Changes In Biological Response Research Articles

Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach

Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter’s increased risk for urinary tract cancers.

Peripheral blood lymphocytes differ in DNA damage response after exposure to X-rays with different physical properties

Introduction: In radiology, low X-ray energies (<140 keV) are used to obtain an optimal image while in radiotherapy, higher X-ray energies (MeV) are used to eradicate tumor tissue. In radiation research, both these X-ray energies being used to extrapolate in vitro research to clinical practice. However, the energy deposition of X-rays depends on their energy spectrum, which might lead to changes in biological response. Therefore, this study compared the DNA damage response (DDR) in peripheral blood lymphocytes (PBLs) exposed to X-rays with varying beam quality, mean photon energy (MPE) and dose rate. Methods: The DDR was evaluated in peripheral blood lymphocytes (PBLs) by the ɣ-H2AX foci assay, the cytokinesis-block micronucleus assay and an SYTOX-based cell death assay, combined with specific cell death inhibitors. Cell cultures were irradiated with a 220 kV X-ray research cabinet (SARRP, X-Strahl) or a 6 MV X-ray linear accelerator (Elekta Synergy). Three main physical parameters were investigated: beam quality (V), MPE (eV) and dose rate (Gy/min). Additional copper (Cu) filtration caused variation in the MPE (78 keV, 94 keV, 118 keV) at SARRP; dose rates were varied by adjusting tube current for 220 kV X-rays (0.33–3 Gy/min) or water-phantom depth in the 6 MV set-up (3–6 Gy/min). Results: The induction of chromosomal damage and initial (30 min) DNA double-stranded breaks (DSBs) were significantly higher for 220 kV X-rays compared to 6 MV X-rays, while cell death induction was similar. Specific cell death inhibitors for apoptosis, necroptosis and ferroptosis were not capable of blocking cell death after irradiation using low or high-energy X-rays. Additional Cu filtration increased the MPE, which significantly decreased the amount of chromosomal damage and DSBs. Within the tested ranges no specific effects of dose rate variation were observed. Conclusion: The DDR in PBLs is influenced by the beam quality and MPE. This study reinforces the need for consideration and inclusion of all physical parameters in radiation-related studies.

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.

Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge.

Human biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2'-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.

Investigating the potential contribution of inter-track interactions within ultra-high dose-rate proton therapy

Objective. Laser-accelerated protons offer an alternative delivery mechanism for proton therapy. This technique delivers dose-rates of ≥109 Gy s−1, many orders of magnitude greater than used clinically. Such ultra-high dose-rates reduce delivery time to nanoseconds, equivalent to the lifetime of reactive chemical species within a biological medium. This leads to the possibility of inter-track interactions between successive protons within a pulse, potentially altering the yields of damaging radicals if they are in sufficient spatial proximity. This work investigates the temporal evolution of chemical species for a range of proton energies and doses to quantify the circumstances required for inter-track interactions, and determine any relevance within ultra-high dose-rate proton therapy. Approach. The TOPAS-nBio Monte Carlo toolkit was used to investigate possible inter-track interactions. Firstly, protons between 0.5 and 100 MeV were simulated to record the radial track dimensions throughout the chemical stage from 1 ps to 1 μs. Using the track areas, the geometric probability of track overlap was calculated for various exposures and timescales. A sample of irradiations were then simulated in detail to compare any change in chemical yields for independently and instantaneously delivered tracks, and validate the analytic model. Main results. Track overlap for a clinical 2 Gy dose was negligible for biologically relevant timepoints for all energies. Overlap probability increased with time after irradiation, proton energy and dose, with a minimum 23 Gy dose required before significant track overlap occurred. Simulating chemical interactions confirmed these results with no change in radical yields seen up to 8 Gy for independently and instantaneously delivered tracks. Significance. These observations suggest that the spatial separation between incident protons is too large for physico-chemical inter-track interactions, regardless of the delivery time, indicating such interactions would not play a role in any potential changes in biological response between laser-accelerated and conventional proton therapy.

