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991.
Marika A. Schulhof Andrew E. Allen Eric E. Allen Natalie Mladenov John P. McCrow Natalie T. Jones Jessica Blanton Hamanda B. Cavalheri Drishti Kaul Celia C. Symons Jonathan B. Shurin 《Molecular ecology》2020,29(11):2080-2093
Warming, eutrophication (nutrient fertilization) and brownification (increased loading of allochthonous organic matter) are three global trends impacting lake ecosystems. However, the independent and synergistic effects of resource addition and warming on autotrophic and heterotrophic microorganisms are largely unknown. In this study, we investigate the independent and interactive effects of temperature, dissolved organic carbon (DOC, both allochthonous and autochthonous) and nitrogen (N) supply, in addition to the effect of spatial variables, on the composition, richness, and evenness of prokaryotic and eukaryotic microbial communities in lakes across elevation and N deposition gradients in the Sierra Nevada mountains of California, USA. We found that both prokaryotic and eukaryotic communities are structured by temperature, terrestrial (allochthonous) DOC and latitude. Prokaryotic communities are also influenced by total and aquatic (autochthonous) DOC, while eukaryotic communities are also structured by nitrate. Additionally, increasing N availability was associated with reduced richness of prokaryotic communities, and both lower richness and evenness of eukaryotes. We did not detect any synergistic or antagonistic effects as there were no interactions among temperature and resource variables. Together, our results suggest that (a) organic and inorganic resources, temperature, and geographic location (based on latitude and longitude) independently influence lake microbial communities; and (b) increasing N supply due to atmospheric N deposition may reduce richness of both prokaryotic and eukaryotic microbes, probably by reducing niche dimensionality. Our study provides insight into abiotic processes structuring microbial communities across environmental gradients and their potential roles in material and energy fluxes within and between ecosystems. 相似文献
992.
Altered patterns of fractionation and exon deletions in Brassica rapa support a two-step model of paleohexaploidy 总被引:2,自引:0,他引:2
Tang H Woodhouse MR Cheng F Schnable JC Pedersen BS Conant G Wang X Freeling M Pires JC 《Genetics》2012,190(4):1563-1574
The genome sequence of the paleohexaploid Brassica rapa shows that fractionation is biased among the three subgenomes and that the least fractionated subgenome has approximately twice as many orthologs as its close (and relatively unduplicated) relative Arabidopsis than had either of the other two subgenomes. One evolutionary scenario is that the two subgenomes with heavy gene losses (I and II) were in the same nucleus for a longer period of time than the third subgenome (III) with the fewest gene losses. This "two-step" hypothesis is essentially the same as that proposed previously for the eudicot paleohexaploidy; however, the more recent nature of the B. rapa paleohexaploidy makes this model more testable. We found that subgenome II suffered recent small deletions within exons more frequently than subgenome I, as would be expected if the genes in subgenome I had already been near maximally fractionated before subgenome III was introduced. We observed that some sequences, before these deletions, were flanked by short direct repeats, a unique signature of intrachromosomal illegitimate recombination. We also found, through simulations, that short--single or two-gene--deletions appear to dominate the fractionation patterns in B. rapa. We conclude that the observed patterns of the triplicated regions in the Brassica genome are best explained by a two-step fractionation model. The triplication and subsequent mode of fractionation could influence the potential to generate morphological diversity--a hallmark of the Brassica genus. 相似文献
993.
Zhang X Zang N Wei Y Yin J Teng R Seftel A Disanto ME 《American journal of physiology. Endocrinology and metabolism》2012,302(2):E243-E253
Testosterone (T) plays a permissive role in the development of benign prostatic hyperplasia (BPH), and phosphodiesterase 5 inhibitors (PDE5is) have been found to be effective for BPH and lower urinary tract symptoms (LUTS) in clinical trials. This study investigated the effect of T on smooth muscle (SM) contractile and regulatory signaling pathways, including PDE5 expression and functional activity in prostate in male rats (sham-operated, surgically castrated, and castrated with T supplementation). In vitro organ bath studies, real-time RT-PCR, Western blot analysis, and immunohistochemistry were performed. Castration heavily attenuated contractility, including sensitivity to phenylephrine with SM myosin immunostaining revealing a disrupted SM cell arrangement in the stroma. PDE5 was immunolocalized exclusively in the prostate stroma, and orchiectomy signficantly reduced PDE5 immunopositivity, mRNA, and protein expression, along with nNOS and ROKβ mRNA, whereas it increased eNOS plus α(1a) and α(1b) adrenoreceptor expression in castrated animals. The PDE5i zaprinast significantly increased prostate strip relaxation to the nitric oxide donor sodium nitroprusside (SNP) in control but not castrated rats. But SNP alone was more effective on castrated rats, comparable with sham treated with SNP plus zaprinast. T supplementation prevented or restored all above changes, including SNP and zaprinast in vitro responsiveness. In conclusion, our data show that T positively regulates PDE5 expression and functional activities in prostate, and T ablation not only suppresses prostate size but also reduces prostatic SM contractility, with several potential SM contraction/relaxation pathways implicated. Zaprinast findings strongly suggest a major role for PDE5/cGMP in this signaling cascade. PDE5 inhibition may represent a novel mechanism for treatment of BPH. 相似文献
994.
995.
Apical actomyosin activity in animal epithelial cells influences tissue morphology and drives morphogenetic movements during development. The molecular mechanisms leading to myosin II accumulation at the apical membrane and its exclusion from other membranes are poorly understood. We show that in the nonmetazoan Dictyostelium discoideum, myosin II localizes apically in tip epithelial cells that surround the stalk, and constriction of this epithelial tube is required for proper morphogenesis. IQGAP1 and its binding partner cortexillin I function downstream of α- and β-catenin to exclude myosin II from the basolateral cortex and promote apical accumulation of myosin II. Deletion of IQGAP1 or cortexillin compromises epithelial morphogenesis without affecting cell polarity. These results reveal that apical localization of myosin II is a conserved morphogenetic mechanism from nonmetazoans to vertebrates and identify a hierarchy of proteins that regulate the polarity and organization of an epithelial tube in?a simple model organism. 相似文献
996.
