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Background Hepatitis C virus (HCV) infection is often persistent and gradually advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm. Method of study the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917, rs12979860 and rs12980275) and the presence of mutations in HCV core protein were analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without HCC). Results the rs12980275-AG genotype was associated with HCC on age-adjusted analysis (OR 2.42, 95% CI 1.03-5.69, P =0.043). Core substitutions R70Q and L91M were mainly found in genotype 1b isolates. Furthermore, a borderline level of statistical significance association was found among the presence of amino acid Glutamine (Q) in the position 70 and IFNL3 genotype AG ( P =0.054). Conclusions the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development. [ABSTRACT FROM AUTHOR]

The social brain hypothesis states that selection pressures associated with complex social relationships have driven the evolution of sophisticated cognitive processes in primates. We investigated how the size of cooperative primate communities depends on the memory of each of its members and on the pressure exerted by natural selection. To this end we devised an evolutionary game theoretical model in which social interactions are modelled in terms of a repeated Prisoner''s Dilemma played by individuals who may exhibit a different memory capacity. Here, memory is greatly simplified and mapped onto a single parameter m describing the number of conspecifics whose previous action each individual can remember. We show that increasing m enables cooperation to emerge and be maintained in groups of increasing sizes. Furthermore, harsher social dilemmas lead to the need for a higher m in order to ensure high levels of cooperation. Finally, we show how the interplay between the dilemma individuals face and their memory capacity m allows us to define a critical group size below which cooperation may thrive, and how this value depends sensitively on the strength of natural selection. [Copyright &y& Elsevier]

Abstract: Many actions take some time to have an impact – their effects only appear at some point in the future. Such time lags turn out to be ubiquitous among living organisms. Here we study the impact of time lags in the evolutionary dynamics of cooperative collective action. We consider a population in which individuals interact via a N-Person Stag Hunt dilemma and must opt to cooperate or defect. In the absence of any delay, the replicator dynamics reveals the existence of regimes in which two internal fixed points appear simultaneously. We show that the presence of time delay in the fitness of individuals leads to a delayed replicator equation exhibiting new evolutionary profiles, each profile being separated by critical values of the delay that we determine explicitly. When we break the symmetry in the time lags, we show that, generally, defectors take more advantage from delay than cooperators. Finally, when we take into consideration, approximately, effects associated with the finite population size, we find that counter-intuitive evolutionary outcomes may occur, resulting from the interplay between delay and the basins of attraction in the neighborhood of the internal fixed-points, and which may lead to full cooperation in conditions under which the outcome would be Full Defection in infinite populations. [Copyright &y& Elsevier]

Every day, human beings make decisions with social consequences. These social consequences matter most when they impact those closest to us. Recent research has shown that humans exhibit reliable preferences when deciding between conflicting outcomes involving close others – for example, prioritizing the interests of one's family member over one's friend. However, virtually nothing is known about the mechanisms that drive these preferences. We conducted a pre-registered study in a large (maximum N = 375) sample to quantify the computational and motivational mechanisms of human social decision-making preferences involving close others. By pairing assessment techniques from behavioral economics and psychological science with computational modeling and random coefficient regression, we show that value-based cognitive computations (e.g., risk and loss aversion) drive social decision-making preferences involving financial outcomes, whereas socioemotional motivations (e.g., relationship quality) underlie preferences involving social outcomes. These results imply mechanistic heterogeneity, underscoring a need for greater attention to contextual specificity in social decision-making. [ABSTRACT FROM AUTHOR]

• Strongyloides Strongyloides co-infection in mice did not alter the schistosome parasite burden. • Co-infection resulted in earlier induction of modulatory response. • Simultaneous co-infection stimulated IFN-γ output, increased inflammation and injury. • Co-infection at acute schistosomiasis intensified Th1/Th2/Th17 response and inflammation. • Co-infection alters immune response and liver inflammation induced by schistosomiasis. Human co-infection by helminth species is frequent, but their consequences are mostly unknown. Here, we investigate the impact of Strongyloides venezuelensis co-infection on the immune response, schistosome burden, and the associated pathology of schistosomiasis in mice. Co-infection did not alter the schistosome parasite burden, but reduced the IL-4/IL-10 ratio during acute schistosomiasis, indicating induction of modulatory mechanisms. Simultaneous infection with S. venezuelensis and S. mansoni increased the liver concentration of IFN-γ and altered the Th2/Th1 balance, leading to great infiltration of neutrophils and macrophages, which resulted in larger liver inflammation and increased serum transaminase activity in comparison with mono-infected mice. Mice infected with S. venezuelensis at two and four weeks after S. mansoni infection showed significant increase of Th1/Th2/Th17/Treg cytokines and strong cellular infiltration in the liver in comparison with mono-infected mice. However, only in mice co-infected after two weeks of schistosomiasis, the liver immune response leads to more intense Th2 polarization, increased liver inflammation, and transaminase serum activity. S. venezuelensis co-infection during chronic schistosomiasis did not significantly alter liver inflammation. Therefore, S. venezuelensis co-infection affects the host immune responses and morbidity of schistosomiasis, but the effects largely depend on the stage of the S. mansoni infection. [ABSTRACT FROM AUTHOR]

