Mutations of the SLX4 gene in Fanconi anemia

Fanconi anemia is a rare recessive disorder characterized by genome instability, congenital malformations, progressive bone marrow failure and predisposition to hematologic malignancies and solid tumors. At the cellular level, hypersensitivity to DNA interstrand crosslinks is the defining feature in Fanconi anemia. Mutations in thirteen distinct Fanconi anemia genes have been shown to interfere with the DNA-replication-dependent repair of lesions involving crosslinked DNA at stalled replication forks. Depletion of SLX4, which interacts with multiple nucleases and has been recently identified as a Holliday junction resolvase, results in increased sensitivity of the cells to DNA crosslinking agents. Here we report the identification of biallelic SLX4 mutations in two individuals with typical clinical features of Fanconi anemia and show that the cellular defects in these individuals' cells are complemented by wildtype SLX4, demonstrating that biallelic mutations in SLX4 (renamed here as FANCP) cause a new subtype of Fanconi anemia, Fanconi anemia-P.     

The Role of Formalisation, Participation and Context in the Success of Public Involvement Mechanisms in Resource Management

In the face of complex and uncertain issues, one important goal of public participation in resource management and research is to foster communication and the inclusion of non-expert knowledge—thus the effective flow of information between project organisers and stakeholders. We compare different methods (instruments, tools) that were employed in the German–Austrian ‘PartizipA’ project to structure information flows in participatory processes. Depending on their goals and context, more or less ‘formalised’ and ‘participatory’ methods were applied, the most important being guided interviews, focus groups, agent-based modelling, nutrient modelling, cognitive mapping and group model building as well as the development of a common document. Two regional case studies, both concerned with European-induced institutional change, are portrayed in which the specific participatory methods were embedded. The Austrian case study involved the analysis and modelling of agricultural land use in the region of St. Pölten against the background of the reform of the Common Agricultural Policy, while the implementation of recent European water policy was the issue in the German agricultural region north of Osnabrück. Presenting both cases in their regional context, the applied methods are first described according to the logic of the entire respective process. Subsequently, the specific methods are systematically analysed and compared according to their objective, context and degrees of participation and formalisation. Finally, we evaluate all methods regarding their effectiveness in terms of goal attainment and their potential generalisation, seeking to respond to the question of when a particular method might best be used.     

The coordinating properties ofd-biotin

Summary The coenzymed-biotin offers in its anionic form to metal ions 3 possible binding sites: the carboxylate group of the valerate side chain, the ureido residue of the 2-imidazolidone ring, and the thioether sulfur of the tetrahydrothiophene ring; the coordinating properties of these groups are summarized and compared. Hydrogen bond formation of the ureido group has also been observed, and hydrogen bonding may possibly be important in biotin-bicarbonate recognition. The aliphatic part of the valeric acid side chain can undergo hydrophobic interactions. Such interactions and/or the stereoselective sulfur-metal ion coordination could be the means for a correct fixation of the biotinyl moiety at the surface of a protein, thus creating the active enzyme-substrate complex.     

The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia

Seven Fanconi anemia-associated proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCL) form a nuclear Fanconi anemia core complex that activates the monoubiquitination of FANCD2, targeting FANCD2 to BRCA1-containing nuclear foci. Cells from individuals with Fanconi anemia of complementation groups D1 and J (FA-D1 and FA-J) have normal FANCD2 ubiquitination. Using genetic mapping, mutation identification and western-blot data, we identify the defective protein in FA-J cells as BRIP1 (also called BACH1), a DNA helicase that is a binding partner of the breast cancer tumor suppressor BRCA1.     

Photocatalytic and electrochemical degradation of methylene blue by titanium dioxide

A photoanode structure for dye-sensitized solar cells has been applied into the photocatalytic/electro- chemical cooperative degradation of methylene blue solu- tions. The low eutectic point of titanium dioxide （TiO2） with a fluorine-doped tin dioxide （FTO） conductive layer results in a high reactivity of TiO2 for the photocatalytic process as well as a good electron transfer for the elec- trochemical process. The porous TiO2 layer maintains a large surface area for the degradations. Through the com- binational process, the degradation velocity was improved by - 36 %, compared to a pure photocatalytic process.