker inner medulla also reported for adults, support renal hypertrophy due to increased renal function in blood-feeding vampires as compared to the earlier life stages. We also report a lower foot process density and its different arrange inside the glomerular capsule in adults, indicating an adaptation to a larger extracellular volume formed by increased glomerular filtration. Taken together, kidney morphological changes reported here for vampire bats may reflect in adults' adaptations to a monotrophic strategy., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Ants, an ecologically successful and numerically dominant group of animals, play key ecological roles as soil engineers, predators, nutrient recyclers, and regulators of plant growth and reproduction in most terrestrial ecosystems. Further, ants are widely used as bioindicators of the ecological impact of land use. We gathered information of ant species in the Atlantic Forest of South America. The ATLANTIC ANTS data set, which is part of the ATLANTIC SERIES data papers, is a compilation of ant records from collections (18,713 records), unpublished data (29,651 records), and published sources (106,910 records; 1,059 references), including papers, theses, dissertations, and book chapters published from 1886 to 2020. In total, the data set contains 153,818 ant records from 7,636 study locations in the Atlantic Forest, representing 10 subfamilies, 99 genera, 1,114 ant species identified with updated taxonomic certainty, and 2,235 morphospecies codes. Our data set reflects the heterogeneity in ant records, which include ants sampled at the beginning of the taxonomic history of myrmecology (the 19th and 20th centuries) and more recent ant surveys designed to address specific questions in ecology and biology. The data set can be used by researchers to develop strategies to deal with different macroecological and region-wide questions, focusing on assemblages, species occurrences, and distribution patterns. Furthermore, the data can be used to assess the consequences of changes in land use in the Atlantic Forest on different ecological processes. No copyright restrictions apply to the use of this data set, but we request that authors cite this data paper when using these data in publications or teaching events., (© 2021 The Authors. Ecology © 2021 The Ecological Society of America.)

Over the last few decades, several emerging or reemerging viral diseases with no readily available vaccines have ravaged the world. A platform to fastly generate vaccines inducing potent and durable neutralizing antibody and T cell responses is sorely needed. Bioinformatically identified epitope-based vaccines can focus on immunodominant T cell epitopes and induce more potent immune responses than a whole antigen vaccine and may be deployed more rapidly and less costly than whole-gene vaccines. Increasing evidence has shown the importance of the CD4+ T cell response in protection against HIV and other viral infections. The previously described DNA vaccine HIVBr18 encodes 18 conserved, promiscuous epitopes binding to multiple HLA-DR-binding HIV epitopes amply recognized by HIV-1-infected patients. HIVBr18 elicited broad, polyfunctional, and durable CD4 + and CD8+ T cell responses in BALB/c and mice transgenic to HLA class II alleles, showing cross-species promiscuity. To fully delineate the promiscuity of the HLA class II vaccine epitopes, we assessed their binding to 34 human class II (HLA-DR, DQ, and -DP) molecules, and immunized nonhuman primates. Results ascertained redundant 100% coverage of the human population for multiple peptides. We then immunized Rhesus macaques with HIVBr18 under in vivo electroporation. The immunization induced strong, predominantly polyfunctional CD4+ T cell responses in all animals to 13 out of the 18 epitopes; T cells from each animal recognized 7-11 epitopes. Our results provide a preliminary proof of concept that immunization with a vaccine encoding epitopes with high and redundant coverage of the human population can elicit potent T cell responses to multiple epitopes, across species and MHC barriers. This approach may facilitate the rapid deployment of immunogens eliciting cellular immunity against emerging infectious diseases, such as COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Being a Re-Emerging Infectious Disease, dengue causes 390 million cases globally and is prevalent in many urban areas in South America. Understanding the fine-scale relationships between dengue incidence and environmental and socioeconomic factors can guide improved disease prevention strategies. This ecological study examines the association between dengue incidence and satellite-based vegetation greenness in 3826 census tracts nested in 474 neighborhoods in Belo Horizonte, Brazil, during the 2010 dengue epidemic. To reduce potential bias in the estimated dengue-greenness association, we adjusted for socioeconomic vulnerability, population density, building height and density, land cover composition, elevation, weather patterns, and neighborhood random effects. We found that vegetation greenness was negatively associated with dengue incidence in a univariate model, and this association attenuated after controlling for additional covariates. The dengue-greenness association was modified by socioeconomic vulnerability: while a positive association was observed in the least vulnerable census tracts, the association was negative in the most vulnerable areas. Using greenness as a proxy for vegetation quality, our results show the potential of vegetation management in reducing dengue incidence, particularly in socioeconomically vulnerable areas. We also discuss the role of water infrastructure, sanitation services, and tree cover in lowering dengue risk., (© 2021 The Authors.)

