The effect of age on cardiac output and its distribution in the rat.

Cardiac output distribution in the rat was found to be affected by age. Cardiac index and blood flow to the liver, kidneys, skin and skeletal muscle were lower in 11-12 month compared to 3-4 month old rats.     

Chromosome banding patterns and the nucleolar organizer region of the eastern mole (Scalopus aquaticus)

Summary The C and G chromosome banding patterns and the AgAS positive sites (NOR regions) of cultured lung cells of the Eastern mole (Scalopus aquaticus) are presented. A distinctive secondary constriction is found on a pair of autosomes instead of on the X-chromosome as previously believed. The presence of a heterochromatic heteromorphism is noted and a large amount of constitutive heterochromatin is present in the karyotype.     

The effect of urethane and pentobarbital anaesthesia and hepatic portal vein catheterization on liver blood flow in the rat

Summary The effect of urethane and pentobarbital anaesthesia and hepatic portal vein catheterization on liver blood flow was investigated in the rat. Liver blood flow with pentobarbital anaesthesia was 40% greater than with urethane. Hepatic portal vein catheterization had no effect under pentobarbital anaesthesia whereas it produced an 18% fall in liver blood flow with urethane.Acknowledgments. This work was supported by grants from ICI Pharmaceuticals and Mersey Regional Health Authority (Research Scheme No. 338). We wish to thank Mr P.J. Roberts for much skilled assistance and Evans Medical Ltd for the kind gift of drugs.     

The landscape of cancer genes and mutational processes in breast cancer

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.     

Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland

The NOTCH4 gene was recently reported to be associated with schizophrenia based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls.     

Wnt proteins are lipid-modified and can act as stem cell growth factors

Wnt signalling is involved in numerous events in animal development, including the proliferation of stem cells and the specification of the neural crest. Wnt proteins are potentially important reagents in expanding specific cell types, but in contrast to other developmental signalling molecules such as hedgehog proteins and the bone morphogenetic proteins, Wnt proteins have never been isolated in an active form. Although Wnt proteins are secreted from cells, secretion is usually inefficient and previous attempts to characterize Wnt proteins have been hampered by their high degree of insolubility. Here we have isolated active Wnt molecules, including the product of the mouse Wnt3a gene. By mass spectrometry, we found the proteins to be palmitoylated on a conserved cysteine. Enzymatic removal of the palmitate or site-directed and natural mutations of the modified cysteine result in loss of activity, and indicate that the lipid is important for signalling. The purified Wnt3a protein induces self-renewal of haematopoietic stem cells, signifying its potential use in tissue engineering.     

Matrix control of scarring

Repair of wounds usually results in restoration of organ function, even if suboptimal. However, in a minority of situations, the healing process leads to significant scarring that hampers homeostasis and leaves the tissue compromised. This scar is characterized by an excess of matrix deposition that remains poorly organized and weakened. While we know much of the early stages of the repair process, the transition to wound resolution that limits scar formation is poorly understood. This is particularly true of the inducers of scar formation. Here, we present a hypothesis that it is the matrix itself that is a primary driver of scar, rather than being simply the result of other cellular dysregulations.