Chemical mutagenesis of a GPCR ligand: Detoxifying "inflammo-attraction" to direct therapeutic stem cell migration.

A transplanted stem cell's engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell's "pathotropism." Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12. Binding of CXCL12 to CXCR4 (a G protein-coupled receptor, GPCR) triggers repair processes within the NSC. Although a tool directing NSCs to where needed has been long-sought, one would not inject this chemokine in vivo because undesirable inflammation also follows CXCL12-CXCR4 coupling. Alternatively, we chemically "mutated" CXCL12, creating a CXCR4 agonist that contained a strong pure binding motif linked to a signaling motif devoid of sequences responsible for synthetic functions. This synthetic dual-moity CXCR4 agonist not only elicited more extensive and persistent human NSC migration and distribution than did native CXCL 12, but induced no host inflammation (or other adverse effects); rather, there was predominantly reparative gene expression. When co-administered with transplanted human induced pluripotent stem cell-derived hNSCs in a mouse model of a prototypical neurodegenerative disease, the agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cerebral cortex (including as electrophysiologically-active cortical neurons) where their secreted cross-corrective enzyme mediated a therapeutic impact unachieved by cells alone. Such a "designer" cytokine receptor-agonist peptide illustrates that treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., "inflammo-attraction").

[Evaluation of the color stability of infiltrant resin in comparison to aesthetic composite resins].

OBJECTIVE: To investigate the color stability of infiltrant resin together with three other composites exposed to staining solution. METHODS: Three types of anterior aesthetic composite resins (Filtek Z250, Filtek Z350 XT, and Beautiful Flow Plus F00) and artificial caries with Icon infiltrant resin were used. The samples were randomly divided into two groups (each contained 10 specimens): coffee solution and distilled water immersion for three weeks. Color parameters were deter-mined with the Crystaleye spectrophotometer. RESULTS: Artificial caries lesions infiltrated by Icon showed much higher ΔE than those infiltrated by other aesthetic resins (P<0.05). The discoloration of all the experimental resins and the artificial caries infil-trated with Icon increased with time, but the discoloration on the 1st week was significantly higher than those on the 2nd and 3rd weeks. CONCLUSIONS: Artificial caries infiltrated with Icon was more vulnerable and susceptive to food color than those infiltrated with other aesthetic composite resins.

[A clinical study of Palodent posterior teeth matrix system].

OBJECTIVE: To set up a clinical evaluation method for the matrix system, and compare two matrix systems, Palodent and circumferential, by this method. METHODS: 101 molars and premolars with class II cavities, which were suitable for resin filling without shift and incline of the adjacent teeth, were randomly divided into study group (Palodent) and control group (circumferential). There were 79 single cavities and 22 paired cavities. One doctor-in-charge completed all cavities filling. Probes were used to test overhang of the filling. Dental floss was used to detect the proximal contact index before and after cavity preparing and immediately and one week after cavity filling. Questionnaires were filled in by patients immediately and one week afrer cavity filling. The tooth models of the filling side were taken, then two doctors-in-charge were responsible for establishing the model evaluation index and one of them conducted the evaluation for all of the models. SPSS 14.0 software was used to analyze the data. RESULTS: An evaluation system including questionnaire, clinical examination and tooth model evaluation was set up. There were nine indexes in this system. Moreover, this clinical evaluation system was used in this study. It was found that there were no differences on questionnaire and overhang indexes between the two groups. Palodent matrix system got tighter proximal contact than traditional circumferential matrix system. When filling the paired posterior teeth, Palodent matrix system formed better marginal ridge than circumferential matrix system. CONCLUSION: Palodent matrix system is better than circumferential matrix system in filling the paired posterior teeth.

A fine physical map of the rice chromosome 4.

As part of an international effort to completely sequence the rice genome, we have produced a fine bacterial artificial chromosome (BAC)-based physical map of the Oryza sativa japonica Nipponbare chromosome 4 through an integration of 114 sequenced BAC clones from a taxonomically related subspecies O. sativa indica Guangluai 4 and 182 RFLP and 407 expressed sequence tag (EST) markers with the fingerprinted data of the Nipponbare genome. The map consists of 11 contigs with a total length of 34.5 Mb covering 94% of the estimated chromosome size (36.8 Mb). BAC clones corresponding to telomeres, as well as to the centromere position, were determined by BAC-pachytene chromosome fluorescence in situ hybridization (FISH). This gave rise to an estimated length ratio of 5.13 for the long arm and 2.9 for the short arm (on the basis of the physical map), which indicates that the short arm is a highly condensed one. The FISH analysis and physical mapping also showed that the short arm and the pericentromeric region of the long arm are rich in heterochromatin, which occupied 45% of the chromosome, indicating that this chromosome is likely very difficult to sequence. To our knowledge, this map provides the first example of a rapid and reliable physical mapping on the basis of the integration of the data from two taxonomically related subspecies.

Sequence and analysis of rice chromosome 4.

Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.