state of polarization changes
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Communicating the scientific consensus that human-caused climate change is real increases climate change beliefs, worry and support for public action in the United States. In this preregistered experiment, we tested two scientific consensus messages, a classic message on the reality of human-caused climate change and an updated message additionally emphasizing scientific agreement that climate change is a crisis. Across online convenience samples from 27 countries (n = 10,527), the classic message substantially reduces misperceptions (d = 0.47, 95% CI (0.41, 0.52)) and slightly increases climate change beliefs (from d = 0.06, 95% CI (0.01, 0.11) to d = 0.10, 95% CI (0.04, 0.15)) and worry (d = 0.05, 95% CI (-0.01, 0.10)) but not support for public action directly. The updated message is equally effective but provides no added value. Both messages are more effective for audiences with lower message familiarity and higher misperceptions, including those with lower trust in climate scientists and right-leaning ideologies. Overall, scientific consensus messaging is an effective, non-polarizing tool for changing misperceptions, beliefs and worry across different audiences.
- MeSH
- dospělí MeSH
- důvěra MeSH
- klimatické změny * MeSH
- komunikace * MeSH
- konsensus * MeSH
- lidé MeSH
- veřejné mínění MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) is well-established in neuronal function, yet its role in immune reactions remains enigmatic. The conflicting data on its inflammatory role, suggesting both pro-inflammatory and anti-inflammatory effects upon TRPV1 stimulation in immune cells, adds complexity. To unravel TRPV1 immunomodulatory mechanisms, we investigated how the TRPV1 agonist capsaicin influences lipopolysaccharide (LPS)-induced pro-inflammatory macrophage phenotypes. RESULTS: Changes in the surface molecules, cytokine production, and signaling cascades linked to the phenotype of M1 or M2 macrophages of the J774 macrophage cell line and bone marrow-derived macrophages, treated with capsaicin before or after the LPS-induced inflammatory reaction were determined. The functional capacity of macrophages was also assessed by infecting the stimulated macrophages with the intracellular parasite Leishmania mexicana. CONCLUSION: Our findings reveal that TRPV1 activation yields distinct macrophage responses influenced by the inflammatory context. LPS pre-treatment followed by capsaicin activation prompted increased calcium influx, accompanied by a shift toward an anti-inflammatory M2b-like polarization state.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Population health is vital to a nation's overall well-being and development. To achieve sustainable human development, a reduction in health inequalities and an increase in interstate convergence in health indicators is necessary. Evaluation of the convergence patterns can aid the government in monitoring the health progress across the Indian states. This study investigates the progressive changes in the convergence and divergence patterns in health status across major states of India from 1990 to 2018. METHODS: Sigma plots (σ), kernel density plots, and log t-test methods are used to test the convergence, divergence, and club convergence patterns in the health indicators at the state level. RESULTS: The result of the sigma convergence suggests that life expectancy at birth has converged across all states. After 2006, however, the infant mortality rate, neonatal mortality rate, and total fertility rate experienced a divergence pattern. The study's findings indicate that life expectancy at birth converges in the same direction across all states, falling into the same club (Club One). However, considerable cross-state variations and evidence of clubs' convergence and divergence are observed in the domains of infant mortality rate, neonatal death rate, and total fertility rate. As suggested by the kernel density estimates, life expectancy at birth stratifies, polarizes, and becomes unimodal over time, although with a single stable state. A bimodal distribution was found for infant, neonatal, and total fertility rates. CONCLUSIONS: Therefore, healthcare strategies must consider each club's transition path while focusing on divergence states to reduce health variations and improve health outcomes for each group of individuals.
