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31.
Reintroduction of fresh water to coastal systems with altered hydrologic regimes is a management option for restoring degraded
wetland habitats. Plant production in these systems is believed to be enhanced by increased nutrient availability and reduced
salinity. Although studies have documented nutrient limitation and salinity stress in coastal marshes, interpreting the effects
of freshwater reintroduction on plant production is difficult because high nutrient availability often is confounded with
low salinity. We tested the hypothesis that plant growth response to nutrients does not vary with salinity in a greenhouse
study. Treatments consisted of four nutrient concentrations and four non-lethal salinity levels; plant response was measured
as biomass accumulation after 144 days of exposure. The significant interaction between salinity and nutrient concentrations
indicates that response of Spartina patens marshes to freshwater inflows would vary by site-specific soil conditions. Biomass decreased with increased salinity at all
four nutrient concentrations with variation among the nutrient concentrations decreasing as salinity increased. We demonstrate
the importance of considering ambient salinity and nutrient soil conditions in restoration planning involving freshwater inflow.
We propose salinity should remain a primary concern in restoration plans targeted at improving degraded S. patens-dominated marsh habitat. 相似文献
32.
Monick MM Powers LS Barrett CW Hinde S Ashare A Groskreutz DJ Nyunoya T Coleman M Spitz DR Hunninghake GW 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(11):7485-7496
A unique feature of human alveolar macrophages is their prolonged survival in the face of a stressful environment. We have shown previously that the ERK MAPK is constitutively active in these cells and is important in prolonging cell survival. This study examines the role of the ERK pathway in maintaining mitochondrial energy production. The data demonstrate that ATP levels in alveolar macrophages depend on intact mitochondria and optimal functioning of the electron transport chain. Significant levels of MEK and ERK localize to the mitochondria and inhibition of ERK activity induces an early and profound depletion in cellular ATP coincident with a loss of mitochondrial transmembrane potential. The effect of ERK suppression on ATP levels was specific, since it did not occur with PI3K/Akt, p38, or JNK suppression. ERK inhibition led to cytosolic release of mitochondrial proteins and caspase activation. Both ERK inhibition and mitochondrial blockers induced loss of plasma membrane permeability and cell death. The cell death induced by ERK inhibition had hallmarks of both apoptotic (caspase activation) and necrotic (ATP loss) cell death. By blocking ERK inhibition-induced reactive oxygen species, caspase activation was prevented, although necrotic pathways continued to induce cell death. This suggests that mitochondrial dysfunction caused by ERK inhibition generates both apoptotic and necrotic cell death-inducing pathways. As a composite, these data demonstrate a novel mitochondrial role for ERK in maintaining mitochondrial membrane potential and ATP production in human alveolar macrophages. 相似文献
33.
Robosky LC Wade K Woolson D Baker JD Manning ML Gage DA Reily MD 《Journal of lipid research》2008,49(3):686-692
A NMR spectroscopic method is described that enables the quantitation of specific lipid classes and components, independent of fatty acid composition. We demonstrate this method for measuring cholesterol, squalene, and pools of sterol esters, wax esters (WEs), and triglyceride (TG) components in sebum and meibum. When 600 MHz NMR equipment is used in conjunction with highly sensitive cryogenically cooled probes, this method has adequate sensitivity, and for some applications, advantages over commonly used HPLC-evaporative light-scattering detection and mass spectrometry-based approaches. This method is shown to be useful for preclinical and clinical monitoring of the efficacy of sebum-reducing agents in animals and humans. In Syrian hamsters, 3% topical flutamide and 20 mg/kg oral isotretinoin reduced sterol esters by 18.7% and 30.0%, respectively, and reduced WEs by 32.9% and 31.8%, respectively, as measured in a punch biopsy of the ear. In a 72 patient clinical methodology study, the assay delivered reproducible and noninvasive measurements of WEs, cholesteryl esters, TGs, and squalene from Sebutape skin blots. The quantitative results of sebum analysis obtained by the NMR method correlate well with those obtained with HPLC-based approaches. This approach may be broadly applicable to cases in which fatty acid-independent quantification of lipid classes is desired. 相似文献
34.
