Sonic hedgehog in the pharyngeal endoderm controls arch pattern via regulation of Fgf8 in head ectoderm

Fgf8 signalling is known to play an important role during patterning of the first pharyngeal arch, setting up the oral region of the head and then defining the rostral and proximal domains of the arch. The mechanisms that regulate the restricted expression of Fgf8 in the ectoderm of the developing first arch, however, are not well understood. It has become apparent that pharyngeal endoderm plays an important role in regulating craniofacial morphogenesis. Endoderm ablation in the developing chick embryo results in a loss of Fgf8 expression in presumptive first pharyngeal arch ectoderm. Shh is locally expressed in pharyngeal endoderm, adjacent to the Fgf8-expressing ectoderm, and is thus a candidate signal regulating ectodermal Fgf8 expression. We show that in cultured explants of presumptive first pharyngeal arch, loss of Shh signalling results in loss of Fgf8 expression, both at early stages before formation of the first arch, and during arch formation. Moreover, following removal of the endoderm, Shh protein can replace this tissue and restore Fgf8 expression. Overexpression of Shh in the non-oral ectoderm leads to an expansion of Fgf8, affecting the rostral-caudal axis of the developing first arch, and resulting in the formation of ectopic cartilage. Shh from the pharyngeal endoderm thus regulates Fgf8 in the ectoderm and the role of the endoderm in pharyngeal arch patterning may thus be indirectly mediated by the ectoderm.     

Surfactin from Bacillus subtilis displays anti-proliferative effect via apoptosis induction, cell cycle arrest and survival signaling suppression

The effect of surfactin on the proliferation of LoVo cells, a human colon carcinoma cell line, was examined. Surfactin strongly blocked the proliferation of LoVo cells by inducing pro-apoptotic activity and arresting the cell cycle, according to several lines of evidence on DNA fragmentation, Annexin V staining, and altered levels of poly (ADP-ribose) polymerase, caspase-3, p21(WAF1/Cip1), p53, CDK2 and cyclin E. The anti-proliferative activity of surfactin was mediated by inhibiting extracellular-related protein kinase and phosphoinositide 3-kinase/Akt activation, as assessed by phosphorylation levels. Therefore, our data suggest that surfactin may have anti-cancer properties as a result of its ability to downregulate the cell cycle and suppress its survival.     

Expansion of symmetric exon-bordering domains does not explain evolution of lineage specific genes in mammals

In order to examine the evolution of lineage specific genes, we analyzed intron phase distributions and exon-bordering domains in primate and rodent specific genes. We found that the expansion of symmetric exon-bordering domains could not explain the evolution of lineage specific genes. Rather internal intron loss of a domain can partially explain the excess of class 1–1 intron phases in the lineage specific genes. We suggest the event that led to excess of symmetric exons in lineage specific genes had little bearing on shaping the phenotypes specific to the individual lineage. Instead, Kruppel-associated box (KRAB) proteins associated with zinc finger C2H2 (zf-C2H2) type are likely to be responsible for the lineage specific function.     

Environmental effects on gene expression phenotype have regional biases in the human genome

Phenotypic discordance between monozygotic twins, such as a difference in disease susceptibility, implicates the role of the environment in determining phenotype. To assess genomewide environmental effects on "gene expression phenotype," we employed a published microarray data set for twins. We found that variations in expression phenotypes between monozygotic twins have biases in their chromosomal locations. They also showed a strong inverse correlation with gene density. Genomic regions of low gene density were environmentally sensitive, containing genes involved in response to external signals, cell differentiation, and development, etc. Genetic factors were found to make no contribution to the observed regional biases, stressing the role of epigenetics. We propose that epigenetic modifications might occur more frequently in heterochromatic, gene-poor regions in response to environmental signals while gene-rich regions tend to remain in an active chromatin configuration for the constitutive expression of underlying genes.     

Egr-1, a new downstream molecule of Epstein-Barr virus latent membrane protein 1

To investigate the effect of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) on human cancer cells, we sought to identify and analyze potential target genes that were differentially expressed in the presence and absence of LMP1. Our cDNA microarray analysis revealed that expression of early growth response gene-1 (Egr-1) was increased by LMP1 expression in MCF7 and Jurkat cells. An NFkappaB inhibitor (SN50) antagonized LMP1-induced enhancement of Egr-1 expression, indicating that LMP1 induced Egr-1 via NFkappaB. Furthermore, three lines of evidence indicated that Egr-1 was required for LMP1-induced cancer cell survival. First, Egr-1 expression enhanced the survival of doxorubicin-treated MCF7 cells. Second, inhibition of Egr-1 expression by siRNA (siEgr-1) effectively suppressed LMP-1-induced survival of MCF7 cells. Third, Egr-1 knockdown decreased LMP1-induced expression of Bfl-1. Similar relationships among EBV infection, Egr-1 and drug resistance were also observed in tissues of peripheral T-cell lymphoma-unspecified (PTCL-u) patients.     

Structure-function relationships in a bacterial DING protein

A recombinant DING protein from Pseudomonas fluorescens has been previously shown to have a phosphate-binding site, and to be mitogenic for human cells. Here we report the three-dimensional structure of the protein, confirming a close similarity to the "Venus flytrap" structure seen in other human and bacterial phosphate-binding proteins. Site-directed mutagenesis confirms the role of a key residue involved in phosphate binding, and that the mitogenic activity is not dependent on this property. Deletion of one of the two hinged domains that constitute the Venus flytrap also eliminates phosphate binding whilst enhancing mitogenic activity.     

Cell cycle arrest of stamen initials in maize sex determination

The maize sex determination pathway results in the arrest of stamen in ear spikelets and the abortion of pistils in both the tassel spikelets and in the secondary florets of ear spikelets. Arrested stamen cells showed no signs of DNA fragmentation, an absence of CYCLIN B expression, and an accumulation of the negative cell cycle regulator WEE1 RNA.