Enhancing Thermal Tolerance By Eliminating The Pejus Range: A Comparative Study With Three Decapod Crustaceans

Marine invertebrates in the intertidal and subtidal zones are often exposed to highly variable environmental conditions, especially rapid changes in temperature. The ability to survive at different temperatures has previously been described using an extended version of Shelford’s law of tolerance, with optimum, pejus (Latin: ‘turning worse’), and pessimum ranges, and the respective thresholds, critical (Tc) and pejus (Tp) temperatures, that mark the transition from one range into the next. The width of the pejus range, in which the scope for activity gradually declines, varies among species. We tested the hypothesis that the width of the pejus range is correlated to the temperature stability of the species’ respective habitats. We used locomotor activity, heart rate, lactate accumulation, heat shock protein 70 (HSP70) levels, and the activation of AMP-activated protein kinase (AMPK) to identify Tc and Tp in 3 decapod crustaceans: green crab Carcinus maenas, rock crab Cancer irroratus, and lobster Homarus americanus. We found species specific patterns of temperature-induced changes in all parameters, especially in HSP70 protein and AMPK activity. The width of the pejus range (between Tp and Tc) was 8 to 12°C for rock crabs and 12 to 16°C for lobsters. Most importantly, green crab, the most temperature-tolerant of our 3 species and which lives in a highly variable habitat, switched directly from optimum to pessimum range, meaning that the pejus range was eliminated completely. Additionally, even lethal temperatures did not activate AMPK in green crabs, pointing to a different cellular tolerance strategy than in rock crabs and lobsters. This modified tolerance pattern might represent a broader strategy to enhance physiological tolerance in a highly variable habitat

The cultural embeddedness of professional service purchasing-A comparative study of German and Swedish companies

Research on professional service purchasing generally takes a culturally universalistic approach, implicitly assuming the generalizability of research findings and normative models to different cultural contexts. However, research in related disciplines points to the influence of national culture on managers' decisions, thereby questioning the culturally universalistic approach. The purpose of this paper is to explore differences in professional service purchasing in different cultural contexts. Based on a survey of large organizations, we analyze how the purchasing process for a specific type of professional services - management consulting services - is organized in two cultural contexts (i.e. Germany and Sweden). The results indicate that organizations in Germany and Sweden differ in the way they approach key aspects of the purchasing process. These differences are discussed in relation to two central cultural dimensions - uncertainty avoidance and masculinity-femininity - in which Germany and Sweden take very different positions. It is proposed that uncertainty avoidance mainly influences the first steps in the purchasing process (specify, select and contract) whereas masculinity-femininity mainly influences the remaining steps (order, expedite and evaluate). The paper contributes to the purchasing and supply management literature by empirically illustrating differences in purchasing practices in different cultural contexts and developing theory-driven propositions for the influence of national culture on the professional service purchasing process

NK cell education: Physiological and pathological influences

Natural killer (NK) cells represent a critical defense against viral infections and cancers. NK cells require integration of activating and inhibitory NK cell receptors to detect target cells and the balance of these NK cell inputs defines the global NK cell response. The sensitivity of the response is largely defined by interactions between self-major histocompatibility complex class I (MHC-I) molecules and specific inhibitory NK cell receptors, so-called NK cell education. Thus, NK cell education is a crucial process to generate tuned effector NK cell responses in different diseases. In this review, we discuss the relationship between NK cell education and physiologic factors (type of self-MHC-I, self-MHC-I allelic variants, variant of the self-MHC-I-binding peptides, cytokine effects and inhibitory KIR expression) underlying NK cell education profiles (effector function or metabolism). Additionally, we describe the broad-spectrum of effector educated NK cell functions on different pathologies (such as HIV-1, CMV and tumors, among others)

Enhanced immune activation linked to endotoxemia in HIV-1 seronegative MSM

This study assessed cellular and soluble markers of immune activation in HIV-1 seronegative MSM. MSM immune profiles were characterized by an increased expression of CD57 on T cells and endotoxemia. Endotoxin presence was linked to recent high-risk exposure and associated with elevated cytokine levels and decreased CD4+/CD8+ T cell ratios. Taken together, these data show elevated levels of inflammation linked to periods of endotoxemia resulting in a significantly different immune phenotype in a subset of MSM at a high risk of HIV-1 acquisition.National Institutes of Health (U.S.) (Grant P01 AI074415

Cell-specific occupancy of an extended repertoire of CREM and CREB binding loci in male germ cells

Background: CREB and CREM are closely related factors that regulate transcription in response to various stress, metabolic and developmental signals. The CREMτ activator isoform is selectively expressed in haploid spermatids and plays an essential role in murine spermiogenesis.Results: We have used chromatin immunoprecipitation coupled to sequencing (ChIP-seq) to map CREM and CREB target loci in round spermatids from adult mouse testis and spermatogonia derived GC1-spg cells respectively. We identify more than 9000 genomic loci most of which are cell-specifically occupied. Despite the fact that round spermatids correspond to a highly specialised differentiated state, our results show that they have a remarkably accessible chromatin environment as CREM occupies more than 6700 target loci corresponding not only to the promoters of genes selectively expressed in spermiogenesis, but also of genes involved in functions specific to other cell types. The expression of only a small subset of these target genes are affected in the round spermatids of CREM knockout animals. We also identify a set of intergenic binding loci some of which are associated with H3K4 trimethylation and elongating RNA polymerase II suggesting the existence of novel CREB and CREM regulated transcripts.Conclusions: We demonstrate that CREM and CREB occupy a large number of promoters in highly cell specific manner. This is the first study of CREM target promoters directly in a physiologically relevant tissue in vivo and represents the most comprehensive experimental analysis of CREB/CREM regulatory potential to date

