Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells

Background & Aims

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis and inflammation, which can further progress into fibrosis and cirrhosis. Recently, we demonstrated that combined deletion of the two main scavenger receptors, CD36 and macrophage scavenger receptor 1 (MSR1), which are important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The individual contributions of these receptors to NASH and the intracellular mechanisms by which they contribute to inflammation have not been established. We hypothesize that CD36 and MSR1 contribute independently to the onset of inflammation in NASH, by affecting intracellular cholesterol distribution inside Kupffer cells (KCs).

Methods & Results

Ldlr^−/− mice were transplanted with wild-type (Wt), Cd36^−/− or Msr1^−/− bone marrow and fed a Western diet for 3months. Cd36^−/−- and Msr1^−/−- transplanted (tp) mice showed a similar reduction in hepatic inflammation compared to Wt-tp mice. While the total amount of cholesterol inside KCs was similar in all groups, KCs of Cd36^−/−- and Msr1^−/−-tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp mice showed increased lysosomal cholesterol accumulation.

Conclusion

CD36 and MSR1 contribute similarly and independently to the progression of inflammation in NASH. One possible explanation for the inflammatory response related to expression of these receptors could be abnormal cholesterol trafficking in KCs. These data provide a new basis for prevention and treatment of NASH.     

Out of Tanganyika: Genesis, explosive speciation, key-innovations and phylogeography of the haplochromine cichlid fishes

Background  

The adaptive radiations of cichlid fishes in East Africa are well known for their spectacular diversity and their astonishingly fast rates of speciation. About 80% of all 2,500 cichlid species in East Africa, and virtually all cichlid species from Lakes Victoria (~500 species) and Malawi (~1,000 species) are haplochromines. Here, we present the most extensive phylogenetic and phylogeographic analysis so far that includes about 100 species and is based on about 2,000 bp of the mitochondrial DNA.     

Differential selection in HIV-1 gp120 between subtype B and East Asian variant B’

HIV-1 evolves strongly and undergoes geographic differentiation as it spreads in diverse host populations around the world. For instance, distinct genomic backgrounds can be observed between the pandemic subtype B, prevalent in Europe and North-America, and its offspring clade B’ in East Asia. Here we ask whether this differentiation affects the selection pressure experienced by the virus. To answer this question we evaluate selection pressure on the HIV-1 envelope protein gp120 at the level of individual codons using a simple and fast estimation method based on the ratio k _a /k _s of amino acid changes to synonymous changes. To validate the approach we compare results to those from a state-of-the-art mixed-effect method. The agreement is acceptable, but the analysis also demonstrates some limitations of the simpler approach. Further, we find similar distributions of codons under stabilizing and directional selection pressure in gp120 for subtypes B and B’ with more directional selection pressure in variable loops and more stabilizing selection in the constant regions. Focusing on codons with increased k _a /k _s values in B’, we show that these codons are scattered over the whole of gp120, with remarkable clusters of higher density in regions flanking the variable loops. We identify a significant statistical association of glycosylation sites and codons with increased k _a /k _s values.     

Investigation of co-genotoxic effects of radiofrequency electromagnetic fields in vivo

We investigated the possible combined genotoxic effects of radiofrequency (RF) electromagnetic fields (900 MHz, amplitude modulated at 217 Hz, mobile phone signal) with the drinking water mutagen and carcinogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). Female rats were exposed to RF fields for a period of 2 years for 2 h per day, 5 days per week at average whole-body specific absorption rates of 0.3 or 0.9 W/kg. MX was given in the drinking water at a concentration of 19 microg/ml. Blood samples were taken at 3, 6 and 24 months of exposure and brain and liver samples were taken at the end of the study (24 months). DNA damage was assessed in all samples using the alkaline comet assay, and micronuclei were determined in erythrocytes. We did not find significant genotoxic activity of MX in blood and liver cells. However, MX induced DNA damage in rat brain. Co-exposures to MX and RF radiation did not significantly increase the response of blood, liver and brain cells compared to MX exposure only. In conclusion, this 2-year animal study involving long-term exposures to RF radiation and MX did not provide any evidence for enhanced genotoxicity in rats exposed to RF radiation.     

Experimental assessment of plant seed retention times in fur of cattle and horse

Epizoochorous dispersal of plant seeds is an important long-distance dispersal mechanism. Yet little is known about retention times of seeds in animal furs and hence about potential dispersal distances of the seeds. Here, we used marked seeds of 12 plant species to determine seed depletion curves on Galloway cattle and Haflinger horse in three vegetation types (forest, tall herbage vegetation and meadow), in both dry and rainy weather conditions. In the long fur of Galloway cattle, seeds were retained significantly longer than in the short fur of Haflinger horse. In general, seed retention times were not considerably affected by the structure of the surrounding vegetation. The impact of the weather was negligible, only affecting the retention of some plant species. Negative exponential functions were fitted to the seed depletion curves. Using the parameters of curve estimations in the different conditions of animal species and vegetation structure, half-life seed retention times of up to 13 h for Galloway cattle and up to more than 4 h for Haflinger horse could be calculated, with corresponding potential half-life dispersal distances in the order of magnitude of tens of metres to a few kilometres. Different seed traits correlated with seed retention times in the long cattle fur and in the short horse fur, respectively.     

