The multielectron ionization dynamics underlying attosecond strong-field spectroscopies     

Boguslavskiy AE  Mikosch J  Gijsbertsen A  Spanner M  Patchkovskii S  Gador N  Vrakking MJ  Stolow A 《Science (New York, N.Y.)》2012,335(6074):1336-1340

Subcycle strong-field ionization (SFI) underlies many emerging spectroscopic probes of atomic or molecular attosecond electronic dynamics. Extending methods such as attosecond high harmonic generation spectroscopy to complex polyatomic molecules requires an understanding of multielectronic excitations, already hinted at by theoretical modeling of experiments on atoms, diatomics, and triatomics. Here, we present a direct method which, independent of theory, experimentally probes the participation of multiple electronic continua in the SFI dynamics of polyatomic molecules. We use saturated (n-butane) and unsaturated (1,3-butadiene) linear hydrocarbons to show how subcycle SFI of polyatomics can be directly resolved into its distinct electronic-continuum channels by above-threshold ionization photoelectron spectroscopy. Our approach makes use of photoelectron-photofragment coincidences, suiting broad classes of polyatomic molecules.  相似文献   

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   

Tickborne encephalitis virus antibodies in wild cervids in Belgium     

Linden A  Wirtgen M  Nahayo A  Heyman P  Niedrig M  Schulze Y 《The Veterinary record》2012,170(4):108

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Immunogenicity of eight Mycobacterium avium subsp. paratuberculosis specific antigens in DNA vaccinated and Map infected mice     

Roupie V  Viart S  Leroy B  Romano M  Trinchero N  Govaerts M  Letesson JJ  Wattiez R  Huygen K 《Veterinary immunology and immunopathology》2012,145(1-2):74-85

Mycobacterium avium subsp. paratuberculosis (Map), the etiological agent of chronic enteritis of the small intestine in domestic and wild ruminants, causes substantial losses to livestock industry. Control of this disease is seriously hampered by the lack of adequate diagnostic tools and vaccines. Here we report on the immunogenicity of eight Map specific antigens, i.e. MAP1693c, Ag3, MAP2677c (identified by post-genomic and immunoproteomic analysis of Map secretome) and Ag5, Ag6, MAP1637c, MAP0388 and MAP3743 (identified by bioinformatic in silico screening of the Map genome). Strong, antigen-specific IFN-γ responses were induced in mice vaccinated with plasmid DNA encoding MAP1693c, MAP1637c, MAP0388 and MAP3743. In contrast, T cell responses in Map infected mice were directed preferentially against Ag5 and to a lesser extent against MAP3743. None of the tested DNA vaccines conferred protection against subsequent challenge with Map.  相似文献   

Molecular typing of Mycoplasma agalactiae: tracing European-wide genetic diversity and an endemic clonal population     

Nouvel LX  Marenda MS  Glew MD  Sagné E  Giammarinaro P  Tardy F  Poumarat F  Rosengarten R  Citti C 《Comparative immunology, microbiology and infectious diseases》2012,35(5):487-496

Mycoplasma agalactiae causes chronic infections in small ruminants and remains endemic in many regions of the world, despite intensive and costly eradication programs. In this study, the innate genomic plasticity of M. agalactiae was exploited to design and assess a combination of molecular epidemiological tools to trace the pathogen in different geographic locations and to understand its emergence or re-emergence after eradication campaigns. For this purpose, two collections of M. agalactiae isolates, representing European outbreaks or localized endemic disease in a single region of France, were subjected to RFLP (Restriction Fragment Length Polymorphism) analyses using two sets of DNA probes (distributed across the genome and specific for the vpma gene locus), and a previously described VNTR (Variable Number Tandem Repeats) analysis. A combination of four genome-specific DNA probes and two VNTRs gave the highest discriminative power. Molecular typing revealed that, while isolates from diverse geographical origins fell into clearly different groups, the endemic disease repeatedly observed in the Western Pyrenees region over the past 30 years has been caused by a unique subtype of M. agalactiae. This indicates that the re-emergence of the pathogen after seemingly successful eradication programs is not due to the importation of exotic strains, but to the persistence of local reservoirs of infection.  相似文献   

Comparative spatiotemporal analysis of the intrathecal immune response in natural listeric rhombencephalitis of cattle and small ruminants     

Di Palma S  Brunetti B  Doherr MG  Forster U  Hilbe M  Zurbriggen A  Vandevelde M  Oevermann A 《Comparative immunology, microbiology and infectious diseases》2012,35(5):429-441

