149,725 research outputs found

    Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength

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    Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites

    CQESTR Simulation of Management Practice Effects on Long-Term Soil Organic Carbon

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    Management of soil organic matter (SOM) is important for soil productivity and responsible utilization of crop residues for additional uses. CQESTR, pronounced “sequester,” a contraction of “C sequestration” (meaning C storage), is a C balance model that relates organic residue additions, crop management, and soil tillage to SOM accretion or loss. Our objective was to simulate SOM changes in agricultural soils under a range of climate and management systems using the CQESTR model. Four long-term experiments (Champaign, IL, \u3e100 yr; Columbia, MO, \u3e100 yr; Lincoln, NE, 20 yr; Sidney, NE, 20 yr) in the United States under various crop rotations, tillage practices, organic amendments, and crop residue removal treatments were selected for their documented history of the long-term effects of management practice on SOM dynamics. CQESTR successfully simulated a substantial decline in SOM with 50 yr of crop residue removal under various rotations at Columbia and Champaign. The increase in SOM following addition of manure was simulated well; however, the model underestimated SOM for a fertilized treatment at Columbia. Predicted and observed values from the four sites were signifi cantly related (r2 = 0.94, n = 113, P \u3c 0.001), with slope not signifi cantly different from 1. Given the high correlation of simulated and observed SOM changes, CQESTR can be used as a reliable tool to predict SOM changes from management practices and offers the potential for estimating soil C storage required for C credits. It can also be an important tool to estimate the impacts of crop residue removal for bioenergy production on SOM level and soil production capacity

    New South Wales Vegetation Classification and Assessment : part 1, plant communities of the NSW Western Plains

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    For the Western Plains of New South Wales, 213 plant communities are classified and described and their protected area and threat status assessed. The communities are listed on the NSW Vegetation Classification and Assessment database (NSWVCA). The full description of the communities is placed on an accompanying CD together with a read-only version of the NSWVCA database. The NSW Western Plains is 45.5 million hectares in size and covers 57% of NSW. The vegetation descriptions are based on over 250 published and unpublished vegetation surveys and maps produced over the last 50 years (listed in a bibliography), rapid field checks and the expert knowledge on the vegetation. The 213 communities occur over eight Australian bioregions and eight NSW Catchment Management Authority areas. As of December 2005, 3.7% of the Western Plains was protected in 83 protected areas comprising 62 public conservation reserves and 21 secure property agreements. Only one of the eight bioregions has greater than 10% of its area represented in protected areas. 31 or 15% of the communities are not recorded from protected areas. 136 or 64% have less than 5% of their pre-European extent in protected areas. Only 52 or 24% of the communities have greater than 10% of their original extent protected, thus meeting international guidelines for representation in protected areas. 71 or 33% of the plant communities are threatened, that is, judged as being ‘critically endangered’, ‘endangered’ or ‘vulnerable’. While 80 communities are recorded as being of ‘least concern’ most of these are degraded by lack of regeneration of key species due to grazing pressure and loss of top soil and some may be reassessed as being threatened in the future. Threatening processes include vegetation clearing on higher nutrient soils in wetter regions, altered hydrological regimes due to draw-off of water from river systems and aquifers, high continuous grazing pressure by domestic stock, feral goats and rabbits, and in some places native herbivores — preventing regeneration of key plant species, exotic weed invasion along rivers and in fragmented vegetation, increased salinity, and over the long term, climate change. To address these threats, more public reserves and secure property agreements are required, vegetation clearing should cease, re-vegetation is required to increase habitat corridors and improve the condition of native vegetation, environmental flows to regulated river systems are required to protect inland wetlands, over-grazing by domestic stock should be avoided and goat and rabbit numbers should be controlled and reduced. Conservation action should concentrate on protecting plant communities that are threatened or are poorly represented in protected areas

    Translation efficiency is a determinant of the magnitude of miRNA-mediated repression

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    Abstract MicroRNAs are well known regulators of mRNA stability and translation. However, the magnitude of both translational repression and mRNA decay induced by miRNA binding varies greatly between miRNA targets. This can be the result of cis and trans factors that affect miRNA binding or action. We set out to address this issue by studying how various mRNA characteristics affect miRNA-mediated repression. Using a dual luciferase reporter system, we systematically analyzed the ability of selected mRNA elements to modulate miRNA-mediated repression. We found that changing the 3′UTR of a miRNA-targeted reporter modulates translational repression by affecting the translation efficiency. This 3′UTR dependent modulation can be further altered by changing the codon-optimality or 5′UTR of the luciferase reporter. We observed maximal repression with intermediate codon optimality and weak repression with very high or low codon optimality. Analysis of ribosome profiling and RNA-seq data for endogenous miRNA targets revealed translation efficiency as a key determinant of the magnitude of miRNA-mediated translational repression. Messages with high translation efficiency were more robustly repressed. Together our results reveal modulation of miRNA-mediated repression by characteristics and features of the 5′UTR, CDS and 3′UTR

