Co-evolutionary dynamics of collective action with signaling for a quorum

Collective signaling for a quorum is found in a wide range of organisms that face collective action problems whose successful solution requires the participation of some quorum of the individuals present. These range from humans, to social insects, to bacteria. The mechanisms involved, the quorum required, and the size of the group may vary. Here we address the general question of the evolution of collective signaling at a high level of abstraction. We investigate the evolutionary dynamics of a population engaging in a signaling N-person game theoretic model. Parameter settings allow for loners and cheaters, and for costly or costless signals. We find a rich dynamics, showing how natural selection, operating on a population of individuals endowed with the simplest strategies, is able to evolve a costly signaling system that allows individuals to respond appropriately to different states of Nature. Signaling robustly promotes cooperative collective action, in particular when coordinated action is most needed and difficult to achieve. Two different signaling systems may emerge depending on Nature's most prevalent states.Funding: This research was supported by FEDER through POFC - COMPETE, FCT-Portugal through grants SFRH/BD/86465/2012, PTDC/MAT/122897/2010, EXPL/EEI-SII/2556/2013, and by multi-annual funding of CMAF-UL, CBMA-UM and INESC-ID (under the projects PEst-OE/BIA/UI4050/2014 and UID/CEC/50021/2013) provided by FCT-Portugal, and by Fundacao Calouste Gulbenkian through the "Stimulus to Research" program for young researchers. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Strong mucosal immune responses in SIV infected macaques contribute to viral control and preserved CD4+ T-cell levels in blood and mucosal tissues

<p>Abstract</p> <p>Background</p> <p>Since there is still no protective HIV vaccine available, better insights into immune mechanism of persons effectively controlling HIV replication in the absence of any therapy should contribute to improve further vaccine designs. However, little is known about the mucosal immune response of this small unique group of patients. Using the SIV-macaque-model for AIDS, we had the rare opportunity to analyze 14 SIV-infected rhesus macaques durably controlling viral replication (controllers). We investigated the virological and immunological profile of blood and three different mucosal tissues and compared their data to those of uninfected and animals progressing to AIDS-like disease (progressors).</p> <p>Results</p> <p>Lymphocytes from blood, bronchoalveolar lavage (BAL), and duodenal and colonic biopsies were phenotypically characterized by polychromatic flow cytometry. In controllers, we observed higher levels of CD4+, CD4+CCR5+ and Gag-specific CD8+ T-cells as well as lower immune activation in blood and all mucosal sites compared to progressors. However, we could also demonstrate that immunological changes are distinct between these three mucosal sites.</p> <p>Intracellular cytokine staining demonstrated a significantly higher systemic and mucosal CD8+ Gag-specific cellular immune response in controllers than in progressors. Most remarkable was the polyfunctional cytokine profile of CD8+ lymphocytes in BAL of controllers, which significantly dominated over their blood response. The overall suppression of viral replication in the controllers was confirmed by almost no detectable viral RNA in blood and all mucosal tissues investigated.</p> <p>Conclusion</p> <p>A strong and complex virus-specific CD8+ T-cell response in blood and especially in mucosal tissue of SIV-infected macaques was associated with low immune activation and an efficient suppression of viral replication. This likely afforded a repopulation of CD4+ T-cells in different mucosal compartments to almost normal levels. We conclude, that a robust SIV-specific mucosal immune response seems to be essential for establishing and maintaining the controller status and consequently for long-term survival.</p

RNase L Mediated Protection from Virus Induced Demyelination

IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL−/−) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL−/− mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination

Comparative Genomics of Mycoplasma: Analysis of Conserved Essential Genes and Diversity of the Pan-Genome

Mycoplasma, the smallest self-replicating organism with a minimal metabolism and little genomic redundancy, is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life. This study employs comparative evolutionary analysis of twenty Mycoplasma genomes to gain an improved understanding of essential genes. By analyzing the core genome of mycoplasmas, we finally revealed the conserved essential genes set for mycoplasma survival. Further analysis showed that the core genome set has many characteristics in common with experimentally identified essential genes. Several key genes, which are related to DNA replication and repair and can be disrupted in transposon mutagenesis studies, may be critical for bacteria survival especially over long period natural selection. Phylogenomic reconstructions based on 3,355 homologous groups allowed robust estimation of phylogenetic relatedness among mycoplasma strains. To obtain deeper insight into the relative roles of molecular evolution in pathogen adaptation to their hosts, we also analyzed the positive selection pressures on particular sites and lineages. There appears to be an approximate correlation between the divergence of species and the level of positive selection detected in corresponding lineages

Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats

<p>Abstract</p> <p>Background</p> <p>The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL), therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses.</p> <p>Results</p> <p>Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL). Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia.</p> <p>Conclusions</p> <p>Our results indicate that mucosal immune pathogenesis could be used as a rapid indicator of vaccine success or failure when combined with a physiologically relevant low dose mucosal challenge. We also show that innate immune responses may play an important role in controlling viral replication following acute mucosal infection, which has not been previously identified.</p

