Cognitive change and the APOE epsilon 4 allele

There is a marked variation in whether people retain sufficient cognitive function to maintain their quality of life and independence in old age, even among those without dementia, so it would be valuable to identify the determinants of normal age-related cognitive change. We have retested non-demented 80-year-olds who were participants in the Scottish Mental Survey of 1932, and find that the variation in their non-pathological cognitive change from age 11 to 80 is related to their apolipoprotein E (APOE) genotype. This effect of the APOE epsilon 4 allele on normal cognitive ageing may be mediated by a mechanism that is at least partly independent of its predisposing effect towards Alzheimer's disease.     

Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus

A T-->G transversion at nt 8993 in mitochondrial DNA of MTATP6 (encoding ATPase 6 of complex V of the respiratory chain) causes impaired mitochondrial ATP synthesis in two related mitochondrial disorders: neuropathy, ataxia and retinitis pigmentosa and maternally inherited Leigh syndrome. To overcome the biochemical defect, we expressed wildtype ATPase 6 protein allotopically from nucleus-transfected constructs encoding an amino-terminal mitochondrial targeting signal appended to a recoded ATPase 6 gene (made compatible with the universal genetic code) that also contained a carboxy-terminal FLAG epitope tag. After transfection of human cells, the precursor polypeptide was expressed, imported into and processed within mitochondria, and incorporated into complex V. Allotopic expression of stably transfected constructs in cytoplasmic hybrids (cybrids) homoplasmic with respect to the 8993T-->G mutation showed a significantly improved recovery after growth in selective medium as well as a significant increase in ATP synthesis. This is the first successful demonstration of allotopic expression of an mtDNA-encoded polypeptide in mammalian cells and could form the basis of a genetic approach to treat a number of human mitochondrial disorders.     

Pathogen stress increases somatic recombination frequency in Arabidopsis

Evolution is based on genetic variability and subsequent phenotypic selection. Mechanisms that modulate the rate of mutation according to environmental cues, and thus control the balance between genetic stability and flexibility, might provide a distinct evolutionary advantage. Stress-induced mutations stimulated by unfavorable environments, and possible mechanisms for their induction, have been described for several organisms, but research in this area has mainly focused on microorganisms. We have analyzed the influence of adverse environmental conditions on the genetic stability of the higher plant Arabidopsis thaliana. Here we show that a biotic stress factor-attack by the oomycete pathogen Peronospora parasitica-can stimulate somatic recombination in Arabidopsis. The same effect was observed when plant pathogen-defense mechanisms were activated by the chemicals 2,6-dichloroisonicotinic acid (INA) or benzothiadiazole (BTH), or by a mutation (cim3). Together with previous studies of recombination induced by abiotic factors, these findings suggest that increased somatic recombination is a general stress response in plants. The increased genetic flexibility might facilitate evolutionary adaptation of plant populations to stressful environments.     

RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases

RNASEL (encoding ribonuclease L) has recently been proposed as a candidate for the hereditary prostate cancer (HPC1) gene. We determined that the RNASEL variant Arg462Gln has three times less enzymatic activity than the wildtype and is significantly associated with prostate cancer risk (P = 0.007). At least one copy of the mutated allele that causes this substitution is carried by nearly 60% of the men in our study. Men that are heterozygous with respect to the mutated allele have 50% greater risk of prostate cancer than non-carriers, and homozygotes have more than double the risk.     

Towards robust regional estimates of CO2 sources and sinks using atmospheric transport models

Information about regional carbon sources and sinks can be derived from variations in observed atmospheric CO2 concentrations via inverse modelling with atmospheric tracer transport models. A consensus has not yet been reached regarding the size and distribution of regional carbon fluxes obtained using this approach, partly owing to the use of several different atmospheric transport models. Here we report estimates of surface-atmosphere CO2 fluxes from an intercomparison of atmospheric CO2 inversion models (the TransCom 3 project), which includes 16 transport models and model variants. We find an uptake of CO2 in the southern extratropical ocean less than that estimated from ocean measurements, a result that is not sensitive to transport models or methodological approaches. We also find a northern land carbon sink that is distributed relatively evenly among the continents of the Northern Hemisphere, but these results show some sensitivity to transport differences among models, especially in how they respond to seasonal terrestrial exchange of CO2. Overall, carbon fluxes integrated over latitudinal zones are strongly constrained by observations in the middle to high latitudes. Further significant constraints to our understanding of regional carbon fluxes will therefore require improvements in transport models and expansion of the CO2 observation network within the tropics.     

Unsuspected diversity among marine aerobic anoxygenic phototrophs

Aerobic, anoxygenic, phototrophic bacteria containing bacteriochlorophyll a (Bchla) require oxygen for both growth and Bchla synthesis. Recent reports suggest that these bacteria are widely distributed in marine plankton, and that they may account for up to 5% of surface ocean photosynthetic electron transport and 11% of the total microbial community. Known planktonic anoxygenic phototrophs belong to only a few restricted groups within the Proteobacteria alpha-subclass. Here we report genomic analyses of the photosynthetic gene content and operon organization in naturally occurring marine bacteria. These photosynthetic gene clusters included some that most closely resembled those of Proteobacteria from the beta-subclass, which have never before been observed in marine environments. Furthermore, these photosynthetic genes were broadly distributed in marine plankton, and actively expressed in neritic bacterioplankton assemblages, indicating that the newly identified phototrophs were photosynthetically competent. Our data demonstrate that planktonic bacterial assemblages are not simply composed of one uniform, widespread class of anoxygenic phototrophs, as previously proposed; rather, these assemblages contain multiple, distantly related, photosynthetically active bacterial groups, including some unrelated to known and cultivated types.     

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.     

Patterns of colonization in a metapopulation of grey seals

The colonization of a new habitat is a fundamental process in metapopulation biology, but it is difficult to study. The emigration of colonists from established populations might be induced by resource competition owing to high local population density. Migration distances are also important because they determine the frequency and scale of recolonization and hence the spatial scale of the metapopulation. Traditionally, these factors have been investigated with demographic approaches that are labour-intensive and are only possible in amenable species. In many cases, genetic differentiation is minimal, preventing traditional genetic approaches from identifying the source of colonists unambiguously. Here we present a bayesian approach that integrates genetic, demographic and geographic distance data. We apply the method to study the British metapopulation of grey seals, which has been growing at 6% per year over the last few decades. Our method reveals differential recruitment to three newly founded colonies and implicates density-dependent dispersal in metapopulation dynamics by using genetic data.     

Poleward heat transport by the atmospheric heat engine

The atmospheric heat transport on Earth from the Equator to the poles is largely carried out by the mid-latitude storms. However, there is no satisfactory theory to describe this fundamental feature of the Earth's climate. Previous studies have characterized the poleward heat transport as a diffusion by eddies of specified horizontal length and velocity scales, but there is little agreement as to what those scales should be. Here we propose instead to regard the baroclinic zone--the zone of strong temperature gradients and active eddies--as a heat engine which generates eddy kinetic energy by transporting heat from a warmer to a colder region. This view leads to a new velocity scale, which we have tested along with previously proposed length and velocity scales, using numerical climate simulations in which the eddy properties have been varied by changing forcing and boundary conditions. The experiments show that the eddy velocity varies in accordance with the new scale, while the size of the eddies varies with the well-known Rhines beta-scale. Our results not only give new insight into atmospheric eddy heat transport, but also allow simple estimates of the intensities of mid-latitude storms, which have hitherto only been possible with expensive general circulation models.