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101.
? Premise of the study: The mechanisms for range expansion in invasive species depend on how genetic variation is structured in the introduced range. This study examined neutral genetic variation in the invasive annual grass Bromus tectorum in the Intermountain Western United States. Patterns of microsatellite (SSR) genotype distribution in this highly inbreeding species were used to make inferences about the roles of adaptively significant genetic variation, broadly adapted generalist genotypes, and facultative outcrossing in the recent range expansion of B. tectorum in this region. ? Methods: We sampled 20 individuals from each of 96 B. tectorum populations from historically and recently invaded habitats throughout the region and used four polymorphic SSR markers to characterize each individual. ? Key results: We detected 131 four-locus SSR genotypes; however, the 14 most common genotypes collectively accounted for 79.2% of the individuals. Common SSR genotypes were not randomly distributed among habitats. Instead, characteristic genotypes sorted into specific recently invaded habitats, including xeric warm and salt desert as well as mesic high-elevation habitats. Other SSR genotypes were common across a range of historically invaded habitats. We observed very few heterozygous individuals (0.58%). ? Conclusions: Broadly adapted, generalist genotypes appear to dominate historically invaded environments, while recently invaded salt and warm desert habitats are dominated by distinctive SSR genotypes that contain novel alleles. These specialist genotypes are not likely to have resulted from recombination; they probably represent more recent introductions from unknown source populations. We found little evidence that outcrossing plays a role in range expansion. 相似文献
102.
Fieldhouse RJ Jørgensen R Lugo MR Merrill AR 《The Journal of biological chemistry》2012,287(25):21176-21188
Certain Vibrio cholerae strains produce cholix, a potent protein toxin that has diphthamide-specific ADP-ribosyltransferase activity against eukaryotic elongation factor 2. Here we present a 1.8 Å crystal structure of cholix in complex with its natural substrate, nicotinamide adenine dinucleotide (NAD+). We also substituted hallmark catalytic residues by site-directed mutagenesis and analyzed both NAD+ binding and ADP-ribosyltransferase activity using a fluorescence-based assay. These data are the basis for a new kinetic model of cholix toxin activity. Further, the new structural data serve as a reference for continuing inhibitor development for this toxin class. 相似文献
103.
Although spatial heterogeneity of prey and landscapes are known to contribute to variation around predator‐prey functional response models, few studies have quantified these effects. We illustrate a new approach using data from winter movement paths of GPS‐collared wolves in the Rocky Mountains of Canada and time‐to‐event models with competing risks for measuring the effect of prey and landscape characteristics on the time‐to‐kill, which is the reciprocal of attack rate (aN) in a Holling's functional response. We evaluated 13 a priori models representing hypothesized mechanisms influencing attack rates in a heterogeneous landscape with two prey types. Models ranged from variants on Holling's disc equation, including search rate and prey density, to a full model including prey density and patchiness, search rates, satiation, and landscape features, which were measured along the wolf's movement path. Movement rates of wolves while searching explained more of the variation in time‐to‐kill than prey densities. Wolves did not compensate for low prey density by increasing movement rates and there was little evidence that spatial aggregation of prey influenced attack rates in this multi‐prey system. The top model for predicting time‐to‐kill included only search rate and landscape features. Wolves killed prey more quickly in flat terrain, likely due to increased vulnerability from accumulated snow, whereas attack rates were lower when wolves hunted near human‐made features presumably due to human disturbance. Understanding the sources of variation in attack rates provides refinements to functional response models that can lead to more effective predator–prey management in human‐dominated landscapes. 相似文献
104.
Of the seven sea turtle species, the critically endangered leatherback sea turtle (Dermochelys coriacea) exhibits the lowest and most variable nest success (i.e., hatching success and emergence success) for reasons that remain largely unknown. In an attempt to identify or rule out causes of low reproductive success in this species, we established the largest sample size (n = 60–70 for most values) of baseline blood parameters (protein electrophoresis, hematology, plasma biochemistry) for this species to date. Hematologic, protein electrophoretic and biochemical values are important tools that can provide information regarding the physiological condition of an individual and population health as a whole. It has been proposed that the health of nesting individuals affects their reproductive output. In order to establish correlations with low reproductive success in leatherback sea turtles from Florida, we compared maternal health indices to hatching success and emergence success of their nests. As expected, hatching success (median = 57.4%) and emergence success (median = 49.1%) in Floridian leatherbacks were low during the study period (2007–2008 nesting seasons), a trend common in most nesting leatherback populations (average global hatching success = ∼50%). One protein electrophoretic value (gamma globulin protein) and one hematologic value (red blood cell count) significantly correlated with hatching success and emergence success. Several maternal biochemical parameters correlated with hatching success and/or emergence success including alkaline phosphatase activity, blood urea nitrogen, calcium, calcium∶phosphorus ratio, carbon dioxide, cholesterol, creatinine, and phosphorus. Our results suggest that in leatherbacks, physiological parameters correlate with hatching success and emergence success of their nests. We conclude that long-term and comparative studies are needed to determine if certain individuals produce nests with lower hatching success and emergence success than others, and if those individuals with evidence of chronic suboptimal health have lower reproductive success. 相似文献
105.
