Attenuated maladaptive emotion processing as a potential mediator of the relationship between dispositional mindfulness and mental health

The emotion processing and regulation mechanisms by which dispositional (personality trait) mindfulness exerts its positive effects on mental health remain unclear. Here, we tested, using structural equation modeling, whether the relationship between higher dispositional mindfulness and better mental health is mediated by reduced maladaptive processing of emotional information (e.g., expressive suppression, impoverished emotional experiences, unprocessed emotions, avoidance, externalizing strategies) and associated lower negative affect, enhanced adaptive processing of emotional information (e.g., cognitive reappraisal) and associated higher positive affect, or a combination of these two emotion processing styles. Dispositional mindfulness, mental health, diverse emotional constructs with adaptive and maladaptive dimensions (including range and differentiation of emotional experiences, use of specific emotion regulation strategies, emotion processing deficits, negative affect repair strategies, negative mood regulation expectancies), and positive and negative affect were assessed using self-report measures in a non-clinical sample of 256 adults. The relationship between higher dispositional mindfulness and better mental health was found to be best explained by reduced maladaptive emotion processing styles and associated lower negative affect, rather than by enhanced adaptive emotion processing and higher positive affect. Further research should investigate whether the same mechanisms explain psychological benefits of cultivated mindfulness in people with low dispositional mindfulness and/or with mental health disorders following mindfulness skills training.Bial Foundation (92/18; awarded to VK and RP) and the Indian Council of Medical Research (3/1/3-ICMR-JRF/2011/HRD/12/81003; awarded to SPM)

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

On the possibility of a terahertz light emitting diode based on a dressed quantum well

We consider theoretically the realization of a tunable terahertz light emitting diode from a quantum well with dressed electrons placed in a highly doped p-n junction. In the considered system the strong resonant dressing field forms dynamic Stark gaps in the valence and conduction bands and the electric field inside the p-n junction makes the QW asymmetric. It is shown that the electrons transiting through the light induced Stark gaps in the conduction band emit photons with energy directly proportional to the dressing field. This scheme is tunable, compact, and shows a fair efficiency.Comment: 6 pages, 5 figure

Neurocognitive functioning in acute or early HIV infection

We examined neurocognitive functioning among persons with acute or early HIV infection (AEH) and hypothesized that the neurocognitive performance of AEH individuals would be intermediate between HIV seronegatives (HIV−) and those with chronic HIV infection. Comprehensive neurocognitive testing was accomplished with 39 AEH, 63 chronically HIV infected, and 38 HIV− participants. All AEH participants were HIV infected for less than 1 year. Average domain deficit scores were calculated in seven neurocognitive domains. HIV−, AEH, and chronically HIV infected groups were ranked from best (rank of 1) to worst (rank of 3) in each domain. All participants received detailed substance use, neuromedical, and psychiatric evaluations and HIV infected persons provided information on antiretroviral treatment and completed laboratory evaluations including plasma and CSF viral loads. A nonparametric test of ordered alternatives (Page test), and the appropriate nonparametric follow-up test, was used to evaluate level of neuropsychological (NP) functioning across and between groups. The median duration of infection for the AEH group was 16 weeks [interquartile range, IQR: 10.3–40.7] as compared to 4.9 years [2.8–11.1] in the chronic HIV group. A Page test using ranks of average scores in the seven neurocognitive domains showed a significant monotonic trend with the best neurocognitive functioning in the HIV− group (mean rank = 1.43), intermediate neurocognitive functioning in the AEH group (mean rank = 1.71), and the worst in the chronically HIV infected (mean rank = 2.86; L statistic = 94, p < 0.01); however, post-hoc testing comparing neurocognitive impairment of each group against each of the other groups showed that the chronically infected group was significantly different from both the HIV− and AEH groups on neurocognitive performance; the AEH group was statistically indistinguishable from the HIV− group. Regression models among HIV infected participants were unable to identify significant predictors of neurocognitive performance. Neurocognitive functioning was worst among persons with chronic HIV infection. Although a significant monotonic trend existed and patterns of the data suggest the AEH individuals may fall intermediate to HIV− and chronic participants, we were not able to statistically confirm this hypothesis

Detecting single viruses and nanoparticles using whispering gallery microlasers

Detection and characterization of individual nano-scale particles, virions, and pathogens are of paramount importance to human health, homeland security, diagnostic and environmental monitoring[1]. There is a strong demand for high-resolution, portable, and cost-effective systems to make label-free detection and measurement of individual nanoparticles, molecules, and viruses [2-6]. Here, we report an easily accessible, real-time and label-free detection method with single nanoparticle resolution that surpasses detection limit of existing micro- and nano-photonic devices. This is achieved by using an ultra-narrow linewidth whispering gallery microlaser, whose lasing line undergoes frequency splitting upon the binding of individual nano-objects. We demonstrate detection of polystyrene and gold nanoparticles as small as 15 nm and 10 nm in radius, respectively, and Influenza A virions by monitoring changes in self-heterodyning beat note of the split lasing modes. Experiments are performed in both air and aqueous environment. The built-in self-heterodyne interferometric method achieved in a microlaser provides a self-reference scheme with extraordinary sensitivity [7,8], and paves the way for detection and spectroscopy of nano-scale objects using micro- and nano-lasers.Comment: Main Text: 14 pages, 5 figures, 27 references. Supplement: 26 pages, 12 figures, 26 reference