The prognosis of most patients with AML is poor due to frequent disease relapse. The cause of relapse is thought to be from the persistence of leukemia initiating cells (LIC's) following treatment. Here we assessed RNA based changes in LICs from matched patient diagnosis and relapse samples using single-cell RNA sequencing. Previous studies on AML progression have focused on genetic changes at the DNA mutation level mostly in bulk AML cells and demonstrated the existence of DNA clonal evolution. Here we identified in LICs that the phenomenon of RNA clonal evolution occurs during AML progression. Despite the presence of vast transcriptional heterogeneity at the single cell level, pathway analysis identified common signaling networks involving metabolism, apoptosis and chemokine signaling that evolved during AML progression and become a signature of relapse samples. A subset of this gene signature was validated at the protein level in LICs by flow cytometry from an independent AML cohort and functional studies were performed to demonstrate co-targeting BCL2 and CXCR4 signaling may help overcome therapeutic challenges with AML heterogeneity. It is hoped this work will facilitate a greater understanding of AML relapse leading to improved prognostic biomarkers and therapeutic strategies to target LIC's., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Metalliferous soils can selectively shape plant species' physiology towards tolerance of high metal concentrations that are usually toxic to organisms. Some adapted plant species tolerate and accumulate metal in their tissues. These metals can serve as an elemental defence but can also decrease growth. Our investigation explored the capacity of natural metal accumulation in a tropical tree species, Eremanthus erythropappus (Asteraceae) and the effects of such bioaccumulation on plant responses to herbivory. Seedlings of E. erythropappus were grown in a glasshouse on soils that represented a metal concentration gradient (Al, Cu, Fe, Mn and Zn), and then the exposed plants were fed to the herbivores in a natural habitat. The effect of herbivory on plant growth was significantly mediated by foliar metal ion concentrations. The results suggest that herbivory effects on these plants change from negative to positive depending on soil metal concentration. Hence, these results provide quantitative evidence for a previously unsuspected interaction between herbivory and metal bioaccumulation on plant growth., (© 2021. The Author(s).)

A second deadlier wave of COVID-19 and the causes of the recent public health collapse of Manaus are compared with the Spanish flu events in that city, and Brazil. Historic sanitarian problems, and its hub position in the Brazilian airway network are combined drivers of deadly events related to COVID-19. These drivers were amplified by misleading governance, highly transmissible variants, and relaxation of social distancing. Several of these same factors may also have contributed to the dramatically severe outbreak of H1N1 in 1918, which caused the death of 10% of the population in seven months. We modelled Manaus parameters for the present pandemic and confirmed that lack of a proper social distancing might select the most transmissible variants. We succeeded to reproduce a first severe wave followed by a second stronger wave. The model also predicted that outbreaks may last for up to five and half years, slowing down gradually before the disease disappear. We validated the model by adjusting it to the Spanish Flu data for the city, and confirmed the pattern experienced by that time, of a first stronger wave in October-November 1918, followed by a second less intense wave in February-March 1919.

Ecological environments research helps to assess the impacts on forests and managing forests. The usage of novel software and hardware technologies enforces the solution of tasks related to this problem. In addition, the lack of connectivity for large data throughput raises the demand for edge-computing-based solutions towards this goal. Therefore, in this work, we evaluate the opportunity of using a Wearable edge AI concept in a forest environment. For this matter, we propose a new approach to the hardware/software co-design process. We also address the possibility of creating wearable edge AI, where the wireless personal and body area networks are platforms for building applications using edge AI. Finally, we evaluate a case study to test the possibility of performing an edge AI task in a wearable-based environment. Thus, in this work, we evaluate the system to achieve the desired task, the hardware resource and performance, and the network latency associated with each part of the process. Through this work, we validated both the design pattern review and case study. In the case study, the developed algorithms could classify diseased leaves with a circa 90% accuracy with the proposed technique in the field. This results can be reviewed in the laboratory with more modern models that reached up to 96% global accuracy. The system could also perform the desired tasks with a quality factor of 0.95, considering the usage of three devices. Finally, it detected a disease epicenter with an offset of circa 0.5 m in a 6 m × 6 m × 12 m space. These results enforce the usage of the proposed methods in the targeted environment and the proposed changes in the co-design pattern.

