The mutational landscape of head and neck squamous cell carcinoma     

Stransky N  Egloff AM  Tward AD  Kostic AD  Cibulskis K  Sivachenko A  Kryukov GV  Lawrence MS  Sougnez C  McKenna A  Shefler E  Ramos AH  Stojanov P  Carter SL  Voet D  Cortés ML  Auclair D  Berger MF  Saksena G  Guiducci C  Onofrio RC  Parkin M  Romkes M  Weissfeld JL  Seethala RR  Wang L  Rangel-Escareño C  Fernandez-Lopez JC  Hidalgo-Miranda A  Melendez-Zajgla J  Winckler W  Ardlie K  Gabriel SB  Meyerson M  Lander ES  Getz G  Golub TR  Garraway LA  Grandis JR 《Science (New York, N.Y.)》2011,333(6046):1157-1160

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.  相似文献   

Effect of a polyphenols-enriched chardonnay white wine in diabetic rats     

Landrault N  Poucheret P  Azay J  Krosniak M  Gasc F  Jenin C  Cros G  Teissedre PL 《Journal of agricultural and food chemistry》2003,51(1):311-318

A Chardonnay white wine enriched in polyphenols was obtained by modification of winemaking and characterized by its enrichment in total polyphenolic content (1346 mg/L as compared to 316 mg/L for traditional Chardonnay) and in various individual polyphenols (catechin, epicatechin, procyanidins dimers B1-B4, gallic acid, cafeic acid, and caftaric acid), as determined from HPLC coupled to a diode array detector. The polyphenols-enriched white wine (W) or its ethanol-free derivative (EFW) was then administered by gavage (10 mL/kg, twice a day) for 6 weeks to rats that have been rendered diabetic by a single iv injection of streptozotocin (55 mg/kg). Treatments had no effect on the symptoms associated with hyperglycemia. However, while a reduction in plasma antioxidant capacity was associated with the diabetic state, administration of W or EFW restored plasma antioxidant capacities to a level not significantly different from that of nondiabetic control animals. In addition, the effect of both treatments was manifested by the enlargement of mesenteric arteries, as determined by quantitative histomorphometry. In summary, our study indicates that white wine, when enriched in polyphenols, is able to induce ethanol-independent in vivo effects in a model of insulin-deficient diabetes characterized by a major oxidative stress.  相似文献   

Influence of the timing of nitrogen additions during synthetic grape must fermentations on fermentation kinetics and nitrogen consumption   总被引：2，自引：0，他引：2  

Beltran G  Esteve-Zarzoso B  Rozès N  Mas A  Guillamón JM 《Journal of agricultural and food chemistry》2005,53(4):996-1002

Nitrogen deficiencies in grape musts are one of the main causes of stuck or sluggish wine fermentations. In the present study, we have supplemented nitrogen-deficient fermentations with a mixture of ammonium and amino acids at various stages throughout the alcoholic fermentation. The timing of the nitrogen additions influenced the biomass yield, the fermentation performance, the patterns of ammonium and amino acid consumption, and the production of secondary metabolites. These nitrogen additions induced a nitrogen-repressed situation in the cells, and this situation determined which nitrogen sources were selected. Glutamine and tryptophan were the main amino acids consumed in all the fermentations. Ammonium is the preferred nitrogen source for biomass production but was hardly consumed when it was added in the final stages of the fermentation. The higher ammonium consumption in some fermentations correlated with a greater synthesis of glycerol, acetate, and acetaldehyde but with a lower synthesis of higher alcohols.  相似文献   

Response of lentil (Lens culinaris) germplasm to high concentrations of soil boron     

Kristy Hobson  Roger Armstrong  Marc Nicolas  David Connor  Michael Materne 《Euphytica》2006,151(3):371-382

