636 research outputs found
Innate Immunity in the C. elegans Intestine Is Programmed by a Neuronal Regulator of AWC Olfactory Neuron Development
Olfactory neurons allow animals to discriminate nutritious food sources from potential pathogens. From a forward genetic screen, we uncovered a surprising requirement for the olfactory neuron gene olrn-1 in the regulation of intestinal epithelial immunity in Caenorhabditis elegans. During nematode development, olrn-1 is required to program the expression of odorant receptors in the AWC olfactory neuron pair. Here, we show that olrn-1 also functions in AWC neurons in the cell non-autonomous suppression of the canonical p38 MAPK PMK-1 immune pathway in the intestine. Low activity of OLRN-1, which activates the p38 MAPK signaling cassette in AWC neurons during larval development, also de-represses the p38 MAPK PMK-1 pathway in the intestine to promote immune effector transcription, increased clearance of an intestinal pathogen, and resistance to bacterial infection. These data reveal an unexpected connection between olfactory receptor development and innate immunity and show that anti-pathogen defenses in the intestine are developmentally programmed
The Lick AGN Monitoring Project: Broad-Line Region Radii and Black Hole Masses from Reverberation Mapping of Hbeta
We have recently completed a 64-night spectroscopic monitoring campaign at
the Lick Observatory 3-m Shane telescope with the aim of measuring the masses
of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected
masses in the range ~10^6-10^7 M_sun and also the well-studied nearby active
galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including
NGC 5548) showed optical variability of sufficient strength during the
monitoring campaign to allow for a time lag to be measured between the
continuum fluctuations and the response to these fluctuations in the broad
Hbeta emission. We present here the light curves for the objects in this sample
and the subsequent Hbeta time lags for the nine objects where these
measurements were possible. The Hbeta lag time is directly related to the size
of the broad-line region, and by combining the lag time with the measured width
of the Hbeta emission line in the variable part of the spectrum, we determine
the virial mass of the central supermassive black hole in these nine AGNs. The
absolute calibration of the black hole masses is based on the normalization
derived by Onken et al. We also examine the time lag response as a function of
velocity across the Hbeta line profile for six of the AGNs. The analysis of
four leads to ambiguous results with relatively flat time lags as a function of
velocity. However, SBS 1116+583A exhibits a symmetric time lag response around
the line center reminiscent of simple models for circularly orbiting broad-line
region (BLR) clouds, and Arp 151 shows an asymmetric profile that is most
easily explained by a simple gravitational infall model. Further investigation
will be necessary to fully understand the constraints placed on physical models
of the BLR by the velocity-resolved response in these objects.Comment: 24 pages, 16 figures and 13 tables, submitted to Ap
The Lick AGN Monitoring Project: Reverberation Mapping of Optical Hydrogen and Helium Recombination Lines
We have recently completed a 64-night spectroscopic monitoring campaign at
the Lick Observatory 3-m Shane telescope with the aim of measuring the masses
of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected
masses in the range ~10^6-10^7M_sun and also the well-studied nearby active
galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including
NGC 5548) showed optical variability of sufficient strength during the
monitoring campaign to allow for a time lag to be measured between the
continuum fluctuations and the response to these fluctuations in the broad
Hbeta emission, which we have previously reported. We present here the light
curves for the Halpha, Hgamma, HeII 4686, and HeI 5876 emission lines and the
time lags for the emission-line responses relative to changes in the continuum
flux. Combining each emission-line time lag with the measured width of the line
in the variable part of the spectrum, we determine a virial mass of the central
supermassive black hole from several independent emission lines. We find that
the masses are generally consistent within the uncertainties. The time-lag
response as a function of velocity across the Balmer line profiles is examined
for six of the AGNs. Finally we compare several trends seen in the dataset
against the predictions from photoionization calculations as presented by
Korista & Goad. We confirm several of their predictions, including an increase
in responsivity and a decrease in the mean time lag as the excitation and
ionization level for the species increases. Further confirmation of
photoionization predictions for broad-line gas behavior will require additional
monitoring programs for these AGNs while they are in different luminosity
states. [abridged]Comment: 37 pages, 18 figures and 15 tables, accepted for publication in the
Astrophysical Journa
Drunk bugs: chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice
The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N = 10) or air (Control, N = 9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (p < 0.05) and beta (p < 0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p < 0.001) and significant reductions in genra Clostridium IV and XIVb (p < 0.001), Dorea (p < 0.01), and Coprococcus (p < 0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress
Risk of nonalcoholic fatty liver disease and associations with gastrointestinal cancers
Metabolic syndrome may contribute to the rising incidence of multiple gastrointestinal (GI) cancers in recent birth cohorts. However, other than hepatocellular carcinoma, the association between nonalcoholic fatty liver disease (NAFLD) and risk of non-liver GI cancers is unexplored. We prospectively examined the associations of NAFLD risk with GI cancers among 319,290 participants in the UK Biobank (2006-2019). Baseline risk for NAFLD was estimated using the Dallas Steatosis Index, a validated prediction tool. Multivariable Cox models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) according to NAFLD risk categories: low (\u3c20%), intermediate (20%-49%), and high (â„50%). We also examined the associations by age of cancer diagnosis (earlier onset [\u3c60] vs. â„60). A total of 273 incident liver cancer and 4789 non-liver GI cancer cases were diagnosed. Compared with individuals at low risk for NAFLD, those at high risk had 2.41-fold risk of liver cancer (RR = 2.41, 95% CI: 1.73-3.35) and 23% increased risk of non-liver GI cancers (RR = 1.23, 95% CI: 1.14-1.32) (all
The Quasar Accretion Disk Size - Black Hole Mass Relation
We use the microlensing variability observed for nine gravitationally lensed
quasars to show that the accretion disk size at 2500 Angstroms is related to
the black hole mass by log(R_2500/cm) = (15.6+-0.2) +
(0.54+-0.28)log(M_BH/10^9M_sun). This scaling is consistent with the
expectation from thin disk theory (R ~ M_BH^(2/3)), but it implies that black
holes radiate with relatively low efficiency, log(eta) = -1.29+-0.44 +
log(L/L_E) where eta=L/(Mdot c^2). These sizes are also larger, by a factor of
~3, than the size needed to produce the observed 0.8 micron quasar flux by
thermal radiation from a thin disk with the same T ~ R^(-3/4) temperature
profile. More sophisticated disk models are clearly required, particularly as
our continuing observations improve the precision of the measurements and yield
estimates of the scaling with wavelength and accretion rate.Comment: 5 pages, 3 figures, submitted to ApJ
Effectiveness of moving on: an Australian designed generic self-management program for people with a chronic illness
Background: This paper presents the evaluation of âMoving Onâ, a generic self-management program for people with a chronic illness developed by Arthritis NSW. The program aims to help participants identify their need for behavior change and acquire the knowledge and skills to implement changes that promote their health and quality of life.