Objective: Reflect on the influence of Florence Nightingale's teachings to face the COVID-19 pandemic and its repercussions for the future of the profession., Methods: Descriptive reflective study, carried out between May and July 2020, through narrative review on the theme and debates between the authors., Results: The findings are divided into two chapters, namely: Environmental Theory and the teachings of Florence Nightingale in the face of the COVID-19 pandemic; and Florence Nightingale: legacy, present and perspectives., Final Considerations: Florence Nightingale's studies with the Environmentalist Theory and her teachings as a nurse are still valid, even after almost two centuries since her prelude, and should continue to serve as a foundation for the consolidation of the nursing profession.

Purpose of Review: People living with HIV who fail to fully reconstitute CD4+T cells after combination antiretroviral therapy therapy (i.e. immune nonresponders or INRs) have higher frequencies of exhausted T cells are enriched in a small pool of memory T cells where HIV persists and have an abundance of plasma metabolites of bacterial and host origins. Here, we review the current understanding of critical features of T cell exhaustion associated with HIV persistence; we propose to develop novel strategies to reinvigorate the effector function of exhausted T cells with the aim of purging the HIV reservoir., Recent Findings: We and others have recently reported the role of microbiota and metabolites in regulating T cell homeostasis, effector function, and senescence. We have observed that bacteria of the Firmicute phyla (specifically members of the genus Lactobacilli), associated metabolites (β-hydroxybutyrate family), and bile acids can promote regulatory T cell differentiation in INRs with a senescent peripheral blood gene expression profile., Summary: The cross-talk between immune cells and gut microbes at the intestinal mucosa (a major effector site of the mucosal immune response), regulates the priming, proliferation, and differentiation of local and distant immune responses. This cross-talk via the production of major metabolite families (like serum amyloid A, polysaccharide A, and aryl hydrocarbon receptor ligands) plays a key role in maintaining immune homeostasis. HIV infection/persistence leads to gut dysbiosis/microbial translocation, resulting in the local and systemic dissemination of microbes. The ensuing increase in immune cell-microbiome (including pathogens) interaction promotes heightened inflammatory responses and is implicated in regulating innate/adaptive immune effector differentiation cascades that drive HIV persistence. The exact role of the microbiota and associated metabolites in regulating T cell- mediated effector functions that can restrict HIV persistence continue to be the subject of on-going studies and are reviewed here., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Wood-boring beetles develop in live trees and dead wood, performing ecological services such as decomposition and regulation of forest resources. Species of the Cerambycidae family, widely distributed in the world, bore into the trunks of trees and dead wood in native and cultivated areas. The objective is to report the first host plant for Thoracibidion lineatocolle (Thomson, 1865) (Coleoptera: Cerambycidae) and a new host plant for Temnopis megacephala (Germar, 1824) (Coleoptera: Cerambycidae) in the Brazilian Atlantic Forest biome. Three logs, with one-meter-long by 20 cm in diameter, were cut from the trunk of a healthy Anadenanthera colubrina (Fabaceae) tree in October 2013 and tied in the understory at 1.5m high in the Rio Doce State Park, Minas Gerais State, Brazil. The logs, exposed in the forest, were each removed after 40, 80 and 120 days and stored individually in a cardboard box in the "Laboratório de Campo do Projeto de Ecologia de Longa Duração (PELD-CNPq)" in the Rio Doce State Park. A total of 94 individuals of T. lineatocolle and 228 of T. megacephala emerged from the A. colubrina logs. This is the first report of a host plant for T. lineatocolle and a new host plant for T. megacephala.

