Cancer predisposing mutations in BRCT domains

Members of the breast cancer 1 (BRCA1) carboxy-terminal (BRCT) superfamily are involved in the cellular response to the DNA damage sensing and repair, as well as in the cell cycle control. All proteins are characterized by one or more BRCT domain(s), which provides a flexible framework representing scaffolding element(s) in multi-protein complexes. In particular, BRCA1, nibrin (NBN), and microcephalin (MCPH1), generally considered as molecular models for cancer-prone syndromes, contain BRCT domains able to bind phosphorylated proteins. Mutations within the BRCT domains of BRCA1, NBN, and MCPH1 are responsible for cancer susceptibility, both at the homozygous and heterozygous status. Here, we report a critical analysis of: (i) the BRCT domain structure, (ii) the role of BRCA1, NBN, and MCPH1 in DNA damage sensing and repair as well as in cell cycle control, and (iii) the pathological effects of mutations within the BRCT domains of BRCA1, NBN, and MCPH1.     

Egg adhesion of the codling moth Cydia pomonella L. (Lepidoptera, Tortricidae) to various substrates: I. Leaf surfaces of different apple cultivars

Codling moths, Cydia pomonella L. (Lepidoptera, Tortricidae), of the first generation deposit eggs on apple leaves in the vicinity of small fruits. The choice of the suitable oviposition sites and proper fixation of eggs are expected to be crucial factors for the survival of the offspring. In this study, we investigated egg adhesion of the codling moth to leaf surfaces of different cultivars of the domestic apple, Malus domestica Borkh., by measuring the pull-off force required to detach the eggs from leaves. Since surface features may influence insect egg adhesion, morphological and physicochemical properties (wettability, free surface energy) of these leaf surfaces were analyzed. Furthermore, eggs and their adhesives covering leaf surfaces were visualized. Eggs on the smooth upper leaf surfaces of all tested cultivars required significantly similar pull-off forces to be detached, at a total average of 6.0?mN. Up to 2?C3 times stronger pull-off forces had to be applied to detach eggs from trichome-covered lower leaves, and these forces differed significantly between cultivars. The role of leaf surface properties is discussed in the context of egg adhesion, oviposition site choice, female attachment, as well as neonate locomotion speed and survival. The obtained results shed light on the susceptibility of various apple cultivars and leaf surfaces to the infestation of apple trees by first-generation codling moths.     

Induction of Paneth cell degranulation by orally administered Toll-like receptor ligands

The secretory activity of Paneth cells is related to the bacterial milieu in the small intestine; however, the molecules involved in inducing Paneth cell secretion of enzymes and antimicrobial peptides are not well-defined. Mice treated orally with CpG-oligodeoxynucleotide (ODN), an agonist of Toll-like receptor (TLR) 9, showed rapid and massive Paneth cell degranulation. CpG-ODN-induced degranulation was not observed in TLR9(-/-) mice or in chimeric TLR9(-/-) mice reconstituted with wild-type (WT) bone marrow, but was observed in WT mice reconstituted with TLR9(-/-) bone marrow, indicating a role for TLR9-expressing gastrointestinal cells in CpG recognition. The TLR3 agonist polyinosinic-polycytidylic acid also induced rapid degranulation, whereas the TLR4 and TLR5 agonists LPS and flagellin, respectively, induced late degranulation mediated by TNF-α. Our evidence that TLR9 and TLR3 agonists induce Paneth cell degranulation points to the need for further studies of the mechanisms underlying Paneth cell function as an avenue toward preventing infection and treating inflammatory bowel diseases.     

Exploring massive, genome scale datasets with the GenometriCorr package

We have created a statistically grounded tool for determining the correlation of genomewide data with other datasets or known biological features, intended to guide biological exploration of high-dimensional datasets, rather than providing immediate answers. The software enables several biologically motivated approaches to these data and here we describe the rationale and implementation for each approach. Our models and statistics are implemented in an R package that efficiently calculates the spatial correlation between two sets of genomic intervals (data and/or annotated features), for use as a metric of functional interaction. The software handles any type of pointwise or interval data and instead of running analyses with predefined metrics, it computes the significance and direction of several types of spatial association; this is intended to suggest potentially relevant relationships between the datasets. AVAILABILITY AND IMPLEMENTATION: The package, GenometriCorr, can be freely downloaded at http://genometricorr.sourceforge.net/. Installation guidelines and examples are available from the sourceforge repository. The package is pending submission to Bioconductor.     

Ecological investigations on lichen fields of the Central Namib

Number, geographic location, extent and characteristics of lichen fields were recorded within the Central Namib fog desert. Their occurrence is restricted to stable surfaces in the near coastal belt, while percentage cover changes with exposure, elevation and distance from the coastline. Maximum coverage of 70% was found at a distance of 5 km from the coast near Wlotzkas Baken. The highest biomass rate of 400 mg/m² was measured here at a distance of 1 km from the coast, where Teloschistes capensis appears as cushion growth type. Distribution patterns on hills, riverbeds and polygon structures are described. In general, fruticose and foliose lichens dominate on SW-exposed, ocean-facing habitats. Crustose species dominate on NE-E-exposed plots.Species composition and distribution, particularly the distribution of the fruticose species T. capensis (L. f.) Vain. ex Müll. Arg., were investigated in seventysix plots along twenty W-E transects in one lichen field near Wlotzkas Baken. T. capensis occurs in three different growth types: tuft, cushion and mat. Four zones are distinguished within the above lichen field, each dominated by a growth form indicating various influences of different climatic, geomorphic or biogenic parameters.     

A General Model for Toxin-Antitoxin Module Dynamics Can Explain Persister Cell Formation in E. coli

Toxin-Antitoxin modules are small operons involved in stress response and persister cell formation that encode a “toxin” and its corresponding neutralizing “antitoxin”. Regulation of these modules involves a complex mechanism known as conditional cooperativity, which is supposed to prevent unwanted toxin activation. Here we develop mathematical models for their regulation, based on published molecular and structural data, and parameterized using experimental data for F-plasmid ccdAB, bacteriophage P1 phd/doc and E. coli relBE. We show that the level of free toxin in the cell is mainly controlled through toxin sequestration in toxin-antitoxin complexes of various stoichiometry rather than by gene regulation. If the toxin translation rate exceeds twice the antitoxin translation rate, toxins accumulate in all cells. Conditional cooperativity and increasing the number of binding sites on the operator serves to reduce the metabolic burden of the cell by reducing the total amounts of proteins produced. Combining conditional cooperativity and bridging of antitoxins by toxins when bound to their operator sites allows creation of persister cells through rare, extreme stochastic spikes in the free toxin level. The amplitude of these spikes determines the duration of the persister state. Finally, increases in the antitoxin degradation rate and decreases in the bacterial growth rate cause a rise in the amount of persisters during nutritional stress.     

Hydrogen sulfide induces nitric oxide release from nitrite

Hydrogen sulfide has recently been considered to have an important role as a gasotransmitter in the cardiovascular system as well as in the central nervous system, but its action seems directly related to the presence of nitric oxide/nitric oxide-derivatives. We report here chemical evidence that emphasizes a prominent role of the hydrogen sulfide as cofactor of NO-derivatives in inducing nitric oxide release.