Bile acids,FGF15/19 and liver regeneration: From mechanisms to clinical applications

The liver has an extraordinary regenerative capacity rapidly triggered upon injury or resection. This response is intrinsically adjusted in its initiation and termination, a property termed the “hepatostat”. Several molecules have been involved in liver regeneration, and among them bile acids may play a central role. Intrahepatic levels of bile acids rapidly increase after resection. Through the activation of farnesoid X receptor (FXR), bile acids regulate their hepatic metabolism and also promote hepatocellular proliferation. FXR is also expressed in enterocytes, where bile acids stimulate the expression of fibroblast growth factor 15/19 (FGF15/19), which is released to the portal blood. Through the activation of FGFR4 on hepatocytes FGF15/19 regulates bile acids synthesis and finely tunes liver regeneration as part of the “hepatostat”. Here we review the experimental evidences supporting the relevance of the FXR-FGF15/19-FGFR4 axis in liver regeneration and discuss potential therapeutic applications of FGF15/19 in the prevention of liver failure. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.     

Persistence of Infectious Shiga Toxin-Encoding Bacteriophages after Disinfection Treatments

In Shiga toxin-producing Escherichia coli (STEC), induction of Shiga toxin-encoding bacteriophages (Stx phages) causes the release of free phages that can later be found in the environment. The ability of Stx phages to survive different inactivation conditions determines their prevalence in the environment, the risk of stx transduction, and the generation of new STEC strains. We evaluated the infectivity and genomes of two Stx phages (Φ534 and Φ557) under different conditions. Infectious Stx phages were stable at 4, 22, and 37°C and at pH 7 and 9 after 1 month of storage but were completely inactivated at pH 3. Infective Stx phages decreased moderately when treated with UV (2.2-log₁₀ reduction for an estimated UV dose of 178.2 mJ/cm²) or after treatment at 60 and 68°C for 60 min (2.2- and 2.5-log₁₀ reductions, respectively) and were highly inactivated (3 log₁₀) by 10 ppm of chlorine in 1 min. Assays in a mesocosm showed lower inactivation of all microorganisms in winter than in summer. The number of Stx phage genomes did not decrease significantly in most cases, and STEC inactivation was higher than phage inactivation under all conditions. Moreover, Stx phages retained the ability to lysogenize E. coli after some of the treatments.     

Weather effect on widely distributed seabirds through migration flyways: a case study with the Northern Gannet Morus bassanus in the Bay of Biscay

Capsule: Northern Gannet Morus bassanus counts obtained from a coastal monitoring network in northern Spain were highly determined by wind conditions.

Aims: To determine how external factors including weather conditions affect seabird counts in a land-based seabird monitoring project (Red de observación de Aves y Mamíferos marinos, RAM project; Seabird & Marine Mammal Observation Network).

Methods: Seabird counts were obtained from four study capes situated in the southeastern part of the Bay of Biscay in northern Spain. Counts were conducted on a monthly-basis for a period of 3 hours starting at dawn on each sampling day. Data used here were compiled over a 10-year period (2006–15).

Results: Northern Gannet numbers were chiefly influenced by meteorological conditions at a local spatial scale. Northwesterly winds were found to positively influence gannet abundance, whereas high relative humidity caused a decrease in abundance. Moreover, gannets were more abundant during the non-breeding period as compared to breeding period.

Conclusion: We recommend considering the effect of the wind and relative humidity on land-based seabird counts in the Bay of Biscay when handling data from the RAM protocol in order to avoid biases and misinterpretation of data. Since seabirds approach the coast during harsh weather conditions, the RAM protocol should be improved in order to better account for the distance at which the birds are seen.     

Association Between Suicide and Environmental Variables in the North of Spain: A 14-Year Analysis

Suicide is a serious public health problem around the world. Since the nineteenth century, the impact of socio-environmental factors on suicide has attracted much public attention, especially in the context of global climate change. We have performed a retrospective correlation study that analyzes the demographic pattern of suicide in Cantabria, a northern coastland region of Spain. Moreover, we have created a multivariable binomial regression model to study the relationship between suicide and environmental factors (atmospheric pollutants and meteorological variables) among January 1, 2000, and December 31, 2013 in the province. During the 14-year study period, there was a suicide annual incidence of 4.9 cases per 100,000 population in Cantabria. The incidence was highest in adults aged 70–74 years old (11.8 per 100,000 population). The most common method group of suicide was hanging, strangulation and suffocation, accounting for 49.3% of all suicide deaths. When correlating suicide and meteorological variables, a statistically significant association was found with the level of cloudiness (p?=?0.007). According to our results, an increase of one eighth of sky cloud-cover correlated to a 7% increase in total deaths by suicide and the association was especially strong during spring.     