Herbivory is ubiquitous. Despite being a potential driver of plant distribution and performance, herbivory remains largely undocumented. Some early attempts have been made to review, globally, how much leaf area is removed through insect feeding. Kozlov et al., in one of the most comprehensive reviews regarding global patterns of herbivory, have compiled published studies regarding foliar removal and sampled data on global herbivory levels using a standardized protocol. However, in the review by Kozlov et al., only 15 sampling sites, comprising 33 plant species, were evaluated in tropical areas around the globe. In Brazil, which ranks first in terms of plant biodiversity, with a total of 46,097 species, almost half (43%) being endemic, a single data point was sampled, covering only two plant species. In an attempt to increase knowledge regarding herbivory in tropical plant species and to provide the raw data needed to test general hypotheses related to plant-herbivore interactions across large spatial scales, we proposed a joint, collaborative network to evaluate tropical herbivory. This network allowed us to update and expand the data on insect herbivory in tropical and temperate plant species. Our data set, collected with a standardized protocol, covers 45 sampling sites from nine countries and includes leaf herbivory measurements of 57,239 leaves from 209 species of vascular plants belonging to 65 families from tropical and temperate regions. They expand previous data sets by including a total of 32 sampling sites from tropical areas around the globe, comprising 152 species, 146 of them being sampled in Brazil. For temperate areas, it includes 13 sampling sites, comprising 59 species. Thus, when compared to the most recent comprehensive review of insect herbivory (Kozlov et al.), our data set has increased the base of available data for the tropical plants more than 460% (from 33 to 152 species) and the Brazilian sampling was increased 7,300% (from 2 to 146 species). Data on precise levels of herbivory are presented for more than 57,000 leaves worldwide. There are no copyright restrictions. Please cite this paper when using the current data in publications; the authors request to be informed how the data is used in the publications., (© 2021 The Authors. Ecology © 2021 The Ecological Society of America.)

Ants have efficient and well-studied social immunity mechanisms, which prevent the colony contamination. Little is known about how workers keep their outside territory clear of diseases. We investigated the interactions between Azteca chartifex ants, their associated bacteria and bacteria on the phyllosphere of Byrsonima sericea trees, comparing plants patrolled and not by the ants. The hypothesis is that bacteria associated with the worker's exoskeleton may outcompete the leaf bacteria. Culturable bacteria were isolated from ants, from the main and satellite nests, and from phyllosphere of B. sericea taken from trees that had A. chartifex nests and from trees without nests. The isolates were grouped by Gram guilds and identified at the genus level. There was a higher percentage of Gram-negative isolates in the ants and on the leaves patrolled by them. There was a higher growth rate of ant bacteria from the main nest compared to those found in ants from the satellite nests. The most representative genus among ant isolates was Enterobacter, also found on leaves patrolled by ants. Under favourable in vitro conditions, A. chartifex Gram-negative bacteria outcompete leaf bacteria by overgrowth, showing a greater competition capacity over the Gram-positive bacteria from leaves with no previous interaction with ants in the field. It was demonstrated that ants carry bacteria capable of outcompeting exogenous bacteria associated with their outside territory. The leaf microbiota of a patrolled tree could be shaped by the ant microbiota, suggesting that large ant colonies may have a key role in structuring canopy plant-microbe interactions.

Bats have adapted to many different feeding habits, which are known to induce morphophysiological adaptations in several tissues, especially those particularly involved with absorption, metabolism and excretion. The common vampire bat (Desmodus rotundus) has a very unique diet (blood), which, among other challenges, seems to pose a risk to their kidneys, due to the increased nitrogen excretion imposed by their remarkably high protein meal. Fruit-eating bats (Artibeus lituratus) consume a high carbohydrate diet and may be taken as a suitable species for this dietary comparative study. Here we aimed at investigating the renal morphology and stereology, kidneys antioxidant capacity, and plasma antidiuretic hormone (ADH) concentrations in adult fruit-eating and vampire bats. Sixteen animals were captured and used in this study, being 8 adult males from each species. Our results showed higher morphological standards of glomerular area, volumetric density of glomeruli, and renal somatic index for vampire bats, as well as higher reactive species of oxygen (ROS) production, such as nitric oxide (NO), higher plasma iron reduction ability (FRAP), higher activity of the antioxidant enzyme glutathione-S-transferase (GST) and a higher malondialdehyde production (MDA) in vampires' kidneys, compared to the fruit-eating species. The activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were higher in fruit-eating bats. Plasma ADH concentrations were not different between species. Taken together, the renal morphophysiology conditions presented by vampire bats might be associated with a high demand for nitrogenous products excretion imposed by protein and iron overload. These features may play an important role on preventing protein-overload nephropathy, allowing vampires to survive under such a unique diet., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

