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Speciation via host-switching is a macroevolutionary process that emerges from a microevolutionary dynamic where individual parasites switch hosts, establish a new association, and reduce reproductive contact with the original parasite lineage. Phylogenetic distance and geographic distribution of the hosts have been shown to be determinants of the capacity and opportunity of the parasite to change hosts. Although speciation via host-switching has been reported in many host-parasite systems, its dynamic on the individual, population and community levels is poorly understood. Here we propose a theoretical model to simulate parasite evolution considering host-switching events on the microevolutionary scale, taking into account the macroevolutionary history of the hosts, to evaluate how host-switching can affect ecological and evolutionary patterns of parasites in empirical communities at regional and local scales. In the model, parasite individuals can switch hosts under variable intensity and have their evolution driven by mutation and genetic drift. Mating is sexual and only individuals that are sufficiently similar can produce offspring. We assumed that parasite evolution occurs at the same evolutionary time scale as their hosts, and that the intensity of host-switching decreases as the host species differentiate. Ecological and evolutionary patterns were characterised by the turnover of parasite species among host species, and parasite evolutionary tree imbalance respectively. We found a range of host-switching intensity that reproduces ecological and evolutionary patterns observed in empirical communities. Our results showed that turnover decreased as host-switching intensity increased, with low variation among the model replications. On the other hand, tree imbalance showed wide variation and non-monotonic tendency. We concluded that tree imbalance was sensitive to stochastic events, whereas turnover may be a good indicator of host-switching. We found that local communities corresponded to higher host-switching intensity when compared to regional communities, highlighting that spatial scale is a limitation for host-switching.

It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in the bone marrow of patients with acute myeloid leukemia (AML) reveal a shift toward a tumor-supportive M2-polarized macrophage landscape with an altered transcriptional program, with enhanced fatty acid oxidation and NAD + generation. Functionally, these AML-associated macrophages display decreased phagocytic activity and intra–bone marrow coinjection of M2 macrophages together with leukemic blasts strongly enhances in vivo transformation potential. A 2-day in vitro exposure to M2 macrophages results in the accumulation of CALR low leukemic blast cells, which are now protected against phagocytosis. Moreover, M2-exposed “trained” leukemic blasts display increased mitochondrial metabolism, in part mediated via mitochondrial transfer. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for targeting strategies aimed at the tumor microenvironment.

he present study aims to analyze the scientifi c production of studies from diff erent areas that focused on racist humor. For the analysis, a systematic review was carried out in the Scielo Brasil and Portal Periódicos CAPES databases in April 2021. The search used the keywords racism, humor and joke. After applying the inclusion and exclusion criteria, 42 articles remained in the sample. For the analysis, the abstracts of the articles composed a textual corpus that was submitted to lexical analysis with the help of the IRAMUTEQ software. The results indicate that the topic has been researched from six diff erent thematic axes: racist humor on platforms, critical discussion of racist humor, blackface, racist Araujo, C. L., Gois, D. F.2Cadernos de Psicologia, Ribeirão Preto, vol. 2, nº 1, p. 1-13 - Abril/2022and everyday humor, racist humor and interracial groups and racist humor and politics. However, we identifi ed a small number of scientifi c publications ahead of the need for debate on the topic of racist humor and racism, especially in the fi eld of psychology. Furthermore, there is a need for studies that aim to analyze the impact and understanding of the phenomenon from the perspective of those aff ected

Tables S1. Fluorochromes and clones of mAbs. Table S2. CD39 expression on human CD8+ TILs from breast cancer patients. Table S3. CD39 and iRs expression on in vitro stimulated human CD8+ T cells.

(1) Figure S1. Expression of CD39 and CD73 on CD8+T cells from different cancer models and tumor-free mice. (2) Figure S2. Expression of CD39 and CD73 on tumor-infiltrating CD45+ cells. Frequency of CD39high CD8+ TILs in tumors with different immunogenicity. (3) Figure S3. Functionality of CD39high CD8+ TILs in tumors with different immunogenicity. Expression of iRs and TFs on CD8+ T cells. (4) Figure S4. Phenotype of exhausted CD8+ T cells after re-stimulation. Data related to co-culture experiments. (5) Figure S5. Identification of tumor-infiltrating CD39+CD4+ Tconv cells. Characterization of CD39+CD8+ T cells from breast cancer patients. (6) Figure S6. Phenotypic and functional study of CD39+CD8+ T cells from melanoma patients. (7) Figure S7. Functional study of CD39+CD8+ T cells induced in vitro. Localization of CD39+CD45+ cells in hypoxic foci.

