Land use intensification in grasslands: higher trophic levels are more negatively affected than lower trophic levels

Increasing land use intensity and human influence are leading to a reduction in plant and animal species diversity. However, little is known about how these changes may affect higher trophic levels, apart from simply reducing species numbers. Here we investigated, over 3 years, the influence of different land practices on a tritrophic system in grassland habitats. The system consisted of the host plant Plantago lanceolata L. (Plantaginaceae), two monophagous weevils, Mecinus labilis Herbst and Mecinus pascuorum Gyllenhal (Coleoptera: Curculionidae), and their parasitoid Mesopolobus incultus Walker (Hymenoptera: Pteromalidae). At over 70 sites across three geographic regions in Germany, we measured plant species diversity and vegetation structure, as well as abundance of P. lanceolata, the two weevils, and the parasitoid. Land use intensity (fertilization) and type (mowing vs. grazing) negatively affected not only plant species richness but also the occurrence of the two specialized herbivores and their parasitoid. In contrast, land use had a mostly positive effect on host plant size, vegetation structure, and parasitization rate. This study reveals that intensification of land use influences higher trophic organisms even without affecting the availability of the host plant. The observed relationships between land use, vegetation complexity, and the tritrophic system are not restricted locally; rather they are measureable along a broad range of environmental conditions and years throughout Germany. Our findings may have important implications for the conservation of insect species of nutrient‐poor grasslands.     

Up-regulation of Na-coupled glucose transporter SGLT1 by caveolin-1

The Na⁺-coupled glucose transporter SGLT1 (SLC5A1) accomplishes concentrative cellular glucose uptake even at low extracellular glucose concentrations. The carrier is expressed in renal proximal tubules, small intestine and a variety of nonpolarized cells including several tumor cells. The present study explored whether SGLT1 activity is regulated by caveolin-1, which is known to regulate the insertion of several ion channels and carriers in the cell membrane. To this end, SGLT1 was expressed in Xenopus oocytes with or without additional expression of caveolin-1 and electrogenic glucose transport determined by dual electrode voltage clamp experiments. In SGLT1-expressing oocytes, but not in oocytes injected with water or caveolin-1 alone, the addition of glucose to the extracellular bath generated an inward current (I_g), which was increased following coexpression of caveolin-1. Kinetic analysis revealed that caveolin-1 increased maximal I_g without significantly modifying the glucose concentration required to trigger half maximal I_g (K_M). According to chemiluminescence and confocal microscopy, caveolin-1 increased SGLT1 protein abundance in the cell membrane. Inhibition of SGLT1 insertion by brefeldin A (5 μM) resulted in a decline of I_g, which was similar in the absence and presence of caveolin-1. In conclusion, caveolin-1 up-regulates SGLT1 activity by increasing carrier protein abundance in the cell membrane, an effect presumably due to stimulation of carrier protein insertion into the cell membrane.     

Biochemical characteristic of biofilm of uropathogenic Escherichia coli Dr+ strains

Urinary tract infections caused by Escherichia coli are very common health problem in the developed countries. The virulence of the uropathogenic E. coli Dr⁺ IH11128 is determined by Dr fimbriae, which are homopolymeric structures composed of DraE subunits with the DraD protein capping the fiber. In this study, we have analyzed the structural and biochemical properties of biofilms developed by E. coli strains expressing Dr fimbriae with or without the DraD tip subunit and the surface-exposed DraD protein. We have also demonstrated that these E. coli strains form biofilms on an abiotic surface in a nutrient-dependent fashion. We present evidence that Dr fimbriae are necessary during the first stage of bacterial interaction with the abiotic surface. In addition, we reveal that the DraD alone is also sufficient for the initial surface attachment at an even higher level than Dr fimbriae and that chloramphenicol is able to reduce the normal attachment of the analyzed E. coli. The action of chloramphenicol also shows that protein synthesis is required for the early events of biofilm formation. Additionally, we have identified reduced exopolysaccharide coverage in E. coli that express only Dr fimbrial polyadhesins at the cell surface with or without the DraD capping subunit.     

Loss of TRAIL-Receptors Is a Recurrent Feature in Pancreatic Cancer and Determines the Prognosis of Patients with No Nodal Metastasis after Surgery

Introduction

Agonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity.

Aims and Methods

Applying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated.

Results

The fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p<0.001, TRAIL-R2: p = 0.006). In addition, subgroup analyses showed that loss of membrane staining for TRAIL-R2 was associated with poorer prognosis in patients without nodal metastases (multivariate Cox regression analysis, Hazard Ratio: 0.44 [95% confidence interval: 0.22−0.87]; p = 0.019). In contrast, analysis of decoy receptors TRAIL-R3 and -R4 in tumor samples showed an exclusively cytoplasmatic staining pattern and no prognostic relevance.

Conclusion

This is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials.     

Alpha1-antitrypsin, old dog, new tricks. Alpha1-antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevating cAMP

Regulation of serine protease activity is considered to be the sole mechanism for the function of alpha1-antitrypsin (AAT). However, recent reports of the anti-inflammatory effects of AAT are hard to reconcile with this classical mechanism. We discovered that two key activities of AAT in vitro, namely inhibition of endotoxin-stimulated tumor necrosis factor-alpha and enhancement of interleukin-10 in human monocytes, are mediated by an elevation of cAMP and activation of cAMP-dependent protein kinase A. As expected with this type of mechanism, the AAT-mediated rise in cAMP and the impact on endotoxin-stimulated tumor necrosis factor-alpha and interleukin-10 was enhanced when the catabolism of cAMP was blocked by the phosphodiesterase inhibitor rolipram. These effects were still observed with modified forms of AAT lacking protease inhibitor activity.     

Immunomodulatory effect of selenosemicarbazides and selenium inorganic compounds, distribution in organs after selenium supplementation

Antioxidant properties of selenium producing a protective barrier against free radicals play an important role in numerous metabolic and immunologic processes associated with oxidation- reduction reactions which take place during intracellular digestion of phagocyted bacteria. The aim of our study was to examine the properties of an organic compound of selenium, 4-(o-tolilo)- selenosemicarbazide of p-chlorobenzoic acid in terms of its retention in organs, effect on erythropoesis and phagocytic abilities of neutrophiles as well as antioxidant properties in neutrophiles tested with NBT test. This compound as well as inorganic sodium selenate was given to Swiss mice at the dose of 10^–3 g Se/kg for the period of 10 days. The concentrations of selenium in livers of mice treated with sodium selenate and selenosemicarbazide were found to be higher than in controls (18,7 g lg^–1 and 23.2 g lg^–1 vs. 12 g lg^–1, respectively). Analysis of blood cells count has shown a significant decrease in neutrophile levels in both groups treated with selenium. The influence of selenium compounds on phagocytosis and especially NBT test has been determined (3.8% of positive cells in the controls vs. 2.2% and 0.9% in the groups treated with sodium selenate and selenosemicarbazide, respectively). Our preliminary investigations suggest that selenosemicarbazides are biologically active compounds and can modify neutrophile functions.