For lentil production to expand further in Australia, adaptation to the less favourable soils of the low to medium rainfall zones is required. To improve adaptation to these regions, varieties are required with increased tolerance to soil constraints such as high concentrations of boron (B), salinity and sodicity. To evaluate the range of B tolerance in lentil germplasm, 310 lines were screened in soil with a high concentration of B and tolerance was assessed at the seedling stage. A wide range in response to high concentrations of soil B was observed in the germplasm tested. Current Australian varieties were generally very intolerant to high concentrations of soil B. High levels of B tolerance was identified in germplasm originating from Afghanistan and Ethiopia. A subsequent experiment comparing lentils with different levels of B tolerance found that tolerant accessions (ILL213A and ILL2024) produced greater above and below ground biomass than intolerant accessions. The tolerant accessions had no significant yield loss under a high B treatment (extractable B = 18.20 mg/kg) compared to the control treatment (extractable B = 1.55 mg/kg). The large improvement in B tolerance, at soil concentrations typical of those found in the target regions, suggests there is potential to improve the tolerance level of adapted varieties and expand lentil production areas to regions with higher concentrations of soil B.  相似文献   

Stem and head reaction of winter wheat cultivars to artificial inoculation by Microdochium nivale under controlled environment and field conditions     

Nicolas Maurin  Laurent Saur  Gilles Capron 《Euphytica》1995,92(3):359-366

Summary Experiments to assess variation in the resistance of winter wheat to infection by Microdochium nivale were conducted over two consecutive years. Resistance was evaluated using an agar disk technique to reproduce stem lesions and by spraying a conidial suspension to reproduce head blight symptoms. Significant variation for stem reaction measured as stem lesion area (SLA), and head reaction measured as disease severity (DS) was found in the 33 winter wheat genotypes tested. Data obtained over two years in controlled environment conditions were significantly correlated (r=0.713 for SLA and r=0.738 for DS), whereas field data showed a significant genotype x year interaction for disease severity. Quantitative variation for susceptibility to stem and head infection by M. nivale was found among the 33 genotypes tested. The majority of genotypes expressed moderate susceptibility, with cultivar Goupil being very susceptible to both stem and head infection, and the remainder, Renan, Arminda, Munstertaler and Saint-Johann were the most resistant. Resistance to stem and head to M. nivale were not correlated (r=0.358).  相似文献   

Biotechnology approaches to overcome biotic and abiotic stress constraints in legumes   总被引：1，自引：0，他引：1  

Miguel A. Dita  Nicolas Rispail  Elena Prats  Diego Rubiales  Karam B. Singh 《Euphytica》2006,147(1-2):1-24

Summary Biotic and abiotic stresses cause significant yield losses in legumes and can significantly affect their productivity. Biotechnology tools such as marker-assisted breeding, tissue culture, in vitro mutagenesis and genetic transformation can contribute to solve or reduce some of these constraints. However, only limited success has been achieved so far. The emergence of “omic” technologies and the establishment of model legume plants such as Medicago truncatula and Lotus japonicus are promising strategies for understanding the molecular genetic basis of stress resistance, which is an important bottleneck for molecular breeding. Understanding the mechanisms that regulate the expression of stress-related genes is a fundamental issue in plant biology and will be necessary for the genetic improvement of legumes. In this review, we describe the current status of biotechnology approaches in relation to biotic and abiotic stresses in legumes and how these useful tools could be used to improve resistance to important constraints affecting legume crops.  相似文献   

Orangutan movement and population dynamics across human-modified landscapes: implications of policy and management     

Seaman  Dave J. I.  Voigt  Maria  Bocedi  Greta  Travis  Justin M. J.  Palmer  Stephen C. F.  Ancrenaz  Marc  Wich  Serge  Meijaard  Erik  Bernard  Henry  Deere  Nicolas J.  Humle  Tatyana  Struebig  Matthew J. 《Landscape Ecology》2021,36(10):2957-2975

Landscape Ecology - Agricultural expansion is a leading cause of deforestation and habitat fragmentation globally. Policies that support biodiversity and facilitate species movement across farmland...  相似文献   

Dissection of white matter association fasciculi in bovine (Bos taurus), pig (Sus scrofa domesticus) and rabbit (Oryctolagus cuniculus) brains     

Marco Guerrero  Carlos Veuthey  Mariano del Sol  Nicolas E. Ottone 《Anatomia, histologia, embryologia》2020,49(4):550-562