Depletion of high energy phosphates implicates post-exercise mortality in carp and trout; an in vivo 31P-NMR study

As in vivo 31P-Nuclear Magnetic Resonance spectroscopy is currently the state of the art method to measure continuously intracellular pH (pH(i)) and energy status of muscle tissue, we used this method to study the recovery from exhaustive exercise. The biochemical changes during recovery are not well understood and it was suggested that post-exercise mortality could be caused by low pH(i); other studies however indicate that energy depletion might be more important. To analyse the mechanism of post-exercise recovery pH(i), ATP, P(i), and PCr must be measured at the same time, which is possible using in vivo 31P-NMR. Common carp and rainbow trout of about 100 g were exercised to exhaustion in a swim tunnel. After swimming 10 h at 1.5 body lengths (BL)/s (aerobic control), 50% of the fish were forced to swim at 6 BL/s until exhaustion. Recovery of energy rich phosphates was found to be faster in carp (1.2-1.9 h) than in trout (1.5-2.3 h). The same applied for the recovery from acidosis, which took 1.75 h in carp and 5.75 h in trout. In parallel experiments the energy phosphates and lactate levels were measured in liver, red muscle, and white muscle. Exhaustion caused a significant drop in the energy status of red and white muscle tissue of trout and carp (corroborates NMR data), while no change at all was observed in liver tissue. The lactate levels were increased in the muscle but not in liver and blood. While all experimental animals looked healthy after exhaustion, 40-50% of the carp as well as trout died during the recovery phase. The energy status of those individuals measured by 31P-NMR was much lower than that of the survivors, while in contrast there was no difference in pH(i). Thus, it appears that not acidosis but depletion of high energy phosphates disabled muscle function and therefore may have been the cause of death of the non-survivors.     

Community assembly in Lake Tanganyika cichlid fish: quantifying the contributions of both niche‐based and neutral processes

The cichlid family features some of the most spectacular examples of adaptive radiation. Evolutionary studies have highlighted the importance of both trophic adaptation and sexual selection in cichlid speciation. However, it is poorly understood what processes drive the composition and diversity of local cichlid species assemblages on relatively short, ecological timescales. Here, we investigate the relative importance of niche‐based and neutral processes in determining the composition and diversity of cichlid communities inhabiting various environmental conditions in the littoral zone of Lake Tanganyika, Zambia. We collected data on cichlid abundance, morphometrics, and local environments. We analyzed relationships between mean trait values, community composition, and environmental variation, and used a recently developed modeling technique (STEPCAM) to estimate the contributions of niche‐based and neutral processes to community assembly. Contrary to our expectations, our results show that stochastic processes, and not niche‐based processes, were responsible for the majority of cichlid community assembly. We also found that the relative importance of niche‐based and neutral processes was constant across environments. However, we found significant relationships between environmental variation, community trait means, and community composition. These relationships were caused by niche‐based processes, as they disappeared in simulated, purely neutrally assembled communities. Importantly, these results can potentially reconcile seemingly contrasting findings in the literature about the importance of either niche‐based or neutral‐based processes in community assembly, as we show that significant trait relationships can already be found in nearly (but not completely) neutrally assembled communities; that is, even a small deviation from neutrality can have major effects on community patterns.     

Chromosomal evolution in the African Arvicanthine rats (Murinae, Rodentia): comparative cytogenetics of Lemniscomys (L. zebra, L. rosalia, L. striatus) and Arvicanthis dembeensis

Chromosomenevolution bei den afrikanischen arvicanthinen Ratten (Murinae, Rodentia): Vergleichende Cytogenetik von Lemniscomys (L. zebra, L. rosalia, L. striatus) und Arvicanthus dembeensis
Chromosomenbänderungsanalysen (G- und C- Bänderung) wurden an zwei Arten von Lemniscomys ( L. zebra, L. rosalia ) und einer dritten Art aus Benin ( L. striatus ) durchgeführt, um den Verlauf der Chromosomenevolution in dieser Gattung zu verfolgen. Ein Mustervergleich mit der G-Bänderung macht es möglich, die Umstrukturierung der Chromosomen der Karyotypen zu erkennen. Die beiden Arten aus Tansania ( L. rosalia 2n=54, FNa=62; und L. zebra 2n=54, FNa=58) sind durch zwei perizentrische Inversionen voneinander unterschieden. Ein Polymorphismus für das X-Chromosom findet sich in beiden Arten. L. rosalia zeigt außerdem zwei verschiedene Formen des Y-Chromosoms. Das Bänderungsmuster von L. striatus (2n=44, FNa=68) aus Benin läßt im Vergleich zu L. zebra fünf Robertsonsche Fusionen erkennen. Außerdem ist der Karyotyp von L. rosalia aus Tansania verschieden von dem der für Südafrika (2n=48, FNa=62) beschrieben wurde und sollte daher als eine eigene Art betrachtet werden. Eine vergleichende Bänderungsanalyse mit einer anderen arvicanthinen Art ( Arvicanthus dembeensis, 2n=62, FNa=62) zeigt zwischen den beiden Gattungen eine vollständige Homologie in den G-Banden und die Unterschiede beruhen ausschließlich auf Tandem-Fusionen, perizentrischen Inversionen und Robertsonschen Fusionen.     

Cell wall anchoring of the Streptococcus pyogenes M6 protein in various lactic acid bacteria.

The M6 protein from Streptococcus pyogenes is the best-characterized member of a family of cell envelope-associated proteins. Based on the observation that the C-terminal sorting signals of these proteins can drive cell wall anchoring of heterologous unanchored proteins, we have cloned and expressed the emm6 structural gene for the M6 protein in various lactic acid bacteria (LAB). The emm6 gene was successfully expressed from lactococcal promoters in several Lactococcus lactis strains, an animal-colonizing Lactobacillus fermentum strain, Lactobacillus sake, and Streptococcus salivarius subsp. thermophilus. The M6 protein was efficiently anchored to the cell wall in all strains tested. In lactobacilli, essentially all detectable M6 protein was cell wall associated. These results suggest the feasibility of using the C-terminal anchor moiety of M6 for protein surface display in LAB.