From organismal physiology to ecological processes: Effects of nutrient enrichment and salinity variation in a freshwater ecosystem

AbstractEnvironmental stressors have profound implications for species, communities, and ecosystems by altering fundamental processes. With increasing human impacts on aquatic ecosystems, two main scenarios have been reported: (1) the spatiotemporal superposition of multiple stressors, leading to interactions among them and (2) intensifying environmental gradients, leading to threshold responses. However, studies designed to assess the effects of multiple stressors (e.g., pulse stressors) along environmental gradients (e.g., press stressors) are uncommon, and interactions between pulse and press stressors may cause abrupt changes in biological responses. We conducted a laboratory experiment to investigate the effects of osmotic stress along a nutrient enrichment gradient on a freshwater community composed of periphyton, microorganisms, and zebra mussels (Dreissena polymorpha). Our objectives were to (1) quantify the individual and combined effects of stressors, (2) delineate thresholds along the nutrient gradient (press) in the absence and presence of osmotic stress (pulse), and (3) test for interactions between the two stressors. We evaluated effects on metabolic rates in D. polymorpha and on microbial activity, as well as phototrophic periphyton biomass and physiological status. We observed interactions between the two stressors for metabolic rates in D. polymorpha and periphytic phaeopigments. In contrast, we found an individual effect of osmotic stress on microbial activity and chlorophyll a content. Thresholds were only identified in the presence of osmotic stress for metabolic rates in D. polymorpha. Our work highlights the importance of combining multiple stressors with environmental gradients and the need to consider multiple biological compartments when evaluating the impacts of stressors on ecosystems.

Early Interferon-Gamma Response in Nonhuman Primate Recipients of Solid-Organ Xenotransplantation

To understand changes in biological responses in nonhuman primate (NHP) recipients of xenotransplantation (XTP), we retrospectively investigated chronological changes in cytokine profiles of NHP recipients after solid-organ XTP. Plasma samples were collected from 7 NHP recipients of pig heart or kidney XTP with α-1,3-galactosyltransferase gene knockout (GTKO)under anti-CD154-based immune suppression at the following time points: immediately before; 2 hours, 3 days, and 7 days after XTP; and weekly thereafter until the graft failed. The plasma levels of the following cytokines were measured: interleukin (IL)-1α, IL-1β, IL-6, IL-12p70, IL-8, IL-10, IL-15, tumor necrosis factor, interferon gamma (IFN-γ), D-dimer, C3a, and histone-complexed DNA fragments. For in vitro experiments, human natural killer (NK) cells were cocultured with wild-type porcine endothelial cells (PECs), GTKO-PECs, and human umbilical vein endothelial cells, with or without anti-CD154 antibody. IFN-γ levels in the culture supernatants were compared. IFN-γ levels peaked on day 7 or 10 of XTP and then decreased to basal levels, whereas proinflammatory cytokine levels increased along with the elevation of histone-complexed DNA fragments and were sustained until xenograft failure. In vitro, human NK cells produced more IFN-γ when in contact with wild-type PECs than with human umbilical vein endothelial cells, which was not reduced by the use of GTKO-PECs or addition of anti-CD154 antibody to the mixture. In NHP recipients of XTP, the early peak of IFN-γ priming subsequent inflammatory responses may be attributed to NK cell activation in response to xenografts.

Biological evidence to define a vitamin A deficiency cutoff using total liver vitamin A reserves.

Vitamin A is a fat-soluble vitamin involved in essential functions including growth, immunity, reproduction, and vision. The vitamin A Dietary Reference Intakes (DRIs) for North Americans suggested that a minimally acceptable total liver vitamin A reserve (TLR) is 0.07 µmol/g, which is not explicitly expressed as a vitamin A deficiency cutoff. The Biomarkers of Nutrition for Development panel set the TLR cutoff for vitamin A deficiency at 0.1 µmol/g based on changes in biological response of several physiological parameters at or above this cutoff. The criteria used to formulate the DRIs include clinical ophthalmic signs of vitamin A deficiency, circulating plasma retinol concentrations, excretion of vitamin A metabolites in the bile, and long-term storage of vitamin A as protection against vitamin A deficiency during times of low dietary intake. This review examines the biological responses that occur as TLRs are depleted. In consideration of all of the DRI criteria, the review concludes that induced biliary excretion and long-term vitamin A storage do not occur until TLRs are >0.10 µmol/g. If long-term storage is to continue to be part of the DRI criteria, vitamin A deficiency should be set at a minimum cutoff of 0.10 µmol/g and should be set higher during times of enhanced requirements where TLRs can be rapidly depleted, such as during lactation or in areas with high infection burden. In population-based surveys, cutoffs are important when using biomarkers of micronutrient status to define the prevalence of deficiency and sufficiency to inform public health interventions. Considering the increasing use of quantitative biomarkers of vitamin A status that indirectly assess TLRs, i.e. the modified-relative-dose response and retinol-isotope dilution tests, setting a TLR as a vitamin A deficiency cutoff is important for users of these techniques to estimate vitamin A deficiency prevalence. Future researchers and policymakers may suggest that DRIs should be set with regard to optimal health and not merely to prevent a micronutrient deficiency.

