Direct and Indirect Gene Regulation by a Life-Extending FOXO Protein in C. elegans: Roles for GATA Factors and Lipid Gene Regulators

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Highlights? DAF-16 regulates genes both cell autonomously and cell nonautonomously ? DAF-16 can act at in the endoderm to delay muscle aging ? DAF-16 can act at a distance to protect animals from amyloid paralysis ? Cell-non-autonomous gene regulation by DAF-16 involves the lipid-gene regulator MDT-15     

Cell Proliferation,Movement and Differentiation during Maintenance of the Adult Mouse Adrenal Cortex

Appropriate maintenance and regeneration of adult endocrine organs is important in both normal physiology and disease. We investigated cell proliferation, movement and differentiation in the adult mouse adrenal cortex, using different 5-bromo-2''-deoxyuridine (BrdU) labelling regimens and immunostaining for phenotypic steroidogenic cell markers. Pulse-labelling showed that cell division was largely confined to the outer cortex, with most cells moving inwards towards the medulla at around 13-20 µm per day, though a distinct labelled cell population remained in the outer 10% of the cortex. Pulse-chase-labelling coupled with phenotypic immunostaining showed that, unlike cells in the inner cortex, most BrdU-positive outer cortical cells did not express steroidogenic markers, while co-staining for BrdU and Ki67 revealed that some outer cortical BrdU-positive cells were induced to proliferate following acute adrenocorticotropic hormone (ACTH) treatment. Extended pulse-chase-labelling identified cells in the outer cortex which retained BrdU label for up to 18-23 weeks. Together, these observations are consistent with the location of both slow-cycling stem/progenitor and transiently amplifying cell populations in the outer cortex. Understanding the relationships between these distinct adrenocortical cell populations will be crucial to clarify mechanisms underpinning adrenocortical maintenance and long-term adaptation to pathophysiological states.     

Maturation in Atlantic salmon (Salmo salar,Salmonidae): a synthesis of ecological,genetic, and molecular processes

Reviews in Fish Biology and Fisheries - Over the past decades, Atlantic salmon (Salmo salar, Salmonidae) has emerged as a model system for sexual maturation research, owing to the high diversity of...     

OVERCOMING STATISTICAL BIAS TO ESTIMATE GENETIC MATING SYSTEMS IN OPEN POPULATIONS: A COMPARISON OF BATEMAN'S PRINCIPLES BETWEEN THE SEXES IN A SEX‐ROLE‐REVERSED PIPEFISH

The genetic mating system is a key component of the sexual selection process, yet methods for the quantification of mating systems remain controversial. One approach involves metrics derived from Bateman's principles, which are based on variances in mating and reproductive success and the relationship between them. However, these measures are extremely difficult to measure for both sexes in open populations, because missing data can result in biased estimates. Here, we develop a novel approach for the estimation of mating system metrics based on Bateman's principles and apply it to a microsatellite‐based parentage analysis of a natural population of the dusky pipefish, Syngnathus floridae. Our results show that both male and female dusky pipefish have significantly positive Bateman gradients. However, females exhibit larger values of the opportunity for sexual selection and the opportunity for selection compared to males. These differences translate into a maximum intensity of sexual selection () for females three times larger than that for males. Overall, this study identifies a critical source of bias that affects studies of mating systems in open populations, presents a novel method for overcoming this bias, and applies this method for the first time in a sex‐role‐reversed pipefish.     

Delivery of Bcl-XL or its BH4 domain by protein transduction inhibits apoptosis in human islets

Viability of isolated islets is one of the main obstacles limiting islet transplantation success. It has been reported that overexpression of Bcl-2/Bcl-XL proteins enhances islet viability. To avoid potential complications associated with long-term expression of anti-apoptotic proteins, we investigated the possibility of delivering Bcl-XL or its anti-apoptotic domain BH4 to islets by protein transduction. Bcl-XL and BH4 molecules were fused to TAT/PTD, the 11-aa cell penetrating peptide from HIV-1 transactivating protein, generating TAT-Bcl-XL and TAT-BH4, respectively. Transduction efficiency was assessed by laser scanning confocal microscopy of live islets. Biological activity was tested as the ability to protect NIT-1 insulinoma cell line from death induced by staurosporine or serum deprivation. Spontaneous caspase activation in human islets and cytotoxicity caused by IL-1beta were significantly reduced in the presence of TAT-Bcl-XL and TAT-BH4. We conclude that both TAT proteins are biologically active after transduction and could be an asset in the improvement of islet viability.     