Sergey Koren Gregory P Harhay Timothy PL Smith James L Bono Dayna M Harhay Scott D Mcvey Diana Radune Nicholas H Bergman Adam M Phillippy 《Genome biology》2013,14(9):R101
Background
The short reads output by first- and second-generation DNA sequencing instruments cannot completely reconstruct microbial chromosomes. Therefore, most genomes have been left unfinished due to the significant resources required to manually close gaps in draft assemblies. Third-generation, single-molecule sequencing addresses this problem by greatly increasing sequencing read length, which simplifies the assembly problem.Results
To measure the benefit of single-molecule sequencing on microbial genome assembly, we sequenced and assembled the genomes of six bacteria and analyzed the repeat complexity of 2,267 complete bacteria and archaea. Our results indicate that the majority of known bacterial and archaeal genomes can be assembled without gaps, at finished-grade quality, using a single PacBio RS sequencing library. These single-library assemblies are also more accurate than typical short-read assemblies and hybrid assemblies of short and long reads.Conclusions
Automated assembly of long, single-molecule sequencing data reduces the cost of microbial finishing to $1,000 for most genomes, and future advances in this technology are expected to drive the cost lower. This is expected to increase the number of completed genomes, improve the quality of microbial genome databases, and enable high-fidelity, population-scale studies of pan-genomes and chromosomal organization. 相似文献35.
Agouti Signaling Protein (ASIP) controls the localized expression of red and black pigment in the domestic dog through interaction with other genes, such as Melanocortin 1 Receptor and Beta-Defensin 103. Specific ASIP alleles are necessary for many of the coat color patterns, such as black-and-tan and saddle tan. Mutations in 2 ASIP alleles, a(y) and a, have previously been identified. Here, we characterize a mutation consisting of a short interspersed nuclear element (SINE) insertion in intron 1 of ASIP that allows for the differentiation of the a(w) wolf sable and a(t) black-and-tan alleles. The SINE insertion is present in dogs with the a(t) and a alleles but absent from dogs with the a(w) and a(y) alleles. Dogs with the saddle tan phenotype were all a(t)/a(t). Schnauzers were all a(w)/a(w). Genotypes of 201 dogs of 35 breeds suggest that there are only 4 ASIP alleles, as opposed to the 5 or 6 predicted in previous literature. These data demonstrate that the dominance hierarchy of ASIP is a(y) > a(w) > a(t) > a. 相似文献
36.
Mansoor UF Vitharana D Reddy PA Daubaras DL McNicholas P Orth P Black T Siddiqui MA 《Bioorganic & medicinal chemistry letters》2011,21(4):1155-1161
Antibiotic resistant hospital acquired infections are on the rise, creating an urgent need for novel bactericidal drugs. Enzymes involved in lipopolysaccharide (LPS) biosynthesis are attractive antibacterial targets since LPS is the major structural component of the outer membrane of Gram-negative bacteria. Lipid A is an essential hydrophobic anchor of LPS and the first committed step in lipid A biosynthesis is catalyzed by a unique zinc dependent metalloamidase, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC). LpxC is an attractive Gram-negative only target that has been chemically validated by potent bactericidal hydroxamate inhibitors that work by coordination of the enzyme’s catalytic zinc ion. An exploratory chemistry effort focused on expanding the SAR around hydroxamic acid zinc-binding ‘warheads’ lead to the identification of novel compounds with enzyme potency and antibacterial activity similar to CHIR-090. 相似文献
37.