Preliminary Study of Catalase Enzyme Activity and Protein Concentrations in the Mediterranean and African Mussels, Mytilus galloprovincialis and Perna perna, Cohabiting on the Same Natural Coastal Site (Figuier, Boumerdes, Algeria)

Biological monitoring has become one of the most widely used approaches in aquatic monitoring. As a result, the effect of the xenobiotics entrained by the organic and inorganic effluents on different aquatic species is therefore entirely distinct. The aim of this study is to assess and to compare changes in biological responses, as non-specified biomarkers, measured in the gills and adductor muscles of the Mediterranean and African mussels, Mytilus galloprovincialis (designated MG) and Perna perna (designated PP) coexisting on Algerian coastal sites (Figuier, W. Boumerdes, Algeria) during the Winter and Spring period (2015/2016). Catalase enzyme activity, total proteins, and condition index were measured in collected samples of two size classes (class1: [2–2.5 cm] and class2: [4.5–5.5 cm]). During the study period, the values of enzymatic activities were relatively higher in MG than in PP (January, class 2, MG: 46.9 U/mg proteins, PP: 39.1U/mg proteins). Additionally, the results obtained showed a slight disturbance of the metabolism in two species of the same size class which resulted in a remarkable increase of catalase activity in March (class 2, MG: 54.2 U/mg protein, PP: 49 U/mg protein) and in April (class 2, MG: 51.9 U/mg protein, PP: 44.8 U/mg protein) compared to the other months. During the study period, the total proteins revealed a variation nonspecific for the two species at various sizes. With regard to the results obtained, biological responses were completely different in the two species with various sizes that were exposed to the natural or anthropogenic changes. Seasonal specificity contributed considerably and differently to the stress of the two species. Moreover, the catalase enzyme activity and total proteins proved their effectiveness as nonspecific, relevant and sensitive biomarkers.

Effects of Low Dose Radiation on Biological Processes in Peri-tumoral and Tumoral Areas n Squamous Cell Skin Cancer

Very low dose ionizing radiation (LDR) may have paradoxically beneficial effects via an adaptive response. This adaptive response can mitigate against the potential adverse effects of high-dose radiation therapy and chemotherapy. In this study we aimed to:1.identify the specific molecular details behind the adaptive response to LDR and2.integrate the LDR adaptive response into clinical practice. Our aim was to determine how low dose radiation modifies genetic expression in both healthy and tumor tissue. To determine this, a human clinical trial (n=8) was conducted in 2018 to ascertain the biological effects of integrating 0.1Gy of LDR into standard radiotherapy (2Gy fractions) over the first two weeks of radiation treatment for epidermoid skin cancers. RNA was obtained from skin biopsies and processed for genetic expression using Affymetrix Human gene chips Clarion-D (138K genes). 8 patients with squamous skin cancer, were studied according to the experimental design showed in Figure 1. Biopsy samples were collected and total RNA preparation (100 ng), labeled cRNA synthesis, hybridization, scanning, and image analysis were performed. Changes in biological response were measured using Affymetrix microarrays. Experiments 17F1 and 17F2 were performed in duplicate, and experiments 18F3 and 18F4 were performed in triplicate. Pathway analysis was performed using the Affymetrix Transcriptome Analysis Console software and the Wikipaths database. Comparisons were performed as noted in Table 1. The difference in gene expression in healthy tissues due to LDR exposure is quite low (only 325 genes, mostly downregulated) as noted in Figures 2A and 3A and Tables 2 and 3. The 20 most important biological processes enriched are shown in Figure 4 and include Senescence and Autophagy in malignant cells, and the Genotoxicity Pathway (both downregulated). The difference in gene expression in tumor tissue due to LDR exposure is significantly more pronounced (5,651 genes, mostly upregulated) as noted in Figures 2C and 3C. The 20 most important biological processes enriched are shown in Figures 5 and 6 and Tables 4-6, and include the Allograft rejection pathway in skin cancer (upregulated). Our results suggest that very low doses of radiation (0.1Gy) have a narrow effect on gene expression when applied in the healthy peritumoral area. Down regulated genes predominate, and DNA repair mechanisms are stimulated by the first low dose in healthy tissue.