Melancon BJ Gogliotti RD Tarr JC Saleh SA Chauder BA Lebois EP Cho HP Utley TJ Sheffler DJ Bridges TM Morrison RD Daniels JS Niswender CM Conn PJ Lindsley CW Wood MR 《Bioorganic & medicinal chemistry letters》2012,22(10):3467-3472
This Letter describes the continued optimization of the MLPCN probe molecule ML071. After introducing numerous cyclic constraints and novel substitutions throughout the parent structure, we produced a number of more highly potent agonists of the M(1) mACh receptor. While many novel agonists demonstrated a promising ability to increase soluble APPα release, further characterization indicated they may be functioning as bitopic agonists. These results and the implications of a bitopic mode of action are presented. 相似文献
997.
Brooks JC Sun W Chiosis G Leifer CA 《Biochemical and biophysical research communications》2012,421(4):780-784
Nucleic acid-sensing Toll-like receptors (TLRs) initiate innate immune responses to foreign RNA and DNA, yet can detect and respond to host DNA. To avoid autoimmune pathologies, nucleic acid sensing TLRs are tightly regulated. TLR9 primarily resides in the endoplasmic reticulum, traffics to endosomes, is proteolytically processed and responds to DNA. The heat shock protein gp96 is one of several accessory proteins that regulate intracellular trafficking of TLR9. In the absence of gp96, TLR9 fails to exit the endoplasmic reticulum, and therefore gp96-deficient macrophages fail to respond to CpG DNA. However, absence of gp96 precludes studies on potential chaperoning functions of gp96 for TLR9. Here we demonstrate that pharmacologic interference with gp96 function inhibits TLR9 signaling. TLR9 remains associated with gp96 during intracellular trafficking, and gp96-specific inhibitors increase TLR9 sensitivity to proteolytic degradation. We propose that gp96 is critical for both TLR9 egress from the ER, and for protein conformational stability in the endosomal compartment. These studies highlight the importance of examining gp96-specific inhibitors for modulating TLR9 activation, and the treatment autoimmune diseases. 相似文献
998.
Woo Jin Kim Alice M Wood Alan F Barker Mark L Brantly Edward J Campbell Edward Eden Gerard McElvaney Stephen I Rennard Robert A Sandhaus James M Stocks James K Stoller Charlie Strange Gerard Turino Edwin K Silverman Robert A Stockley Dawn L DeMeo 《Respiratory research》2012,13(1):16
Background
The development of COPD in subjects with alpha-1 antitrypsin (AAT) deficiency is likely to be influenced by modifier genes. Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3) and IREB2 (iron regulatory binding protein 2).We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency.Methods
The current analysis included 378 PIZZ subjects in the AAT Genetic Modifiers Study and a replication cohort of 458 subjects from the UK AAT Deficiency National Registry. Nine SNPs in LOC123688, CHRNA3 and IREB2 were selected for genotyping. FEV1 percent of predicted and FEV1/FVC ratio were analyzed as quantitative phenotypes. Family-based association analysis was performed in the AAT Genetic Modifiers Study. In the replication set, general linear models were used for quantitative phenotypes and logistic regression models were used for the presence/absence of emphysema or COPD.Results
Three SNPs (rs2568494 in IREB2, rs8034191 in LOC123688, and rs1051730 in CHRNA3) were associated with pre-bronchodilator FEV1 percent of predicted in the AAT Genetic Modifiers Study. Two SNPs (rs2568494 and rs1051730) were associated with the post-bronchodilator FEV1 percent of predicted and pre-bronchodilator FEV1/FVC ratio; SNP-by-gender interactions were observed. In the UK National Registry dataset, rs2568494 was significantly associated with emphysema in the male subgroup; significant SNP-by-smoking interactions were observed.Conclusions
IREB2 and CHRNA3 are potential genetic modifiers of COPD phenotypes in individuals with severe AAT deficiency and may be sex-specific in their impact. 相似文献999.
A Copeland A Zeytun M Yassawong M Nolan S Lucas N Hammon S Deshpande JF Cheng C Han R Tapia LA Goodwin S Pitluck K Mavromatis K Liolios I Pagani N Ivanova N Mikhailova A Pati A Chen K Palaniappan M Land L Hauser CD Jeffries EM Brambilla M Rohde J Sikorski R Pukall M Göker JC Detter T Woyke J Bristow JA Eisen V Markowitz P Hugenholtz NC Kyrpides HP Klenk A Lapidus 《Standards in genomic sciences》2012,6(2):240-250
Deinococcus proteolyticus (ex Kobatake et al. 1973) Brook and Murray 1981 is one of currently 47 species in the genus Deinococcus within the family Deinococcaceae. Strain MRP(T) was isolated from feces of Lama glama and possesses extreme radiation resistance, a trait is shares with various other species of the genus Deinococcus, with D. proteolyticus being resistant up to 1.5 Mrad of gamma radiation. Strain MRP(T) is of further interest for its carotenoid pigment. The genome presented here is only the fifth completed genome sequence of a member of the genus Deinococcus (and the forth type strain) to be published, and will hopefully contribute to a better understanding of how members of this genus adapted to high gamma- or UV ionizing-radiation. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,886,836 bp long genome with its four large plasmids of lengths 97 kbp, 132 kbp, 196 kbp and 315 kbp harbors 2,741 protein-coding and 58 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
1000.