Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human

The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well

Coping with multiple enemies : pairwise interactions do not predict evolutionary change in complex multitrophic communities

Predicting the ecological and evolutionary trajectories of populations in multispecies communities is one of the fundamental challenges in ecology. Many of these predictions are made by scaling patterns observed from pairwise interactions. Here, we show that the coupling of ecological and evolutionary outcomes is likely to be weaker in increasingly complex communities due to greater chance of life-history trait correlations. Using model microbial communities comprising a focal bacterial species (Bacillus subtilis), a bacterial competitor, protist predator and phage parasite, we found that increasing the number of enemies in a community had an overall negative effect on B. subtilis population growth. However, only the competitor imposed direct selection for B. subtilis trait evolution in pairwise cultures and this effect was weakened in the presence of other antagonists that had a negative effect on the competitor. In contrast, adaptation to parasites was driven indirectly by correlated selection where competitors had a positive and predators a negative effect. For all measured traits, selection in pairwise communities was a poor predictor of B. subtilis evolution in more complex communities. Together, our results suggest that coupling of ecological and evolutionary outcomes is interaction-specific and weakly coupled in more complex communities. We conclude that understanding 2 the ecological and evolutionary mechanisms underpinning trait correlations is crucial to predict species response to global change in complex microbial communitie

[Accepted Manuscript] Worldwide comparison of ovarian cancer survival: Histological group and stage at diagnosis (CONCORD-2)

Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15-99years) diagnosed with ovarian cancer during 1995-2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from 67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated age-standardised 5-year net survival by stage at diagnosis (localised or advanced). Survival from type I epithelial ovarian tumours for women diagnosed during 2005-09 ranged from 40 to 70%. Survival from type II epithelial tumours was much lower (20-45%). Survival from germ cell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology

Observations of GRB 990123 by the Compton Gamma-Ray Observatory

GRB 990123 was the first burst from which simultaneous optical, X-ray and gamma-ray emission was detected; its afterglow has been followed by an extensive set of radio, optical and X-ray observations. We have studied the gamma-ray burst itself as observed by the CGRO detectors. We find that gamma-ray fluxes are not correlated with the simultaneous optical observations, and the gamma-ray spectra cannot be extrapolated simply to the optical fluxes. The burst is well fit by the standard four-parameter GRB function, with the exception that excess emission compared to this function is observed below ~15 keV during some time intervals. The burst is characterized by the typical hard-to-soft and hardness-intensity correlation spectral evolution patterns. The energy of the peak of the nu f_nu spectrum, E_p, reaches an unusually high value during the first intensity spike, 1470 +/- 110 keV, and then falls to \~300 keV during the tail of the burst. The high-energy spectrum above ~MeV is consistent with a power law with a photon index of about -3. By fluence, GRB 990123 is brighter than all but 0.4% of the GRBs observed with BATSE, clearly placing it on the -3/2 power-law portion of the intensity distribution. However, the redshift measured for the afterglow is inconsistent with the Euclidean interpretation of the -3/2 power-law. Using the redshift value of >= 1.61 and assuming isotropic emission, the gamma-ray fluence exceeds 10E54 ergs.Comment: Submitted to The Astrophysical Journal. 16 pages including 4 figure

Total prostatectomy as a treatment for prostatic carcinoma in 25 dogs

Objective: To describe the complications and outcome after total prostatectomy in dogs with histologically confirmed prostatic carcinoma. Study Design: Multi-institutional retrospective case series. Animals: 25 client-owned dogs. Methods: Medical records of dogs undergoing total prostatectomy were reviewed from 2004 to 2016. Data retrieved included signalment, presenting signs, preoperative clinical findings, laboratory data, diagnostic imaging, surgical technique, histologic diagnosis, postoperative complications, occurrence of postoperative metastasis, and survival. Results: Twenty-five dogs underwent total prostatectomy for prostatic carcinoma. Urinary anastomotic techniques included urethrourethral anastomosis in 14 dogs, cystourethral anastomosis in 9 dogs, ureterocolonic anastomosis in 1 dog, and anastomosis between the bladder neck and penile urethra in 1 dog. All dogs survived to discharge. Fifteen dogs were diagnosed with transitional cell carcinoma, 8 dogs with prostatic adenocarcinoma, 1 with prostatic cystadenocarcinoma, and 1 with an undifferentiated carcinoma. Permanent postoperative urinary incontinence was present in 8 of 23 dogs. The median survival time was shorter in dogs with extracapsular tumor extension compared with those with intracapsular tumors. The overall median survival time was 231 days (range, 24-1255), with 1- and 2-year survival rates equal to 32% and 12%, respectively. Conclusion and Clinical Significance: Total prostatectomy, combined with adjunct therapies, prolongs survival and lowers complication rates compared to previous reports of dogs with prostatic carcinoma. It should be noted, however, that case selection likely played a significant role in postoperative outcome

A One-sided, Highly Relativistic Jet from Cygnus X-3

Very Long Baseline Array images of the X-ray binary, Cygnus X-3, were obtained 2, 4 and 7 days after the peak of a 10 Jy flare on 4 February 1997. The first two images show a curved one-sided jet, the third a scatter-broadened disc, presumably at the position of the core. The jet curvature changes from the first to the second epoch, which strongly suggests a precessing jet. The ratio of the flux density in the approaching to that in the (undetected) receding jet is > 330; if this asymmetry is due to Doppler boosting, the implied jet speed is > 0.81c. Precessing jet model fits, together with the assumptions that the jet is intrinsically symmetric and was ejected during or after the major flare, yield the following constraints: the jet inclination to the line of sight must be < 14 degrees; the cone opening angle must be < 12 degrees; and the precession period must be > 60 days.Comment: 12 pages 7 figures, accepted by Ap

The Dynamic Exponent of the Two-Dimensional Ising Model and Monte Carlo Computation of the Sub-Dominant Eigenvalue of the Stochastic Matrix

We introduce a novel variance-reducing Monte Carlo algorithm for accurate determination of autocorrelation times. We apply this method to two-dimensional Ising systems with sizes up to $15 \times 15$, using single-spin flip dynamics, random site selection and transition probabilities according to the heat-bath method. From a finite-size scaling analysis of these autocorrelation times, the dynamical critical exponent $z$ is determined as $z=2.1665$ (12)