Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation     

Jain M  Nilsson R  Sharma S  Madhusudhan N  Kitami T  Souza AL  Kafri R  Kirschner MW  Clish CB  Mootha VK 《Science (New York, N.Y.)》2012,336(6084):1040-1044

Metabolic reprogramming has been proposed to be a hallmark of cancer, yet a systematic characterization of the metabolic pathways active in transformed cells is currently lacking. Using mass spectrometry, we measured the consumption and release (CORE) profiles of 219 metabolites from media across the NCI-60 cancer cell lines, and integrated these data with a preexisting atlas of gene expression. This analysis identified glycine consumption and expression of the mitochondrial glycine biosynthetic pathway as strongly correlated with rates of proliferation across cancer cells. Antagonizing glycine uptake and its mitochondrial biosynthesis preferentially impaired rapidly proliferating cells. Moreover, higher expression of this pathway was associated with greater mortality in breast cancer patients. Increased reliance on glycine may represent a metabolic vulnerability for selectively targeting rapid cancer cell proliferation.  相似文献   

Adenosine-5'-triphosphate release by Mannheimia haemolytica, lipopolysaccharide, and interleukin-1 stimulated bovine pulmonary epithelial cells     

M Craddick  R Patel  A Lower  S Highlander  M Ackermann  D McClenahan 《Veterinary immunology and immunopathology》2012,149(1-2):58-65

Mannheimia haemolytica, one of the agents associated with bovine respiratory disease complex, can cause severe lung pathology including the leakage of vascular products into the airways and alveoli. Previous work by this laboratory has demonstrated that bovine lung endothelial and epithelial cells undergo dramatic permeability increases when exposed to adenosine-5'-triphosphate (ATP). Therefore, we wanted to determine if ATP levels were elevated in bronchoalveolar lavage (BAL) samples from calves experimentally infected with M. haemolytica. In addition, cultured bovine pulmonary epithelial (BPE) cells were stimulated with heat-killed and live M. haemolytica bacteria, lipopolysaccharide (LPS), lipoteichoic acid (LTA), interleukin-1 (IL-1), and zymosan activated plasma (ZAP) to determine whether they might release extracellular ATP during in vitro infection. Calves experimentally exposed to M. haemolytica had an approximately 2-fold higher level of ATP in their BAL samples compared to control. BPE cells exposed to increasing numbers of heat-killed or live M. haemolytica had significantly increased levels of ATP release as compared to time-matched controls. Finally, BPE cells treated with several concentrations of LPS and IL-1 had increases in ATP release as compared to time-matched controls. This increase appeared to be a result of active ATP secretion by the cells, as cell viability was similar between treated and non-treated cells. Neither ZAP nor LTA induced any ATP release by the cells. In conclusion, ATP levels are elevated in lung secretions from calves infected with M. haemolytica. In addition, lung epithelial cells can actively release ATP when exposed to heat-killed or live M. haemolytica, LPS or IL-1.  相似文献   

Twenty year site preparation effects on sub-boreal lodgepole pine performance   总被引：2，自引：2，他引：0  

Jacob O. Boateng  Jean L. Heineman  Lorne Bedford  Amanda F. Linnell Nemec  John McClarnon  R. Allan Powelson 《New Forests》2012,43(4):457-472

We examined the effects of various mechanical site preparation methods and windrow burning on container-grown planted lodgepole pine (Pinus contorta var. latifolia) survival and growth for 20?years after treatment at a sub-boreal site in north-central British Columbia, Canada. Survival was uniformly high (??80%) regardless of treatment, indicating that site preparation was not necessary to establish pine on this site. Significant treatment effects on height, diameter, and stem volume were present at all assessment dates, but only the windrow burning treatment was associated with growth gains over the untreated control after two decades. Pine planted at the disk trench hinge were significantly larger than control pine only until year five. Of the mechanical treatments, only coarse mixing (by bedding plow) continued to have a significant effect on pine growth for as many as 9?years after treatment. Despite the disappearance of significant differences between mechanical treatments and the untreated control by year 20, the magnitude of stand volume increases suggests the potential for mechanical site preparation to have a beneficial effect on future timber supply. Repeated measures analysis confirmed that trends in early diameter growth differed between the untreated control and the windrow burning or coarse mixing treatments. These data are also potentially valuable for verifying growth and yield or carbon budgeting modelling tools.  相似文献   

