Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88

Inflammation is increasingly recognized as an important component of tumorigenesis, although the mechanisms and pathways involved are not well understood. Tumor development is regulated by products of several modifier genes, but instructions for their tumor-specific expression are currently unknown. We show that the signaling through the adaptor protein MyD88 has a critical role in spontaneous tumor development in mice with heterozygous mutation in the adenomatous polyposis coli (APC) gene. We found that MyD88-dependent signaling controls the expression of several key modifier genes of intestinal tumorigenesis and has a critical role in both spontaneous and carcinogen-induced tumor development. This study thus reveals the important role of an innate immune signaling pathway in intestinal tumorigenesis.     

Disease tolerance as a defense strategy

The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogen's presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of "disease tolerance" into the conceptual tool kit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases.     

Metal concentrations in soil and invertebrates in the vicinity of a metallurgical factory near Tula (Russia)

To investigate the effects of emissions from a large metal works near Tula in the Russian Federation, we measured concentrations of iron, manganese, zinc, copper, nickel, lead and cadmium in soil, litter and invertebrates at four sampling sites at different distances from the factory. The sites were located in woodlands in the bed of the Voronka river, near the town of Kosaya Gora in the district of Tula. Additional soil properties (organic matter content, clay content, water holding capacity, Ca, Mg, N, P, and pH) were measured that could explain differences in the bioavailability of the metal burdens. It appeared that the factory is a source of Fe, Mn, Zn, Cu, Ni and Pb. One of the sampling sites had a high nitrogen content in the litter due to emissions from a fertilizer plant in the area. Most of the metal contamination was limited to the immediate surroundings and did not extend beyond a distance of 5 km. Only the site close to the factory can be considered as polluted, however, background concentrations of metals in the Tula area seem to be significantly lower than in present Western European soils and a reference system still has to be developed. Exchangeable metal concentrations (0.01 M CaCl₂ extracts from soil) were very low and were not correlated with the total concentrations, indicating low bioavailability of the pollution. At the most polluted site, concentrations of all metals were positively correlated with each other; correlations decreased with increasing distance. Metal concentrations in soil were often negatively correlated with organic matter content, especially so for nickel. Metal concentrations in invertebrates showed considerable variation between individual species, however, some general patterns were obvious. Concentrations were high in earthworms, oribatid mites and carabid beetles, and low in springtails, centipedes and spiders. There was no relationship between the trophic position of a species and its metal accumulating ability. Iron concentrations in invertebrates at the polluted site were a factor of 2 to 4 higher than at the most remote (reference) site; for zinc and copper the internal concentrations were also elevated, but to a lesser extent than the soil concentrations. The data illustrate the extremely complicated relationship between metal residues in invertebrates and metal concentrations in soil. For most of the saprophageous and predatory arthropods studied total concentrations nor exchangeable concentrations in soil are good predictors; species-specific feeding mechanisms and metal physiologies seem to be the main determinants.     

Toll-like receptor signaling pathways

Members of the Toll-like receptor (TLR) family recognize conserved microbial structures, such as bacterial lipopolysaccharide and viral double-stranded RNA, and activate signaling pathways that result in immune responses against microbial infections. All TLRs activate MyD88-dependent pathways to induce a core set of stereotyped responses, such as inflammation. However, individual TLRs can also induce immune responses that are tailored to a given microbial infection. Thus, these receptors are involved in both innate and adaptive immune responses. The mechanisms and components of these varied responses are only partly understood. Given the importance of TLRs in host defense, dissection of the pathways they activate has become an important emerging research focus. TLRs and their pathways are numerous; Science's Signal Transduction Knowledge Environment's TLR Connections Map provides an immediate, clear overview of the known components and relations of this complex system.     

Decoding the patterns of self and nonself by the innate immune system

The innate immune system evolved several strategies of self/nonself discrimination that are based on the recognition of molecular patterns demarcating infectious nonself, as well as normal and abnormal self. These patterns are deciphered by receptors that either induce or inhibit an immune response, depending on the meaning of these signals.     

A major constituent of brown algae for use in high-capacity Li-ion batteries

The identification of similarities in the material requirements for applications of interest and those of living organisms provides opportunities to use renewable natural resources to develop better materials and design better devices. In our work, we harness this strategy to build high-capacity silicon (Si) nanopowder-based lithium (Li)-ion batteries with improved performance characteristics. Si offers more than one order of magnitude higher capacity than graphite, but it exhibits dramatic volume changes during electrochemical alloying and de-alloying with Li, which typically leads to rapid anode degradation. We show that mixing Si nanopowder with alginate, a natural polysaccharide extracted from brown algae, yields a stable battery anode possessing reversible capacity eight times higher than that of the state-of-the-art graphitic anodes.     

Regulation of phagosome maturation by signals from toll-like receptors

In higher metazoans, phagocytosis is essential in host defense against microbial pathogens and in clearance of apoptotic cells. Both microbial and apoptotic cells are delivered on a common route from phagosomes to lysosomes for degradation. Here, we found that activation of the Toll-like receptor (TLR) signaling pathway by bacteria, but not apoptotic cells, regulated phagocytosis at multiple steps including internalization and phagosome maturation. Phagocytosis of bacteria was impaired in the absence of TLR signaling. Two modes of phagosome maturation were observed, constitutive and inducible; their differential engagement depended on the ability of the cargo to trigger TLR signaling.     

Application of five DNA marker techniques to distinguish between five apple (Malus × domestica Borkh.) cultivars and their sports

Summary

Genetic variation between five apple cultivars (‘Golden Delicious’, ‘Gala’, ‘Jonagold’, ‘?ampion’, and ‘Idared’) and ten of their sports (‘Golden Delicious Reinders’, ‘Goldrosio’, ‘Gala Must’, ‘Gala Schniga Schnitzer’, ‘Jonagored’, ‘Jonagold Excel’, ‘Szampion Arno’, ‘Szampion Reno Malinowy’, ‘Idaredest’, and ‘Red Idared’) was investigated using five types of DNA markers: Inter-Simple Sequence Repeats (ISSR), Simple Sequence Repeats (SSR), Amplified Fragment Length Polymorphism (AFLP), Sequence-Specific Amplified Polymorphism (S-SAP), and Inter-Primer Binding Site (iPBS) amplification. In total, 941 polymorphic amplified fragments were obtained using 12 ISSR, 12 SSR, ten AFLP, 19 iPBS, and 15 S-SAP primers or primer pairs. Four of the above-described techniques (except for SSRs with the primer pairs used in this study) were able to distinguish between the sports and their parental cultivar. The most effective technique to distinguish between the genotypes analysed was S-SAP, which detects variations in DNA regions flanking retrotransposon insertion sites.The combined use of ISSR,AFLP, iPBS, and S-SAP markers identified and distinguished all of the sports tested.     

Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells

Toll-like receptors (TLRs) control activation of adaptive immune responses by antigen-presenting cells (APCs). However, initiation of adaptive immune responses is also controlled by regulatory T cells (TR cells), which act to prevent activation of autoreactive T cells. Here we describe a second mechanism of immune induction by TLRs, which is independent of effects on costimulation. Microbial induction of the Toll pathway blocked the suppressive effect of CD4+CD25+ TR cells, allowing activation of pathogen-specific adaptive immune responses. This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of microbial products.