Matia B. Solomon Aynara C. Wulsin Taylor Rice Dayna Wick Brent Myers Jessica McKlveen Jonathan N. Flak Yvonne Ulrich-Lai James P. Herman 《Hormones and behavior》2014
Pre-clinical and clinical studies have employed treatment with glucocorticoid receptor (GR) antagonists in an attempt to limit the deleterious behavioral and physiological effects of excess glucocorticoids. Here, we examined the effects of GR antagonists on neuroendocrine and behavioral stress responses, using two compounds: mifepristone, a GR antagonist that is also a progesterone receptor antagonist, and CORT 108297, a specific GR antagonist lacking anti-progestin activity. Given its well-documented impact on neuroendocrine and behavioral stress responses, imipramine (tricyclic antidepressant) served as a positive control. Male rats were treated for five days with mifepristone (10 mg/kg), CORT 108297 (30 mg/kg and 60 mg/kg), imipramine (10 mg/kg) or vehicle and exposed to forced swim test (FST) or restraint stress. Relative to vehicle, imipramine potently suppressed adrenocorticotropin hormone (ACTH) responses to FST and restraint exposure. Imipramine also decreased immobility in the FST, consistent with antidepressant actions. Both doses of CORT 108297 potently suppressed peak corticosterone responses to FST and restraint stress. However, only the higher dose of CORT 108297 (60 mg/kg) significantly decreased immobility in the FST. In contrast, mifepristone induced protracted secretion of corticosterone in response to both stressors, and modestly decreased immobility in the FST. Taken together, the data indicate distinct effects of each compound on neuroendocrine stress responses and also highlight dissociation between corticosterone responses and immobility in the FST. Within the context of the present study, our data suggest that CORT 108297 may be an attractive alternative for mitigating neuroendocrine and behavioral states associated with excess glucocorticoid secretion. 相似文献
38.
A Rose Brannon Efsevia Vakiani Brooke E Sylvester Sasinya N Scott Gregory McDermott Ronak H Shah Krishan Kania Agnes Viale Dayna M Oschwald Vladimir Vacic Anne-Katrin Emde Andrea Cercek Rona Yaeger Nancy E Kemeny Leonard B Saltz Jinru Shia Michael I D’Angelica Martin R Weiser David B Solit Michael F Berger 《Genome biology》2014,15(8)
Background
Colorectal cancer is the second leading cause of cancer death in the United States, with over 50,000 deaths estimated in 2014. Molecular profiling for somatic mutations that predict absence of response to anti-EGFR therapy has become standard practice in the treatment of metastatic colorectal cancer; however, the quantity and type of tissue available for testing is frequently limited. Further, the degree to which the primary tumor is a faithful representation of metastatic disease has been questioned. As next-generation sequencing technology becomes more widely available for clinical use and additional molecularly targeted agents are considered as treatment options in colorectal cancer, it is important to characterize the extent of tumor heterogeneity between primary and metastatic tumors.Results
We performed deep coverage, targeted next-generation sequencing of 230 key cancer-associated genes for 69 matched primary and metastatic tumors and normal tissue. Mutation profiles were 100% concordant for KRAS, NRAS, and BRAF, and were highly concordant for recurrent alterations in colorectal cancer. Additionally, whole genome sequencing of four patient trios did not reveal any additional site-specific targetable alterations.Conclusions
Colorectal cancer primary tumors and metastases exhibit high genomic concordance. As current clinical practices in colorectal cancer revolve around KRAS, NRAS, and BRAF mutation status, diagnostic sequencing of either primary or metastatic tissue as available is acceptable for most patients. Additionally, consistency between targeted sequencing and whole genome sequencing results suggests that targeted sequencing may be a suitable strategy for clinical diagnostic applications.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0454-7) contains supplementary material, which is available to authorized users. 相似文献39.
Probst MM Fletcher R Seelig DS 《Journal of strength and conditioning research / National Strength & Conditioning Association》2007,21(2):451-455
The purposes of this study were to compare the lower-body flexibility, strength, and knee stability of karate athletes against that of non-karate controls and to determine whether regular karate training results in adaptations that may result in an increased risk for knee injury. Flexibility measurements included knee flexion and extension, hip flexion and extension, hip internal and external rotation, and foot inversion and eversion. Nine karate athletes (4 women and 5 men, age = 24.3 +/- 6.7 years) and 15 active, non-karate controls (7 women and 8 men, age = 22.1 +/- 3.2 years) participated. No subjects reported recent knee surgery or chronic or acute knee pain. Concentric quadriceps and hamstrings strength and endurance were measured using a Biodex II isokinetic dynamometer at 60 degrees .s(-1) and 180 degrees .s(-1). Eccentric strength was measured at 150 degrees .s(-1) and 250 ft-lb (339 N.m). Knee stability was measured via varus and valgus stress and anterior drawer testing. Karate athletes demonstrated a significantly greater right hip flexion (p 相似文献
40.