Model-Based Inference and Classification of Immunologic Control Mechanisms from TKI Cessation and Dose Reduction in Patients with CML

Recent clinicalfindings in patients with chronic myeloid leukemia (CML) suggest that the risk of molecular recurrence after stopping tyrosine kinase inhibitor (TKI) treatment substantially depends on an individual's leukemia-specific immune response. However, it is still not possible to prospectively identify patients that will remain in treatment-free remission (TFR). Here, we used an ordinary differential equation model for CML, which explicitly includes an antileukemic immunologic effect, and applied it to 21 patients with CML for whom BCR-ABL1/ABL1 time courses had been quantified before and after TKI cessation. Immunologic control was conceptually necessary to explain TFR as observed in about half of the patients. Fitting the model simulations to data, we identified patient-specific parameters and classified patients into three different groups according to their predicted immune system configuration ("immunologic landscapes"). While one class of patients required complete CML eradication to achieve TFR, other patients were able to control residual leukemia levels after treatment cessation. Amongthem were a third class of patients that maintained TFR only if an optimal balance between leukemia abundance and immunologic activation was achieved before treatment cessation. Model simulations further suggested that changes in the BCR-ABL1 dynamics resulting from TKI dose reduction convey information about the patient-specific immune system and allow prediction of outcome after treatment cessation. This inference of individual immunologic configurations based on treatment alterations can also be applied to other cancer types in which the endogenous immune system supports maintenance therapy, long-term disease control, or even cure. Significance: This mathematical modeling approach provides strong evidence that different immunologic configurations in patients with CML determine their response to therapy cessation and that dose reductions can help to prospectively infer different risk groups.Peer reviewe

A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples

Phagocytosis can be induced via the engagement of Fcγ receptors by antibody-opsonized material. Furthermore, the efficiency of antibody-induced effector functions has been shown to be dramatically modulated by changes in antibody glycosylation. Because infection can modulate antibody glycans, which in turn modulate antibody functions, assays capable of determining the induction of effector functions rather than neutralization or titer provide a valuable opportunity to more fully characterize the quality of the adaptive immune response. Here we describe a robust and high-throughput flow cytometric assay to define the phagocytic activity of antigen-specific antibodies from clinical samples. This assay employs a monocytic cell line that expresses numerous Fc receptors: including inhibitory and activating, and high and low affinity receptors—allowing complex phenotypes to be studied. We demonstrate the adaptability of this high-throughput, flow-based assay to measure antigen-specific antibody-mediated phagocytosis against an array of viruses, including influenza, HIV, and dengue. The phagocytosis assay format further allows for simultaneous analysis of cytokine release, as well as determination of the role of specific Fcγ-receptor subtypes, making it a highly useful system for parsing differences in the ability of clinical and vaccine induced antibody samples to recruit this critical effector function.Neutralizing Antibody Consortium (International AIDS Vaccine Initiative)National Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health (U.S.) (AI055332)National Institutes of Health (U.S.) (AI080289)Ragon Institute of MGH, MIT and Harvar

MHC class I chain-related protein A shedding in chronic HIV-1 infection is associated with profound NK cell dysfunction

Natural killer (NK) cells play a critical role in host defense against viral infections. However chronic HIV-1 infection is associated with an accumulation of dysfunctional NK cells, that poorly control viral replication. The underlying mechanisms for this NK cell mediated dysfunction are not understood. Certain tumors evade NK cell mediated detection by dampening NK cell activity through the downregulation of NKG2D, via the release of soluble NKG2D-ligands, resulting in a potent suppression of NK cell function. Here we show that chronic HIV-1 infection is associated with a specific defect in NKG2D-mediated NK cell activation, due to reduced expression and transcription of NKG2D. Reduced NKG2D expression was associated with elevated levels of the soluble form of the NKG2D-ligand, MICA, in patient sera, likely released by HIV+CD4+ T cells. Thus, like tumors, HIV-1 may indirectly suppress NK cell recognition of HIV-1-infected CD4+ T cells by enhancing NKG2D-ligand secretion into the serum resulting in a profound impairment of NK cell function

MOTIVAÇÕES E EXPECTATIVAS DAS IDOSAS COM O CURSO “AGENTES SOCIAIS DE LAZER”

Com o objetivo de incentivar a participação das pessoas idosas como sujeitos das ações desenvolvidas no projeto foi desenvolvido o curso “agentes sociais de lazer”. Para investigar sobre a motivação para participar do curso e a expectativa em ser agente social foram realizadas entrevistas semi-estruturadas com 8 alunas do curso. Da análise do conteúdo das entrevistas emergiram 3 categorias: a aprendizagem como motivação, o protagonismo das alunas nas ações do projeto e o significado do ser agente social. Os resultados obtidos sugerem que as pessoas idosas querem continuar aprendendo, querem participar, querem aplicar o conhecimento, querem ser reconhecidas como úteis e capazes. A vontade de aprender serviu como motivação para participarem do curso e a atuação como agente social está proporcionando a participação ativa na sociedade. palavras-chaveAgente Social. Lazer. Idosas. Motivações. Expectativas. abstract In order to encourage the participation of older people as subjects of the actions developed in the project we developed the course “social agents of leisure”. In order to investigate the motivation to attend the course and expectations on being a social agent, semi-structured interviews were conducted involving eight students of the course. From the analysis of the interviews emerged three categories: learning as motivation, the role of students in the project’s actions and the meaning of being a social agent. The results suggest that older people want to keep learning, want to participate, they want to apply their knowledge, and they want to be recognized as useful and capable. The willingness to learn has served as motivation to attend the course and acting as the agent is providing social participation in society. Keywords Social Agent. Leisure. Elderly. Motivation. Expectations