Strategies of exploitation of mammalian reservoirs by Bartonella species     

Deng H  Le Rhun D  Buffet JP  Cotté V  Read A  Birtles RJ  Vayssier-Taussat M 《Veterinary research》2012,43(1):15

ABSTRACT: Numerous mammal species, including domestic and wild animals such as ruminants, dogs, cats and rodents, as well as humans, serve as reservoir hosts for various Bartonella species. Some of those species that exploit non-human mammals as reservoir hosts have zoonotic potential. Our understanding of interactions between bartonellae and reservoir hosts has been greatly improved by the development of animal models for infection and the use of molecular tools allowing large scale mutagenesis of Bartonella species. By reviewing and combining the results of these and other approaches we can obtain a comprehensive insight into the molecular interactions that underlie the exploitation of reservoir hosts by Bartonella species, particularly the well-studied interactions with vascular endothelial cells and erythrocytes.  相似文献   

Circulating biomarkers associated with pelvic organ prolapse risk in late gestation sows     

Zoë E Kiefer  Jamie M Studer  Amanda L Chipman  Malavika K Adur  Christine Mainquist-Whigham  Nicholas K Gabler  Aileen F Keating  Jason W Ross 《Journal of animal science》2021,99(8)

Sow mortality, as the result of pelvic organ prolapse (POP), has been increasing in the last decade in the U.S. swine industry. The objective of this study was to identify potential biological markers associated with risk of POP in sows. We hypothesized that sows differing in perineal score (PS) from PS1–PS3 (PS1—a presumed low POP risk; PS2—a presumed moderate POP risk; and PS3—a presumed high POP risk) would differ in circulatory biomarkers of inflammation and hormonal profiles. On gestation week 15, 2,864 individual sows were assigned a PS, and subsequently, 1.0%, 2.7%, and 23.4% of PS1, PS2, or PS3 sows, respectively, experienced POP. During PS assignment at days 107–116 of gestation, blood samples were collected from sows on two farms of similar genetics, feed sources, and health status. Whole blood was subjected to complete blood count (CBC) analysis (n = 212) and steroid hormones were measured in serum from a subset (n = 110) of animals assigned PS3 parity matched to PS1. Lipopolysaccharide-binding protein (LBP), tumor necrosis factor-alpha (TNF-α), haptoglobin, C-reactive protein (CRP), and creatine kinase (CK) levels were also evaluated. Complete blood count analysis revealed decreased (P ≤ 0.05) mean platelet volume (3.9%), lymphocytes (6.5%), and monocytes (7.5%) in PS3 compared to PS1 sows. Increased (P ≤ 0.02) abundance of androstenedione (13.4%), androsterone (18.2%), estrone (24.8%), and 17β-estradiol (26.2%) was observed in PS3 compared to PS1 sows. Additionally, a 25.8% increase (P = 0.04) in LBP in PS3 compared to PS1 sows was observed. Many dynamic physiological changes occur in sows during late gestation as they approach farrowing. The data presented herein demonstrate that distinct differences in concentrations of circulating biomarkers exist between late gestation sows at high or low risk for POP and may serve as a useful tool for understanding the etiology of POP and evaluation of mitigation strategies.  相似文献   

Characterization and Distribution of Three New Clonal Lineages of Phytophthora infestans Causing Late Blight in Wisconsin from 2009 to 2012     

Anna C. Seidl  Amanda J. Gevens 《American Journal of Potato Research》2013,90(6):551-560

Phytophthora infestans causes late blight of potato and tomato, a disease that has been estimated to cost U.S. potato growers $287.8 million annually. We collected isolates of P. infestans from Wisconsin from 2009 to 2012 and determined distribution of clonal lineages and mating types and sensitivity to the systemic fungicide mefenoxam. We also sought to evaluate the current utility of an analysis of the Glucose-6-phosphate isomerase (Gpi) allozyme locus for predicting mefenoxam sensitivity with the aim of delivering timely information to growers. Overall, 143 isolates were collected from 52 locations in 20 Wisconsin counties from 2009 to 2012. Three clonal lineages, US-22, US-23, and US-24, were identified and were novel to Wisconsin and the U.S. US-22 is of the A2 mating type and sensitive to mefenoxam, with Gpi 100/122. US-23 and US-24 are of the A1 mating type and primarily intermediately sensitive to mefenoxam, with Gpi 100/100 and 100/100/111, respectively. Because of this close correlation and the unique Gpi patterns for each lineage present, we were able to predict mefenoxam sensitivity directly from samples using the allozyme assay and quickly deliver management information to growers. Both mating types were present in Wisconsin in 2009 and 2010 but were spatially separated and no evidence of sexual recombination or soil persistence was detected. The presence of new clonal lineages of P. infestans in Wisconsin indicates a need for continued close monitoring of late blight to facilitate generation of timely information for enhanced short-term and long-term late blight management.  相似文献   