The activity of the immune system is controlled by circadian clocks present in different immune cells. The brain-resident subtype of immune cells, microglia, exhibits a wide range of functional phenotypes depending on the signaling molecules in their microenvironment. The exact role of microglia in the hypothalamic suprachiasmatic nuclei (SCN), the central circadian clock, has not been known. Therefore, the aim of this study was to determine (1) whether microenvironment-induced changes in microglial polarization affect circadian clocks in these cells and (2) whether the presence of microglia contributes to SCN clock function. Microglial and SCN clocks were monitored using PER2-driven bioluminescence rhythms at the tissue and single-cell levels. We found that polarization of resting microglia to a pro-inflammatory (M1) or anti-inflammatory (M2) state significantly altered the period and amplitude of their molecular circadian clock; importantly, the parameters changed plastically with the repolarization of microglia. This effect was reflected in specific modulations of the expression profiles of individual clock genes in the polarized microglia. Depletion of microglia significantly reduced the amplitude of the SCN clock, and co-cultivation of the SCN explants with M2-polarized microglia specifically improved the amplitude of the SCN clock. These results demonstrate that the presence of M2-polarized microglia has beneficial effects on SCN clock function. Our results provide new insight into the mutual interaction between immune and circadian systems in the brain.
- MeSH
- cirkadiánní hodiny * genetika MeSH
- cirkadiánní rytmus fyziologie MeSH
- mikroglie MeSH
- mozek MeSH
- myši MeSH
- nucleus suprachiasmaticus metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
P2X receptors (P2X1-7) are trimeric ion channels activated by extracellular ATP. Each P2X subunit contains two transmembrane helices (TM1 and TM2). We substituted all residues in TM1 of rat P2X7 with alanine or leucine one by one, expressed mutants in HEK293T cells, and examined the pore permeability by recording both membrane currents and fluorescent dye uptake in response to agonist application. Alanine substitution of G27, K30, H34, Y40, F43, L45, M46, and D48 inhibited agonist-stimulated membrane current and dye uptake, and all but one substitution, D48A, prevented surface expression. Mutation V41A partially reduced both membrane current and dye uptake, while W31A and A44L showed reduced dye uptake not accompanied by reduced membrane current. Mutations T28A, I29A, and L33A showed small changes in agonist sensitivity, but they had no or small impact on dye uptake function. Replacing charged residues with residues of the same charge (K30R, H34K, and D48E) rescued receptor function, while replacement with residues of opposite charge inhibited (K30E and H34E) or potentiated (D48K) receptor function. Prolonged stimulation with agonist-induced current facilitation and a leftward shift in the dose-response curve in the P2X7 wild-type and most functional mutants, but sensitization was absent in the W31A, L33A, and A44L. Detailed analysis of the decay of responses revealed two kinetically distinct mechanisms of P2X7 deactivation: fast represents agonist unbinding, and slow might represent resetting of the receptor to the resting closed state. These results indicate that conserved and receptor-specific TM1 residues control surface expression of the P2X7 protein, non-polar residues control receptor sensitization, and D48 regulates intrinsic channel properties.
- MeSH
- adenosintrifosfát farmakologie metabolismus MeSH
- biologický transport MeSH
- HEK293 buňky MeSH
- iontové kanály * metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mutace genetika MeSH
- proteinové domény MeSH
- purinergní receptory P2X7 * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Macrophages exhibit a range of functional pro- and anti-inflammatory states that induce changes in their cellular metabolism. We aimed to elucidate whether these changes affect the molecular properties of their circadian clock focusing on their anti-inflammatory phenotype. Primary cell cultures of bone marrow-derived macrophages (BMDMs; nonpolarized M0 BMDM) from PER2::LUC (fusion protein of PERIOD2 and LUCIFERASE) mice were polarized into the M1 (proinflammatory) or M2 (anti-inflammatory) phenotype, and PER2-driven bioluminescence was recorded in real-time at the cell-population and single-cell levels. Viability, clock gene expression profiles, polarization plasticity and peroxisome proliferator-activated receptor γ (PPARγ) protein levels were analyzed. The effects of pharmacological activation/inhibition of PPARγ (rosiglitazone/GW9662) and inhibition of fatty acid oxidation (FAO) by etomoxir in M2 BMDM cell cultures were examined. The parameters of PER2-driven bioluminescence rhythms differed between M0, M1 and M2 BMDM cultures at cell-population and single-cell levels. Compared with M0, polarization to M2 did not change the period but increased amplitude, mean bioluminescence level and rhythm persistence. Polarization to M1 shortened the period but had no effect on the amplitude of the rhythm. The same period changes were observed after a bidirectional switch between M1- and M2-polarized states in the same culture. Both PPARγ activation/inhibition and FAO inhibition modulated the clock in M2 BMDMs, suggesting metabolic regulation of the M2 clock. Our results indicate that bidirectional changes in the properties of BMDM circadian clocks in response to their actual polarization are mediated via changes in their metabolic state. They provide new information on the interrelationship between the BMDM polarization, their circadian clock and cellular metabolism.
