Highlights • TRPA1 mediates acute muscle mechanical hypersensitivity induced by ATP and glutamate. • TRPA1 contributes to the maintenance of mechanical hypersensitivity under a myositis condition. • ...TRPA1 contributes to the maintenance of spontaneous muscle pain under a myositis condition. • Inflammation in the masseter muscle significantly up-regulates TRPA1 expression in trigeminal ganglia.
Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying ...LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth modulates TRPV1 in trigeminal nociceptors. By assessing the levels of protein and transcript of TRPV1 in mouse trigeminal ganglia, we demonstrate that dentinal application of LPS increases the expression of TRPV1. Our results suggest that the up-regulation of TRPV1 in trigeminal nociceptors following bacterial infection could contribute to hyperalgesia under pulpitis conditions.
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Material corrosion is one of the outstanding challenging problems in the industry, and it strongly influences refining and petrochemical plants lifetime. Therefore, prevention of the ...corrosion of different metals and alloys is imperative in the viewpoint of industrial safety and productivity. For this purpose, the application of suitable corrosion inhibitors is one of the most applicable solutions. The present paper focuses on the anticorrosive properties of three biologically active chalcones, namely (E)-2-(4-(3-(2,5 dimethoxyphenyl)acryloyl) phenoxy)acetic acid (AA-3), 2-(4-(3-(4-methoxyphenyl)propanoyl)phenoxy)acetic acid (AA-2) and (E)-2-(4-(3-(p-tolyl)acryloyl)phenoxy)acetic acid (AA-1) for mild steel in hydrochloric acid at temperature range 303−333 K. The corrosion inhibition performances of chalcones were evaluated by electrochemical tests, gravimetrical method, SEM, molecular orbital theory and molecular dynamics (MD) simulations. Results show that at the concentration of 5 × 10−3 molL-1, chalcone derivatives show high corrosion inhibition activities. All compounds are found to act via adsorption at the metal/solution interface, and their adsorption follows Langmuir isotherm model. Electrochemical tests indicate that the three chalcones act as mixed-type inhibitors. The thermodynamic data of adsorption were determined and discussed. Density Functional Theory (DFT) and MD simulations were used to assess the active sites of adsorption of the three inhibitors and their interaction with the iron surface, respectively. Scanning electron microscope (SEM) was used to analyze the surface morphological changes that chalcones induce in the corroded mild steel. The comparison of experimental results with theoretical data indicates that methoxy functional groups have a considerable influence on the anticorrosive properties of tested chalcones.
Life events refer to status changes in important demographic variables, such as employment or marital status. Life events offer an interesting opportunity for studying transactions between ...environmental changes and personality traits, which are of relevance for diverging theories about the role of environmental factors in life span personality development. Yet in spite of the potential importance of life events for personality development, nuanced and sufficiently powered longitudinal designs with frequent assessments of life events and personality traits are lacking. The current study aims to address this gap by examining the associations between different life events and personality trait change, using data from a large, nationally representative, and prospective longitudinal study. Results demonstrated a number of selection effects, indicating that personality traits affect the likelihood that individuals experience certain types of life events. Less frequently, results indicated average effects of life events on personality trait development, both in anticipation of a life event change as well as resulting from it. However, some of these event-related changes ran counter to the notion that personality maturity increases as a result of adopting mature social roles, like parenthood or paid employment. Furthermore, we found significant variation around average event-related trajectories, suggesting that individuals differ in their reactions to life events. Theoretical implications and recommendations for future research are discussed.
IgE antibodies may elicit potent allergic reactions, and their production is tightly controlled. The tendency to generate IgE has been thought to reflect the balance between type 1 and type 2 ...cytokines, with the latter promoting IgE. Here, we reevaluated this paradigm by a direct cellular analysis, demonstrating that IgE production was not limited to type 2 immune responses yet was generally constrained in vivo. IL-21 was a critical negative regulator of IgE responses, whereas IFN-γ, IL-6, and IL-10 were dispensable. Follicular helper T cells were the primary source of IL-21 that inhibited IgE responses by directly engaging the IL-21 receptor on B cells and triggering STAT3-dependent signaling. We reconciled previous discordant results between mouse and human B cells and revealed that the inhibition of IgE class switch recombination by IL-21 was attenuated by CD40 signaling, whereas IgG1 class switch recombination was potentiated by IL-21 in the context of limited IL-4. These findings establish key features of the extrinsic regulation of IgE production by cytokines.
Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential ...contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance.
Holding information in working memory (WM) is an active and effortful process that is accompanied by sustained load-dependent changes in oscillatory brain activity. These proportional power increases ...are often reported in EEG studies recording theta over frontal midline sites. Intracranial recordings, however, yield mixed results, depending on the brain area being recorded from. We recorded intracranial EEG with depth electrodes in 13 patients with epilepsy who were performing a Sternberg WM task. Here, we investigated patterns of theta power changes as a function of memory load during maintenance in three areas critical for WM: dorsolateral prefrontal cortex (DLPFC), dorsal ACC (dACC), and hippocampus. Theta frequency power in both hippocampus and dACC increased during maintenance. In contrast, theta frequency power in the DLPFC decreased during maintenance, and this decrease was proportional to memory load. Only the power decreases in DLPFC, but not the power increases in hippocampus and dACC, were predictive of behavior in a given trial. The extent of the load-related theta power decreases in the DLPFC in a given participant predicted a participant's RTs, revealing that DLPFC theta explains individual differences in WM ability between participants. Together, these data reveal a pattern of theta power decreases in the DLPFC that is predictive of behavior and that is opposite of that in other brain areas. This result suggests that theta band power changes serve different cognitive functions in different brain areas and specifically that theta power decreases in DLPFC have an important role in maintenance of information.
Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality. Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a ...disorder affecting 1:15,000-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci. Here we show that the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated.
Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a ...crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD.
To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD.
A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated.
The intervention group had a significantly lower incidence of BPD or death (55 of 131 42.0% vs. 89 of 134 66%; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days.
In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).
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