TLRs in the Gut. IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction

Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize conserved molecular motifs on microorganisms. Ligand binding to TLRs initiates signaling cascades that activate NF-kappaB, MAPK, and interferon response factors. These culminate in cellular responses including activation of antimicrobial killing mechanisms, production of cytokines and chemokines, maturation of antigen presenting cells, and the recruitment of the adaptive immune response. Intestinal epithelial cells represent a unique population of cells that exist in direct contact with a biomass of bacteria. Initiation of TLR signaling is tightly regulated because prolonged and excessive activation of TLRs can lead to uncontrolled inflammation detrimental to the host. Varied mechanisms appear to contribute to control of TLR activation in the intestinal epithelium. These include the collective effects of several negative regulators that include IRAK-M, TOLLIP, SIGIRR, A20, Nod2, and PPARgamma. However, it remains to be determined whether they comprise the entire spectrum of negative control mechanisms and how they are bypassed to trigger activation during challenge by pathogens.     

Gene expression profiles during short‐term heat stress in the red sea coral Stylophora pistillata

During the past several decades, corals worldwide have been affected by severe bleaching events leading to wide‐spread coral mortality triggered by global warming. The symbiotic Red Sea coral Stylophora pistillata from the Gulf of Eilat is considered an opportunistic ‘r’ strategist. It can thrive in relatively unstable environments and is considered a stress‐tolerant species. Here, we used a S. pistillata custom microarray to examine gene expression patterns and cellular pathways during short‐term (13‐day) heat stress. The results allowed us to identify a two‐step reaction to heat stress, which intensified significantly as the temperature was raised to a 32 °C threshold, beyond which, coping strategies failed at 34 °C. We identified potential ‘early warning genes’ and ‘severe heat‐related genes’. Our findings suggest that during short‐term heat stress, S. pistillata may divert cellular energy into mechanisms such as the ER‐unfolded protein response (UPR) and ER‐associated degradation (ERAD) at the expense of growth and biomineralization processes in an effort to survive and subsequently recover from the stress. We suggest a mechanistic theory for the heat stress responses that may explain the success of some species which can thrive under a wider range of temperatures relative to others.     

Sox2, a marker for stem‐like tumor cells in skin squamous cell carcinoma and hedgehog subgroup medulloblastoma

Heterogeneity within tumors is becoming increasingly recognized as an important cause of treatment failure in cancer. Two recent studies use fate‐mapping and limiting dilution transplantation assays to identify SRY (sex determining region Y)‐box 2 (Sox2) as cancer stem‐cell marker and driver of cancer stemness.     

Early Events in the Fusarium verticillioides-Maize Interaction Characterized by Using a Green Fluorescent Protein-Expressing Transgenic Isolate

The infection of maize by Fusarium verticillioides can result in highly variable disease symptoms ranging from asymptomatic plants to severe rotting and wilting. We produced F. verticillioides green fluorescent protein-expressing transgenic isolates and used them to characterize early events in the F. verticillioides-maize interaction that may affect later symptom appearance. Plants grown in F. verticillioides-infested soil were smaller and chlorotic. The fungus colonized all of the underground parts of a plant but was found primarily in lateral roots and mesocotyl tissue. In some mesocotyl cells, conidia were produced within 14 to 21 days after infection. Intercellular mycelium was detected, but additional cells were not infected until 21 days after planting. At 25 to 30 days after planting, the mesocotyl and main roots were heavily infected, and rotting developed in these tissues. Other tissues, including the adventitious roots and the stem, appeared to be healthy and contained only a small number of hyphae. These results imply that asymptomatic systemic infection is characterized by a mode of fungal development that includes infection of certain tissues, intercellular growth of a limited number of fungal hyphae, and reproduction of the fungus in a few cells without invasion of other cells. Development of visibly rotted tissue is associated with massive production of fungal mycelium and much less organized growth.     

Improved pestalotiollide B production by deleting competing polyketide synthase genes in <Emphasis Type="Italic">Pestalotiopsis microspora</Emphasis>

Pestalotiollide B, an analog of dibenzodioxocinones which are inhibitors of cholesterol ester transfer proteins, is produced by Pestalotiopsis microspora NK17. To increase the production of pestalotiollide B, we attempted to eliminate competing polyketide products by deleting the genes responsible for their biosynthesis. We successfully deleted 41 out of 48 putative polyketide synthases (PKSs) in the genome of NK17. Nine of the 41 PKS deleted strains had significant increased production of pestalotiollide B (P < 0.05). For instance, deletion of pks35, led to an increase of pestalotiollide B by 887%. We inferred that these nine PKSs possibly lead to branch pathways that compete for precursors with pestalotiollide B, or that convert the product. Deletion of some other PKS genes such as pks8 led to a significant decrease of pestalotiollide B, suggesting they are responsible for its biosynthesis. Our data demonstrated that improvement of pestalotiollide B production can be achieved by eliminating competing polyketides.     

Performance of two Picea abies (L.) Karst. stands at different stages of decline

Summary A declining Picea abies (L.) Karst. stand produced as much foliage and branches as a healthy stand but less stemwood at a similar leaf area index and climate. Nutrient analyses revealed that most biomass components at the declining site had lower concentrations of calcium and magnesium, but similar nitrogen and potassium (except for lower potassium in younger needles) and higher phosphorus, manganese and aluminum than the respective components at the healthy site. Comparison of these data with the results from studies on the nutrition and growth of P. abies seedlings (Ingestad 1959) led to the conclusion that the healthy stand is in a balanced nutritional state, while trees at the declining stand have only 56% of the foliar magnesium concentration required to permit growth at a rate which could be achieved at their nitrogen status. It appears that acidic deposition, which involves an input of nitrogen and a leaching of cations from the soil, causes an imbalance in the availability of nitrogen and magnesium. Growth is eventually reduced as magnesium becomes limiting.     

Reduction of nitrosubstituted aromatic compounds by the halophilic anaerobic eubacteria Haloanaerobium praevalens and Sporohalobacter marismortui.

The moderately halophilic, obligately anaerobic eubacteria Haloanaerobium praevalens DSM 2228 and Sporohalobacter marismortui ATCC 35420 are able to reduce a variety of nitrosubstituted aromatic compounds at a high rate to the corresponding amines. Compounds degraded included nitrobenzene, o-nitrophenol, m-nitrophenol, p-nitrophenol, nitroanilines, 2,4-dinitrophenol, and 2,4-dinitroaniline. Most of these compounds, when added at concentrations of 50 to 100 mg/liter, were completely transformed within 24 h, but at the highest concentrations growth rates were somewhat lowered. Growth of H. praevalens in the presence of 14C-labeled p-nitrophenol showed that the compound was not incorporated by the cells or degraded to acid-volatile compounds.