- MeSH
- antiflogistika metabolismus MeSH
- cirkadiánní hodiny * MeSH
- makrofágy metabolismus MeSH
- myši MeSH
- PPAR gama metabolismus MeSH
- rosiglitazon metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lithium is regarded as a unique therapeutic agent for the management of bipolar disorder (BD). In efforts to explain the favourable effects of lithium in BD, a wide range of mechanisms was suggested. Among those, the effect of clinically relevant concentrations of lithium on the plasma membrane was extensively studied. However, the biophysical properties of brain membranes isolated from experimental animals exposed to acute, short-term and chronic lithium have not been performed to-date. In this study, we compared the biophysical parameters and level of lipid peroxidation in membranes isolated from forebrain cortex (FBC) of therapeutic lithium-treated and/or sleep-deprived rats. Lithium interaction with FBC membranes was characterized by appropriate fluorescent probes. DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH (1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulphonate) were used for characterization of the hydrophobic lipid core and Laurdan (6-dodecanoyl-2-dimethylaminonaphthalene) for the membrane-water interface. Lipid peroxidation was determined by immunoblot analysis of 4-HNE-(4-hydroxynonenal)-protein adducts. The organization of polar head-group region of FBC membranes, measured by Laurdan generalized polarization, was substantially altered by sleep deprivation and augmented by lithium treatment. Hydrophobic membrane interior characterized by steady-state anisotropy of DPH and TMA-DPH fluorescence was unchanged. Chronic lithium had a protective effect against peroxidative damage of membrane lipids in FBC. In summary, lithium administration at a therapeutic level and/or sleep deprivation as an animal model of mania resulted in changes in rat FBC membrane properties.
- MeSH
- fluidita membrány účinky léků MeSH
- krysa rodu rattus MeSH
- lipidové dvojvrstvy metabolismus MeSH
- lithium farmakologie MeSH
- membránové lipidy metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- přední mozek účinky léků metabolismus MeSH
- spánková deprivace metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Insulin resistance and cachexia represent severe metabolic syndromes accompanying a variety of human pathological states, from life-threatening cancer and sepsis to chronic inflammatory states, such as obesity and autoimmune disorders. Although the origin of these metabolic syndromes has not been fully comprehended yet, a growing body of evidence indicates their possible interconnection with the acute and chronic activation of an innate immune response. Current progress in insect immuno-metabolic research reveals that the induction of insulin resistance might represent an adaptive mechanism during the acute phase of bacterial infection. In Drosophila, insulin resistance is induced by signaling factors released by bactericidal macrophages as a reflection of their metabolic polarization toward aerobic glycolysis. Such metabolic adaptation enables them to combat the invading pathogens efficiently but also makes them highly nutritionally demanding. Therefore, systemic metabolism has to be adjusted upon macrophage activation to provide them with nutrients and thus support the immune function. That anticipates the involvement of macrophage-derived systemic factors mediating the inter-organ signaling between macrophages and central energy-storing organs. Although it is crucial to coordinate the macrophage cellular metabolism with systemic metabolic changes during the acute phase of bacterial infection, the action of macrophage-derived factors may become maladaptive if chronic or in case of infection by an intracellular pathogen. We hypothesize that insulin resistance evoked by macrophage-derived signaling factors represents an adaptive mechanism for the mobilization of sources and their preferential delivery toward the activated immune system. We consider here the validity of the presented model for mammals and human medicine. The adoption of aerobic glycolysis by bactericidal macrophages as well as the induction of insulin resistance by macrophage-derived factors are conserved between insects and mammals. Chronic insulin resistance is at the base of many human metabolically conditioned diseases such as non-alcoholic steatohepatitis, atherosclerosis, diabetes, and cachexia. Therefore, revealing the original biological relevance of cytokine-induced insulin resistance may help to develop a suitable strategy for treating these frequent diseases.