In Vitro Induction of T Helper 17 Cells by Synergistic Activation of Human Monocyte-Derived Langerhans Cell-Like Cells with Bacterial Agonists.

In the case of epidermal barrier disruption, pathogens encounter skin-resident Langerhans cells (LCs) and are recognized by pathogen recognition receptors such as Toll-like receptors (TLRs). As the majority of microorganisms exhibit more than one TLR ligand, the mechanisms of subsequent T cell differentiation are complex and far from clear. In this study, we investigated combinatory effects on Th cell polarization by bacterial cell wall compounds peptidoglycan (PGN) and lipopolysaccharide (LPS) and by bacterial nucleic acid (DNA).

Probiotic Treatment Decreases the Number of CD14-Expressing Cells in Porcine Milk Which Correlates with Several Intestinal Immune Parameters in the Piglets.

Modulating the mucosal immune system of neonates by probiotic treatment of their mothers is a promising approach which can only be investigated through the use of animal models. Here, we used sows and their piglets to investigate the impact of a bacterial treatment on the sow's milk and on the neonate piglet intestinal immune system. In previous experiments, feed supplementation of sows with the probiotic Enterococcus faecium NCIMB 10415 during pregnancy and lactation had been shown to affect intestinal microbiota and cytokine expression of the offspring during the suckling and weaning periods.

Single Nucleotide Polymorphisms Caused by Assembly Errors.

We compare the results of three different assembler programs, Celera, Phrap and Mira2, for the same set of about a hundred thousand Sanger reads derived from an unknown bacterial genome. In difference to previous assembly comparisons we do not focus on speed of computation and numbers of assembled contigs but on how the different sequence assemblies agree by content. Threefold consistently assembled genome regions are identified in order to estimate a lower bound of erroneously identified single nucleotide polymorphisms (SNP) caused by nothing but the process of mathematical sequence assembly.

Computer-assisted identification of small-molecule Bcl-2 modulators.

Apoptosis, the programmed cell death, is a highly regulated process, necessary for normal development and homeostasis of the functions of organisms. The Bcl-2 inhibitors BH3I-1 and BH3I-2 were used as lead compounds to find possible Bcl-2 or Bcl-X(L) inhibitors by using computer-assisted screening with our in-house database, containing more than four million commercially available molecules. Identified compounds were further investigated regarding their possible application as a drug.

TLR2-activated human langerhans cells promote Th17 polarization via IL-1beta, TGF-beta and IL-23.

The cytokines IL-6, IL-1beta, TGF-beta, and IL-23 are considered to promote Th17 commitment. Langerhans cells (LC) represent DC in the outer skin layers of the epidermis, an environment extensively exposed to pathogenic attack. The question whether organ-resident DC like LC can evoke Th17 immune response is still open.

Identification of brain- and bone-specific breast cancer metastasis genes.

In breast cancer, metastases are relatively widely distributed, with the most common sites being bone, regional lymph nodes, lung, liver, and brain. The detailed mechanism of organ-specific metastasis is poorly understood. In this study, we initiated a search for genes that are implicated in brain or bone metastasis of primary human breast cancer.

SuperToxic: a comprehensive database of toxic compounds.

Within our everyday life, we are confronted with a variety of toxic substances of natural or artificial origin. Toxins are already used, e.g.

SuperScent--a database of flavors and scents.

Volatiles are efficient mediators of chemical communication acting universally as attractant, repellent or warning signal in all kingdoms of life. Beside this broad impact volatiles have in nature, scents are also widely used in pharmaceutical, food and cosmetic industries, so the identification of new scents is of great industrial interest. Despite this importance as well as the vast number and diversity of volatile compounds, there is currently no comprehensive public database providing information on structure and chemical classification of volatiles.

SuperSite: dictionary of metabolite and drug binding sites in proteins.

The increasing structural information about target-bound compounds provide a rich basis to study the binding mechanisms of metabolites and drugs. SuperSite is a database, which combines the structural information with various tools for the analysis of molecular recognition. The main data is made up of 8000 metabolites including 1300 drugs, bound to about 290,000 different receptor binding sites.

JAIL: a structure-based interface library for macromolecules.

The increasing number of solved macromolecules provides a solid number of 3D interfaces, if all types of molecular contacts are being considered. JAIL annotates three different kinds of macromolecular interfaces, those between interacting protein domains, interfaces of different protein chains and interfaces between proteins and nucleic acids. This results in a total number of about 184,000 database entries.

A new dendritic cell type suitable as sentinel of contact allergens.

Establishing of alternatives to animal tests is ethically desirable and gains in importance in context of new European Union regulations such as REACH. We have refined our new in vitro assay for prediction of the sensitizing potency of xenobiotics. Monocytes cocultured with primary human keratinocytes develop to a novel class of in vitro generated dendritic cells after treatment with transforming growth factor beta and Interleukin-4 in serum-free medium.

A structural genomics approach to the regulation of apoptosis: chimp vs. human.

After the sequencing of the human genome, the publication of the genome of our nearest relative, the chimpanzee (Pan troglodytes) provided groundbreaking data improving the understanding of the recent human evolution. There are about forty million changes, most of them single nucleotide substitutions, which teach us about ourselves, both in terms of similarities and differences with chimpanzees. From a medical point of view differences in incidence and severity of diseases are of special importance to pinpoint novel targets and to develop innovative therapies.

SuperPred: drug classification and target prediction.