The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39+CD8+ T cells inhibited IFNγ production by responder CD8+ T cells. In specimens from breast cancer and melanoma patients, CD39+CD8+ T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNγ, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induce CD39 on human CD8+ T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8+ T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule on CD8+ T cells, with implications for defining a biomarker of T-cell dysfunction and a target for immunotherapeutic intervention.Significance: The tumor microenvironment elicits a subset of functionally exhausted CD8+ T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function. Cancer Res; 78(1); 115–28. ©2017 AACR.

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Supplementary Data 1 from Prostatic Acid Phosphatase Is Not a Prostate Specific Target

SummaryRecent guidelines recommend screening for patients with chronic gastroesophageal reflux disease who have three or more additional risk factors for Barrett’s esophagus (BE). Failure to screen high-risk individuals represents a missed opportunity in esophageal adenocarcinoma prevention and early detection. We aimed to determine the frequency of upper endoscopy and prevalence of BE and esophageal cancer in a cohort of United States veterans who possessed four or more risk factors for BE. All patients at VA New York Harbor Healthcare System with at least four risk factors for BE between 2012 and 2017 were identified. Procedure records were reviewed for upper endoscopies performed between January 2012 and December 2019. Multivariable logistic regression was used to determine risk factors associated with undergoing endoscopy and factors associated with BE and esophageal cancer. 4505 patients with at least four risk factors for BE were included. 828 patients (18.4%) underwent upper endoscopy, of which 42 (5.1%) were diagnosed with BE and 11 (1.3%) with esophageal cancer (10 adenocarcinoma; 1 squamous cell carcinoma). Among individuals who underwent upper endoscopy, risk factors associated with undergoing endoscopy included obesity (OR, 1.79; 95% CI, 1.41–2.30; P

Individual behaviour and local context can influence the evolution of ecological interactions and how they structure into networks. In trophic interactions, consumers can increase their fitness by actively choosing resources that they are more likely to explore successfully. Mathematical modelling is often employed in theoretical studies to understand the coevolutionary dynamics between consumers and resources. However, they often disregard the individual consumer behaviour since the complexity of these systems usually requires simplifying assumptions about interaction details. Using an individual-based model, we model a community of several species that interact antagonistically. Each individual has a trait (attack or defence) that is explicitly modelled and the probability of the interaction to occur successfully increases with increased trait-matching. In addition, consumers can actively choose resources that guarantee greater fitness. We show that active consumer choice can generate coevolutionary units over time. It means that the traits of both consumers and resources converge into multiple groups with similar traits and the species interactions stay restricted to these groups over time. We also observed that network structure is more dependent on the parameter that delimits active consumer choice than on the intensity of selective pressure. Thus, our results support the idea that consumer active choice behaviour plays an important role in the ecological and evolutionary processes that structure interacting communities.

The role of IL-17 mediated immune responses in cancer is conflicting as pre-clinical and clinical results show tumor-promoting as wel as tumor-repressing functions. Herein, we used syngeneic tumor models from different tissue origins as a tool to evaluate the role of IL-17 signaling in cancer progression, dissecting the effects in cancer cell growth and tumor immunity. We show that absence of IL-17RA or IL-17A/F expression in the host has contrasting effects in thein vivogrowth of different tumor types. We observed that lack of IL-17A/F-IL-17RA signaling in host cells changed the expression pattern of several mediators within the tumor microenvironment in a cancer-type specific manner. Deficiencies in host IL-17RA or IL-17A/F expression resulted in reduced antitumor CD8+ T cell immunity in all cancer models and in tumor-specific changes in several lymphoid cell populations. These findings were associated to particular patterns of expression of cytokines (IL-17A and IL-17F) and receptor subunits (IL-17RA, IL-17RC and IL-17RD) of the IL-17 family in the injected tumor cell lines that, in turn, dictated tumor cell responsiveness to IL-17. We identified IL-17RC as an important determinant of the IL-17-mediated transcriptional response in tumor cells and; consequently, as a predictive biomarker of the overall effect of IL-17 signaling in tumor progression. Our findings contribute to unraveling the molecular mechanisms underlying the divergent activities of IL-17 in cancer and provide rational targets for immunotherapies based on personalized approaches.

