Environmental genomics can describe all forms of organisms—cellular and viral—present in a community. The analysis of such eco-systems biology data relies heavily on reference databases, e.g., taxonomy or gene function databases. Reference databases of symbiosis sensu lato, although essential for the analysis of organism interaction networks, are lacking. By mining existing databases and literature, we here provide a comprehensive and manually curated database of taxonomic links between viruses and their cellular hosts.
CLOCK is a positive component of a transcription/ translation-based negative feedback loop of the central circadian oscillator in the suprachiasmatic nucleus in mammals. To examine CLOCK-regulated circadian transcription in peripheral tissues, we performed microarray analyses using liver RNA isolated from Clock mutant mice. We also compared expression profiles with those of Cryptochromes (Cry1 and Cry2) double knockout mice. We identified more than 100 genes that fluctuated from day to night and of which expression levels were decreased in Clock mutant mice. In Cry-deficient mice, the expression levels of most CLOCK-regulated genes were elevated to the upper range of normal oscillation. Most of the screened genes had a CLOCK/BMAL1 binding site (E box) in the 5-flanking region. We found that CLOCK was absolutely concerned with the circadian transcription of one type of liver genes (such as DBP, TEF, and Usp2) and partially with another (such as mPer1, mPer2, mDec1, Nocturnin, P450 oxidoreductase, and FKBP51) because the latter were damped but remained rhythmic in the mutant mice. Our results showed that CLOCK and CRY proteins are involved in the transcriptional regulation of many circadian output genes in the mouse liver. In addition to being a core component of the negative feedback loop that drives the circadian oscillator, CLOCK also appears to be involved in various physiological functions such as cell cycle, lipid metabolism, immune functions, and proteolysis in peripheral tissues.
Sorption coefficients (K(oc) values) of selected endocrine disruptors for a wide variety of dissolved organic matter (DOM) were measured using fluorescence quenching and solubility enhancement. 17beta-Estradiol, estriol, 17alpha-ethynylestradiol, p-nonylphenol, p-tert-octylphenol, and dibutylphthalate were selected as endocrine disruptors. Aldrich humic acid, Suwannee River humic and fulvic acids, Nordic fulvic acid, alginic acid, dextran, and tannic acid were selected as DOM surrogates. The resulting sorption coefficients (log K(oc)) were independent of octanol-water partitioning coefficients (log K(ow)) of the selected endocrine disruptors, indicating the hydrophobic interaction is not the predominant sorption mechanism. Moreover, the K(oc) values for the selected endocrine disruptors, especially the steroid estrogens, correlated much better with UV absorptivity at 272 nm (A272) and phenolic group concentration of the DOM than with either the H/O or the (O+N)/C atomic ratio of the DOM. This suggests that the sorption mechanism is closely related to the interaction between pi-electrons and the hydrogen bonds, i.e., the affinity between phenolic groups of the steroid estrogens and DOM is suggested to provide a relatively large contribution to the overall sorption and yield the K(oc) values of the steroid estrogens as high as those of the alkylphenols and dibutylphthalate, which are suggested to be dominated by nonspecific hydrophobic interaction.
Recent advances in genome editing have facilitated the generation of nonhuman primate (NHP) models, with potential to unmask the complex biology of human disease not revealed by rodent models. However, their broader use is hindered by the challenges associated with generation of adult NHP models as well as the cost of their production. Here, we describe the generation of a marmoset model of severe combined immunodeficiency (SCID). This study optimized zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) to target interleukin-2 receptor subunit gamma (IL2RG) in pronuclear stage marmoset embryos. Nine of 21 neonates exhibited mutations in the IL2RG gene, concomitant with immunodeficiency, and three neonates have currently survived from 240 days to 1.8 years. Our approach demonstrates highly efficient production of founder NHP with SCID phenotypes, with promises of multiple pre-clinical and translational applications.
Atypical bovine spongiform encephalopathy (BSE) has recently been identified in Europe, North America, and Japan. It is classified as H-type and L-type BSE according to the molecular mass of the disease-associated prion protein (PrPSc). To investigate the topographical distribution and deposition patterns of immunolabeled PrPSc, H-type BSE isolate was inoculated intracerebrally into cattle. H-type BSE was successfully transmitted to 3 calves, with incubation periods between 500 and 600 days. Moderate to severe spongiform changes were detected in the cerebral and cerebellar cortices, basal ganglia, thalamus, and brainstem. H-type BSE was characterized by the presence of PrP-immunopositive amyloid plaques in the white matter of the cerebrum, basal ganglia, and thalamus. Moreover, intraglial-type immunolabeled PrPSc was prominent throughout the brain. Stellate-type immunolabeled PrPSc was conspicuous in the gray matter of the cerebral cortex, basal ganglia, and thalamus, but not in the brainstem. In addition, PrPSc accumulation was detected in the peripheral nervous tissues, such as trigeminal ganglia, dorsal root ganglia, optic nerve, retina, and neurohypophysis. Cattle are susceptible to H-type BSE with a shorter incubation period, showing distinct and distinguishable phenotypes of PrPSc accumulation.
Polyketide synthases (PKSs) catalyze the sequential condensation of simple acetate units to produce a large class of natural products, including pharmacologically valuable compounds. PKSs are classified into three types on the basis of their domain structures; type III PKSs have the simplest domain structure, although their products have various structures and functions. The sequence–function relationship is fundamental for predicting enzyme functions, but it has not been well investigated in type III PKSs to date. Consequently, the current methods for predicting type III PKS functions are still immature in comparison with those that target type I/II PKSs. In this review we summarize the current functional and phylogenomic knowledge about type III PKSs and propose a new classification of their enzymatic reactions. We also discuss possible directions for the development of better computational tools for functional prediction of type III PKS homologues.
The nin1‐1 mutant of Saccharomyces cerevisiae cannot perform the G1/S and G2/M transitions at restrictive temperatures. At such temperatures, nin1‐1 strains fail to activate histone H1 kinase after release from alpha factor‐imposed G1 block and after release from hydroxyurea‐imposed S block. The nin1‐1 mutation shows synthetic lethality with certain cdc28 mutant alleles such as cdc28‐IN. Two lines of evidence indicate that Nin1p is a component of the 26S proteasome complex: (i) Nin1p, as well as the known component of the 26S proteasome, shifted to the 26S proteasome peak in the glycerol density gradient after preincubation of crude extract with ATP‐Mg2+, and (ii) nin1‐1 cells accumulated polyubiquitinated proteins under restrictive conditions. These results suggest that activation of Cdc28p kinase requires proteolysis. We have cloned a human cDNA encoding a regulatory subunit of the 26S proteasome, p31, which was found to be a homolog of Nin1p.
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