Role of Cytolethal Distending Toxin in Altered Stool Form and Bowel Phenotypes in a Rat Model of Post-infectious Irritable Bowel Syndrome.

Background/aimsCampylobacter jejuni infection is a leading cause of acute gastroenteritis, which is a trigger for post-infectious irritable bowel syndrome (PI-IBS). Cytolethal distending toxin (CDT) is expressed by enteric pathogens that cause PI-IBS. We used a rat model of PI-IBS to investigate the role of CDT in long-term altered stool form and bowel phenotypes.MethodsAdult Sprague-Dawley rats were gavaged with wildtype C. jejuni (C+), a C. jejunicdtB knockout (CDT-) or saline vehicle (controls). Four months after gavage, stool from 3 consecutive days was assessed for stool form and percent wet weight. Rectal tissue was analyzed for intraepithelial lymphocytes, and small intestinal tissue was stained with anti-c-kit for deep muscular plexus interstitial cells of Cajal (DMP-ICC).ResultsAll 3 groups showed similar colonization and clearance parameters. Average 3-day stool dry weights were similar in all 3 groups, but day-to-day variability in stool form and stool dry weight were significantly different in the C+ group vs both controls (P < 0.01) and the CDT- roup (P < 0.01), but were not different in the CDT- vs controls. Similarly, rectal lymphocytes were significantly higher after C. jejuni (C+) infection vs both controls (P < 0.01) and CDT-exposed rats (P < 0.05). The counts in the latter 2 groups were not significantly different. Finally, c-kit staining revealed that DMP-ICC were reduced only in rats exposed to wildtype C. jejuni.ConclusionsIn this rat model of PI-IBS, CDT appears to play a role in the development of chronic altered bowel patterns, mild chronic rectal inflammation and reduction in DMP-ICC

Computational Analysis of Hybrid Norwood Circulation with Distal Aortic Arch Obstruction and Reverse Blalock-Taussig Shunt

BACKGROUND: The hemodynamics characteristics of the hybrid Norwood (HN) procedure differ from those of the conventional Norwood and are not fully understood. We present a multi-scale model of HN circulation to understand local hemodynamics and effects of aortic arch stenosis and a reverse Blalock-Taussig shunt (RBTS) on coronary and carotid perfusion. METHODS: Four 3-dimensional models of four HN anatomic variants were developed, with and without 90% distal preductal arch stenosis and with and without a 4-mm RBTS. A lumped parameter model of the circulation was coupled to a local 3-dimensional computational fluid dynamics model. Outputs from the lumped parameter model provided waveform boundary conditions for the computational fluid dynamics model. RESULTS: A 90% distal arch stenosis reduced pressure and net flow-rate through the coronary and carotid arteries by 30%. Addition of the RBTS completely restored pressure and flow rate to baseline in these vessels. Zones of flow stagnation, flow reversal, and recirculation in the presence of stenosis were rendered more orderly by addition of the RBTS. In the absence of stenosis, presence of the shunt resulted in extensive zones of disturbed flow within the RBTS and arch. CONCLUSIONS: We found that a 4-mm × 21-mm RBTS completely compensated for the effects of a 90% discrete stenosis of the distal aortic arch in the HN. Placed preventatively, the RBTS and arch displayed zones with thrombogenic potential showing recirculation and stagnation that persist for a substantial fraction of the cardiac cycle, indicating that anticoagulation should be considered with a prophylactic RBTS

A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry

Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens

Potential Drivers of Mid-Infrared Variability in Young Stars: Testing Physical Models with Multiepoch Near-Infrared Spectra of YSOs in ρ Oph

Recent studies have identified several young stellar objects (YSOs) which exhibit significant mid-infrared (mid-IR) variability. A wide range of physical mechanisms may be responsible for these variations, including changes in a YSO’s accretion rate or in the extinction or emission from the inner disk. We have obtained and analyzed multiepoch near-infrared (NIR) spectra for five actively accreting YSOs in the ρ Oph star-forming region along with contemporaneous mid-IR light curves obtained as part of the YSOVAR Spitzer/IRAC survey. Four of the five YSOs exhibit mid-IR light curves with modest (∼0.2–0.4 mag) but statistically significant variations over our 40-day observation window. Measuring the strengths of prominent photospheric absorption lines and accretion sensitive H I and He I lines in each NIR spectrum, we derive estimates of each YSO’s spectral type, effective temperature (T_eff), and H-band extinction (A_H), and analyze the time evolution of their NIR veiling (r_H and r_K) and mass accretion rates (Ṁ_acc). Defining a YSO’s evolutionary stage such that heavily veiled, high accretion rate objects are less evolved than those with lower levels of veiling and ongoing accretion, we infer that GY 314 is the most evolved YSO in our sample, with GY 308 and GY 292 at progressively earlier evolutionary stages. Leveraging our multiepoch, multiwavelength dataset, we detect significant variations in mass accretion rates over timescales of days to weeks, but find that extinction levels in these YSOs remain relatively constant. We find no correlation between these YSO mid-IR light curves and time-resolved veiling or mass accretion rates, such that we are unable to link their mid-IR variability with physical processes localized near the inner edge of the circumstellar disk or within regions which are directly responsive to mass accretion. We do find, however, that redshifted He I λ10830 emission, where present in our spectra, shows both quantitative and qualitative temporal correlations with accretion-sensitive H I emission lines. Blueshifted He I absorption, on the other hand, does not demonstrate a similar correlation, although the time-averaged strength of this blueshifted absorption is correlated with the time-averaged accretion rate in our sample of YSOs