An endoscopist’s adenoma detection rate (ADR) is inversely related to interval colorectal cancer risk and cancer mortality. Previous studies evaluating the impact of gastroenterology fellow participation in colonoscopy on ADR have generated conflicting results. We aimed to determine the impact of fellow participation, duration of fellowship training, and physician sex on ADR and advanced ADR (AADR). We retrospectively analyzed average-risk patients undergoing screening colonoscopy at Veterans Affairs New York Harbor Healthcare System Brooklyn Campus and Kings County Hospital Center. Review of colonoscopy and pathology reports were performed to obtain adenoma-specific details, including the presence of advanced adenoma and adenoma location (right vs. left colon). There were 893 colonoscopies performed by attending only and 502 performed with fellow participation. Fellow participation improved overall ADR (44.6% vs. 35.4%, p

Objectif : Les patients présentant des signes d’accident vasculaire cérébral (AVC) nécessitent une prise en charge rapide. En France, il a été mis en place une filière « neurovasculaire » dédiée à ces patients. L’objectif de cette étude était de décrire la filière de prise en charge des patients présentant des signes évocateurs d’AVC dans le système de soins français. Méthodes : Étude prospective observationnelle de courte durée pendant trois jours dans 35 régulations Samu, 27 Smur et 85 services d’urgences en France, incluant tout patient de plus de 18 ans présentant un signe évocateur d’AVC ou d’accident ischémique transitoire (AIT). Les patients suivaient ou non la filière neurovasculaire définie au préalable. Résultats : Du 29 novembre au 1er décembre 2016, 827 patients ont été inclus, d’âge moyen 68 ans. Parmi eux, 418 avaient un AVC confirmé, dont 231 accidents ischémiques constitués. La filière UNVa été suivie pour 279 patients (44 %). Le délai médian de prise en charge médicale était de 3 heures 49. Pour les patients avec AVC confirmé, ce délai était significativement plus court dans la filière neurovasculaire (2 heures 45 vs 5 heures 56 ; p < 0,001). Conclusion : En France, la prise en charge dans une filière dédiée des patients suspects d’AVC n’est actuellement effective que dans la moitié des cas. Cette filière nécessite d’être promue.

While it is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones, the tumor microenvironment (TME) in acute myeloid leukemias (AML) remains poorly understood. Here, we uncover the functional and prognostic relevance of an M2-polarized macrophage compartment. Intra bone marrow co-injection of M2d-macrophages together with leukemic blasts that fail to engraft on their own now induce fatal leukemia in mice. Even a short-term two-day in vitro exposure to M2d macrophages can “train” leukemic blasts after which cells are protected against phagocytosis, display increased mitochondrial metabolism and improved in vivo homing, resulting in full-blown leukemia. Single-cell RNAseq analysis of AML associated macrophages revealed metabolic-related pathways such as Fatty Acid Oxidation and NAD+ generation as therapeutical targetable vulnerabilities. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for effective targeting strategies.

The free vibration of laminated composite (C) and hybrid axisymmetric shell structures, consisting of a composite laminated material sandwiched between two functionally graded material laminas (F1/C/F2), is analysed in the present work. The numerical solutions are obtained by expanding the variables in Fourier series in the circumferential direction and using conical frustum finite elements in the meridional direction. The implemented finite element is a simple conical frustum with two nodal circles, with ten degrees of freedom per nodal circle. This model requires only a reduced number of finite elements to model the geometry of axisymmetric structures, the integration procedures use one Gauss point, and the through the thickness properties variation in FGM laminas is modelled by a small number of virtual layers, resulting a very high computational efficiency. The inhouse developed code presents very good solutions when compared with results obtained by alternative available models. info:eu-repo/semantics/publishedVersion

Despite the great interest to quantify the structure of host–parasite interaction networks, the real influence of some factors such as taxonomy, host body size and ecological opportunity remains poorly understood. In this paper, we investigate the general patterns of organization and structure of interactions in two anuran–parasite networks in the Brazilian Pantanal (seasonally flooded environment) and Atlantic Forest (non-flooded forest). We present theoretical models to test whether the structures of these host–parasite interaction networks are influenced by neutrality, host taxonomy and host body size. Subsequently, we calculated metrics of connectance, nestedness and modularity to characterize the network structure. We demonstrated the structure networks were influenced mainly by body size and taxonomy of the host. Moreover, our results showed that the seasonally flooded environment present networks with higher connectance/nestedness and lower modularity compared to the other environment. The results also suggest that seasonal floods may promote ecological opportunities for new species associations.