Proposed model of eosinophil participation in Schistosoma mansoni induced granuloma formation/modulation and disease severity. The absence of eosinophils during S. mansoni infection resulted in significant lower concentration of cytokines from the Th2 profile, such as IL-13, IL-5, IL33 in liver of ∆dblGATA infected mice. There was also reduction in liver concentration of IL-17, and in the regulatory cytokines, IL-10 and TGF- β. In contrast, the liver concentration of TNF- α and INF- γ increased. The changes in liver immune response observed in ∆dblGATA infected mice was accompanied by stronger activation of M1 macrophages, lower expression of COLI and COLII genes and liver content of hydroxyproline, no evident signs of granuloma modulation at chronic schistosomiasis and increase in liver damage, which would contribute to higher mortality rate of ∆dblGATA infected mice. [Display omitted] • Ablation of eosinophils did not alter the S. mansoni load in infected mice. • Infected ΔdblGATA mice displayed reduced liver Th2 and regulatory responses. • S. mansoni infection led to increased liver Th1 response in ΔdblGATA mice. • Infected ΔdblGATA mice displayed larger granulomas and more intense tissue damage. • S. mansoni infection resulted in higher mortality rate in ΔdblGATA mice. The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-β and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni , which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity. [ABSTRACT FROM AUTHOR]

Over the past decade extensive research has examined the segregation of the human brain into large-scale functional networks. The resulting network maps, i.e. parcellations, are now commonly used for the a priori identification of functional networks. However, the use of these parcellations, particularly in developmental and clinical samples, hinges on four fundamental assumptions: (1) the various parcellations are equally able to recover the networks of interest; (2) adult-derived parcellations well represent the networks in children's brains; (3) network properties, such as within-network connectivity, are reliably measured across parcellations; and (4) parcellation selection does not impact the results with regard to individual differences in given network properties. In the present study we examined these assumptions using eight common parcellation schemes in two independent developmental samples. We found that the parcellations are equally able to capture networks of interest in both children and adults. However, networks bearing the same name across parcellations (e.g., default network) do not produce reliable within-network measures of functional connectivity. Critically, parcellation selection significantly impacted the magnitude of associations of functional connectivity with age, poverty, and cognitive ability, producing meaningful differences in interpretation of individual differences in functional connectivity based on parcellation choice. Our findings suggest that work employing parcellations may benefit from the use of multiple schemes to confirm the robustness and generalizability of results. Furthermore, researchers looking to gain insight into functional networks may benefit from employing more nuanced network identification approaches such as using densely-sampled data to produce individual-derived network parcellations. A transition towards precision neuroscience will provide new avenues in the characterization of functional brain organization across development and within clinical populations. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights • S. venezuelensis acute infection reduces severity of DSS-induced colitis. • Nematode infection increased IL-10 production in DSS-treated mice. • The infection reduced Th1/Th2/Th17 cytokine production in DSS-treated mice. • S. venezuelensis induces mucus production and colon repair in DSS-treated mice. Abstract Helminth infection can reduce the severity of inflammatory bowel disease. However, the modulatory mechanisms elicited by helminth infection are not yet fully understood and vary depending on the experimental model. Herein we evaluated the effect of acute infection of BALB/c mice with Strongyloides venezuelensis on the clinical course of ulcerative colitis induced by Dextran Sulfate Sodium (DSS) treatment of these animals. For the experiments, S. venezuelensis -infected BALB/c mice were treated orally with 4% DSS solution for seven days. As controls, we used untreated S. venezuelensis infected, DSS-treated uninfected, and untreated/uninfected BALB/c mice. During DSS treatment, mice from the different groups were compared with regards to the clinical signs related to the severity of colitis and intestinal inflammation. Mice acutely infected with S. venezulensis and treated with DSS had reduced clinical score, shortening of the colon, and tissue inflammation. Moreover, DSS-treated and infected mice showed reduced IL-4, INF-γ, and IL-17 levels and increase of IL-10 production in the colon and/or in the supernatant of mesenteric lymph nodes cell cultures that resulted in lower eosinophil peroxidase and myeloperoxidase activity in colon homogenates, when compared with DSS-treated uninfected mice. DSS-treated infected mice also preserved the intestine architecture and had normal differentiation of goblet cells and mucus production in the colon mucosa. In conclusion, the data indicate that the clinical improvement reported in DSS-treated infected mice was accompanied by the lower production of Th1/Th2/Th17 pro-inflammatory cytokines, stimulation of IL-10, and induction of mucosal repair mechanisms. [ABSTRACT FROM AUTHOR]

One of the major challenges in Glioblastoma (GBM) therapy relates with the existence of glioma stem-like cells (GSCs), known to be chemo- and radio-resistant. GSCs and non-stem GBM cells have the ability to interchange, emphasizing the importance of identifying common molecular targets among those cell sub-populations. Nucleolin overexpression has been recently associated with breast cancer sub-populations with different stem-like phenotype. The goal of this work was to evaluate the potential of cell surface nucleolin as a target in GBM cells. Different levels of nucleolin expression resulted in a 3.4-fold higher association of liposomes targeting nucleolin (functionalized with the nucleolin-binding F3 peptide) in U87, relative to GBM11 glioblastoma cells. Moreover, nucleolin was suggested as a potential marker in OCT4-, NANOG-positive GSC, and in the corresponding non-stem GBM cells, as well as in SOX2-positive GSC. Doxorubicin delivered by liposomes targeting nucleolin enabled a level of cytotoxicity that was 2.5- or 4.6-fold higher compared to the non-targeted counterparts. Importantly, an overexpression of nucleolin was also observed in cells of patient-derived samples, as compared with normal brain. Overall, these results suggested nucleolin as a therapeutic target in GBM. [ABSTRACT FROM AUTHOR]