The cerebral fasciculi (association, commissural and projection) pass through the cerebral white matter in organized groups connecting regions, hemispheres, gyri, areas and brain lobes to each other. The study can be done in vivo through diffusion tensor imaging (DTI) but presenting some technical problems. The post-mortem study by dissection allows to have a clearer view of its location, path and connections. In this work, we dissect, identify and compare the fasciculi of association of the white matter of the dorsolateral face of bovine hemispheres (Bos taurus), pig hemispheres (Sus scrofa domesticus) and rabbit hemispheres (Oryctolagus cuniculus), applying the Klingler´s technique. In 30 cerebral hemispheres (10 of each species, five right and five left), we applied the Klingler technique to identify and isolate the occipitofrontal fasciculus, uncinate fasciculus, inferior longitudinal fasciculus and superior longitudinal fasciculus; we established its location by fixing landmarks, and determined the difference in its length and width between the right and left hemispheres as well as between species using the statistical tests of t-student and one-way ANOVA. We identify the gyri, sulci and fasciculi of the dorsolateral surface of the cerebral hemispheres of the three species. We found statistically significant differences in several fasciculi between species principally in the occipitofrontal fasciculus. The preparation of the brains through the modified Klingler technique allowed a successful identification of the fascicules of association of the dorsolateral face of the cerebral hemispheres and the empowerment of these animal models for future research work in this field.  相似文献   

Effect of combinations of morphine,dexmedetomidine and maropitant on the electroencephalogram in response to acute electrical stimulation in anaesthetized dogs     

Sandeep Raj Karna  Paul Chambers  Craig B. Johnson  Preet Singh  Lauren A. Stewart  Nicolas Lopez-Villalobos  Kavitha Kongara 《Journal of veterinary pharmacology and therapeutics》2020,43(6):538-546

This study was conducted to compare the efficacy of combinations of morphine, dexmedetomidine and maropitant in preventing the changes in electroencephalographic (EEG) indices of nociception in anaesthetized dogs subjected to a noxious electrical stimulus. In a crossover study, eight healthy adult dogs were randomly allocated to four groups: Mor: morphine 0.6 mg/kg; Dex + Mor: morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; Maro + Mor: morphine 0.3 mg/kg + maropitant 1 mg/kg; and Dex + Maro + Mor: morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Following intramuscular administration of test drugs in a minimal anaesthesia model, a supramaximal electrical stimulus (50 V at 50 Hz for 2 s) was applied and the EEG data were recorded. There were significant increases (p < .05) in the poststimulus median frequency (F50) only in groups Mor and Maro + Mor. Dex + Mor group had a significantly lower change in F50 and F95 compared to all other treatment groups. There was no correlation of the changes in EEG frequencies with blood plasma concentration of the drugs during and after noxious stimulation. Combination of dexmedetomidine and morphine was most effective in abolishing the changes in EEG indices in response to a noxious stimulus indicating a supra-additive interaction between these two drugs.  相似文献   

Laparoscopic gonadectomy in dogs with ovotesticular disorder of sexual development     

Nicolas Vallarino  Eline Wydooghe  Bart van Goethem 《Reproduction in domestic animals》2020,55(9):1172-1179

Disorders of sexual development (DSD) in dogs involve most commonly an XX sex reversal syndrome, treated conventionally by gonadohysterectomy. The objective of the present case series is to describe the surgical treatment and long-term follow-up of dogs undergoing laparoscopic gonadectomy without hysterectomy for treatment of ovotesticular DSD. Six female dogs clinically diagnosed with DSD were retrospectively included in the study when laparoscopic gonadectomy was performed and histology confirmed the presence of abnormal gonads. The dogs were evaluated by ultrasound after 6 months, and owners were contacted by phone for the long-term reevaluation. Laparoscopic gonadectomy was performed using 2- or 3-portal midline techniques with 3- and/or 5-mm instruments. Additional procedures were performed in 5 dogs, including os clitoris removal in 4 dogs and vulvoplasty in 1 dog. Histological analysis of the gonads reported 11 ovotestes and 1 testis. No major or minor complications occurred perioperatively. Ultrasonographic reevaluation was performed in 5/6 dogs and the remaining abdominal genital system was considered normal. Median long-term follow-up was 617 days (range, 265–1597) with none of the dogs having any symptom related to DSD. Therefore, laparoscopic gonadectomy is a valid alternative for dogs with ovotesticular DSD and is less invasive than conventional open techniques. Removal of the gonads avoids future development of hormone-related diseases of the remaining genital tract.  相似文献