Wnt and lithium: a common destiny in the therapy of nervous system pathologies?

Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the mechanisms of action of Wnt signaling pathways and their implication in the development and correct functioning of the nervous system. We also illustrate how a dysregulated Wnt pathway could lead to psychiatric, neurodegenerative and demyelinating pathologies. Lithium, used for the treatment of bipolar disease, inhibits GSK3β, a central enzyme of the Wnt/β-catenin pathway. Thus, lithium could, to some extent, mimic Wnt pathway. We highlight the possible dialogue between lithium therapy and modulation of Wnt pathway in the treatment of the diseases of the nervous system.     

Genetics and pathogenesis of inflammatory bowel disease

Recent advances have provided substantial insight into the maintenance of mucosal immunity and the pathogenesis of inflammatory bowel disease. Cellular programs responsible for intestinal homeostasis use diverse intracellular and intercellular networks to promote immune tolerance, inflammation or epithelial restitution. Complex interfaces integrate local host and microbial signals to activate appropriate effector programs selectively and even drive plasticity between these programs. In addition, genetic studies and mouse models have emphasized the role of genetic predispositions and how they affect interactions with microbial and environmental factors, leading to pro-colitogenic perturbations of the host-commensal relationship.     

Alkaline phosphatase binds to collagen; a hypothesis on the mechanism of extravesicular mineralization in epiphyseal cartilage

Summary Affinity chromatography on Sepharose 4B-collagen gels was used to test the affinity of alkaline phosphatase for collagen. Results indicate that 1) alkaline phosphatase of preosseous cartilage binds to collagen probably by electrostatic interactions, 2) this interaction is inhibited by proteoglycan subunits. These results suggest that, in vivo, the formation of a collagen-alkaline phosphatase complex may be a step of the process leading to cartilage calcification.This investigation was supported by research grants of C.N.R. (C.T. 82.02437.04), of Ministero della Pubblica Istruzione and of the University of Trieste.To whom correspondence and reprint requests should be addressed.     

Note Textuelle sur un (Problème de) Lieu Géométrique dans les Météorologiques d'Aristote (III. 5, 375 b 16 – 376 b 22)

Sans résumé Manuscrit re?u 31 juillet 2001     

Electrophoretic profiles of proteins and glycoproteins of chick embryo fibroblasts during development]

The variations of proteins and glycoproteins of Chick embryo fibroblasts are studied during development. This investigation is carried out using polyacrylamide disc gel electrophoresis in SDS. Two glycoproteins of high apparent molecular weight (250,000 and 200,000) undergo quantitative modification: they increase from the 8th to 12th day of development and then remain unchanged to the 16th day. They are cell surface components as suggested by fluorescamine labelling and trypsin sensitivity. The results are discussed in terms of relationship between tumor- and embryo cells.     

Hierarchically Clustered HMM for Protein Sequence Motif Extraction with Variable Length

Protein sequence motifs extraction is an important field of bioinformatics since its relevance to the structural analysis. Two major problems are related to this field：（1） searching the motifs within the same protein family; and（2） assuming a window size for the motifs search. This work proposes the Hierarchically Clustered Hidden Markov Model（HC-HMM） approach, which represents the behavior and structure of proteins in terms of a Hidden Markov Model chain and hierarchically clusters each chain by minimizing distance between two given chains＇ structure and behavior. It is well known that HMM can be utilized for clustering, however, methods for clustering on Hidden Markov Models themselves are rarely studied. In this paper, we developed a hierarchical clustering based algorithm for HMMs to discover protein sequence motifs that transcend family boundaries with no assumption on the length of the motif. This paper carefully examines the effectiveness of this approach for motif extraction on 2593 proteins that share no more than 25% sequence identity. Many interesting motifs are generated.Three example motifs generated by the HC-HMM approach are analyzed and visualized with their tertiary structure.We believe the proposed method provides a unique protein sequence motif extraction strategy. The related data mining fields using Hidden Markova Model may also benefit from this clustering on HMM themselves approach.     

Characterization and photoluminescence properties of ultrafine copper molybdate (α-CuMoO4) powders prepared via a combustion-like process

We report a simple method for preparing copper(II) molybdate (CuMoO₄) powders via a combustion-like process. A gel was first prepared by the polymerizable complex method, where citric acid was used as a complexing and polymerizing agent and nitric acid was used as an oxidizing agent. The thermal decomposition behavior of the (CuMo)-precursor gel was studied by thermogravimetry–differential thermal analysis (TG–DTA), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). We observed that the crystallization of CuMoO₄ powder was completed at 450°C. The obtained homogeneous powder was composed of grains with sizes in the range from 150 to 500 nm and exhibited a specific surface area of approximately 5 m2/g. The average grain size increased with increasing annealing temperature. The as-prepared CuMoO₄ crystals showed a strong green photoluminescence emission at room temperature under excitation at 290 nm, which we mainly interpreted on the basis of the Jahn-Teller effect on [MoO₄2- ] complex anions. We also observed that the photoluminescence intensity increased with increasing crystallite size.     

The clonal and mutational evolution spectrum of primary triple-negative breast cancers

Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.