SARS-CoV-2-induced hypercytokinemia and inflammation are critically associated with COVID-19 severity. Baricitinib, a clinically approved JAK1/JAK2 inhibitor, is currently being investigated in COVID-19 clinical trials. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages, and tissues was not reduced with baricitinib. Type I interferon (IFN) antiviral responses and SARS-CoV-2-specific T cell responses remained similar between the two groups. Animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of inflammatory cells, reduced NETosis activity, and more limited lung pathology. Importantly, baricitinib-treated animals had a rapid and remarkably potent suppression of lung macrophage production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for inflammation induced by SARS-CoV-2 infection., Competing Interests: Declaration of interests R.F.S. served as an unpaid consultant for Eli Lilly whose drugs are being evaluated in the research described in this paper. In addition, R.F.S. owns shares in Eli Lilly. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. Eli Lilly had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. All other authors do not have any conflicts to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We provide the first evidence of a recent invasion of Aedes aegypti (Linnaeus in Hasselquist, 1762) and Aedes albopictus (Skuse 1894), followed by dengue virus, in tropical montane cities in south-eastern Brazil, Mariana, and Ouro Preto, at mid and high altitudes, respectively. Long-term temperature variation, dengue public data, and sampling of immature and adult mosquitoes (ovitraps and mosquitraps) in contrasting habitats were used to explain the distribution of Aedes in what in these two cities. From 1961 to 2014, the annual temperature increased significantly due to increases in winter temperatures. In the 1990s/2000s, the winter temperature was 1.3°C warmer than in the 1960s, when it varied from 21.2 to 18.9°C. After 2007, the winter temperatures increased and ranged from 21.6 to 21.3°C. The first autochthonous dengue cases in Mariana and Ouro Preto were in 2007, followed by few occurrences until in 2012, when the mean numbers increased three-fold, and peak at 2013. The continuous 'warmer winter' may have trigged the Aedes invasion. Aedes species benefited from higher winter temperatures, which was an important driver of their invasion of the state of Minas Gerais in the 1980s and, more recently, in the remaining montane urban habitats in this region. In both 2009 and 2011, we found more Aedes in Mariana than Ouro Preto, and more Ae. albopictus in green areas and Ae. aegypti in houses, the expected pattern for well-established populations., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Rio Doce State Park ("PERD") is the largest Atlantic Forest remnant in Minas Gerais State, Brazil, with predominantly semi-deciduous forests. The longhorned beetles of the Cerambycinae subfamily (Coleoptera: Cerambycidae) are distributed worldwide, developing on healthy, stressed or recently dead trees. Faunistic surveys are necessary to understand about the Minas Gerais' cerambycid fauna due to a lack of research, especially in the eastern region of the state. A list of species of the subfamily Cerambycinae (Coleoptera: Cerambycidae), collected in the PERD during the rainy season (September 2013- February 2014), is presented. The beetles were collected using a light trap and through their emergence from Anadenanthera colubrina (Vell.) Brenan (Fabaceae) logs. A total of 663 individuals of 33 species, 30 genera, and 15 tribes of the Cerambycinae subfamily were collected. The species Malacopterus tenellus (Fabricius, 1801) was registered for the first time in Minas Gerais State, while A. colubrina is a new host plant for 14 Cerambycinae species. The geographical distribution, number of host plants and materials examined are presented for each species collected. This is the first list of Cerambycidae species from the Rio Doce State Park.

The spread of SARS-CoV-2 and the distribution of cases worldwide followed no clear biogeographic, climatic, or cultural trend. Conversely, the internationally busiest cities in all countries tended to be the hardest hit, suggesting a basic, mathematically neutral pattern of the new coronavirus early dissemination. We tested whether the number of flight passengers per time and the number of international frontiers could explain the number of cases of COVID-19 worldwide by a stepwise regression. Analysis were taken by 22 May 2020, a period when one would claim that early patterns of the pandemic establishment were still detectable, despite of community transmission in various places. The number of passengers arriving in a country and the number of international borders explained significantly 49% of the variance in the distribution of the number of cases of COVID-19, and number of passengers explained significantly 14.2% of data variance for cases per million inhabitants. Ecological neutral theory may explain a considerable part of the early distribution of SARS-CoV-2 and should be taken into consideration to define preventive international actions before a next pandemic.