Determinants of public T cell responses

Historically, sharing T cell receptors (TCRs) between individuals has been speculated to be impossible, considering the dramatic discrepancy between the potential enormity of the TCR repertoire and the limited number of T cells generated in each individual. However, public T cell response, in which multiple individuals share identical TCRs in responding to a same antigenic epitope, has been extensively observed in a variety of immune responses across many species. Public T cell responses enable individuals within a population to generate similar antigen-specific TCRs against certain ubiquitous pathogens, leading to favorable biological outcomes. However, the relatively concentrated feature of TCR repertoire may limit T cell response in a population to some other pathogens. It could be a great benefit for human health if public T cell responses can be manipulated. Therefore, the mechanistic insight of public TCR generation is important to know. Recently, high-throughput DNA sequencing has revolutionized the study of immune receptor repertoires, which allows a much better understanding of the factors that determine the overlap of TCR repertoire among individuals. Here, we summarize the current knowledge on public T-cell response and discuss future challenges in this field.     

Mobile phones, heat shock proteins and cancer

There are several reports which indicate that electromagnetic radiation (such as from mobile phones) at non-thermal levels may elicit a biological effect in target cells or tissues. Whether or not these biological effects lead to adverse health effects, including cancer, is unclear. To date there is limited scientific evidence of health issues, and no mechanism by which mobile phone radiation could influence cancer development. In this paper, we develop a theoretical mechanism by which radiofrequency radiation from mobile phones could induce cancer, via the chronic activation of the heat shock response. Upregulation of heat shock proteins (Hsps) is a normal defence response to a cellular stress. However, chronic expression of Hsps is known to induce or promote oncogenesis, metastasis and/or resistance to anticancer drugs. We propose that repeated exposure to mobile phone radiation acts as a repetitive stress leading to continuous expression of Hsps in exposed cells and tissues, which in turn affects their normal regulation, and cancer results. This hypothesis provides the possibility of a direct association between mobile phone use and cancer, and thus provides an important focus for future experimentation.     

Coal Fly Ash Impairs Airway Antimicrobial Peptides and Increases Bacterial Growth

Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM), which is comprised of a number of particles that contain iron, such as coal fly ash (CFA). Since free iron concentrations are extremely low in airway surface liquid (ASL), we hypothesize that CFA impairs antimicrobial peptides (AMP) function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01) and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.     

A minimized Fc binding peptide from protein A induces immunocyte proliferation and evokes Th1-type response in mice

It is now well established that PA is a potent biological response modifier, showing simultaneously antitumor, antitoxic, anticarcinogenic, antifungal, antiparasitic and immunomodulatory properties. Since PA is a foreign protein, it is quite logical to assume that it may be cleaved into smaller peptide fragments in vivo which may be responsible for biological activities of whole PA molecule. The present study was undertaken to dissect out the structural entities of PA responsible for its biological properties. Protein A (PA) of Staphylococcus aureus has a unique property of binding with immunoglobulins. On the basis of molecular modeling and energy minimization studies a 20-mer tryptic fragment (theoretical) was predicted to retain IgG binding capacity which has been verified by immunoblot. This peptide sequence was selected to carry out experimental studies to show its functional mimicry of PA. We observed in the sera of 20-mer peptide treated mice that the concentrations of IFNgamma, TNFalpha and IL1alpha increase to a peak level by 4 h; on the other hand, there was a decrease in IL4, IL6 and IL10 concentrations at the same time (4 h). The ratio of IFNgamma to IL4 showed Th1 type of response with the peptide as well as with that of PA. The nitric oxide concentration in sera also increases and the peak increase was in 6 h with both the peptide and PA. Cell cycle analysis using FACS shows that 20 micrograms dose of peptide was non-toxic to thymocytes and spleenocytes; on the other hand, it was immunoproliferative, shifting the thymocytes and spleenocytes from G0/G1 to S phase of the cell cycle. Further studies are in progress to evaluate other biological properties of the peptide, to evaluate if this peptide could be used as a substitute of PA to mimic at least some of its biological activities.     