Unlabelled: The drug classification scheme of the World Health Organization (WHO) [Anatomical Therapeutic Chemical (ATC)-code] connects chemical classification and therapeutic approach. It is generally accepted that compounds with similar physicochemical properties exhibit similar biological activity. If this hypothesis holds true for drugs, then the ATC-code, the putative medical indication area and potentially the medical target should be predictable on the basis of structural similarity.

Human Langerhans cells selectively activated via Toll-like receptor 2 agonists acquire migratory and CD4+T cell stimulatory capacity.

In epidermal Langerhans cells (LCs), the expression pattern and the functions of TLRs have been poorly characterized. By using mAb, we show that LCs from human skin express TLR1, -2, -5, -6, and -9, the cognate receptors for detection of specific bacteria-derived molecules. As compared with other TLR agonists, LCs acquired a more matured phenotype when activated by specific bacterial or synthetic TLR2 agonists.

Toxicity versus potency: elucidation of toxicity properties discriminating between toxins, drugs, and natural compounds.

Within our everyday life we are confronted with a variety of toxic substances. A number of these compounds are already used as lead structures for the development of new drugs, but the amount of toxic substances is still a rich resource of new bioactive compounds. During the identification and development of new potential drugs, risk estimation of health hazards is an essential and topical subject in pharmaceutical industry.

Suffix techniques as a rapid method for RNA substructure search.

The RNA Ontology Consortium recently proposed a two-letter representation of the RNA backbone conformation. In this study, we compare the suite notation to a custom string representation that utilizes eta - theta pseudotorsion angles. Both representations were used to assess similarity and self-similarity in several RNA structure datasets.

A loose-fit coculture of activated keratinocytes and dendritic cell-related cells for prediction of sensitizing potential.

Protection against contact allergy begins with the collection of reliable data about the sensitizing potential of chemicals. Today, the local lymph node assay (LLNA) in mice is widely used to identify sensitizing substances. For several reasons, an in vitro assay could be preferable to animal experiments.

SuperTarget and Matador: resources for exploring drug-target relationships.

The molecular basis of drug action is often not well understood. This is partly because the very abundant and diverse information generated in the past decades on drugs is hidden in millions of medical articles or textbooks. Therefore, we developed a one-stop data warehouse, SuperTarget that integrates drug-related information about medical indication areas, adverse drug effects, drug metabolization, pathways and Gene Ontology terms of the target proteins.

Hydrogen-bonding and packing features of membrane proteins: functional implications.

The recent structural elucidation of about one dozen channels (in which we include transporters) has provided further evidence that these membrane proteins typically undergo large movements during their function. However, it is still not well understood how these proteins achieve the necessary trade-off between stability and mobility. To identify specific structural properties of channels, we compared the helix-packing and hydrogen-bonding patterns of channels with those of membrane coils; the latter is a class of membrane proteins whose structures are expected to be more rigid.

Docking without docking: ISEARCH--prediction of interactions using known interfaces.

The increasing number of solved protein structures provides a solid number of interfaces, if protein-protein interactions, domain-domain contacts, and contacts between biological units are taken into account. An interface library gives us the opportunity to identify surface regions on a target molecule that are similar by local structure and residue composition. If both unbound components of a possible protein complex exhibit structural similarities to a known interface, the unbound structures can be superposed onto the known interfaces.

Antibody blocking of MHC II on human activated regulatory T cells abrogates their suppressive potential.

Natural regulatory CD4(+)CD25(+)Foxp3(+) T cells control peripheral immune responses. Freshly isolated regulatory T-cell populations are regarded as being unable to suppress the proliferation of strongly stimulated effector T cells. We now provide evidence that it is not the strength of the proliferative signal to effector T cells but activation and accessibility of regulatory T cells that determine whether suppression may occur.

Design and biological evaluation of photo-switchable inhibitors.

Photo-switchable compounds are becoming increasingly popular for a series of biological applications based on the reversible photo-control of structure and function of biomolecules. Three applications for the usage of BODTCM and hemithioindigo as photo-reactive compounds are described here. The structure of the villin headpiece was modified by replacing a part of the backbone with hemithioindigo, aiming at induction of the folding process by irradiation with a defined wavelength.

Comparison of gene expression data from human and mouse breast cancers: identification of a conserved breast tumor gene set.

The aim of our work was to establish a database for breast cancer gene expression data in order to compare human and mouse breast cancer. We identified human and mouse homologues genes and compared the expression profile of 24 human breast tumors with 6 WAP-SVT/t breast tumors (WAP-SVT/t animals, line 8). Our studies confirmed the heterogeneity in gene expression of human as well as mouse breast cancer cells.

SuperHapten: a comprehensive database for small immunogenic compounds.

The immune system protects organisms from foreign proteins, peptide epitopes and a multitude of chemical compounds. Among these, haptens are small molecules, eliciting an immune response when conjugated with carrier molecules. Known haptens are xenobiotics or natural compounds, which can induce a number of autoimmune diseases like contact dermatitis or asthma.

Human monocyte-derived dendritic cells express TLR9 and react directly to the CpG-A oligonucleotide D19.

Oligodeoxynucleotides (ODNs) containing unmethylated CpG exhibit their immunostimulatory activities by binding to TLR. Here, we show that human monocyte-derived dendritic cells (moDC) contain TLR9 protein, surprisingly, in amounts comparable with plasmacytoid DC (pDC). Immature moDC but not mature moDC nor monocytes captured CpG-ODNs.