Neutrophil extracellular traps formation and clearance is enhanced in fever and attenuated in hypothermia

Fever and hypothermia represent two opposite strategies for fighting systemic inflammation. Fever results in immune activation; hypothermia is associated with energy conservation. Systemic Inflammatory Response Syndrome (SIRS) remains a significant cause of mortality worldwide. SIRS can lead to a broad spectrum of clinical symptoms but importantly, patients can develop fever or hypothermia. During infection, polymorphonuclear cells (PMNs) such as neutrophils prevent pathogen dissemination through the formation of neutrophil extracellular traps (NETs) that ensnare and kill bacteria. However, when dysregulated, NETs also promote host tissue damage. Herein, we tested the hypothesis that temperature modulates NETs homeostasis in response to infection and inflammation. NETs formation was studied in response to infectious (Escherichia coli, Staphylococcus aureus) and sterile (mitochondria) agents. When compared to body temperature (37°C), NETs formation increased at 40°C; interestingly, the response was stunted at 35°C and 42°C. While CD16+ CD49d+ PMNs represent a small proportion of the neutrophil population, they formed ~45-85% of NETs irrespective of temperature. Temperature increased formyl peptide receptor 1 (FPR1) expression to a differential extent in CD16+ CD49d- vs. CD49d+ PMNSs, suggesting further complexity to neutrophil function in hypo/hyperthermic conditions. The capacity of NETs to induce Toll-like receptor 9 (TLR9)-mediated NF-κB activation was found to be temperature independent. Interestingly, NET degradation was enhanced at higher temperatures, which corresponded with greater plasma DNase activity in response to temperature increase. Collectively, our observations indicate that NETs formation and clearance are enhanced at 40°C whilst temperatures of 35°C and 42°C attenuate this response. Targeting PMN-driven immunity may represent new venues for intervention in pathological inflammation

The female menstrual cycle does not influence testosterone concentrations in male partners

<p>Abstract</p> <p>Background</p> <p>The time of ovulation has since long been believed to be concealed to male heterosexual partners. Recent studies have, however, called for revision of this notion. For example, male testosterone concentrations have been shown to increase in response to olfactory ovulation cues, which could be biologically relevant by increasing sexual drive and aggressiveness. However, this phenomenon has not previously been investigated in real-life human settings. We therefore thought it of interest to test the hypothesis that males' salivary testosterone concentrations are influenced by phases of their female partners' menstrual cycle; expecting a testosterone peak at ovulation.</p> <p>Methods</p> <p>Thirty young, healthy, heterosexual couples were recruited. During the course of 30-40 days, the women registered menses and ovulation, while the men registered sexual activity, physical exercise, alcohol intake and illness (confounders), and obtained daily saliva samples for testosterone measurements. All data, including the registered confounders, were subjected to multiple regression analysis.</p> <p>Results</p> <p>In contrast to the hypothesis, the ovulation did not affect the testosterone levels, and the resulting testosterone profile during the menstrual cycle was on the average flat. The specific main hypothesis, that male testosterone levels on the day of ovulation would be higher than day 4 of the cycle, was clearly contradicted by a type II error(β)-analysis (< 14.3% difference in normalized testosterone concentration; β = 0.05).</p> <p>Conclusions</p> <p>Even though an ovulation-related salivary testosterone peak was observed in individual cases, no significant effect was found on a group level.</p

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Molecular Targets for 17α-Ethynyl-5-Androstene-3β,7β,17β-Triol, an Anti-Inflammatory Agent Derived from the Human Metabolome

HE3286, 17α-ethynyl-5-androstene-3β, 7β, 17β-triol, is a novel synthetic compound related to the endogenous sterol 5-androstene-3β, 7β, 17β-triol (β-AET), a metabolite of the abundant adrenal steroid dehydroepiandrosterone (DHEA). HE3286 has shown efficacy in clinical studies in impaired glucose tolerance and type 2 diabetes, and in vivo models of types 1 and 2 diabetes, autoimmunity, and inflammation. Proteomic analysis of solid-phase HE3286-bound bead affinity experiments, using extracts from RAW 264.7 mouse macrophage cells, identified 26 binding partners. Network analysis revealed associations of these HE3286 target proteins with nodes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for type 2 diabetes, insulin, adipokine, and adipocyte signaling. Binding partners included low density lipoprotein receptor-related protein (Lrp1), an endocytic receptor; mitogen activated protein kinases 1 and 3 (Mapk1, Mapk3), protein kinases involved in inflammation signaling pathways; ribosomal protein S6 kinase alpha-3 (Rsp6ka3), an intracellular regulatory protein; sirtuin-2 (Sirt2); and 17β-hydroxysteroid dehydrogenase 1 (Hsd17β4), a sterol metabolizing enzyme

