145 research outputs found
WD40 Domain Divergence Is Important for Functional Differences between the Fission Yeast Tup11 and Tup12 Co-Repressor Proteins
We have previously demonstrated that subsets of Ssn6/Tup target genes have distinct requirements for the Schizosaccharomyces pombe homologs of the Tup1/Groucho/TLE co-repressor proteins, Tup11 and Tup12. The very high level of divergence in the histone interacting repression domains of the two proteins suggested that determinants distinguishing Tup11 and Tup12 might be located in this domain. Here we have combined phylogenetic and structural analysis as well as phenotypic characterization, under stress conditions that specifically require Tup12, to identify and characterize the domains involved in Tup12-specific action. The results indicate that divergence in the repression domain is not generally relevant for Tup12-specific function. Instead, we show that the more highly conserved C-terminal WD40 repeat domain of Tup12 is important for Tup12-specific function. Surface amino acid residues specific for the WD40 repeat domain of Tup12 proteins in different fission yeasts are clustered in blade 3 of the propeller-like structure that is characteristic of WD40 repeat domains. The Tup11 and Tup12 proteins in fission yeasts thus provide an excellent model system for studying the functional divergence of WD40 repeat domains
The Main Belt Comets and ice in the Solar System
We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies
Choline Dehydrogenase Polymorphism rs12676 Is a Functional Variation and Is Associated with Changes in Human Sperm Cell Function
Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Deletion of the choline dehydrogenase (Chdh) gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh−/− males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. Several SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non-synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second SNP located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm
Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster
Epistasis may have important consequences for a number of issues in quantitative genetics and evolutionary biology. In
particular, synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and
recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations
appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating
in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally
segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are
exposed in inbred lines. Nevertheless, evidence of epistasis from these studies is scarce and controversial. In this paper, we
report the results of two independent inbreeding experiments carried out with two different populations of Drosophila
melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis
among deleterious alleles. We also performed computer simulations assuming different possible models of epistasis and
mutational parameters for fitness, finding some of them to be compatible with the results observed. Our results suggest that
synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but
also among segregating alleles in natural populationsWe acknowledge the support by Uvigo
Marine Research Centre funded by the “Excellence in Research
(INUGA)” Programme from the Regional Council of Culture, Education and Universities, with co-funding from the European Union
through the ERDF Operational Programme Galicia 2014-2020. This
work was funded by Agencia Estatal de Investigación (AEI) (CGL2016-75904-C2-1-P), Xunta de Galicia (ED431C 2016-037) and
Fondos Feder: “Unha maneira de facer Europa.” SD was founded by a
predoctoral (FPI) grant from Ministerio de Economía y
Competitividad, SpainS
LNCaP Atlas: Gene expression associated with in vivo progression to castration-recurrent prostate cancer
<p>Abstract</p> <p>Background</p> <p>There is no cure for castration-recurrent prostate cancer (CRPC) and the mechanisms underlying this stage of the disease are unknown.</p> <p>Methods</p> <p>We analyzed the transcriptome of human LNCaP prostate cancer cells as they progress to CRPC <it>in vivo </it>using replicate LongSAGE libraries. We refer to these libraries as the LNCaP atlas and compared these gene expression profiles with current suggested models of CRPC.</p> <p>Results</p> <p>Three million tags were sequenced using <it>in vivo </it>samples at various stages of hormonal progression to reveal 96 novel genes differentially expressed in CRPC. Thirty-one genes encode proteins that are either secreted or are located at the plasma membrane, 21 genes changed levels of expression in response to androgen, and 8 genes have enriched expression in the prostate. Expression of 26, 6, 12, and 15 genes have previously been linked to prostate cancer, Gleason grade, progression, and metastasis, respectively. Expression profiles of genes in CRPC support a role for the transcriptional activity of the androgen receptor (<it>CCNH, CUEDC2, FLNA, PSMA7</it>), steroid synthesis and metabolism (<it>DHCR24, DHRS7</it>, <it>ELOVL5, HSD17B4</it>, <it>OPRK1</it>), neuroendocrine (<it>ENO2, MAOA, OPRK1, S100A10, TRPM8</it>), and proliferation (<it>GAS5</it>, <it>GNB2L1</it>, <it>MT-ND3</it>, <it>NKX3-1</it>, <it>PCGEM1</it>, <it>PTGFR</it>, <it>STEAP1</it>, <it>TMEM30A</it>), but neither supported nor discounted a role for cell survival genes.</p> <p>Conclusions</p> <p>The <it>in vivo </it>gene expression atlas for LNCaP was sequenced and support a role for the androgen receptor in CRPC.</p
Altered myocardial response in patients with diabetic retinopathy: an exercise echocardiography study
Distribution of histone H4 modifications as revealed by a panel of specific monoclonal antibodies
Stress modulation as a means to improve yeasts for lignocellulose bioconversion
The second-generation (2G) fermentation environment for lignocellulose conversion presents unique challenges to the fermentative organism that do not necessarily exist in other industrial fermentations. While extreme osmotic, heat, and nutrient starvation stresses are observed in sugar- and starch-based fermentation environments, additional pre-treatment-derived inhibitor stress,
potentially exacerbated by stresses such as pH and product tolerance, exist in the 2G environment. Furthermore, in a consolidated
bioprocessing (CBP) context, the organism is also challenged to secrete enzymes that may themselves lead to unfolded protein
response and other stresses. This review will discuss responses of the yeast Saccharomyces cerevisiae to 2G-specific stresses and
stress modulation strategies that can be followed to improve yeasts for this application. We also explore published –omics data
and discuss relevant rational engineering, reverse engineering, and adaptation strategies, with the view of identifying genes or
alleles that will make positive contributions to the overall robustness of 2G industrial strains
Childhood Hepatocellular Carcinoma and Hepatoblastoma: Integrated Sonography and Dynamic CT
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