Signaling-dependent immobilization of acylated proteins in the inner monolayer of the plasma membrane

Phospholipids play a critical role in the recruitment and activation of several adaptors and effectors during phagocytosis. Changes in lipid metabolism during phagocytosis are restricted to the phagocytic cup, the area of the plasmalemma lining the target particle. It is unclear how specific lipids and lipid-associated molecules are prevented from diffusing away from the cup during the course of phagocytosis, a process that often requires several minutes. We studied the mobility of lipid-associated proteins at the phagocytic cup by measuring fluorescence recovery after photobleaching. Lipid-anchored (diacylated) fluorescent proteins were freely mobile in the unstimulated membrane, but their mobility was severely restricted at sites of phagocytosis. Only probes anchored to the inner monolayer displayed reduced mobility, whereas those attached to the outer monolayer were unaffected. The immobilization persisted after depletion of plasmalemmal cholesterol, ruling out a role of conventional “rafts.” Corralling of the probes by the actin cytoskeleton was similarly discounted. Instead, the change in mobility required activation of tyrosine kinases. We suggest that signaling-dependent recruitment of adaptors and effectors with lipid binding domains generates an annulus of lipids with restricted mobility

Insomnia, Psychiatric Disorders and Suicidal Ideation in a National Representative Sample of Active Canadian Forces Members

Background Past research on the association between insomnia and suicidal ideation (SI) has produced mixed findings. The current study explored the relationship between insomnia, SI, and past-year mental health status among a large Canadian Forces (CF) sample. Method Data was obtained from the 2013 Canadian Forces Mental Health Survey (CFMHS), and included a large representative sample of Canadian Regular Forces personnel (N = 6700). A series of univariate logistic regressions were conducted to test individual associations between past-year mental health status, insomnia, and potential confounds and SI. Mental health status included three groups: 0, 1, or two or more probable diagnoses of posttraumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder (PD) and alcohol abuse/dependence. Stepwise multivariate logistic regression was used to assess the relationship between insomnia and SI with mental health status as a moderator. Results 40.8% of respondents reported experiencing insomnia. Both insomnia and number of mental health conditions incrementally increased the risk of SI. However, past-year mental health status was a significant moderator of this relationship, such that for CF personnel with either no (AOR = 1.61, 1.37–1.89) or only one past-year mental health condition (AOR = 1.39, 1.12–1.73), an incremental increase in insomnia was associated with an increased likelihood of SI. However, in personnel with two or more past-year mental health disorders, insomnia was no longer significantly associated with SI (AOR = 1.04, 0.81–1.33). Conclusions Insomnia significantly increased the odds of SI, but only among individuals with no or one mental health condition. Findings highlight the importance of assessing insomnia among CF members in order to further suicide prevention efforts

Atypical neural responses to vocal anger in attention-deficit/hyperactivity disorder

Background Deficits in facial emotion processing, reported in attention-deficit/hyperactivity disorder (ADHD), have been linked to both early perceptual and later attentional components of event-related potentials (ERPs). However, the neural underpinnings of vocal emotion processing deficits in ADHD have yet to be characterised. Here, we report the first ERP study of vocal affective prosody processing in ADHD. Methods Event-related potentials of 6–11-year-old children with ADHD (n = 25) and typically developing controls (n = 25) were recorded as they completed a task measuring recognition of vocal prosodic stimuli (angry, happy and neutral). Audiometric assessments were conducted to screen for hearing impairments. Results Children with ADHD were less accurate than controls at recognising vocal anger. Relative to controls, they displayed enhanced N100 and attenuated P300 components to vocal anger. The P300 effect was reduced, but remained significant, after controlling for N100 effects by rebaselining. Only the N100 effect was significant when children with ADHD and comorbid conduct disorder (n = 10) were excluded. Conclusion This study provides the first evidence linking ADHD to atypical neural activity during the early perceptual stages of vocal anger processing. These effects may reflect preattentive hyper-vigilance to vocal anger in ADHD

Colonoscopic screening for colorectal cancer improves quality of life measures: a population-based screening study