Results of an explorative empirical study on human mating in Germany: handsome men, not high-status men, succeed in courtship

Recent research on human mating depicts men as searching for physical attractiveness (PA) and women as searching for status. To identify the mechanisms which lead to universal, biologically interpretable structures in social processes, we focused on the proximate causes for inter- and intrasexual differences in human mating preferences, attraction, and tactics. We collected data on 180 young singles (mean age 26.9 years) without a steady relationship. A questionnaire and a video sequence (20-30 seconds) of each subject was taken. Next, each video sequence was rated by approximately 20 individuals of the opposite sex, who also participated in this study. Surprisingly, the answers given by male and female subjects regarding sociosexual behaviour and mating preferences are predominantly congruent. Sex differences among preferences for good looking and high-status partners were small or even insignificant. Lower educated subjects had considerably higher status preferences than higher educated individuals. In both sexes, PA was much more preferred in a potential partner than status. For both sexes, physical appearance was decisive for the subject's dating attractiveness. Male, but not female dating attractiveness also correlates with a kind and charismatic appearance. Furthermore, there was a positive linear relationship between men's PA and their number of sexual partners within the last year. Men with more than four sexual partners were all above-average in PA, while the most attractive women had a medium number of sexual partners. However, in this respect, status had no influence. The results show that sex differences in mating are more complex than hitherto assumed.     

Pathways to interleukin-6 in healthy males and serious leisure male athletes: physical activity, body composition and age

Physical activity (PA) is beneficial to overall health, in part due to physiological changes that lower risk factors for cardiovascular disease, including reduced inflammation. However, the mechanism by which PA reduces inflammation is unclear. One possible pathway is that PA improves body composition which in turn reduces inflammation. To test this hypothesis, we used structural equation modeling (SEM) to assess PA-body composition -inflammation pathways, as well as influences of age. In a sample of 72 healthy males with a range of PA profiles (age 18-65, mean ± sd = ), we measured PA as metabolic equivalent tasks (as per the International PA Questionnaire), body composition as percent body fat, lean mass, and fat mass, and inflammation as plasma interleukin-6 (IL-6). We treated body composition in the SEM analysis as a latent variable indicated by the three measures. We performed statistical corrections for missing values and one outlier. The model demonstrated significant effects of PA on IL-6 both directly and through body composition. Percent body fat, fat mass, and lean mass were significant indicators of the body composition latent variable. Additionally, age showed an indirect effect on IL-6 through body composition, but no direct effect. The findings suggest that PA does improve inflammatory profile through improving body composition, but that other pathways also exist.     

Network stability is a balancing act of personality, power, and conflict dynamics in rhesus macaque societies

Stability in biological systems requires evolved mechanisms that promote robustness. Cohesive primate social groups represent one example of a stable biological system, which persist in spite of frequent conflict. Multiple sources of stability likely exist for any biological system and such robustness, or lack thereof, should be reflected and thus detectable in the group's network structure, and likely at multiple levels. Here we show how network structure and group stability are linked to the fundamental characteristics of the individual agents in groups and to the environmental and social contexts in which these individuals interact. Both internal factors (e.g., personality, sex) and external factors (e.g., rank dynamics, sex ratio) were considered from the level of the individual to that of the group to examine the effects of network structure on group stability in a nonhuman primate species. The results yielded three main findings. First, successful third-party intervention behavior is a mechanism of group stability in rhesus macaques in that successful interventions resulted in less wounding in social groups. Second, personality is the primary factor that determines which individuals perform the role of key intervener, via its effect on social power and dominance discrepancy. Finally, individuals with high social power are not only key interveners but also key players in grooming networks and receive reconciliations from a higher diversity of individuals. The results from this study provide sound evidence that individual and group characteristics such as personality and sex ratio influence network structures such as patterns of reconciliation, grooming and conflict intervention that are indicators of network robustness and consequent health and well-being in rhesus macaque societies. Utilizing this network approach has provided greater insight into how behavioral and social processes influence social stability in nonhuman primate groups.     

Phosphatidic acid induces leaf cell death in Arabidopsis by activating the Rho-related small G protein GTPase-mediated pathway of reactive oxygen species generation

Phosphatidic acid (PA) level increases during various stress conditions. However, the physiological roles of this lipid in stress response remain largely unknown. In this study, we report that PA induced leaf cell death and elevated the levels of reactive oxygen species (ROS) in the whole leaf and single cells. To further elucidate the mechanism of PA-induced cell death, we then examined whether Rho-related small G protein (ROP) 2, which enhanced ROS production in an in vitro assay, is involved in PA-induced ROS production and cell death. In response to PA, transgenic leaves of Arabidopsis expressing a constitutively active rop2 mutant exhibited earlier cell death and higher levels of ROS than wild type (WT), whereas those expressing a dominant-negative rop2 mutant exhibited later cell death and lower ROS. However, in the absence of exogenous PA, no spontaneous cell death or elevated ROS was observed in constitutively active rop2 plants, suggesting that the activation of ROP GTPase alone is insufficient to activate the ROP-mediated ROS generation pathway. These results suggest that PA modulates an additional factor required for the active ROP-mediated ROS generation pathway. Therefore, PA may be an important regulator of ROP-regulated ROS generation and the cell death process during various stress and defense responses of plants.     