Increased Soil Frost Versus Summer Drought as Drivers of Plant Biomass Responses to Reduced Precipitation: Results from a Globally Coordinated Field Experiment

Reduced precipitation treatments often are used in field experiments to explore the effects of drought on plant productivity and species composition. However, in seasonally snow-covered regions reduced precipitation also reduces snow cover, which can increase soil frost depth, decrease minimum soil temperatures and increase soil freeze–thaw cycles. Therefore, in addition to the effects of reduced precipitation on plants via drought, freezing damage to overwintering plant tissues at or below the soil surface could further affect plant productivity and relative species abundances during the growing season. We examined the effects of both reduced rainfall (via rain-out shelters) and reduced snow cover (via snow removal) at 13 sites globally (primarily grasslands) within the framework of the International Drought Experiment, a coordinated distributed experiment. Plant cover was estimated at the species level, and aboveground biomass was quantified at the functional group level. Among sites, we observed a negative correlation between the snow removal effect on minimum soil temperature and plant biomass production the next growing season. Three sites exhibited significant rain-out shelter effects on plant productivity, but there was no correlation among sites between the rain-out shelter effect on minimum soil moisture and plant biomass. There was no interaction between snow removal and rain-out shelters for plant biomass, although these two factors only exhibited significant effects simultaneously for a single site. Overall, our results reveal that reduced snowfall, when it decreases minimum soil temperatures, can be an important component of the total effect of reduced precipitation on plant productivity.     

A comparison of reproduction, growth and acute toxicity in two populations of Tubifex tubifex (Müller,1774) from the North American Great Lakes and Northern Spain

Reproduction in Tubifex tubifex is being used as part of a suite of indicators of sediment toxicity in Canada and Spain, and reproduction of T. tubifex is being considered as a component of sediment objectives for environmental regulation and clean-up in the Canadian Great Lakes. The data being used to set these reproductive targets have been developed from a single culture of T. tubifex from Lake Erie. The plasticity of this particular species is well known and before it can be adopted widely as a test organism it is necessary to determine whether a single culture source should be used or if cultures derived from different populations respond similarly. A series of experiments with two cultures, one from Lake Erie the second from a small mountain stream in Northern Spain have shown that the Spanish worms appear to produce fewer cocoons per adult (mean 8.6 S.D. 1.0) than those from Lake Erie (mean 10.4 S.D. 0.3) at 22.5 °C, a standard test temperature. The number of young produced per adult by the Spanish culture is also lower (mean 19.0 S.D. 4.6) than the L. Erie population (mean 30.6 S.D. 2.3), however, the Spanish population has higher reproductions rates at a lower temperature. The Spanish worms also have lower and more variable growth rates than the Canadian population. There also appear to be slight differences in the sensitivities to toxicants, with the Canadian worms having higher LC50s for copper, chromium and cadmium. While there are differences in the responses in the two cultures these are not considered to be sufficient to invalidate the use of either population in a standard bioassay protocol as long as appropriate calibration and validation are undertaken.     

Effects of an Exercise Programme on Functional Capacity,Body Composition and Risk of Falls in Patients with Cirrhosis: A Randomized Clinical Trial

Patients with cirrhosis often have functional limitations, decreased muscle mass, and a high risk of falls. These variables could improve with exercise. The aim was to study the effects of moderate exercise on functional capacity, body composition and risk of falls in patients with cirrhosis. Twenty-three cirrhotic patients were randomized to an exercise programme (n = 14) or to a relaxation programme (n = 9). Both programmes consisted of a one-hour session 3 days a week for 12 weeks. At the beginning and end of the study, we measured functional capacity using the cardiopulmonary exercise test, evaluated body composition using anthropometry and dual energy X-ray absorptiometry, and estimated risk of falls using the Timed Up&Go test. In the exercise group, cardiopulmonary exercise test showed an increase in total effort time (p<0.001) and ventilatory anaerobic threshold time (p = 0.009). Upper thigh circumference increased and mid-arm and mid-thigh skinfold thickness decreased. Dual energy X-ray absorptiometry showed a decrease in fat body mass (-0.94 kg, 95%CI -0.48 to -1.41, p = 0.003) and an increase in lean body mass (1.05 kg, 95%CI 0.27 to 1.82, p = 0.01), lean appendicular mass (0.38 kg, 95%CI 0.06 to 0.69, p = 0.03) and lean leg mass (0.34 kg, 95%CI 0.10 to 0.57, p = 0.02). The Timed Up&Go test decreased at the end of the study compared to baseline (p = 0.02). No changes were observed in the relaxation group. We conclude that a moderate exercise programme in patients with cirrhosis improves functional capacity, increases muscle mass, and decreases body fat and the Timed Up&Go time.Trial Registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01447537","term_id":"NCT01447537"}}NCT01447537     

Bicarbonate gradients modulate growth and colony morphology in Aspergillus nidulans

A new insertion sequence (IS), IS 1642 , was identified in a Mycobacterium avium strain isolated from a human patient. IS 1642 had a size of 1642 bp and contained a single ORF encoding a probable transposase of 503 amino acid residues homologous (79% identity) to that of IS 1549 found in Mycobacterium smegmatis . The IS 1642 included imperfect inverted repeats (5'-cctgacttttatca-3', 5'-tgataaaagtcggg-3') on its ends, and was flanked by direct repeats of variable length ranging from 5 to 161 bp. It was suggested that the IS 1642 was widely distributed in many M. avium strains of human patients, and the Southern blot profile of IS 1642 was very diverse among the strains examined. The transposition event of IS 1642 was observed by in vitro repeated passages, showing that the IS 1642 is actually a transposable element. In light of these characteristics, IS 1642 could be a new useful marker when genotyping with high discrimination is required.