The effect of ultraviolet light (UVL) on the lysosomes of hairless mouse epidermis

Summary An increased release of acid phosphatase from the lysosomes of UVL irradiated hairless mouse epidermis is demonstrated. The results indicate that lysosomal membrane stability is decreased when the hairless mouse is exposed to either acute or chronic UVL.Acknowledgments. The authors would like to thank Miss Gail Brown for technical assistance. This research was supported in part by the Morrison Trust, San Antonio, Texas, and USPHS, grant CA-13464-04, from the NCI.     

Structural basis for modulation and agonist specificity of HCN pacemaker channels

The family of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels are crucial for a range of electrical signalling, including cardiac and neuronal pacemaker activity, setting resting membrane electrical properties and dendritic integration. These nonselective cation channels, underlying the I(f), I(h) and I(q) currents of heart and nerve cells, are activated by membrane hyperpolarization and modulated by the binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated enhancement of channel activity is largely responsible for the increase in heart rate caused by beta-adrenergic agonists. Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore. X-ray crystallographic structures of this C-terminal fragment bound to cAMP or cGMP, together with equilibrium sedimentation analysis, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation. On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism.     

A site of action of light on14C-acetate incorporation into human skin sterols

Zusammenfassung Die Synthese von Sterolen in menschlicher Haut, welche im langwelligen Spektralbereich bestrahlt worden war, wurde mit radioaktiv markiertem Acetyl-Co A, Acetat and Pyruvat geprüft. Von Acetyl-Co A konnte nur geringe Hemmung nachgewiesen werden, während Licht eine merkbare Hemmung von Acetat und Pyruvatinkorporation verursachte. Die Resultate lassen vermuten dass die Acetataktivierung die von Licht beeinflussbare Stufe in der Biosynthese von Sterolen ist.     

Quality assessment of the human genome sequence

As the final sequencing of the human genome has now been completed, we present the results of the largest examination of the quality of the finished DNA sequence. The completed study covers the major contributing sequencing centres and is based on a rigorous combination of laboratory experiments and computational analysis.     

The DNA sequence and comparative analysis of human chromosome 5

Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.