Superantigen-induced apoptotic death of tumor cells is mediated by cytotoxic lymphocytes, cytokines, and nitric oxide.

The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer of CTL activity and cytokine production in vivo. Protein A (PA) of Staphylococcal aureus has been found to have diverse biological response modifying properties and to possess antitumor, antitoxic and antiparasitic effects. In this study we examined the anti-tumor effect of these two superantigens used separately as well as in combination in mice carrying the Ehrlich ascites tumor. With combined treatment, DNA cell cycle analysis of tumor cells showed a significant (P < 0.05) percentage of tumor cell death. Levels of the soluble mediators TNF-alpha, IFN-gamma and IL-1 as well as NO were elevated. Additionally, CD4(+) and CD8(+) specific T cells in spleen, thymus and PBMC in tumor carrying mice were increased (P < 0.01). Our data altogether suggests that enhanced tumor cell death is caused by the increased CTL activity, cytokine and nitric oxide levels, in response to the combined effect of SEA + PA.     

Influenza A virus protein PA-X suppresses host Ankrd17-mediated immune responses

Influenza A virus (IAV) PA-X is a critical ribonuclease protein involved in host cell shutoff but its role in modulating the host immune response to IAV infection remains to be addressed. In this study, host cellular proteins that directly interact with PA-X were screened to investigate the biological function of PA-X in the pathogenesis of IAV infection. The protein ankyrin repeat domain 17 (Ankrd17), a positive regulator of inflammatory responses via the retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) signaling pathway, was identified as a specific PA-X binding partner that preferred PA-X to the PA protein. The N-terminal ankyrin repeats of Ankrd17 are the key domain for the interaction with PA-X rather than PA, which is required for the function of Ankrd17 in elevating the host immune response. Using Ankrd17 knockout and overexpression, we confirmed that PA-X significantly affected the Ankrd17-mediated response to infection in host cells. Our data therefore reveal a novel function for PA-X in the regulation of innate immune pathways via the interaction between PA-X and Ankrd17.     

Intra-population variation in anemia status and its relationship to economic status and self-perceived health in the Mexican Family Life Survey: Implications for bioarchaeology

Recently scholars have advocated for the use of a critical biocultural approach in bioarchaeology, where osteological and dental markers of stress are used to understand the broader biosocial context of past populations. However, the ability to accomplish this task rests on the assumption that ultimate-level environmental stressors and well-being in the past can be reconstructed from the prevalence of pathologies in skeletal collections. Here we test this assumption using anemia prevalence in the Mexican Family Life Survey. Specifically we test three hypotheses: (1) that individuals sharing the same household are more likely to share anemia status; (2) anemia status is a predictor of economic status (a common proxy for broader environmental context); and (3) anemia status is related to self-rated health. Results demonstrate that: anemia status was not commonly shared between household members; there was a significant overlap in economic status between anemic and nonanemic individuals (i.e., anemia poorly predicted economic status) and; while anemia status was associated with self-perceived health, the majority of those who reported poor health were nonanemic while a significant number of those who reported very good health were anemic. We argue that these findings are likely related to variation in individual frailty, which is shaped by biological and cultural risk factors. Therefore, we advocate for greater incorporation of individual frailty into bioarchaeological investigations, and, in effort to overcome some of the difficulties associated with this task, increased use of data from living populations and greater collaboration between bioarchaeologists and human biologists. Am J Phys Anthropol 155:210–220, 2014. © 2014 Wiley Periodicals, Inc.     

Physical and Social Environment Are Associated to Leisure Time Physical Activity in Adults of a Brazilian City: A Cross-Sectional Study

The physical activity practice is highlighted as a strategy to health promotion and to avoid chronic diseases. In addition to individual factors, environmental characteristics in which people live, may offer opportunities or barriers in adopting healthy habits and this is related to the physical activity (PA) practice among individuals. The aim of this study is to investigate the associations between neighborhood environment and leisure-time physical activity in adults. This is a cross-sectional study, developed using the database of Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey (VIGITEL 2008/2010) of Belo Horizonte, Brazil. Individuals with the habit of practicing PA for at least 150 minutes of moderate-intensity PA or at least 75 minutes of vigorous-intensity PA throughout the week in leisure time were classified as active in leisure time. To characterize the built and social environment we used georeferenced data of public and private places for physical activity, population density, residential density, homicide rate and total income of the coverage area of the basic health units. The covered area of the basic health units was used as context unit. For data analysis, we used multilevel logistic regression. The study included 5779 adults, 58.77% female. There was variability of physical activity in leisure time between area covered by the basic health units (Median Odds ratio = 1.30). After adjusting for individual characteristics, the increase of density of private places for physical activity (Odds ratios—OR = 1.31; 95% confidence interval—95% CI: 1.15 to 1.48) and the smaller homicide rate (OR = 0.82; IC95%: 0.70 to 0.96) in the neighborhood increased physical activity in leisure time. The evidence of this study shows that neighborhood environment may influence the physical activity practice in leisure time and should be considered in future interventions and health promotion strategies.     