Minimally-invasive methods for examining biological changes in response to chronic stress: A scoping review

BackgroundNurse researchers are increasingly interested in incorporating biological indicators related to chronic stress, or repeated or constant exposure to psychological stressors. Minimally invasive collection methods may improve access to vulnerable populations. ObjectiveTo map biological indicators measured through minimally invasive methods investigating biological changes in response to chronic stress. Design, data sources, and methodsThe paper seeks to answer two questions: What are the characteristics of the minimally-invasive methods used to measure the biological correlates of chronic stress? What are the limitations regarding the use of the minimally-invasive methods and/or biological indicators identified above? Authors completed a scoping review following guidelines from the Joanna Briggs Institute Manual and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews. A literature search was completed in PubMed, PsycINFO, and Scopus. 2518 articles were screened and 145 studies were included. Data were extracted using a standardized extraction tool, compiled, and coded. ResultsStudies included minimally-invasive methods to measure the hypothalamic–adrenal–pituitary axis (N = 173), immune and inflammatory markers (N = 118), and adult neurogenesis (N = 6). Cortisol was most frequently measured (N = 136), usually in saliva (N = 86). Studies included a variety of limitations for the methods and indicators, including concerns about timing and accuracy of collection, frequency of sampling, and controlling for acute stressors. ConclusionsNurse researchers have access to many minimally-invasive methods to measure altered biological processes related to chronic stress. A gap identified by this review is the paucity of minimally-invasive methods for investigating neurogenesis; the measurement of brain derived neurotrophic factor in plasma is a distal proxy and further research is needed to test the response of peripheral levels to psychosocial stress interventions. Additionally, while this scoping review allows nurse researchers to consider possible biological indicators to include in their research, future research is still needed on some of the basic premises of stress research, including agreement on the conceptualization of chronic stress.

Acute stress-induced cortisol elevation during memory consolidation enhances pattern separation.

Stress is a potent modulator of brain function and particularly mnemonic processes. While chronic stress is associated with long-term deficits in memory, the effects of acute stress on mnemonic functions are less clear as previous reports have been inconsistent. Some studies suggest that cortisol, a stress hormone that modulates biological changes in response to stress, may enhance memory consolidation and impair memory retrieval. However, other studies report no effect of cortisol on either memory consolidation or retrieval. These discrepancies could be due to differences in the timing and sequencing of the experimental procedures or individual differences in participants’ stress response. In the present study, we examined the effect of increased cortisol levels due to acute stress, induced by the Trier Social Stress Test (TSST), on a pattern separation memory task while differentiating the distinct stages of memory processing and controlling for the effects of diurnal variation. Sixty-nine young adults completed a 2-d study in which subjects either underwent the TSST immediately following the encoding part of the memory task, targeting memory consolidation, or immediately prior to the recognition part of the memory task on the second day, targeting memory retrieval. Control subjects completed the same study procedures but underwent a control version of the TSST that did not induce a stress response. Mnemonic discrimination of highly similar stimuli was enhanced by stress induced during consolidation with better discrimination showing a significant correlation with increased cortisol responses. Stress induced during memory retrieval showed no significant effect on memory performance. These findings suggest that stress induced changes in cortisol differentially affect the consolidation and retrieval stages of memory function.

Gene expression profiling toward the next generation safety control of influenza vaccines and adjuvants in Japan

Influenza becomes epidemic worldwide every year, and many individuals receive vaccination annually. Quality control relating to safety and potency of influenza vaccines is important to maintain public confidence. The safety of influenza vaccines has been assessed by clinical trials, and animal safety tests are performed to monitor the consistent quality between vaccines used for clinical trials and marketing; the biological responses in vaccinated animals are evaluated, including changes in body weight and white blood cell count. Animal safety tests have been contributing to the quality relating to the safety of influenza vaccines for decades, but improvements are needed. Although precise mechanisms involving biological changes in animal safety tests have not been fully elucidated, the application of cDNA microarray technology make it possible to reliably identify genes related to biological responses in vaccinated animals. From analysis of the expression profile of >10,000 genes of lung in animals treated with an inactivated whole virion influenza vaccine, we identified 17 marker genes whose expression patterns correlated well to changes in body weight and leukocyte count in vaccinated animals. In influenza HA vaccine-treated animals exhibiting subtle changes in biological responses, a robust expression pattern of marker genes was found. Furthermore, these marker genes could also be used in the evaluation of adjuvanted influenza vaccines. The expression profile of marker genes is expected to be an alternative indicator for safety control of various influenza vaccines conferring high sensitivity and short turnaround time. Thus, gene expression profiling may be a powerful tool for safety control of vaccines in the future.