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: The purpose of the study was to evaluate cerebral morphological changes in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and their relationship to the cerebellum. METHODS: The study cohort included 21 patients with intractable TLE-HS (14 left-sided, 7 right-sided) and 38 healthy controls (HC). All patients later underwent anteromedial temporal lobe resection. All subjects were examined using a 1.5-T magnetic resonance imaging (MRI). Volumes of distinct cerebral and cerebellar structures were measured using voxel-based morphometry. The structural covariance of temporal lobe structures, insula, and thalamus with cerebellar substructures was examined using partial least squares regression. RESULTS: Morphological changes were more significant in the group with left TLE-HS when comparing left-sided with right-sided structures as well as when comparing patients with controls. The gray matter volume (GMV) of the temporal lobe structures was smaller ipsilaterally to the seizure onset side in most cases. There was a significant amygdala enlargement contralateral to the side of hippocampal sclerosis in both patients with right and left TLE-HS as compared with controls. Selected vermian structures in patients with left but not right TLE-HS had significantly larger GMV than the identical substructures in controls. The structural covariance differed significantly between patients with left and right TLE-HS as compared with HC. The analysis revealed significant negative covariance between anterior vermis and mesial temporal structures in the group with left TLE-HS. No significance was observed for the group with right TLE-HS. CONCLUSION: There is significant asymmetry in the GMV of cerebral and cerebellar structures in patients with TLE-HS. Morphological changes are distinctly more pronounced in patients with left TLE-HS. The observed structural covariance between the cerebellum and supratentorial structures in TLE-HS suggests associations beyond the mesial temporal lobe structures and thalamus.
- MeSH
- dospělí MeSH
- epilepsie temporálního laloku diagnostické zobrazování chirurgie MeSH
- hipokampus diagnostické zobrazování MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozeček diagnostické zobrazování MeSH
- mozková kůra diagnostické zobrazování MeSH
- šedá hmota diagnostické zobrazování MeSH
- skleróza diagnostické zobrazování chirurgie MeSH
- spánkový lalok diagnostické zobrazování chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Litter decomposition is a vital part of the global carbon cycle as it determines not only the amount of carbon to be sequestered, but also how fast carbon re-enters the cycle. Freshwater systems play an active role in the carbon cycle as it receives, and decomposes, terrestrial litter material alongside decomposing aquatic plant litter. Decomposition of organic matter in the aquatic environment is directly controlled by water temperature and nutrient availability, which are continuously affected by global change. We adapted the Tea Bag Index (TBI), a highly standardized methodology for determining soil decomposition, for lakes by incorporating a leaching factor. By placing Lipton pyramid tea bags in the aquatic environment for 3 h, we quantified the period of intense leaching which usually takes place prior to litter (tea) decomposition. Standard TBI methodology was followed after this step to determine how fast decomposition takes place (decomposition rate, k1) and how much of the material cannot be broken down and is thus sequestered (stabilization factor, S). A Citizen Science project was organized to test the aquatic TBI in 40 European lakes located in four climate zones, ranging from oligotrophic to hypereutrophic systems. We expected that warmer and/or eutrophic lakes would have a higher decomposition rate and a more efficient microbial community resulting in less tea material to be sequestered. The overall high decomposition rates (k1) found confirm the active role lakes play in the global carbon cycle. Across climate regions the lakes in the warmer temperate zone displayed a higher decomposition rate (k1) compared to the colder lakes in the continental and polar zones. Across trophic states, decomposition rates were higher in eutrophic lakes compared to oligotrophic lakes. Additionally, the eutrophic lakes showed a higher stabilization (S), thus a less efficient microbial community, compared to the oligotrophic lakes, although the variation within this group was high. Our results clearly show that the TBI can be used to adequately assess the decomposition process in aquatic systems. Using "alien standard litter" such as tea provides a powerful way to compare decomposition across climates, trophic states and ecosystems. By providing standardized protocols, a website, as well as face to face meetings, we also showed that collecting scientifically relevant data can go hand in hand with increasing scientific and environmental literacy in participants. Gathering process-based information about lake ecosystems gives managers the best tools to anticipate and react to future global change. Furthermore, combining this process-based information with citizen science, thus outreach, is in complete agreement with the Water Framework Directive goals as set in 2010.
- MeSH
- čaj MeSH
- ekosystém * MeSH
- jezera * MeSH
- podnebí MeSH
- uhlík MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