Achievement of public health recommendations for physical activity and prevention of gains in adiposity in adults

Physical activity (PA) is considered a cornerstone in weight control and public health guidelines recommend regular participation to prevent gains in adiposity. It may therefore come as a surprise that the cumulative evidence from observational studies to support this is not strong. A weakness of many published observational studies on this topic has been a reliance on a single baseline assessment of PA. Using only the baseline information on PA in a prospective study cause misclassification because of participants often change activity level during follow‐up. In turn this causes regression dilution bias and decreases the precision of the estimate of an association between PA and adiposity. Furthermore, because gains in adiposity often are caused by a small average daily energy imbalance over many years, following individuals for longer periods of time is essential to characterize a relationship.     

Effect of 2-fluorohistidine labeling of the anthrax protective antigen on stability, pore formation, and translocation

The action of anthrax toxin relies in part upon the ability of the protective antigen (PA) moiety to form a heptameric pore in the endosomal membrane, providing a portal for entry of the enzymic moieties of the toxin into the cytosol. Pore formation is dependent on a conformational change in the heptameric prepore that occurs in the neutral to mildly acidic pH range, and it has been hypothesized that protonation of one or more histidine residues triggers this transition. To test this hypothesis, we used biosynthetic methods to incorporate the unnatural amino acid analogue 2-fluorohistidine (2-FHis) into PA. 2-FHis is isosteric with histidine but resists protonation at physiological pH values due to a dramatically reduced side-chain pKa ( approximately 1). We found that 2-FHis-labeled PA was biologically inactive, as judged by its inability to deliver a model intracellular effector, LFN-DTA, to the cytosol of CHO-K1 cells. However, whereas 2-FHis blocked a conformational transition in the full-length PA83 protein in the pH 5-6 range, the pH dependence of prepore-to-pore conversion of (PA63)7 was unchanged from the wild-type protein, implying that this conversion is not dependent on His protonation. Consistent with this result, the labeled, trypsin-activated PA was able to permeabilize liposomes to K+ and retained pore-forming activity in planar phospholipid bilayers. The pores in planar bilayers were incapable, however, of translocating a model ligand in response to a transmembrane pH gradient or elevated voltage. The results indicate that protonation of residues other than His, presumably Glu and/or Asp side chains, triggers pore formation in vitro, but His residues are nonetheless important for PA functioning in vivo.     

Morphological, phytochemical and genetic variation in mixed stands and a hybrid swarm of Senecio germanicus and S. ovatus (Compositae, Senecioneae)

Mixed stands of Senecio ovatus subsp. ovatus and S. germanicus subsp. germanicus occur in the colline belt of central and eastern Europe. The latter species is adapted to more continental climate conditions and shows a later flowering time (August?CSeptember) than the widespread S. ovatus (July?CAugust) that grows in more oceanic climates. We have surveyed 253 plants from 15 populations north of Regensburg (south-eastern Germany) using 16 qualitative and quantitative morphological characters and molecular markers [amplified fragment length polymorphisms (AFLP)] to detect introgressive hybridisation between these two species. Both multivariate statistical analyses based on morphological characters and the Bayesian clustering based on AFLP fingerprint data show that in most populations under study the two species form distinct entities and do not hybridise with each other. However, in one population from the Upper Palatine Forest a high number of intermediate individuals were found. A more detailed genetic (AFLP) and phytochemical (pyrrolizidine alkaloid, PA) analysis based on 125 individuals from this hybrid swarm indicated that these intermediate individuals are backcrosses towards S. germanicus. It is shown that the two species differ considerably concerning the qualitative and quantitative PA patterns and that backcrossed individuals either show an additive PA pattern or a PA pattern similar to S. germanicus, while in quantitative respects all of these individuals are approaching S. germanicus. These findings are discussed in terms of differential selection regimes influencing the fitness of pure and hybrid plants in an area which is an eco-climatological optimum for the more oceanic S. ovatus but which forms a distributional edge for the more continental S. germanicus.     