Method: A prospective pragmatic randomised controlled trial involving two group programs in community settings: the intervention program (Moving On) and a control program (light physical activity). Participants were recruited by primary health care providers across the north-west region of metropolitan Sydney, Australia between June 2009 and October 2010. Patient outcomes were self-reported via pre- and post-program surveys completed at the time of enrolment and sixteen weeks after program commencement. Primary outcomes were change in self-efficacy (Self-efficacy for Managing Chronic Disease 6-Item Scale), self-management knowledge and behaviour and perceived health status (Self-Rated Health Scale and the Health Distress Scale).
Results: A total of 388 patient referrals were received, of whom 250 (64.4%) enrolled in the study. Three patients withdrew prior to allocation. 25 block randomisations were performed by a statistician external to the research team: 123 patients were allocated to the intervention program and 124 were allocated to the control program. 97 (78.9%) of the intervention participants commenced their program. The overall attrition rate of 40.5% included withdrawals from the study and both programs. 24.4% of participants withdrew from the intervention program but not the study and 22.6% withdrew from the control program but not the study. A total of 62 patients completed the intervention program and follow-up evaluation survey and 77 patients completed the control program and follow- up evaluation survey.
At 16 weeks follow-up there was no significant difference between intervention and control groups in self-efficacy; however, there was an increase in self-efficacy from baseline to follow-up for the intervention participants (t=â1.948, p=0.028). There were no significant differences in self-rated health or health distress scores between groups at follow-up, with both groups reporting a significant decrease in health distress scores. There was no significant difference between or within groups in self-management knowledge and stage of change of behaviours at follow-up. Intervention group attenders had significantly higher physical activity (t=â4.053, p=0.000) and nutrition scores (t=2.315, p= 0.01) at follow-up; however, these did not remain significant after adjustment for covariates.
At follow-up, significantly more participants in the control group (20.8%) indicated that they did not have a self-management plan compared to those in the intervention group (8.8%) (X2=4.671, p=0.031). There were no significant changes in other self-management knowledge areas and behaviours after adjusting for covariates at follow-up.
Conclusions: The study produced mixed findings. Differences between groups as allocated were diluted by the high proportion of patients not completing the program. Further monitoring and evaluation are needed of the impact and cost effectiveness of the program.
Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN1260900029821
Managerial Work in a Practice-Embodying Institution - The role of calling, the virtue of constancy
What can be learned from a small scale study of managerial work in a highly marginal and under-researched working community? This paper uses the âgoods-virtues-practices-institutionsâ framework to examine the managerial work of owner-directors of traditional circuses. Inspired by MacIntyreâs arguments for the necessity of a narrative understanding of the virtues, interviews explored how British and Irish circus directors accounted for their working lives. A purposive sample was used to select subjects who had owned and managed traditional touring circuses for at least 15 years, a period in which the economic and reputational fortunes of traditional circuses have suffered badly. This sample enabled the research to examine the self-understanding of people who had, at least on the face of it, exhibited the virtue of constancy. The research contributes to our understanding of the role of the virtues in organizations by presenting evidence of an intimate relationship between the virtue of constancy and a âcallingâ work orientation. This enhances our understanding of the virtues that are required if management is exercised as a domain-related practice
Impact of water filling on terminal ileum intubation with a distal-tip mucosal exposure device
Background and Aims
Endocuff improves detection at colonoscopy but seems to impede terminal ileal (TI) intubation. We assessed the impact of Endocuff Vision (EV) on TI intubation using adult or pediatric colonoscopes and evaluated whether filling the cecum with gas versus water affected the impact of EV on TI intubation.
Methods
Using a prospectively recorded quality control database, we explored the impact of EV on TI intubation in â€1 minute. We used adult and pediatric colonoscopes and tested the effect of filling the cecum with gas versus water. If the initial attempt failed, then the alternative (water vs gas) was tried as a rescue method.
Results
TI intubation in â€1 minute occurred in 91% of colonoscopies without EV versus 65% with EV, but the use of the pediatric colonoscope with EV had a higher success rate for TI intubation in â€1 minute compared with the adult colonoscope with EV (73% vs 57%, P = .043). TI intubation in â€1 minute was more successful with EV when the cecum was filled with water rather than gas (74% vs 56%, P = .019), but the benefit of water filling was limited to the adult colonoscope with EV. When EV was in place, water filling was more successful as a rescue method of TI intubation (58% vs 21%, P = .011).
Conclusions
EV adversely affects TI intubation, particularly for adult colonoscopes. Water filling of the cecum mitigates the impact of EV on TI intubation with adult colonoscopes
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