Expression of INK4 inhibitors of cyclin D-dependent kinases during mouse brain development

In situ hybridization of mouse embryo sections demonstrated expression of mRNAs encoding two polypeptide inhibitors (p18INK4c and p19INK4d) of cyclin D-dependent kinase (CDK) 4 and CDK6 in the central nervous system. No expression of two other INK4 members, p16INK4a and p15INK4b, was observed. The p19INK4d and p18INK4c proteins formed complexes with either CDK4 or CDK6 in a temporal pattern consistent with the results of in situ hybridization. Expression of INK4c was observed at embryonic day 13.5 in neuroepithelial zones of the developing brain, being restricted to dividing neuroblasts but absent from differentiating postmitotic neurons. In the neocortex, p18INK4c was expressed precisely at those developmental stages when neuroblasts switch from a symmetric to an asymmetric pattern of cell division with concomitant increases in their G1 interval. INK4d RNA was detected from embryonic day 11.5 onward, at higher levels than INK4c and with a distinctly different spatial and temporal pattern. Marked INK4d expression was seen in dorsal root ganglia, spinal cord, and focally throughout the brain, but primarily in postmitotic neurons. Neural expression of INK4d continued postnatally into adulthood in postmitotic cells of the dentate gyrus, the pyramidal layer of the hippocampus, and in discrete regions of the cerebral cortex, cerebellum, thalamus, and brainstem. Downregulation of p19INK4d in the dentate gyrus after kainic acid-induced seizures indicated that its expression could also be modified in nondividing cells by excitotoxic stress. Therefore, p19INK4d may contribute to maintaining the quiescent state, acting as a buffer to prevent reactivation of cyclin D-dependent kinases in terminally differentiated cells.     

Topographical Properties of Generic Images

Topographical curves in images are defined by certain extremality conditions involving the gradient of the greyvalue function. Curves extracted by some edge operators and watersheds studied in geography are both examples of such topographical curves.In the first part of this article we list the possible geometrical features of certain topographical curves—such as intersection points, singular points, endpoints, curvature extrema and inflections—for generic images and for generic 1-parameter families of, linearly or non-linearly, diffused images (intuitively, generic phenomena arise with probability 1).In a second experimental part the same topographical curves are computed in discrete images and in Gaussian blurred families of images. It turns out that the geometrical features of the smooth classification also figure in these discrete approximations. The consequences of these results for edge-linking algorithms are briefly discussed.     

Actin and fimbrin are required for the internalization step of endocytosis in yeast

In Saccharomyces cerevisiae, alpha-factor is internalized by receptor-mediated endocytosis and transported via vesicular intermediates to the vacuole where the pheromone is degraded. Using beta-tubulin and actin mutant strains, we showed that actin plays a direct role in receptor-mediated internalization of alpha-factor, but is not necessary for transport from the endocytic intermediates to the vacuole. beta-tubulin mutant strains showed no defect in these processes. In addition, cells lacking the actin-binding protein, Sac6p, which is the yeast fimbrin homologue, are defective for internalization of alpha-factor suggesting that actin filament bundling might be required for this step. The actin dependence of endocytosis shows some interesting similarities to endocytosis from the apical membrane in polarized mammalian cells.     

Westernized food habits and concentrations of serum lipids in the Japanese

It has recently been reported that there exists a new 'RING-finger' protein family among the zinc-finger (Zf) proteins. Previously, we had isolated the mouse Mel-18 cDNA (mMel-18) encoding the nuclear RING-finger protein that exhibits an ability to bind to a nonspecific DNA column. Here, we have isolated and characterized the human Mel-18 cDNA (hMel-18) using the mMel-18 cDNA as a probe. The deduced hMel-18 protein contains 344 amino acids (38 kDa) with a RING-finger motif, a helix-loop-helix (HLH)-like structure and a Pro/Ser-rich region. The hMel-18 gene is conserved among vertebrates. Its mRNA is highly expressed in placenta, lung and kidney, but the level is low in liver, pancreas and skeletal muscle. Using in situ hybridization, we mapped hMel-18 to band q22 of chromosome 12. It is possible that the Mel-18/bmi-1 gene family represents a mammalian homologue of the Drosophila polycomb gene group.