Quantifying Access Disparities in Response Plans

Effective response planning and preparedness are critical to the health and well-being of communities in the face of biological emergencies. Response plans involving mass prophylaxis may seem feasible when considering the choice of dispensing points within a region, overall population density, and estimated traffic demands. However, the plan may fail to serve particular vulnerable subpopulations, resulting in access disparities during emergency response. For a response plan to be effective, sufficient mitigation resources must be made accessible to target populations within short, federally-mandated time frames. A major challenge in response plan design is to establish a balance between the allocation of available resources and the provision of equal access to PODs for all individuals in a given geographic region. Limitations on the availability, granularity, and currency of data to identify vulnerable populations further complicate the planning process. To address these challenges and limitations, data driven methods to quantify vulnerabilities in the context of response plans have been developed and are explored in this article.     

Economic development,intergenerational mobility,and health in South Korea

A growing number of studies reported the association between social mobility and health. However, few studies investigated whether the association varies by age group. Drawing on the economic environment that facilitated social mobility in South Korea, we postulate each age group had a different extent of social mobility, which would vary with the extent of economic growth and affect the association between social mobility and health. We used data from KDI National Happiness Survey 2018 and measured perceived mobility using respondents’ perceived social position and their parents’ social position. We examined whether social mobility was associated with self-rated health and psychological well-being. The upwardly mobile individuals were more likely than the stable ones to report ‘happy’. Such a positive association between upward mobility and happiness was consistently found when the sample was restricted to the ages 30–59 and 40–49. For self-rated health, the downwardly mobile individuals were less likely to report good health. However, no significant difference in self-rated health was found after the youngest and oldest age groups were excluded. We found that perceived social mobility was strongly associated with psychological well-being rather than self-rated health. Moreover, we found a stronger association between upward mobility and happiness among the aged 40–49, who had the largest proportion of upwardly mobile individuals and spent their adolescence during rapid economic growth. The findings underscore the importance of the economic and social context in which individuals perceive their social position and shape their well-being.     

Phosphatidic acid production in chitosan-elicited tomato cells, via both phospholipase D and phospholipase C/diacylglycerol kinase, requires nitric oxide

Nitric oxide (NO) and the lipid second messenger phosphatidic acid (PA) are involved in plant defense responses during plant-pathogen interactions. NO has been shown to be involved in the induction of PA production in response to the pathogen associated molecular pattern (PAMP) xylanase in tomato cells. It was shown that NO is critical for PA production induced via phospholipase C (PLC) in concerted action with diacylglycerol kinase (DGK) but not for the xylanase-induced PA via phospholipase D (PLD). In order to study whether this is a general phenomenon during PAMP perception or if it is particular for xylanase, we studied the effect of the PAMP chitosan in tomato cell suspensions. We observed a rapid NO production in tomato cells treated with chitosan. Chitosan induced the formation of PA by activating both PLD and PLC/DGK. The activation of either phospholipase-mediated signaling pathway was inhibited in cells treated with the NO scavenger cPTIO. This indicates that NO is required for PA generation via both the PLD and PLC/DGK pathway during plant defense response in chitosan elicited cells. Responses downstream PA were studied. PLC inhibitors neomycin and U73122 inhibited chitosan-induced ROS production. Differences between xylanase and chitosan-induced phospholipid signaling pathways are discussed.     

Cat odor causes long-lasting contextual fear conditioning and increased pituitary-adrenal activation, without modifying anxiety

A single exposure to a cat or cat odors has been reported by some groups to induce contextual and auditory fear conditioning and long-lasting changes in anxiety-like behaviour, but there is no evidence for parallel changes in biological stress markers. In the present study we demonstrated in male rats that exposure to a novel environment containing a cloth impregnated with cat fur odor resulted in avoidance of the odor, lower levels of activity and higher pituitary-adrenal (PA) response as compared to those exposed to the novel environment containing a clean cloth, suggesting increased levels of stress in the former animals. When re-exposed 9 days later to the same environment with a clean cloth, previously cat fur exposed rats again showed avoidance of the cloth area and lower levels of activity, suggesting development of contextual fear conditioning, which again was associated with a higher PA activation. In contrast, unaltered both anxiety-like behaviour and PA responsiveness to an elevated plus-maze were found 7 days after cat odor exposure. It is concluded that: (i) PA activation is able to reflect both the stressful properties of cat fur odor and odor-induced contextual fear conditioning; (ii) development of cat odor-induced contextual fear conditioning is independent of the induction of long-lasting changes in anxiety-like behaviour; and (iii) greater PA activation during exposure to the odor context is not explained by non-specific sensitization of the PA axis caused by previous exposure to cat fur odor.