Developing and testing a measure of consultation-based reassurance for people with low back pain in primary care:a cross-sectional study

BACKGROUND: Reassurance from physicians is commonly recommended in guidelines for the management of low back pain (LBP), but the process of reassurance and its impact on patients is poorly researched. We aimed to develop a valid and reliable measure of the process of reassurance during LBP consultations. METHODS: Items representing the data-gathering stage of the consultation and affective and cognitive reassurance were generated from literature on physician-patient communication and piloted with expert researchers and physicians, a Patient and Public Involvement group, and LBP patients to form a questionnaire. Patients presenting for LBP at 43 General Practice surgeries were sent the questionnaire. The questionnaire was analysed with Rasch modelling, using two samples from the same population of recent LBP consultations: the first (n = 157, follow-up n = 84) for exploratory analysis and the second (n = 162, follow-up n = 74) for confirmatory testing. Responses to the questionnaire were compared with responses to satisfaction and enablement scales to assess the external validity of the items, and participants completed the questionnaire again one-week later to assess test-retest reliability. RESULTS: The questionnaire was separated into four subscales: data-gathering, relationship-building, generic reassurance, and cognitive reassurance, each containing three items. All subscales showed good validity within the Rasch models, and good reliability based on person- and item-separations and test-retest reliability. All four subscales were significantly positively correlated with satisfaction and enablement for both samples. The final version of the questionnaire is presented here. CONCLUSIONS: Overall, the measure has demonstrated a good level of validity and generally acceptable reliability. This is the first measure to focus specifically on reassurance for LBP in primary care settings, and will enable researchers to further understanding of what is reassuring within the context of low back pain consultations, and how outcomes are affected by different types of reassurance. Additionally, the measure may provide a useful training and audit tool for physicians. The new measure requires testing in prospective cohorts, and would benefit from further validation against ethnographic observation of consultations in real time

Biocontrol of larval mosquitoes by Acilius sulcatus (Coleoptera: Dytiscidae)

<p>Abstract</p> <p>Background</p> <p>Problems associated with resistant mosquitoes and the effects on non-target species by chemicals, evoke a reason to find alternative methods to control mosquitoes, like the use of natural predators. In this regard, aquatic coleopterans have been explored less compared to other insect predators. In the present study, an evaluation of the role of the larvae of <it>Acilius sulcatus </it>Linnaeus 1758 (Coleoptera: Dytiscidae) as predator of mosquito immatures was made in the laboratory. Its efficacy under field condition was also determined to emphasize its potential as bio-control agent of mosquitoes.</p> <p>Methods</p> <p>In the laboratory, the predation potential of the larvae of <it>A. sulcatus </it>was assessed using the larvae of <it>Culex quinquefasciatus </it>Say 1823 (Diptera: Culicidae) as prey at varying predator and prey densities and available space. Under field conditions, the effectiveness of the larvae of <it>A. sulcatus </it>was evaluated through augmentative release in ten cemented tanks hosting immatures of different mosquito species at varying density. The dip density changes in the mosquito immatures were used as indicator for the effectiveness of <it>A. sulcatus </it>larvae.</p> <p>Results</p> <p>A single larva of <it>A. sulcatus </it>consumed on an average 34 IV instar larvae of <it>Cx. quinquefasciatus </it>in a 24 h period. It was observed that feeding rate of <it>A. sulcatus </it>did not differ between the light-on (6 a.m. – 6 p.m.), and dark (6 p.m. – 6 a.m.) phases, but decreased with the volume of water i.e., space availability. The prey consumption of the larvae of <it>A. sulcatus </it>differed significantly (P < 0.05) with different prey, predator and volume combinations, revealed through univariate ANOVA. The field study revealed a significant decrease (p < 0.05) in larval density of different species of mosquitoes after 30 days from the introduction of <it>A. sulcatus </it>larvae, while with the withdrawal, a significant increase (p < 0.05) in larval density was noted indicating the efficacy of <it>A. sulcatus </it>in regulating mosquito immatures. In the control tanks, mean larval density did not differ (p > 0.05) throughout the study period.</p> <p>Conclusion</p> <p>the larvae of the dytiscid beetle <it>A. sulcatus </it>proved to be an efficient predator of mosquito immatures and may be useful in biocontrol of medically important mosquitoes.</p

Regulation of Human Formyl Peptide Receptor 1 Synthesis: Role of Single Nucleotide Polymorphisms, Transcription Factors, and Inflammatory Mediators