124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

<p>Abstract</p> <p>Background</p> <p>¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of ¹⁸F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized C_H2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaC_H2), radiolabeled with iodine-124 (¹²⁴I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging.</p> <p>Methods</p> <p>HuCC49deltaC_H2 was radiolabeled with ¹²⁴I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of ¹²⁴I-HuCC49deltaC_H2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of ¹⁸F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection.</p> <p>Results</p> <p>At approximately 1 hour after i.v. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, ¹²⁴I-HuCC49deltaC_H2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, ¹⁸F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder.</p> <p>Conclusions</p> <p>On microPET imaging, ¹²⁴I-HuCC49deltaC_H2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while ¹⁸F-FDG failed to demonstrate this. The antigen-directed and cancer-specific ¹²⁴I-radiolabled anti-TAG-72 monoclonal antibody conjugate, ¹²⁴I-HuCC49deltaC_H2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.</p

Looking Back - The History of Biochemistry in India

The name Biochemistry was coined in 1903 by a German chemist named Carl Neuber. However, work in this very living, aspect of chemistry had started much earlier..

Brief Report - Lipid Peroxidation and Antioxidant Enzymes in Male Infertility

Background and Aim: Mammalian spermatozoa are rich in polyunsaturated fatty acids and are very susceptible to attack by reactive oxygen species (ROS) and membrane lipid peroxide ion. Normally a balance is maintained between the amount of ROS produced and that scavenged. Cellular damage arises when this equilibrium is disturbed. A shift in the levels of ROS towards pro-oxidants in semen and vaginal secretions can induce an oxidative stress on spermatozoa. The aim was to study lipid peroxidation and antioxidant enzymes such as catalase, glutathione peroxidase and superoxide dismutase (SOD) and to correlate the same, with the "water test", in male infertility. Settings: Experimental study. Subjects and Methods: Ejaculates from a total of 83 infertile and fertile healthy individuals were obtained. Lipid peroxidation and antioxidant enzyme levels were studied and correlated with water test. Results: The results indicate that (i) the antioxidant enzyme catalase showed no significant changes in the various pathological samples, (ii) antioxidant enzymes SOD and glutathione peroxidase correlate positively with asthenozoospermic samples and (iii) the degree of lipid peroxidation also correlates positively with the poorly swollen sperm tails. The increase in SOD and glutathione peroxidase values, in the pathological cases represents an attempt made to overcome the reactive oxygen species. Conclusion: Water test could be used as a preliminary marker test for sperm tail damage by reactive oxygen species, since it correlates very well with lipid peroxidation and antioxidant enzymes. (J Postgrad Med 2002;48:186-190

The outcome of ART in males with impaired spermatogenesis

Aims: This study was conducted to evaluate the outcomes of assisted reproductive technology (ART) procedures, viz., intrauterine insemination (IUI), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in males with impaired spermatogenesis. Settings and Design: The subjects of the study were infertile couples who were undergoing ART treatment due to male factor indications. The project was designed to correlate the outcome of the ART treatment and its efficacy in different study groups. Methods: Males were grouped as: 1. oligozoospermia (n = 153), 2. asthenoteratozoospermia (n = 158), 3. obstructive azoospermia (n = 110) and 4. nonobstructive azoospermia (n = 58). Patients from groups 1 and 2 were considered for IUI, IVF and ICSI. Those from group 3 were considered for IVF and ICSI and the 4th group underwent only ICSI treatment. Results: Oligozoospermia showed lower pregnancy rates with IUI than with both IVF and ICSI. An average minimum native and postharvest count was obtained to get an acceptable IUI outcome. Asthenoteratozoospermia had the lowest pregnancy rate with IUI as compared to IVF, whereas ICSI showed significantly higher pregnancy rates in this group. Obstructive azoospermia showed significant improvement with ICSI over IVF. In nonobstructive azoospermia, ICSI resulted in a 27.58% pregnancy rate. Conclusion: The IUI outcome was impressive though less effective whereas there was no difference between the IVF and ICSI outcomes in oligozoospermia. In asthenoteratozoospermia, ICSI showed a significant advantage over IUI and IVF, with IUI resulting in poor outcome in this group. In obstructive azoospermia, ICSI had a distinct advantage over IVF whereas in nonobstructive azoospermia, ICSI, the only option, was found to be effective and helpful in achieving an acceptable pregnancy rate

<i>In vitro</i> macrophage activation: A technique for screening anti-inflammatory, immunomodulatory and anticancer activity of phytomolecules

133-141Macrophage activation plays a significant role in homeostasis of organisms. Various internal and external stress factors may affect their function, leading to adverse effects on the body. ‘In vitro macrophage activation techniques provide us with a window to understand the mechanisms of inflammation and response of macrophages to the modulating interventions. Apart from infectious diseases, inflammation is also the major culprit in pathogenesis of many noncommunicable diseases such as arthritis, obesity, metabolic syndrome, diabetes, cancer, cardiovascular disease etc. In vitro macrophage activation allows us to study the role of polarized macrophages in the process of pathogenesis. This emerging technique leads to newer diagnostics, understanding pathophysiological mechanism/s, drug development and management of chronic inflammatory diseases. We, at MRC-KHS, use this technique for screening of medicinal plant-derived phytomolecules for their anti-inflammatory, immunomodulatory and anticancer activities. This review briefly outlines the different experimental models of in vitro macrophage activation and their applications for understanding the pathophysiological mechanisms of underlying chronic inflammation and screening of therapeutic activity of plant-based phytomolecules