Subcellular localization of noradrenaline and ATP in C1300 mouse neuroblastoma

Summary A density and velocity gradient centrifugation study of C₁₃₀₀ mouse neuroblastoma showed that ATP is nearly absent from noradrenaline-containing granules and is mainly localized in mitochondria, suggesting that in this tissue ATP is not involved in the storage of noradrenaline.This work was supported by a grant from the ASLK Cancer Fund (Belgium).     

Chromosomal instability in ulcerative colitis is related to telomere shortening

Ulcerative colitis, a chronic inflammatory disease of the colon, is associated with a high risk of colorectal carcinoma that is thought to develop through genomic instability. We considered that the rapid cell turnover and oxidative injury observed in ulcerative colitis might accelerate telomere shortening, thereby increasing the potential of chromosomal ends to fuse, resulting in cycles of chromatin bridge breakage and fusion and chromosomal instability associated with tumor cell progression. Here we have used quantitative fluorescence in situ hybridization to compare chromosomal aberrations and telomere shortening in non-dysplastic mucosa taken from individuals affected by ulcerative colitis, either with (UC progressors) or without (UC non-progressors) dysplasia or cancer. Losses, but not gains, of chromosomal arms and centromeres are highly correlated with telomere shortening. Chromosomal losses are greater and telomeres are shorter in biopsy samples from UC progressors than in those from UC non-progressors or control individuals without ulcerative colitis. A mechanistic link between telomere shortening and chromosomal instability is supported by a higher frequency of anaphase bridges--an intermediate in the breakage and fusion of chromatin bridges--in UC progressors than in UC non-progressors or control individuals. Our study shows that telomere length is correlated with chromosomal instability in a precursor of human cancer.     

Release of 5-hydroxytryptamine and histamine from neoplastic mast cells by alkaline tissue extracts

Zusammenfassung Alkalische Extrakte diverser Rattengewebe setzen 5-Hydroxytryptamin (Serotonin) und Histamin aus Suspensionen neoplastischer Mastzellen der Maus frei. Gehirnund Nierenextrakte zeigen die grösste Aktivität. Zugabe von Glukose in die Nährlösung verhindert das Freiwerden der Amine. Eine vorläufige Charakterisierung des aktiven Materials ist unternommen worden.

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Aided in part by grant B-940 from National Institute of Neurological Diseases and Blindness, and in part by the James Hudson Brown Memorial Fund of Yale Medical School.

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This work was done in partial fulfillment of the requirements for the degree of Doctor of Medicine by L. T. P.

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Squibb post-doctoral fellow in Pharmacology; present address, Department of Pharmacology, Royal College of Surgeons, London.     

Links between climate and sea levels for the past three million years

The oscillations between glacial and interglacial climate conditions over the past three million years have been characterized by a transfer of immense amounts of water between two of its largest reservoirs on Earth -- the ice sheets and the oceans. Since the latest of these oscillations, the Last Glacial Maximum (between about 30,000 and 19,000 years ago), approximately 50 million cubic kilometres of ice has melted from the land-based ice sheets, raising global sea level by approximately 130 metres. Such rapid changes in sea level are part of a complex pattern of interactions between the atmosphere, oceans, ice sheets and solid earth, all of which have different response timescales. The trigger for the sea-level fluctuations most probably lies with changes in insolation, caused by astronomical forcing, but internal feedback cycles complicate the simple model of causes and effects.     

Growth and the average duration of larval life in the southern hemisphere lamprey,Geotria australis Gray

Summary The average duration of larval life in the anadromous lamprey,Geotria australis (the sole representative of the Geotriidae) is estimated as 41/4 years. Compared with other lampreys, the ammocoetes ofG. australis have a slow growth rate, increase in length during the year preceding metamorphosis and typically enter metamorphosis at a small mean length (<100 mm) and weight (<1.2 g).     

Mys, a family of mammalian transposable elements isolated by phylogenetic screening

It has recently been demonstrated both emperically and mathematically that transposable elements may spread rapidly throughout a population once introduced even when they dramatically reduce the fitness of individuals that carry them. Such events result in pronounced differences in the phylogenetic distribution of genetic elements capable of rapid genome invasion. Using a simple and general procedure to screen the genome of the white-footed mouse Peromyscus leucopus, we have isolated a family of retrovirus-like elements which is apparently absent from the genome of the house mouse Mus domesticus. Here, we report this procedure and an analysis of the organization, phylogenetic distribution and sequence of this family of transposable elements.     

Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19

Hartnup disorder (OMIM 234500) is an autosomal recessive abnormality of renal and gastrointestinal neutral amino acid transport noted for its clinical variability. We localized a gene causing Hartnup disorder to chromosome 5p15.33 and cloned a new gene, SLC6A19, in this region. SLC6A19 is a sodium-dependent and chloride-independent neutral amino acid transporter, expressed predominately in kidney and intestine, with properties of system B(0). We identified six mutations in SLC6A19 that cosegregated with disease in the predicted recessive manner, with most affected individuals being compound heterozygotes. The disease-causing mutations that we tested reduced neutral amino acid transport function in vitro. Population frequencies for the most common mutated SLC6A19 alleles are 0.007 for 517G --> A and 0.001 for 718C --> T. Our findings indicate that SLC6A19 is the long-sought gene that is mutated in Hartnup disorder; its identification provides the opportunity to examine the inconsistent multisystemic features of this disorder.     

A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2.

We recently described a disorder termed Huntington disease-like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W). We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.