BACKGROUND: Screening asymptomatic individuals for neoplasia can have adverse consequences on quality of life. Colon cancer screening is widespread but the quality of life (QOL) consequences are unknown. This study determined the impact of screening colonoscopy on QOL measures in asymptomatic average-risk participants. METHODS: Asymptomatic male and female participants aged 55–74 years were randomly selected from the Australian Electoral Roll or six primary care physicians' databases. Participants completed the Short-Form (SF-36) Quality of Life Assessment at baseline and at a mean of 39 days after colonoscopy. Outcome measures were (i) significant changes in raw scores in any of the eight SF-36 domains assessed following colonoscopic screening and (ii) improvements or declines in previously validated categories, representing clinically significant changes, within any of the eight SF-36 domains. RESULTS: Baseline QOL measures were similar to those of a matched general population sample. Role Limitations due to Emotions, Mental Health and Vitality raw scores significantly improved following colonoscopy (P < 0.05, 2-tailed t-test). Health ratings according to Category were similar (same clinical status) in the majority of participants. However, 30% participants recorded clinically significant improvement in the Mental Health and Vitality domains (P < 0.05, Wilcoxon Signed-Ranks test). This improvement was not offset by declines in other domains or in other participants. Improvement in QOL was not related to colonoscopy results. CONCLUSION: Average-risk persons benefit significantly from colon cancer screening with colonoscopy, improving in Mental Health and Vitality domains of Quality of Life. This improvement is not offset by declines in other domains

The cosmological evolution of quasar black-hole masses

Virial black-hole mass estimates are presented for 12698 quasars in the redshift interval 0.1<z<2.1, based on modelling of spectra from the Sloan Digital Sky Survey (SDSS) first data release. The black-hole masses of the SDSS quasars are found to lie between \simeq10^{7}\Msun and an upper limit of \simeq 3\times 10^{9}\Msun, entirely consistent with the largest black-hole masses found to date in the local Universe. The estimated Eddington ratios of the broad-line quasars (FWHM\geq 2000 kms^{-1}) show a clear upper boundary at $L_{bol}/L_{Edd}\simeq 1$, suggesting that the Eddington luminosity is still a relevant physical limit to the accretion rate of luminous broad-line quasars at $z\leq 2$. By combining the black-hole mass distribution of the SDSS quasars with the 2dF quasar luminosity function, the number density of active black holes at $z\simeq 2$ is estimated as a function of mass. In addition, we independently estimate the local black-hole mass function for early-types using the $M_{bh}-\sigma$ and $M_{bh}-L_{bulge}$ correlations. Based on the SDSS velocity dispersion function and the 2MASS $K-$band luminosity function, both estimates are found to be consistent at the high-mass end (M_{bh}\geq 10^{8}\Msun). By comparing the estimated number density of active black holes at $z\simeq 2$ with the local mass density of dormant black holes, we set lower limits on the quasar lifetimes and find that the majority of black holes with mass \geq 10^{8.5}\Msun are in place by $\simeq 2$.Comment: 15 pages, 10 figures, revised version, accepted for publication by MNRA

A randomized clinical trial on the effects of progestin contraception in the genital tract of HIV-infected and uninfected women in Lilongwe, Malawi: Addressing evolving research priorities

Hormonal contraception is central in the prevention of unintended pregnancy; however there are concerns that certain methods may increase the risk of HIV acquisition and transmission. Hormonal contraceptives may modify the genital mucosa in several ways, however the mechanisms are incompletely understood. Few studies have examined genital HIV shedding prospectively before and after initiation of hormonal contraception. The effects of hormonal contraception on genital HIV shedding in the setting of antiretroviral therapy (ART) are also unknown. We designed a pilot clinical trial in which HIV-infected and uninfected women were randomized to either depot medroxyprogesterone acetate (DMPA) injectable or levonorgestrel (LNG) implant in Lilongwe, Malawi. The objectives were to: 1) assess the effect and compare the impact of type of progestin contraception (injectable versus implant) on HIV genital shedding among HIV-infected women, 2) assess the effect and compare the impact of type of progestin contraception on inflammatory/immune markers in the genital tract of both HIV-infected and uninfected women, and 3) assess the interaction of progestin contraception and ART by examining contraceptive efficacy and ART efficacy. An additional study aim was to determine the feasibility and need for a larger study of determinants of HIV transmissibility and acquisition