The Spin-Resolved Atomic Velocity Distribution and 21-cm Line Profile of Dark-Age Gas

The 21-cm hyperfine line of atomic hydrogen (HI) is a promising probe of the cosmic dark ages. In past treatments of 21-cm radiation it was assumed the hyperfine level populations of HI could be characterized by a velocity-independent ``spin temperature'' T_s determined by a competition between 21-cm radiative transitions, spin-changing collisions, and (at lower redshifts) Lyman-alpha scattering. However we show here that, if the collisional time is comparable to the radiative time, the spin temperature will depend on atomic velocity, T_s=T_s(v), and one must replace the usual hyperfine level rate equations with a Boltzmann equation describing the spin and velocity dependence of the HI distribution function. We construct here the Boltzmann equation relevant to the cosmic dark ages and solve it using a basis-function method. Accounting for the actual spin-resolved atomic velocity distribution results in up to a 2 per cent suppression of the 21-cm emissivity, and a redshift and angular-projection dependent suppression or enhancement of the linear power spectrum of 21-cm fluctuations of up to 5 per cent. The effect on the 21-cm line profile is more dramatic -- its full-width at half maximum (FWHM) can be enhanced by up to 60 per cent relative to the velocity-independent calculation. We discuss the implications for 21-cm tomography of the dark ages.Comment: 25 pages, 6 figures, submitted to Mon. Not. Roy. Astron. So

Thermal Emission and Tidal Heating of the Heavy and Eccentric Planet XO-3b

We determined the flux ratios of the heavy and eccentric planet XO-3b to its parent star in the four IRAC bands of the Spitzer Space Telescope: 0.101% +- 0.004% at 3.6 micron; 0.143% +- 0.006% at 4.5 micron; 0.134% +- 0.049% at 5.8 micron and 0.150% +- 0.036% at 8.0 micron. The flux ratios are within [-2.2,0.3, -0.8, -1.7]-sigma of the model of XO-3b with a thermally inverted stratosphere in the 3.6 micron, 4.5 micron, 5.8 micron and 8.0 micron channels, respectively. XO-3b has a high illumination from its parent star (Fp ~(1.9 - 4.2) x 10^9 ergs cm^-2 s^-1) and is thus expected to have a thermal inversion, which we indeed observe. When combined with existing data for other planets, the correlation between the presence of an atmospheric temperature inversion and the substellar flux is insufficient to explain why some high insolation planets like TrES-3 do not have stratospheric inversions and some low insolation planets like XO-1b do have inversions. Secondary factors such as sulfur chemistry, atmospheric metallicity, amounts of macroscopic mixing in the stratosphere or even dynamical weather effects likely play a role. Using the secondary eclipse timing centroids we determined the orbital eccentricity of XO-3b as e = 0.277 +- 0.009. The model radius-age trajectories for XO-3b imply that at least some amount of tidal-heating is required to inflate the radius of XO-3b, and the tidal heating parameter of the planet is constrained to Qp < 10^6 .Comment: Accepted for publications in The Astrophysical Journa

Assessing for interaction between APOE ε4, sex and lifestyle on cognitive abilities

Objective: To test for interactions between APOE ε4 genotype and lifestyle factors on worse cognitive abilities in UK Biobank. Methods: Using UK Biobank cohort data, we tested for interactions between APOE ε4 allele presence, lifestyle factors of alcohol intake, smoking, total physical activity and obesity, and sex, on cognitive tests of reasoning, information processing speed, and executive function (n range = 70,988–324,725 depending on the test). We statistically adjusted for potential confounders of age, sex, deprivation, cardiometabolic conditions, and educational attainment. Results: There were significant associations between APOE ε4 and worse cognitive abilities, independent of potential confounders, and between lifestyle risk factors and worse cognitive abilities; however, there were no interactions at multiple correction-adjusted p &lt; 0.05, against our hypotheses. Conclusions: Our results do not provide support for the idea that ε4 genotype increases vulnerability to the negative effects of lifestyle risk factors on cognitive ability, but rather support a primarily outright association between APOE ε4 genotype and worse cognitive ability

Gridded and direct Epoch of Reionisation bispectrum estimates using the Murchison Widefield Array

We apply two methods to estimate the 21~cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly-spaced triangles of antenna tiles, as well as an estimate based on data gridded to the $uv$-plane. The direct and gridded bispectrum estimators are applied to 21 hours of high-band (167--197~MHz; $z$=6.2--7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 hours, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21~cm bispectrum may be accessible in less time than the 21~cm power spectrum for some wave modes, with detections in hundreds of hours.Comment: 19 pages, 10 figures, accepted for publication in PAS