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Metabolic network analysis reveals microbial community interactions in anammox granules.
Microbial communities mediating anaerobic ammonium oxidation (anammox) represent one of the most energy-efficient environmental biotechnologies for nitrogen removal from wastewater. However, little is known about the functional role heterotrophic bacteria play in anammox granules. Here, we use genome-centric metagenomics to recover 17 draft genomes of anammox and heterotrophic bacteria from a laboratory-scale anammox bioreactor. We combine metabolic network reconstruction with metatranscriptomics to examine the gene expression of anammox and heterotrophic bacteria and to identify their potential interactions. We find that Chlorobi-affiliated bacteria may be highly active protein degraders, catabolizing extracellular peptides while recycling nitrate to nitrite. Other heterotrophs may also contribute to scavenging of detritus and peptides produced by anammox bacteria, and potentially use alternative electron donors, such as H2, acetate and formate. Our findings improve the understanding of metabolic activities and interactions between anammox and heterotrophic bacteria and offer the first transcriptional insights on ecosystem function in anammox granules
Genomic and proteomic profiling of responses to toxic metals in human lung cells.
Examining global effects of toxic metals on gene expression can be useful for elucidating patterns of biological response, discovering underlying mechanisms of toxicity, and identifying candidate metal-specific genetic markers of exposure and response. Using a 1,200 gene nylon array, we examined changes in gene expression following low-dose, acute exposures of cadmium, chromium, arsenic, nickel, or mitomycin C (MMC) in BEAS-2B human bronchial epithelial cells. Total RNA was isolated from cells exposed to 3 M Cd(II) (as cadmium chloride), 10 M Cr(VI) (as sodium dichromate), 3 g/cm2 Ni(II) (as nickel subsulfide), 5 M or 50 M As(III) (as sodium arsenite), or 1 M MMC for 4 hr. Expression changes were verified at the protein level for several genes. Only a small subset of genes was differentially expressed in response to each agent: Cd, Cr, Ni, As (5 M), As (50 M), and MMC each differentially altered the expression of 25, 44, 31, 110, 65, and 16 individual genes, respectively. Few genes were commonly expressed among the various treatments. Only one gene was altered in response to all four metals (hsp90), and no gene overlapped among all five treatments. We also compared low-dose (5 M, noncytotoxic) and high-dose (50 M, cytotoxic) arsenic treatments, which surprisingly, affected expression of almost completely nonoverlapping subsets of genes, suggesting a threshold switch from a survival-based biological response at low doses to a death response at high doses
Antibody Therapy for Histoplasmosis
The endemic human pathogenic fungus Histoplasma capsulatum is a major fungal pathogen with a broad variety of clinical presentations, ranging from mild, focal pulmonary disease to life-threatening systemic infections. Although azoles, such as itraconazole and voriconazole, and amphotericin B have significant activity against H. capsulatum, about 1 in 10 patients hospitalized due to histoplasmosis die. Hence, new approaches for managing disease are being sought. Over the past 10 years, studies have demonstrated that monoclonal antibodies (mAbs) can modify the pathogenesis of histoplasmosis. Disease has been shown to be impacted by mAbs targeting either fungal cell surface proteins or host co-stimulatory molecules. This review will detail our current knowledge regarding the impact of antibody therapy on histoplasmosis
Disruption of Histone Modification and CARM1 Recruitment by Arsenic Represses Transcription at Glucocorticoid Receptor-Regulated Promoters
Chronic exposure to inorganic arsenic (iAs) found in the environment is one of the most significant and widespread environmental health risks in the U.S. and throughout the world. It is associated with a broad range of health effects from cancer to diabetes as well as reproductive and developmental anomalies. This diversity of diseases can also result from disruption of metabolic and other cellular processes regulated by steroid hormone receptors via aberrant transcriptional regulation. Significantly, exposure to iAs inhibits steroid hormone-mediated gene activation. iAs exposure is associated with disease, but is also used therapeutically to treat specific cancers complicating an understanding of iAs action. Transcriptional activation by steroid hormone receptors is accompanied by changes in histone and non-histone protein post-translational modification (PTM) that result from the enzymatic activity of coactivator and corepressor proteins such as GRIP1 and CARM1. This study addresses how iAs represses steroid receptor-regulated gene transcription. PTMs on histones H3 and H4 at the glucocorticoid receptor (GR)-activated mouse mammary tumor virus (MMTV) promoter were identified by chromatin immunoprecipitation analysis following exposure to steroid hormone 6 iAs. Histone H3K18 and H3R17 amino acid residues had significantly different patterns of PTMs after treatment with iAs. Promoter interaction of the coactivator CARM1 was disrupted, but the interaction of GRIP1, a p160 coactivator through which CARM1 interacts with a promoter, was intact. Over-expression of CARM1 was able to fully restore and GRIP1 partially restored iAs-repressed transcription indicating that these coactivators are functionally associated with iAs-mediated transcriptional repression. Both are essential for robust transcription at steroid hormone regulated genes and both are associated with disease when inappropriately expressed. We postulate that iAs effects on CARM1 and GRIP1 may underlie some of its therapeutic effects and as well be associated with its toxic effects
Reflected Light from Sand Grains in the Terrestrial Zone of a Protoplanetary Disk
We show that grains have grown to ~mm size (sand sized) or larger in the
terrestrial zone (within ~3 AU) of the protoplanetary disk surrounding the 3
Myr old binary star KH 15D. We also argue that the reflected light in the
system reaches us by back scattering off the far side of the same ring whose
near side causes the obscuration.Comment: 22 pages, 5 figures. To be published in Nature, March 13, 2008.