Alberto Molano Zhaofeng Huang Melissa G. Marko Angelo Azzi Dayong Wu Elaine Wang Samuel L. Kelly Alfred H. Merrill Jr Stephen C. Bunnell Simin Nikbin Meydani 《PloS one》2012,7(10)
To determine whether changes in sphingolipid composition are associated with age-related immune dysfunction, we analyzed the core sphingolipidome (i.e., all of the metabolites through the first headgroup additions) of young and aged CD4+ T cells. Since sphingolipids influence the biophysical properties of membranes, we evaluated the compositions of immune synapse (IS) and non-IS fractions prepared by magnetic immuno-isolation. Broadly, increased amounts of sphingomyelins, dihydrosphingomyelins and ceramides were found in aged CD4+ T cells. After normalizing for total sphingolipid content, a statistically significant decrease in the molar fraction of glucosylceramides was evident in both the non-IS and IS fractions of aged T cells. This change was balanced by less dramatic increases in the molar fractions of sphingomyelins and dihydrosphingomyelins in aged CD4+ T cells. In vitro, the direct or enzymatic enhancement of ceramide levels decreased CD4+ T cell proliferation without regard for the age of the responding T cells. In contrast, the in vitro inhibition of glucosylceramidase preferentially increased the proliferation of aged CD4+ T cells. These results suggest that reductions in glucosylceramide abundance contribute to age-related impairments in CD4+ T cell function. 相似文献
106.
ABSTRACT: BACKGROUND: Dopaminergic (DA) neurons in the ventral midbrain selectively degenerate in Parkinsons disease (PD) in part because their oxidative environment in the substantia nigra (SN) may render them vulnerable to neuroinflammatory stimuli. Chronic inhibition of soluble Tumor Necrosis Factor (TNF) with dominant-negative TNF inhibitors protects DA neurons in rat models of parkinsonism, yet the molecular mechanisms and pathway(s) that mediate TNF toxicity remain(s) to be clearly identified. Here we investigated the contribution of ceramide sphingolipid signaling in TNF-dependent toxicity. RESULTS: Ceramide dose-dependently reduced the viability of DA neuroblastoma cells and primary DA neurons and pharmacological inhibition of sphingomyelinases (SMases) with three different inhibitors during TNF treatment afforded significant neuroprotection by attenuating increased endoplasmic reticulum (ER) stress, loss of mitochondrial membrane potential, caspase-3 activation and decreases in Akt phosphorylation. Using lipidomics mass spectrometry we confirmed that TNF treatment not only promotes generation of ceramide, but also leads to accumulation of several atypical deoxy-sphingoid bases (DSBs). Exposure of DA neuroblastoma cells to atypical DSBs in the micromolar range reduced cell viability and inhibited neurite outgrowth and branching in primary DA neurons, suggesting that TNFinduced de novo synthesis of atypical DSBs may be a secondary mechanism involved in mediating its neurotoxicity in DA neurons. CONCLUSIONS: We conclude that TNF/TNFR1-dependent activation of SMases generates ceramide and sphingolipid species that promote degeneration and caspase-dependent cell death of DA neurons. Ceramide and atypical DSBs may represent novel drug targets for development of neuroprotective strategies that can delay or attenuate the progressive loss of nigral DA neurons in patients with PD. 相似文献
107.
Parise RA Beumer JH Kangani CO Holleran JL Eiseman JL Smith NF Covey JM Perrine SP Egorin MJ 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2008,862(1-2):168-174
2,2-Dimethylbutyrate (DMB) is a potential treatment for thalassemia and hemoglobinopathies. To facilitate pharmacokinetic evaluation of DMB, we developed an LC-MS assay and quantitated DMB in plasma of rats after an oral dose of 500mg/kg. After acetonitrile protein precipitation, DMB and dimethylvaleric acid (DMV) internal standard were derivatized to benzylamides, chromatographed on a Hydro-RP column with acetonitrile, water, and 0.1% formic acid, and detected by electrospray positive-mode ionization mass spectrometry. The assay was accurate (97-107%) and precise (3.4-6.2%) between 100 and 10,000ng/mL. Recovery from plasma was >62%. Plasma freeze-thaw and room temperature stability were acceptable. 相似文献
108.