    Transverse tunneling current through guanine traps in DNA

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    The current - voltage dependence of the transverse tunneling current through the electron or hole traps in a DNA is investigated. The hopping of the charge between the sites of the trap and the charge-phonon coupling results in a staircase structure of the I-V curve. For typical parameters of the DNA molecule the energy characteristics of a DNA trap can be extracted from the I-V dependence, viz., for a small gate voltage the phonon frequency and for a large gate voltage the hopping integral can be found from the positions of the steps in the I-V curve. Formation of the polaronic state also results in the redistribution of the tunneling current between the different sites of the traps

    Gene regulatory factors of the sea urchin embryo. II. Two dissimilar proteins, P3A1 and P3A2, bind to the same target sites that are required for early territorial gene expression

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    Previous work demonstrated that a negative regulatory interaction mediated by factor(s) termed 'P3A' is required for correct territory-specific gene expression in the sea urchin embryo. A probe derived from a P3A target site in the skeletogenic SM50 gene of Strongylocentrotus purpuratus was used to isolate a cDNA clone coding for a factor that binds specifically to this site. This factor, called P3A1, contains two sequence elements that belong to the Zn finger class of DNA-binding motifs, and in these regions is most closely similar to the Drosophila hunchback factor. The P3A1 factor also binds to a similar target sequence in a second gene, CyIIIa, expressed in embryonic aboral ectoderm. Another sea urchin embryo protein factor, P3A2, has been isolated by affinity chromatography and cloned, as described in Calzone et al. Development 112, 335-350 (1991). P3A2 footprints the same target sites in the SM50 and CyIIIa genes as does P3A1, but lacks the Zn finger sequence motifs and in amino acid sequence is almost entirely dissimilar to P3A1. A deletion analysis of P3A2 delimited the DNA-binding region, revealing that five specific amino acids in the first P3A1 finger region and four in the second P3A1 finger region are also present in equivalent positions in P3A2. The P3A1 and P3A2 factors could function as regulatory antagonists, having evolved similar target specificities from dissimilar DNA-binding domains

    Genome-wide transcription start site profiling in biofilm-grown Burkholderia cenocepacia J2315

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    Background: Burkholderia cenocepacia is a soil-dwelling Gram-negative Betaproteobacterium with an important role as opportunistic pathogen in humans. Infections with B. cenocepacia are very difficult to treat due to their high intrinsic resistance to most antibiotics. Biofilm formation further adds to their antibiotic resistance. B. cenocepacia harbours a large, multi-replicon genome with a high GC-content, the reference genome of strain J2315 includes 7374 annotated genes. This study aims to annotate transcription start sites and identify novel transcripts on a whole genome scale. Methods: RNA extracted from B. cenocepacia J2315 biofilms was analysed by differential RNA-sequencing and the resulting dataset compared to data derived from conventional, global RNA-sequencing. Transcription start sites were annotated and further analysed according to their position relative to annotated genes. Results: Four thousand ten transcription start sites were mapped over the whole B. cenocepacia genome and the primary transcription start site of 2089 genes expressed in B. cenocepacia biofilms were defined. For 64 genes a start codon alternative to the annotated one was proposed. Substantial antisense transcription for 105 genes and two novel protein coding sequences were identified. The distribution of internal transcription start sites can be used to identify genomic islands in B. cenocepacia. A potassium pump strongly induced only under biofilm conditions was found and 15 non-coding small RNAs highly expressed in biofilms were discovered. Conclusions: Mapping transcription start sites across the B. cenocepacia genome added relevant information to the J2315 annotation. Genes and novel regulatory RNAs putatively involved in B. cenocepacia biofilm formation were identified. These findings will help in understanding regulation of B. cenocepacia biofilm formation

    Biochemical and immunochemical analysis of the arrangement of connexin43 in rat heart gap junction membranes

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    A 43 × 10^3 M_r protein (designated connexin43 or Cx43) is a major constituent of heart gap junctions. The understanding of its arrangement in junctional membranes has been extended by means of site-directed antibodies raised against synthetic peptides of Cx43. These represent part of the first extracellular loop (EL-46), the cytoplasmic loop (CL-100), the second extracellular loop (EL-186) and carboxy-terminal sequences (CT-237 and CT-360). All of the antibodies raised reacted with their respective peptides and the Cx43 protein on Western blots. By immunoelectron microscopy two of the antibodies (CL-100 and CT-360) were shown to label the cytoplasmic surface of isolated gap junction membranes. Immunofluorescent labeling at locations of neonatal cardiac myocyte-myocyte apposition required an alkali/urea treatment when the EL-46 and EL-186 antibodies were used. Immunoblot analysis of endoproteinase Lys-C-digested gap junctions revealed that the Cx43 protein passed through the lipid bilayer four times. Alkaline phosphatase digestion of isolated junctions was used to show that the CT-360 antibody recognized many phosphorylated forms of Cx43. Our results unequivocally confirm models of the organization of Cx43 that were based on a more limited set of data and a priori considerations of the sequence
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