Cancer of the Lung In Rhodesian Blacks

A retrospective survey has been carried out on lung cancer as seen in a large referral hospital in Rhodesia. The incidence of this disease is less common than in Europe and North America, but more common than in some other countries in Africa. Smoking was one important aetiological factor and mining, particularly gold mining, may have been another. Squamous cell tumours were more common and anaplastic tumours less common than in many other parts of the world. Both types were associated with cigarette smoking. The clinical presentation was similar to that in other series. Many patients presented with advanced disease and only 10% underwent radical surgery. Most of the patients were lost to follow-up and the remainder died wiihin 5 years

Parameterization of mixed layer eddies. III: Implementation and impact in global ocean climate simulations

A parameterization for the restratification by finite-amplitude, submesoscale, mixed layer eddies, formulated as an overturning streamfunction, has been recently proposed to approximate eddy fluxes of density and other tracers. Here, the technicalities of implementing the parameterization in the coarse-resolution ocean component of global climate models are made explicit, and the primary impacts on model solutions of implementing the parameterization are discussed. Three global ocean general circulation models including this parameterization are contrasted with control simulations lacking the parameterization. The MLE parameterization behaves as expected and fairly consistently in models differing in discretization, boundary layer mixing, resolution, and other parameterizations. The primary impact of the parameterization is a shoaling of the mixed layer, with the largest effect in polar winter regions. Secondary impacts include strengthening the Atlantic meridional overturning while reducing its variability, reducing CFC and tracer ventilation, modest changes to sea surface temperature and air–sea fluxes, and an apparent reduction of sea ice basal melting.National Science Foundation (U.S.) (Grant OCE-0612143)National Science Foundation (U.S.) (Grant OCE-0612059)National Science Foundation (U.S.) (Grant OCE-0825376)National Science Foundation (U.S.) (Grant DMS-0855010)National Science Foundation (U.S.) (Grant OCE-0934737

Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans

Mutant mitochondrial genomes (mtDNA) can be viewed as selfish genetic elements that persist in a state of heteroplasmy despite having potentially deleterious metabolic consequences. We sought to study regulation of selfish mtDNA dynamics. We establish that the large 3.1-kb deletion-bearing mtDNA variant uaDf5 is a selfish genome in Caenorhabditis elegans. Next, we show that uaDf5 mutant mtDNA replicates in addition to, not at the expense of, wild-type mtDNA. These data suggest the existence of a homeostatic copy-number control that is exploited by uaDf5 to “hitchhike” to high frequency. We also observe activation of the mitochondrial unfolded protein response (UPRmt) in uaDf5 animals. Loss of UPRmt causes a decrease in uaDf5 frequency, whereas its constitutive activation increases uaDf5 levels. UPRmt activation protects uaDf5 from mitophagy. Taken together, we propose that mtDNA copy-number control and UPRmt represent two homeostatic response mechanisms that play important roles in regulating selfish mitochondrial genome dynamics

Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger-Huet anomaly

The nature of the wild-type gene product at the mouse ichthyosis (ic) locus has been of great interest because mutations at this locus cause marked abnormalities in nuclear heterochromatin, similar to those observed in Pelger-Huët anomaly (PHA). We recently found that human PHA is caused by mutations in the gene (LBR) encoding lamin B receptor, an evolutionarily conserved inner nuclear membrane protein involved in nuclear assembly and chromatin binding. Mice homozygous for deleterious alleles at the ichthyosis (ic) locus present with a blood phenotype similar to PHA, and develop other phenotypic abnormalities, including alopecia, variable expression of syndactyly and hydrocephalus. The ic locus on mouse chromosome 1 shares conserved synteny with the chromosomal location of the human LBR locus on human chromosome 1. In this study, we identified one nonsense (815ins) and two frameshift mutations (1088insCC and 1884insGGAA) within the Lbr gene of mice homozygous for either of three independent mutations (ic, ic(J) and ic(4J), respectively) at the ichthyosis locus. These allelic mutations are predicted to result in truncated or severely impaired LBR protein. Our studies of mice homozygous for the ic(J) mutation revealed a complete loss of LBR protein as shown by immunofluorescence microscopy and immunoblotting. The findings provide the molecular basis for the heterochromatin clumping and other distinct phenotypes caused by ic mutations. These spontaneous Lbr mutations confirm the molecular basis of human PHA and provide a small animal model for determination of the precise function of LBR in normal and pathological states