Jørgensen R Purdy AE Fieldhouse RJ Kimber MS Bartlett DH Merrill AR 《The Journal of biological chemistry》2008,283(16):10671-10678
The ADP-ribosyltransferases are a class of enzymes that display activity in a variety of bacterial pathogens responsible for causing diseases in plants and animals, including those affecting mankind, such as diphtheria, cholera, and whooping cough. We report the characterization of a novel toxin from Vibrio cholerae, which we call cholix toxin. The toxin is active against mammalian cells (IC(50) = 4.6 +/- 0.4 ng/ml) and crustaceans (Artemia nauplii LD(50) = 10 +/- 2 mug/ml). Here we show that this toxin is the third member of the diphthamide-specific class of ADP-ribose transferases and that it possesses specific ADP-ribose transferase activity against ribosomal eukaryotic elongation factor 2. We also describe the high resolution crystal structures of the multidomain toxin and its catalytic domain at 2.1- and 1.25-A resolution, respectively. The new structural data show that cholix toxin possesses the necessary molecular features required for infection of eukaryotes by receptor-mediated endocytosis, translocation to the host cytoplasm, and inhibition of protein synthesis by specific modification of elongation factor 2. The crystal structures also provide important insight into the structural basis for activation of toxin ADP-ribosyltransferase activity. These results indicate that cholix toxin may be an important virulence factor of Vibrio cholerae that likely plays a significant role in the survival of the organism in an aquatic environment. 相似文献
109.
Dagda RK Merrill RA Cribbs JT Chen Y Hell JW Usachev YM Strack S 《The Journal of biological chemistry》2008,283(52):36241-36248
The neurodegenerative disorder spinocerebellar ataxia 12 (SCA12) is caused by CAG repeat expansion in the non-coding region of the PPP2R2B gene. PPP2R2B encodes Bbeta1 and Bbeta2, alternatively spliced and neuron-specific regulatory subunits of the protein phosphatase 2A (PP2A) holoenzyme. We show here that in PC12 cells and hippocampal neurons, cell stressors induced a rapid translocation of PP2A/Bbeta2 to mitochondria to promote apoptosis. Conversely, silencing of PP2A/Bbeta2 protected hippocampal neurons against free radical-mediated, excitotoxic, and ischemic insults. Evidence is accumulating that the mitochondrial fission/fusion equilibrium is an important determinant of cell survival. Accordingly, we found that Bbeta2 expression induces mitochondrial fragmentation, whereas Bbeta2 silencing or inhibition resulted in mitochondrial elongation. Based on epistasis experiments involving Bcl2 and core components of the mitochondrial fission machinery (Fis1 and dynamin-related protein 1), mitochondrial fragmentation occurs upstream of apoptosis and is both necessary and sufficient for hippocampal neuron death. Our data provide the first example of a proapoptotic phosphatase that predisposes to neuronal death by promoting mitochondrial division and point to a possible imbalance of the mitochondrial morphogenetic equilibrium in the pathogenesis of SCA12. 相似文献
110.
Merrill SC Peairs FB Miller HR Randolph TL Rudolph JB Talmich EE 《Journal of economic entomology》2008,101(2):541-545
The Russian wheat aphid, Diuraphis noxia (Kurdjumov), is an economically important pest of small grains. Since its introduction into North America in 2003, Russian wheat aphid Biotype 2 has been found to be virulent to all commercially available winter wheat, Triticum aestivum L., cultivars. Our goal was to examine differences in Russian wheat aphid reproduction and development on a variety of plant hosts to gain information about 1) potential alternate host refuges, 2) selective host pressures on Russian wheat aphid genetic variation, and 3) general population dynamics of Russian wheat aphid Biotype 2. We studied host quality of two wheatgrasses (crested wheatgrass, Agropyron cristatum [L.] Gaertn., and intermediate wheatgrass, Agropyron intermedium [Host] Beauvoir) and two types of winter wheat (T. aestivum, one Biotype 2 susceptible wheat, 'Custer' and one biotype 2 resistant wheat, STARS02RWA2414-11). The susceptible wheat had the highest intrinsic rate of increase, greatest longevity and greatest fecundity of the four host studied. Crested wheatgrass and the resistant wheat showed similar growth rates. Intermediate wheatgrass had the lowest intrinsic rate of increase and lowest fecundity of all tested hosts. 相似文献