The gene encoding the human formyl peptide receptor 1 (FPR1) is heterogeneous, containing numerous single nucleotide polymorphisms (SNPs). Here, we examine the effect of these SNPs on gene transcription and protein translation. We also identify gene promoter sequences and putative FPR1 transcription factors. To test the effect of codon bias and codon pair bias on FPR1 expression, four FPR1 genetic variants were expressed in human myeloid U937 cells fused to a reporter gene encoding firefly luciferase. No significant differences in luciferase activity were detected, suggesting that the translational regulation and protein stability of FPR1 are modulated by factors other than the SNP codon bias and the variant amino acid properties. Deletion and mutagenesis analysis of the FPR1 promoter showed that a CCAAT box is not required for gene transcription. A −88/41 promoter construct resulted in the strongest transcriptional activity, whereas a −72/41 construct showed large reduction in activity. The region between −88 and −72 contains a consensus binding site for the transcription factor PU.1. Mutagenesis of this site caused significant reduction in reporter gene expression. The PU.1 binding was confirmed in vivo by chromatin immunoprecipitation, and the binding to nucleotides −84 to −76 (TTCCTATTT) was confirmed in vitro by an electrophoretic mobility shift assay. Thus, similar to many other myeloid genes, FPR1 promoter activity requires PU.1. Two single nucleotide polymorphisms at −56 and −54 did not significantly affect FPR1 gene expression, despite differences in binding of transcription factor IRF1 in vitro. Inflammatory mediators such as interferon-γ, tumor necrosis factor-α, and lipopolysaccharide did not increase FPR1 promoter activity in myeloid cells, whereas differentiation induced by DMSO and retinoic acid enhanced the activity. This implies that the expression of FPR1 in myeloid cells is developmentally regulated, and that the differentiated cells are equipped for immediate response to microbial infections

Tumor-Shed PGE2 Impairs IL2Rγc-Signaling to Inhibit CD4+ T Cell Survival: Regulation by Theaflavins

BACKGROUND:Many tumors are associated with decreased cellular immunity and elevated levels of prostaglandin E2 (PGE2), a known inhibitor of CD4+ T cell activation and inducer of type-2 cytokine bias. However, the role of this immunomodulator in the survival of T helper cells remained unclear. Since CD4+ T cells play critical roles in cell-mediated immunity, detail knowledge of the effect tumor-derived PGE2 might have on CD4+ T cell survival and the underlying mechanism may, therefore, help to overcome the overall immune deviation in cancer. METHODOLOGY/PRINCIPAL FINDINGS:By culturing purified human peripheral CD4+ T cells or Jurkat cells with spent media of theaflavin- or celecoxib-pre-treated MCF-7 cells, we show that tumor-shed PGE2 severely impairs interleukin 2 receptor gammac (IL2Rgammac)-mediated survival signaling in CD4+ T cells. Indeed, tumor-shed PGE2 down-regulates IL2Rgammac expression, reduces phosphorylation as well as activation of Janus kinase 3 (Jak-3)/signal transducer and activator of transcription 5 (Stat-5) and decreases Bcl-2/Bax ratio thereby leading to activation of intrinsic apoptotic pathway. Constitutively active Stat-5A (Stat-5A1 6) over-expression efficiently elevates Bcl-2 levels in CD4+ T cells and protects them from tumor-induced death while dominant-negative Stat-5A over-expression fails to do so, indicating the importance of Stat-5A-signaling in CD4+ T cell survival. Further support towards the involvement of PGE2 comes from the results that (a) purified synthetic PGE2 induces CD4+ T cell apoptosis, and (b) when knocked out by small interfering RNA, cyclooxygenase-2 (Cox-2)-defective tumor cells fail to initiate death. Interestingly, the entire phenomena could be reverted back by theaflavins that restore cytokine-dependent IL2Rgammac/Jak-3/Stat-5A signaling in CD4+ T cells thereby protecting them from tumor-shed PGE2-induced apoptosis. CONCLUSIONS/SIGNIFICANCE:These data strongly suggest that tumor-shed PGE2 is an important factor leading to CD4+ T cell apoptosis during cancer and raise the possibility that theaflavins may have the potential as an effective immunorestorer in cancer-bearer

Hypoxia-Induced Invadopodia Formation Involves Activation of NHE-1 by the p90 Ribosomal S6 Kinase (p90RSK)

The hypoxic and acidic microenvironments in tumors are strongly associated with malignant progression and metastasis, and have thus become a central issue in tumor physiology and cancer treatment. Despite this, the molecular links between acidic pH- and hypoxia-mediated cell invasion/metastasis remain mostly unresolved. One of the mechanisms that tumor cells use for tissue invasion is the generation of invadopodia, which are actin-rich invasive plasma membrane protrusions that degrade the extracellular matrix. Here, we show that hypoxia stimulates the formation of invadopodia as well as the invasive ability of cancer cells. Inhibition or shRNA-based depletion of the Na+/H+ exchanger NHE-1, along with intracellular pH monitoring by live-cell imaging, revealed that invadopodia formation is associated with alterations in cellular pH homeostasis, an event that involves activation of the Na+/H+ exchange rate by NHE-1. Further characterization indicates that hypoxia triggered the activation of the p90 ribosomal S6 kinase (p90 RSK), which resulted in invadopodia formation and site-specific phosphorylation and activation of NHE-1. This study reveals an unsuspected role of p90RSK in tumor cell invasion and establishes p90RS kinase as a link between hypoxia and the acidic microenvironment of tumors