The three main monotheistic religions and gm food technology: an overview of perspectives

Abstract Background Public acceptance of genetically modified crops is partly rooted in religious views. However, the views of different religions and their potential influence on consumers' decisions have not been systematically examined and summarized in a brief overview. We review the positions of the Judaism, Islam and Christianity – the three major monotheistic religions to which more than 55% of humanity adheres to – on the controversies aroused by GM technology. Discussion The article establishes that there is no overarching consensus within the three religions. Overall, however, it appears that mainstream theology in all three religions increasingly tends towards acceptance of GM technology per se, on performing GM research, and on consumption of GM foods. These more liberal approaches, however, are predicated on there being rigorous scientific, ethical and regulatory scrutiny of research and development of such products, and that these products are properly labeled. Summary We conclude that there are several other interests competing with the influence exerted on consumers by religion. These include the media, environmental activists, scientists and the food industry, all of which function as sources of information and shapers of perception for consumers

Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms

Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration

Factors determining the kinetics of a single dose of testosterone in rats

The results from different authors regarding testosterone and cognitive research show controversial results. One of the reasons may be the form of testosterone used in the experiment. The aim of our study was to evaluate the testosterone levels in plasma and its kinetics after the single application of either a long-acting or a short-acting form of this hormone. Twenty female and twenty male adult Wistar rats were divided into two groups that were either gonadectomized or not. The two groups were divided into 4 subgroups depending on whether the animals received testosterone propionate or testosterone isobutyrate intramuscularly. Samples for analysis were collected before and at 2, 4, 24, 48, 72, 96 and 168 h after injection. The results showed significant differences in the dynamics between rapid and depot forms of testosterone, together with the rebound effect and hormonal negative feedback. These aspects of testosterone kinetics need to be considered when planning experiments on the physiology of testosterone

Oxidative status in plasma, urine and saliva of girls with anorexia nervosa and healthy controls: a cross-sectional study

2-s2.0-85104635276Background: Anorexia nervosa (AN) is a serious psychosomatic disorder with unclear pathomechanisms. Metabolic dysregulation is associated with disruption of redox homeostasis that might play a pivotal role in the development of AN. The aim of our study was to assess oxidative status and carbonyl stress in plasma, urine and saliva of patients with AN and healthy controls. Methods: Plasma, spot urine, and saliva were collected from 111 girls with AN (aged from 10 to 18 years) and from 29 age-matched controls. Markers of oxidative stress and antioxidant status were measured using spectrophotometric and fluorometric methods. Results: Plasma advanced oxidation protein products (AOPP) and advanced glycation end products (AGEs) were significantly higher in patients with AN than in healthy controls (by 96, and 82%, respectively). Accordingly, urinary concentrations of AOPP and fructosamines and salivary concentrations of AGEs were higher in girls with AN compared with controls (by 250, and 41% in urine; by 92% in saliva, respectively). Concentrations of thiobarbituric acid reactive substances (TBARS) in saliva were 3-times higher in the patients with AN than in the controls. Overall antioxidants were lower in plasma of girls with AN compared to the controls, as shown by total antioxidant capacity and ratio of reduced and oxidized glutathione (by 43, and 31%, respectively). Conclusions: This is the first study assessing wide range of markers of oxidative status in plasma, urine and saliva of the patients with AN. We showed that both, higher levels of markers of oxidative stress and lower antioxidants play a role in redox disruption. Restoration of redox homeostasis might be of the clinical relevance © 2021, The Author(s).2018/36-LFUK-10 Ministerstvo školstva, vedy, v?skumu a športu Slovenskej republiky: 1/0613/17This study was supported by the Grant of Ministry of Health of the Slovak republic 2018/36-LFUK-10 and by the Grant Agency of Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 1/0613/17