On the relationship between vertical microdistribution and adaptations to oxygen stress in littoral Chironomidae (Diptera)

Animals that dwell at different depths in the sediment, are adapted to different respiratory environments. It is possible that animals that occur deep in the sediment have a higher hemoglobin concentration than surface-dwelling animals. To test this hypothesis, hemoglobin concentrations and weights of eight chironomid species that dwell in the littoral zone were measured. High hemoglobin concentration and weight both seemed to contribute to an ability to cope with low oxygen concentrations, and determined the vertical distribution of chironomids in the sediment. A multiple regression equation, including these factors, was derived. It may be used to predict the median depth of occurrence for species that were not included in this study. High sensitivity of small animals to oxygen stress is discussed from a theoretical point of view.Research Assistant of the Belgian National Fund for Scientific ResearchResearch Assistant of the Belgian National Fund for Scientific Research     

Live longer through PHAsting

Dietary restriction provides considerable health benefits and may even increase life span in humans. Panowski et al. (2007) have now identified PHA-4/FoxA as an essential and specific component of DR-induced life-span extension in C. elegans.     

Using the ratio of means as the effect size measure in combining results of microarray experiments

Background  

Development of efficient analytic methodologies for combining microarray results is a major challenge in gene expression analysis. The widely used effect size models are thought to provide an efficient modeling framework for this purpose, where the measures of association for each study and each gene are combined, weighted by the standard errors. A significant disadvantage of this strategy is that the quality of different data sets may be highly variable, but this information is usually neglected during the integration. Moreover, it is widely known that the estimated standard deviations are probably unstable in the commonly used effect size measures (such as standardized mean difference) when sample sizes in each group are small.     

A high-resolution map of synteny disruptions in gibbon and human genomes

Gibbons are part of the same superfamily (Hominoidea) as humans and great apes, but their karyotype has diverged faster from the common hominoid ancestor. At least 24 major chromosome rearrangements are required to convert the presumed ancestral karyotype of gibbons into that of the hominoid ancestor. Up to 28 additional rearrangements distinguish the various living species from the common gibbon ancestor. Using the northern white-cheeked gibbon (2n = 52) (Nomascus leucogenys leucogenys) as a model, we created a high-resolution map of the homologous regions between the gibbon and human. The positions of 100 synteny breakpoints relative to the assembled human genome were determined at a resolution of about 200 kb. Interestingly, 46% of the gibbon–human synteny breakpoints occur in regions that correspond to segmental duplications in the human lineage, indicating a common source of plasticity leading to a different outcome in the two species. Additionally, the full sequences of 11 gibbon BACs spanning evolutionary breakpoints reveal either segmental duplications or interspersed repeats at the exact breakpoint locations. No specific sequence element appears to be common among independent rearrangements. We speculate that the extraordinarily high level of rearrangements seen in gibbons may be due to factors that increase the incidence of chromosome breakage or fixation of the derivative chromosomes in a homozygous state.     

Microarray analysis of bleomycin-exposed lymphoblastoid cells for identifying cancer susceptibility genes

The uncovering of genes involved in susceptibility to the sporadic cancer types is a great challenge. It is well established that the way in which an individual deals with DNA damage is related to the chance to develop cancer. Mutagen sensitivity is a phenotype that reflects an individual's susceptibility to the major sporadic cancer types, including colon, lung, and head and neck cancer. A standard test for mutagen sensitivity is measuring the number of chromatid breaks in lymphocytes after exposure to bleomycin. The aim of the present study was to search for the pathways involved in mutagen sensitivity. Lymphoblastoid cell lines of seven individuals with low mutagen sensitivity were compared with seven individuals with a high score. RNA was isolated from cells exposed to bleomycin (4 hours) and from unexposed cells. Microarray analysis (19K) was used to compare gene expression of insensitive and sensitive cells. The profile of most altered genes after bleomycin exposure, analyzed in all 14 cell lines, included relatively many genes involved in biological processes, such as cell growth and/or maintenance, proliferation, and regulation of cell cycle, as well as some genes involved in DNA repair. When comparing the insensitive and sensitive individuals, other differentially expressed genes were found that are involved in signal transduction and cell growth and/or maintenance (e.g., BUB1 and DUSP4). This difference in expression profiles between mutagen-sensitive and mutagen-insensitive individuals justifies further studies aimed at elucidating the genes responsible for the development of sporadic cancers.     

Indexes of diastolic RV function: load dependence and changes after chronic RV pressure overload in lambs

Diastolic function is a major determinant of ventricular performance, especially when loading conditions are altered. We evaluated biventricular diastolic function in lambs and studied possible load dependence of diastolic parameters [minimum first derivative of pressure vs. time (dP/dt(min)) and time constant of isovolumic relaxation (tau)] in normal (n = 5) and chronic right ventricular (RV) pressure-overloaded (n = 5) hearts by using an adjustable band on the pulmonary artery (PAB). Pressure-volume relations were measured during preload reduction to obtain the end-diastolic pressure-volume relationship (EDPVR). In normal lambs, absolute dP/dt(min) and tau were lower in the RV than in the left ventricle whereas the chamber stiffness constant (b) was roughly the same. After PAB, RV tau and dP/dt(min) were significantly higher compared with control. The RV EDPVR indicated impaired diastolic function. During acute pressure reduction, both dP/dt(min) and tau showed a relationship with end-systolic pressure. These relationships could explain the increased dP/dt(min) but not the increased tau-value after banding. Therefore, the increased tau after banding reflects intrinsic myocardial changes. We conclude that after chronic RV pressure overload, RV early relaxation is prolonged and diastolic stiffness is increased, both indicative of impaired diastolic function.     

Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330)

We present a family with autosomal-dominant inheritance of renal insufficiency caused by renal hypoplasia in six individuals. In all affected individuals, signs of optic disk dysplasia were detected, but most patients were asymptomatic. A heterozygous missense mutation in the PAX2 gene causing a Gly75 to Ser substitution was present in all affected individuals. A second, unrelated patient presented with ocular complaints related to optic disk dysplasia, and had a history of vesico-ureteral reflux. A heterozygous hexanucleotide duplication in the PAX2 gene was detected leading to the duplication of GluThr at positions 74 and 75. The mutations in these two families are the first mutations in the PAX2 gene that do not lead to a truncated protein. Mechanistically, these mutations are expected to result in abnormal folding of the PAX2 protein. These observations further expand the spectrum of clinical features associated with PAX2 mutations, and suggest that a distinct genetic disorder can be identified in patients with renal dysplasia through a careful eye examination. As the ocular manifestations in this syndrome are variable anomalies of retinal and optic disk dysplasia, we prefer the term “papillo-renal syndrome”. Received: 29 January 1998 / Accepted: 25 March 1998