Contaminants of emerging concern presence and adverse effects in fish: A case study in the Laurentian Great Lakes.

The Laurentian Great Lakes are a valuable natural resource that is affected by contaminants of emerging concern (CECs), including sex steroid hormones, personal care products, pharmaceuticals, industrial chemicals, and new generation pesticides. However, little is known about the fate and biological effects of CECs in tributaries to the Great Lakes. In the current study, 16 sites on three rivers in the Great Lakes basin (Fox, Cuyahoga, and Raquette Rivers) were assessed for CEC presence using polar organic chemical integrative samplers (POCIS) and grab water samplers. Biological activity was assessed through a combination of invitro bioassays (focused on estrogenic activity) and invivo assays with larval fathead minnows. In addition, resident sunfish, largemouth bass, and white suckers were assessed for changes in biological endpoints associated with CEC exposure. CECs were present in all water samples and POCIS extracts. A total of 111 and 97 chemicals were detected in at least one water sample and POCIS extract, respectively. Known estrogenic chemicals were detected in water samples at all 16 sites and in POCIS extracts at 13 sites. Most sites elicited estrogenic activity in bioassays. Ranking sites and rivers based on water chemistry, POCIS chemistry, or total invitro estrogenicity produced comparable patterns with the Cuyahoga River ranking as most and the Raquette River as least affected by CECs. Changes in biological responses grouped according to physiological processes, and differed between species but not sex. The Fox and Cuyahoga Rivers often had significantly different patterns in biological response Our study supports the need for multiple lines of evidence and provides a framework to assess CEC presence and effects in fish in the Laurentian Great Lakes basin.

Aldo-keto reductase and alcohol dehydrogenase contribute to benznidazole natural resistance in Trypanosoma cruzi.

The improvement of Chagas disease treatment is focused not only on the development of new drugs but also in understanding mechanisms of action and resistance to drugs conventionally used. Thus, some strategies aim to detect specific changes in proteins between sensitive and resistant parasites and to evaluate the role played in these processes by functional genomics. In this work, we used a natural Trypanosoma cruzi population resistant to benznidazole, which has clones with different susceptibilities to this drug without alterations in the NTR I gene. Using 2DE-gel electrophoresis, the aldo-keto reductase and the alcohol dehydrogenase proteins were found up regulated in the natural resistant clone and therefore their possible role in the resistance to benznidazole and glyoxal was investigated. Both genes were overexpressed in a drug sensitive T. cruzi clone and the biological changes in response to these compounds were evaluated. The results showed that the overexpression of these proteins enhances resistance to benznidazole and glyoxal in T. cruzi. Moreover, a decrease in mitochondrial and cell membrane damage was observed, accompanied by a drop in the intracellular concentration of reactive oxygen species after treatment. Our results suggest that these proteins are involved in the mechanism of action of benznidazole.

IgA You Assay? The Correlation between Sleep and Stress

Abstract The most well known fact about sleep is that humans need it - while we are asleep our metabolic processes slow down and during long periods of sleep our bodies repair the damage that the stress our bodies have undergone throughout the day. Throughout the day our bodies are bombarded by signals from the environment, and undergoes biological changes in response to external and internal stimuli. Sleep is a period of time to restore the body to optimum condition to continue the process all over again the next day. The human body regulates stress by producing glucocorticoid steroid hormones, which also function as immune response suppressants. During sleep cortisol levels are decreased as they inhibit the body’s period of restoration. The production of immunoglobulin A, an antibody associated with mucosal membranes, is inhibited by glucocorticoids, and thus shows a relationship with sleep and other factors associated with stress. This experiment focused on correlations between sleep and stress found on the campus of Radford University. Our groups recorded the amount of sleep participants acquired the previous night and how long they had been awake, and correlated these with the concentration of salivary IgA. According to our initial data collection there was no significant correlation between the amount of sleep (p=0.305) or hours awake (0.670) to IgA levels. Additional sampling later in the semester will be used to supplement this data set and mapped using geospatial coordinates.