APPLICATION AND MACHINE ACCURACY OF A NEW FRAMELESS COMPUTED TOMOGRAPHY‐GUIDED STEREOTACTIC BRAIN BIOPSY SYSTEM IN DOGS     

Amanda R. Taylor  Noah D. Cohen  Stephen Fletcher  John F. Griffin  Jonathan M. Levine 《Veterinary radiology & ultrasound》2013,54(4):332-342

The purpose of this study was to describe application and machine accuracy for a new computed tomography (CT) guided, frameless, stereotactic brain biopsy system in dogs. Heads from ten canine cadavers were secured to a bite‐plate with six attached fiducial markers and imaged using CT. Fiducialized CT images were imported into stereotactic software and spherical phantom lesions between 3.9 and 5.5 mm in diameter were created in six locations. Infrared cameras and reflective markers were used to register fiducials to the reconstructed image set. Coordinates in the X, Y, and Z planes were identified for each lesion center. Iohexol (1.5 μl of 240 mgI/ml) was injected into the center of each lesion and CT scans were repeated. Pre‐ and postinjection CT images for each cadaver were fused using the system software. Application accuracy was calculated using the center of each phantom lesion and the center of each injected contrast material location. Machine accuracy was calculated using a phantom with known distances between four fixed points in the X, Y, and Z planes. Mean application accuracy in the first 5 cadavers was 4.3 mm (95% confidence interval [CI] 2.9–4.3 mm) and in the second 5 cadavers was 2.9 mm (95% CI 2–3.9 mm). The more superficial lesions were targeted significantly less accurately than the deeper lesions (P = 0.0183). Median machine accuracy was 0.1 mm and the range was 0.1–0.2 mm. Findings supported use of the new biopsy system for canine brain lesions >3.9 mm in diameter.  相似文献   

Actinomyces bowdenii ulcerative keratitis in a dog     

Amanda Sherman  Joshua B. Daniels  David A. Wilkie  Elizabeth Lutz 《Veterinary ophthalmology》2013,16(5):386-391

A 5‐year‐old spayed female diabetic mixed‐breed dog underwent phacoemulsification and intraocular lens implantation to correct bilateral hypermature cataracts. Two months postsurgery, the patient presented with ulcerative keratitis and multifocal stromal abscessation OD, which was controlled, but never resolved, with topical fluoroquinolone therapy. The patient re‐presented 2 months later with a new, raised, white gritty corneal opacity associated with hyperemia, chemosis, and blepharospasm OD. Cytology of the right cornea revealed filamentous bacteria, suggestive of Actinomyces spp. Actinomyces bowdenii was subsequently isolated in pure culture and identified via 16s rDNA sequencing. Actinomyces bowdenii has never before been described as a cause of ocular infection. An immunosuppressed corneal environment likely contributed to this opportunistic Actinomycosis. The infection was not controlled with fluoroquinolone therapy, and the isolate, in vitro, was resistant to three fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin), which also has not been previously reported for this species of Actinomyces. A superficial keratectomy with conjunctival graft was employed to successfully manage the infection.  相似文献   

Positive impact of an emergency department protocol on time to antimicrobial administration in dogs with septic peritonitis     

Amanda L. Abelson DVM  DACVECC  Gareth J. Buckley MA  VetMB  DACVECC  Elizabeth A. Rozanski DVM  DACVIM  DACVECC 《Journal of Veterinary Emergency and Critical Care》2013,23(5):551-556

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Diagnostic Accuracy of Tissue Impedance Measurement Interpretation for Correct Veress Needle Placement in Feline Cadavers     

Sara Hyink DVM  Jacqueline C. Whittemore DVM  PhD  Diplomate ACVIM  Amanda Mitchell DVM  Ann Reed MS 《Veterinary surgery : VS》2013,42(5):623-628

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