Understanding the links between snoring,OSA and aortic root pathologies in Marfan syndrome

Sleep and Biological Rhythms -     

Endoplasmic reticulum-quality control chaperones facilitate the biogenesis of Cf receptor-like proteins involved in pathogen resistance of tomato

Cf proteins are receptor-like proteins (RLPs) that mediate resistance of tomato (Solanum lycopersicum) to the foliar pathogen Cladosporium fulvum. These transmembrane immune receptors, which carry extracellular leucine-rich repeats that are subjected to posttranslational glycosylation, perceive effectors of the pathogen and trigger a defense response that results in plant resistance. To identify proteins required for the functionality of these RLPs, we performed immunopurification of a functional Cf-4-enhanced green fluorescent protein fusion protein transiently expressed in Nicotiana benthamiana, followed by mass spectrometry. The endoplasmic reticulum (ER) heat shock protein70 binding proteins (BiPs) and lectin-type calreticulins (CRTs), which are chaperones involved in ER-quality control, were copurifying with Cf-4-enhanced green fluorescent protein. The tomato and N. benthamiana genomes encode four BiP homologs and silencing experiments revealed that these BiPs are important for overall plant viability. For the three tomato CRTs, virus-induced gene silencing targeting the plant-specific CRT3a gene resulted in a significantly compromised Cf-4-mediated defense response and loss of full resistance to C. fulvum. We show that upon knockdown of CRT3a the Cf-4 protein accumulated, but the pool of Cf-4 protein carrying complex-type N-linked glycans was largely reduced. Together, our study on proteins required for Cf function reveals an important role for the CRT ER chaperone CRT3a in the biogenesis and functionality of this type of RLP involved in plant defense.     

In search of a hydrological explanation for vegetation changes along a fen gradient in the Biebrza Upper Basin (Poland)

The understanding of succession from rich fen to poorer fen types requires knowledge of changes in hydrology, water composition, peat chemistry and peat accumulation in the successional process. Water flow patterns, water levels and water chemistry, mineralisation rates and nutrient concentrations in above-ground vegetation were studied along a extreme-rich fen-moderate-rich fen gradient at Biebrza (Poland). The extreme-rich fen was a temporary groundwater discharge area, while in the moderate-rich fen groundwater flows laterally towards the river. The moderate-rich fen has a rainwater lens in spring and significant lower concentrations of calcium and higher concentrations of phosphate in the surface water. Mineralisation rates for N, P and K were higher in the moderate-rich fen. Phosphorus concentrations in plant material of the moderate-rich fen were higher than in the extreme-rich fen, but concentrations of N and K in plant material did not differ between both fen types. Water level dynamics and macro-remains of superficial peat deposits were similar in both fen types.We concluded that the differences observed in the moderate-rich and the extreme-rich fens were caused by subtile differences in the proportion of water sources at the peat surface (rainwater and calcareous groundwater, respectively). Development of an extreme-rich fen into a moderate-rich fen was ascribed to recent changes in river hydrology possibly associated with a change in management practices. The observed differences in P-availability between the fen types did not result in significantly different biomass. Moreover, biomass production in both fen types was primarily N-limited although P-availability was restricted too in the extreme-rich fen. Aulacomnium palustre, the dominant moss in the moderate-rich fen, might be favoured in competition because of its broad nutrient tolerance and its quick establishment after disturbance. It might outcompete low productive rich fen species which were shown to be N-limited in both fens. We present a conceptual model of successional pathways of rich fen vegetation in the Biebrza region.     

Cholesterol accumulation caused by low density lipoprotein receptor deficiency or a cholesterol-rich diet results in ectopic bone formation during experimental osteoarthritis

Introduction

Osteoarthritis (OA) is associated with the metabolic syndrome, however the underlying mechanisms remain unclear. We investigated whether low density lipoprotein (LDL) accumulation leads to increased LDL uptake by synovial macrophages and affects synovial activation, cartilage destruction and enthesophyte/osteophyte formation during experimental OA in mice.

Methods

LDL receptor deficient (LDLr^−/−) mice and wild type (WT) controls received a cholesterol-rich or control diet for 120 days. Experimental OA was induced by intra-articular injection of collagenase twelve weeks after start of the diet. OA knee joints and synovial wash-outs were analyzed for OA-related changes. Murine bone marrow derived macrophages were stimulated with oxidized LDL (oxLDL), whereupon growth factor presence and gene expression were analyzed.

Results

A cholesterol-rich diet increased apolipoprotein B (ApoB) accumulation in synovial macrophages. Although increased LDL levels did not enhance thickening of the synovial lining, S100A8 expression within macrophages was increased in WT mice after receiving a cholesterol-rich diet, reflecting an elevated activation status. Both a cholesterol-rich diet and LDLr deficiency had no effect on cartilage damage; in contrast, ectopic bone formation was increased within joint ligaments (fold increase 6.7 and 6.1, respectively). Moreover, increased osteophyte size was found at the margins of the tibial plateau (4.4 fold increase after a cholesterol-rich diet and 5.3 fold increase in LDLr^−/− mice). Synovial wash-outs of LDLr^−/− mice and supernatants of macrophages stimulated with oxLDL led to increased transforming growth factor-beta (TGF-β) signaling compared to controls.

Conclusions

LDL accumulation within synovial lining cells leads to increased activation of synovium and osteophyte formation in experimental OA. OxLDL uptake by macrophages activates growth factors of the TGF-superfamily.     

Population studies of the wild tomato species Solanum chilense reveal geographically structured major gene-mediated pathogen resistance

Natural plant populations encounter strong pathogen pressure and defence-associated genes are known to be under selection dependent on the pressure by the pathogens. Here, we use populations of the wild tomato Solanum chilense to investigate natural resistance against Cladosporium fulvum, a well-known ascomycete pathogen of domesticated tomatoes. Host populations used are from distinct geographical origins and share a defined evolutionary history. We show that distinct populations of S. chilense differ in resistance against the pathogen. Screening for major resistance gene-mediated pathogen recognition throughout the whole species showed clear geographical differences between populations and complete loss of pathogen recognition in the south of the species range. In addition, we observed high complexity in a homologues of Cladosporium resistance (Hcr) locus, underlying the recognition of C. fulvum, in central and northern populations. Our findings show that major gene-mediated recognition specificity is diverse in a natural plant-pathosystem. We place major gene resistance in a geographical context that also defined the evolutionary history of that species. Data suggest that the underlying loci are more complex than previously anticipated, with small-scale gene recombination being possibly responsible for maintaining balanced polymorphisms in the populations that experience pathogen pressure.