Contains a Supplemen
The Orbit and Occultations of KH 15D
The unusual flux variations of the pre-main-sequence binary star KH 15D have
been attributed to occultations by a circumbinary disk. We test whether or not
this theory is compatible with newly available data, including recent radial
velocity measurements, CCD photometry over the past decade, and photographic
photometry over the past 50 years. We find the model to be successful, after
two refinements: a more realistic motion of the occulting feature, and a halo
around each star that probably represents scattering by the disk. The occulting
feature is exceptionally sharp-edged, raising the possibility that the dust in
the disk has settled into a thin layer, and providing a tool for fine-scale
mapping of the immediate environment of a T Tauri star. However, the window of
opportunity is closing, as the currently visible star may be hidden at all
orbital phases by as early as 2008.Comment: To appear in ApJ [16 pages, 13 figures
Nucleotide Excision Repair- and Polymerase Eta-Mediated Error-Prone Removal of Mitomycin C Interstrand Cross-Links
Interstrand cross-links (ICLs) make up a unique class of DNA lesions in which both strands of the double helix are covalently joined, precluding strand opening during replication and transcription. The repair of DNA ICLs has become a focus of study since ICLs are recognized as the main cytotoxic lesion inflicted by an array of alkylating compounds used in cancer treatment. As is the case for double-strand breaks, a damage-free homologous copy is essential for the removal of ICLs in an error-free manner. However, recombination-independent mechanisms may exist to remove ICLs in an error-prone fashion. We have developed an in vivo reactivation assay that can be used to examine the removal of site-specific mitomycin C-mediated ICLs in mammalian cells. We found that the removal of the ICL from the reporter substrate could take place in the absence of undamaged homologous sequences in repair-proficient cells, suggesting a cross-link repair mechanism that is independent of homologous recombination. Systematic analysis of nucleotide excision repair mutants demonstrated the involvement of transcription-coupled nucleotide excision repair and a partial requirement for the lesion bypass DNA polymerase eta encoded by the human POLH gene. From these observations, we propose the existence of a recombination-independent and mutagenic repair pathway for the removal of ICLs in mammalian cells
Genome -Scale Reconstruction of Metabolic Networks of Lactobacillus casei ATCC 334 and 12A
Lactobacillus casei strains are widely used in industry and the utility of this organism in these industrial applications is straindependent. Hence, tools capable of predicting strain specific phenotypes would have utility in the selection of strains forspecific industrial processes. Genome-scale metabolic models can be utilized to better understand genotype-phenotyperelationships and to compare different organisms. To assist in the selection and development of strains with enhancedindustrial utility, genome-scale models for L. casei ATCC 334, a well characterized strain, and strain 12A, a corn silage isolate,were constructed. Draft models were generated from RAST genome annotations using the Model SEED database and refined by evaluating ATP generating cycles, mass-and-charge-balances of reactions, and growth phenotypes. After the validation process was finished, we compared the metabolic networks of these two strains to identify metabolic, genetic and ortholog differences that may lead to different phenotypic behaviors. We conclude that the metabolic capabilities of the two networks are highly similar. The L. casei ATCC 334 model accounts for 1,040 reactions, 959 metabolites and 548 genes, while the L. casei 12A model accounts for 1,076 reactions, 979 metabolites and 640 genes. The developed L. casei ATCC 334 and 12A metabolic models will enable better understanding of the physiology of these organisms and be valuable tools in the development and selection of strains with enhanced utility in a variety of industrial applications
Small non-coding RNAs are altered by short-term sprint interval training in men
Small non-coding RNAs (ncRNAs) are emerging as important molecules for normal biological processes and are deregulated in disease. Exercise training is a powerful therapeutic strategy that prevents cardiometabolic disease and improves cardiorespiratory fitness and performance. Despite the known systemic health benefits of exercise training, the underlying molecular mechanisms are incompletely understood. Recent evidence suggests a role for epigenetic mechanisms, such as microRNAs, but whether other small ncRNAs are modulated by chronic exercise training is unknown. Here, we used small RNA sequencing to explore whether sprint interval training (SIT) controls the abundance of circulating small ncRNAs in human whole blood samples. Ten healthy men performed SIT three times a week for 6 weeks. After training, subjects showed marked improvements in maximal oxygen consumption and cycling performance with concurrent changes to the abundance of diverse species of circulating small ncRNAs (n = 1266 small ncRNAs, n = 13 microRNAs, q n = 24, all P > 0.05). Relative to older individuals, younger subjects exhibited an increased acute SIT-induced fold change in miR-1301-3p ( 0.05). Relative to older individuals, younger subjects exhibited an increased acute SIT-induced fold change in miR-1301-3p (P = 0.02) – a microRNA predicted to target mRNAs involved in alternative splicing, phosphoprotein and chromosomal rearrangement processes (all
Constraints on Galaxy Bias, Matter Density, and Primordial Non--Gausianity from the PSCz Galaxy Redshift Survey
We compute the bispectrum for the \IRAS PSCz catalog and find that the galaxy
distribution displays the characteristic signature of gravity. Assuming
Gaussian initial conditions, we obtain galaxy biasing parameters
and , with no sign of
scale-dependent bias for h/Mpc. These results impose stringent
constraints on non-Gaussian initial conditions. For dimensional scaling models
with statistics, we find N>49, which implies a constraint on
primordial skewness .Comment: 4 pages, 3 embedded figures, uses revtex style file, minor changes to
reflect published versio
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