Background Brazil has been dramatically hit by the SARS-CoV-2 pandemic and is a world leader in COVID-19 morbidity and mortality. Additionally, the largest country of Latin America has been a continuous source of SARS-CoV-2 variants and shows extraordinary variability of the pandemic strains probably related to the country´s outstanding position as a Latin American economical and transportation hub. Not all regions of the country show sufficient infrastructure for SARS-CoV-2 diagnosis and genotyping which can negatively impact the pandemic response. Methods Due to this reason and to disburden the diagnostic system of the inner São Paulo State, the Butantan Institute established the Mobile Laboratory (in Portuguese: LabMovel) for SARS-CoV-2 testing which started a trip of the most important “hotspots” of the most populous Brazilian region. The LabMovel initiated in two important cities of the State: Aparecida do Norte (an important religious center) and the Baixada Santista region which incorporates the port of Santos, the busiest in Latin America. The LabMovel was fully equipped with an automatized system for SARS-CoV-2 diagnosis and sequencing/genotyping. It also integrated the laboratory systems for patient records and results divulgation including in the Federal Brazilian Healthcare System. Results Currently,16,678 samples were tested, among them 1,217 from Aparecida and 4,564 from Baixada Santista. We tracked the delta introductio in the tested regions with its high diversification. The established mobile SARS-CoV-2 laboratory had a major impact on the Public Health System of the included cities including timely delivery of the results to the healthcare agents and the Federal Healthcare system, evaluation of the vaccination status of the positive individuals in the background of exponential vaccination process in Brazil and scientific and technological divulgation of the fieldwork to the most vulnerable populations. Conclusions The SARS-CoV-2 pandemic has demonstrated worldwide the importance of science to fight against this viral agent and the LabMovel shows that it is possible to integrate researchers, clinicians, healthcare workers and patients to take rapid actions that can in fact mitigate this and other epidemiological situations.

Geographic isolation is a central mechanism of speciation, but perfect isolation of populations is rare. Although speciation can be hindered if gene flow is large, intermediate levels of migration can enhance speciation by introducing genetic novelty in the semi-isolated populations or founding small communities of migrants. Here, we consider a two-island neutral model of speciation with continuous migration and study diversity patterns as a function of the migration probability, population size, and number of genes involved in reproductive isolation (dubbed as genome size). For small genomes, low levels of migration induce speciation on the islands that otherwise would not occur. Diversity, however, drops sharply to a single species inhabiting both islands as the migration probability increases. For large genomes, sympatric speciation occurs even when the islands are strictly isolated. Then species richness per island increases with the probability of migration, but the total number of species decreases as they become cosmopolitan. For each genome size, there is an optimal migration intensity for each population size that maximizes the number of species. We discuss the observed modes of speciation induced by migration and how they increase species richness in the insular system while promoting asymmetry between the islands and hindering endemism.

The present study focuses on the first electrochemical immunosensor built with polymeric mats enriched with nanomaterials, targeting the dust mite protein, for the detection of allergens in flour sources with important implications in allergic reactions. As a proof-of-concept, we have used the Blo t 5 allergen from Blomia tropicalis (target) and established electrochemical parameters to recognize and detect the specific allergen using a polyclonal immunoglobulin (Ig) Y (probe). Detection was performed in a portable potentiostat (EmStat) using a graphite screen-printed electrode. For that, the nanofibrous mats of poly(lactic acid)/poly(ethylene glycol) (PLA/PEG), and carbon nanotubes (CNTs) were placed in contact with the surface of the electrodes. The functionalization that occurs through the deposition of the polymer was induced through the passage of current. Subsequently, the modification was validated by cyclic voltammetry (CV) readings and ferri/ferrocyanide was used as a redox indicator in CV analyses. The novel immunosensor was able to discriminate between allergen-contaminated and uncontaminated farinaceous samples. The immunosensor displays high sensitivity detecting up to 50 μg ml−1 in the calibration curve with a linear response between 5 and 500 μg ml−1. The new biosensor shows great potential in the detection of farinaceous contaminants in laboratories, food factories and in the field.