Erratum to: Polyvinylpyrrolidone and arsenic-induced changes in biological responses of model aquatic organisms exposed to iron-based nanoparticles

The efficiency of zero-valent iron particles used in the remediation of contaminated groundwater has, with the emergence of nanotechnology, stimulated interest on the use of nano-size particles to take advantage of high-specific surface area and reactivity characteristics of nanoparticles (NPs). Accordingly, engineered iron-NPs are among the most widely used nanomaterials for in situ remediation. However, while several ecotoxicity studies have been conducted to investigate the adverse impacts of these NPs on aquatic organisms, research on the implications of spent iron-based NPs is lacking. In this study, a comparative approach is used, in which the biological effects of three iron-based NPs (Fe3O4 and γ-Fe2O3 NPs with particle sizes ranging from 20 to 50 nm, and Fe0-NPs with an average particle size of 40 nm) on Raphidocelis subcapitata (formely known as Pseudokirchneriella subcapitata) and Daphnia magna were investigated using both as-prepared and pollutant-doped Fe-based NPs. For the latter, arsenic (As) was used as example sorbed pollutant. The results show that improved degree of NP dispersion by use of polyvinylpyrrolidone overlapped with both increased arsenic adsorption capacity and toxicity to the tested organisms. For R. subcapitata, Fe-oxide NPs were more toxic than Fe0-NPs, due primarily to differences in the degree of NPs aggregation and ability to produce reactive oxygen species. For the invertebrate D. magna, a similar trend of biological responses was observed, except that sorption of As to Fe0-NPs significantly increased the toxic response when compared to R. subcapitata. Overall, these findings point to the need for research on downstream implications of NP-pollutant complexes generated during water treatment by injection of NPs into aquatic systems.

Aging of the Liver: What This Means for Patients with HIV.

As the HIV population continues to live longer as a result of antiretroviral therapy, liver-related mortality has become one of the leading causes of non-AIDS related death in this patient population. The liver possesses a remarkable regenerative capacity but undergoes complex biological changes in response to aging and inflammation that result in decreased cellular regeneration and a tipping of the scales towards fibrogenesis. Patients with HIV infection have serological evidence of ongoing inflammation, with elevations in some biomarkers persisting despite adequate virologic control. In addition, HIV-co-infected patients have markers of advanced age on liver biopsy and increased prevalence of fibrosis as compared to an age-matched HCV mono-infected cohort. In this review, we will discuss the biology of aging, age-related changes in the liver, and the relevant mechanisms by which HIV causes inflammation in the context of accelerated aging, fibrosis of the liver, and other viral co-infection.

Polyvinylpyrrolidone and arsenic-induced changes in biological responses of model aquatic organisms exposed to iron-based nanoparticles

Polyvinylpyrrolidone and arsenic-induced changes in biological responses of model aquatic organisms exposed to iron-based nanoparticles

Adiponectin affects vascular smooth muscle cell proliferation and apoptosis through modulation of the mitofusin-2-mediated Ras-Raf-Erk1/2 signaling pathway

Vascular smooth muscle cells (VSMCs) undergo cell biological changes in response to a variety of cytokines and growth factors. Adiponectin inhibits neointimal formation through suppressing the proliferation and migration of VSMCs. However, the mechanisms underlying the effect of adiponectin on VSMC proliferation and apoptosis require further investigation. The present study was designed to investigate the mechanisms of adiponectin on VSMC proliferation and apoptosis, focusing on the mitofusin‑2 (MFN2) mediated Ras‑Raf‑extracellular signal regulated kinase (Erk)1/2 signaling pathway. The results of western blot analysis revealed that adiponectin increased the expression of MFN2 in a concentration‑dependent manner. Adiponectin also suppressed VSMC proliferation and induced VSMC apoptosis. However, transfection of the VSMCs with small interfering (si)RNA, to knock down the expression of MFN2 attenuated the effect of adiponectin on VSMC proliferation and apoptosis. The decreased expression levels of Ras, phosphorlated (p)‑c‑Raf and p‑Erk1/2, observed in the VSMCs treated with adiponectin were also reversed by the transfection of the VSMCs with MFN2 siRNA to knock down the expression of MFN2. The results of the present study demonstrated for the first time, to the best of our knowledge, that adiponectin exhibits an inhibitory effect on VSMC proliferation and induces cell proliferation via regulation of the expression levels of MFN2. Adiponectin upregulated the expression of MFN2, inhibiting the Ras‑Raf‑Erk1/2 signaling pathway, which led to the inhibition of VSMC proliferation and the induction of VSMC apoptosis. The results of the present study may provide a novel basis for the therapy of vascular disease.