The Age-1 and Daf-2 Genes Function in a Common Pathway to Control the Lifespan of Caenorhabditis Elegans

Recessive mutations in two genes, daf-2 and age-1, extend the lifespan of Caenorhabditis elegans significantly. The daf-2 gene also regulates formation of an alternative developmental state called the dauer. Here we asked whether these two genes function in the same or different lifespan pathways. We found that the longevity of both age-1 and daf-2 mutants requires the activities of the same two genes, daf-16 and daf-18. In addition, the daf-2(e1370); age-1(hx546) double mutant did not live significantly longer than the daf-2 single mutant. We also found that, like daf-2 mutations, the age-1(hx546) mutation affects certain aspects of dauer formation. These findings suggest that age-1 and daf-2 mutations do act in the same lifespan pathway and extend lifespan by triggering similar if not identical processes.     

RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis

Background

To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH) and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH).

Methods

Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test.

Results

We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase.

Conclusion

Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively.     

The effects of land use change on native dung beetle diversity and function in Australia's Wet Tropics

The impacts of land use change on biodiversity and ecosystem functions are variable, particularly in fragmented tropical rainforest systems with high diversity. Dung beetles (Scarabaeinae) are an ideal group to investigate the relationship between land use change, diversity and ecosystem function as they are easily surveyed, sensitive to habitat modification and perform many ecosystem functions. Although this relationship has been investigated for dung beetles in some tropical regions, there has been no study assessing how native dung beetles in Australia's tropical rainforests respond to deforestation, and what the corresponding consequences are for dung removal (a key ecosystem function fulfilled by dung beetles). In this study we investigated the relationship between dung beetle community attributes (determined through trapping) and function (using dung removal experiments that allowed different dung beetle functional groups to access the dung) in rainforest and cleared pasture in a tropical landscape in Australia's Wet Tropics. Species richness, abundance and biomass were higher in rainforest compared to adjacent pasture, and species composition between these land use types differed significantly. However, average body size and evenness in body size were higher in pasture than in rainforest. Dung removal was higher in rainforest than in pasture when both functional groups or tunnelers only could access the dung. Increased dung removal in the rainforest was explained by higher biodiversity and dominance of a small number of species with distinct body sizes, as dung removal was best predicted by the evenness in body size of the community. Our findings suggest that functional traits (including body size and dung relocation behaviour) present in a dung beetle community are key drivers of dung removal. Overall, our results show that deforestation has reduced native dung beetle diversity in Australian tropical landscapes, which negatively impacts on the capacity for dung removal by dung beetles in this region.     

Impact of individual mutations on increased fitness in adaptively evolved strains of Escherichia coli

We measured the relative fitness among a set of experimentally evolved Escherichia coli strains differing by a small number of adaptive mutations by directly measuring allelic frequencies in head-to-head competitions using a mass spectrometry-based method. We compared the relative effects of mutations to the same or similar genes acquired in multiple strains when expressed in allele replacement strains. We found that the strongest determinant of fitness among the evolved strains was the impact of beneficial mutations to the RNA polymerase beta and beta' subunit genes. We also identified several examples of epistatic interactions between rpoB/C and glpK mutations and identified two other mutations that are beneficial only in the presence of previously acquired mutations but that have little or no adaptive benefit to the wild-type strain. Allele frequency estimation is shown to be a highly sensitive method for measuring selection rates during competitions between strains differing by as little as a single-nucleotide polymorphism and may be of great use for investigating epistatic interactions.