This study examined the spatiotemporal immune response in listeric rhombencephalitis of ruminants in situ. Our data support the view that astrocytes facilitate the containment of infectious lesions. Results on the natural disease recapitulate observations in experimental rodent models and suggest that the mounted adaptive lymphocytic response of ruminants is effective in eliminating Listeria monocytogenes (LM). However, our data indicate earlier participation of the adaptive immune response, a stronger B lymphocyte contribution and a more protracted macrophage infiltration in the natural disease than it has been deduced from experimental models. Therefore, such models should be complemented by studies in natural host systems. Various macrophage and microglia subsets are involved in listeric rhombencephalitis and their differential contribution may account for species differences in clinical course and outcome of infection as might species differences in the B-cell response. Future functional ex vivo and in vitro studies are necessary to further investigate the findings obtained in the present study.  相似文献   

Antimicrobial use in Belgian broiler production     

Persoons D  Dewulf J  Smet A  Herman L  Heyndrickx M  Martel A  Catry B  Butaye P  Haesebrouck F 《Preventive veterinary medicine》2012,105(4):320-325

The use of antimicrobials in production animals has become a worldwide concern in the face of rising resistance levels in commensal, pathogenic and zoonotic bacteria. In the years 2007 and 2008 antimicrobial consumption records were collected during two non consecutive production cycles in 32 randomly selected Belgian broiler farms. Antimicrobials were used in 48 of the 64 monitored production cycles, 7 farms did not use any antimicrobials in both production cycles, 2 farms only administered antimicrobials in one of the two production cycles, the other 23 farms applied antimicrobial treatment in both production cycles. For the quantification of antimicrobial drug use, the treatment incidences (TI) based on the defined daily doses (the dose as it should be applied: DDD) and used daily doses (the actual dose applied: UDD) were calculated. A mean antimicrobial treatment incidence per 1000 animals of 131.8 (standard deviation 126.8) animals treated daily with one DDD and 121.4 (SD 106.7) animals treated daily with one UDD was found. The most frequently used compounds were amoxicillin, tylosin and trimethoprim-sulphonamide with a mean TI(UDD) of 37.9, 34.8, and 21.7, respectively. The ratio of the UDD/DDD gives an estimate on correctness of dosing. Tylosin was underdosed in most of the administrations whereas amoxicillin and trimethoprim-sulphonamide were slightly overdosed in the average flock.  相似文献   

Characterization of different wood samples using a new combined method of evolved gas analysis and pyrolysis–gas chromatography/mass spectrometry     

A. Heigenmoser  R. Fuchs  E. Windeisen  G. Wegener 《Wood Science and Technology》2012,46(4):637-642

Evolved gas analysis (EGA) in combination with analytical pyrolysis is presented as a new technique for rapid investigations into wooden materials. In a first analytical step, the thermal behaviour of three wood samples was determined by EGA. Based on these results, analytical pyrolysis–gas chromatography/mass spectrometry was carried out to investigate the influence of wood-specific thermal behaviour and the chemical composition on the results. Furthermore, the influence of sample mass and particle size was examined.  相似文献   

Pathogenicity of Eimeria praecox alone or associated with Eimeria acervulina in experimentally infected broiler chickens     

Répérant JM  Dardi M  Pagès M  Thomas-Hénaff M 《Veterinary parasitology》2012,187(1-2):333-336

Eimeria praecox and Eimeria acervulina are two species of coccidia parasites infecting chickens, which develop in the duodenum. The purpose of this study was to evaluate the pathogenicity of E. praecox and to study interactions of this coccidium with E. acervulina. The results showed that the pathogenicity of E. praecox was related to the infective dose, and that its impact on individual weight and weight gain was significant from the lowest administered dose: 5000 oocysts per bird. No morbidity was observed, even with the highest infective dose, but faecal consistency alteration was higher with increasing infective doses. No consistent lesion was observed. When E. praecox was associated with E. acervulina with a low infective dose, performance deterioration seemed to be an additional effect of the two species. However, in the case of heavy infections, signs worsened along with duration of negative impact on growth, compared to a mono-infection.  相似文献   

Characterization of In Vitro Synthesized Equine Metabolites of the Selective Androgen Receptor Modulators S24 and S4     

Oliver Krug  Andreas Thomas  Simon Beuck  Ina Schenk  Marc Machnik  Wilhelm Schänzer  Ulf Bondesson  Mikael Hedeland  Mario Thevis 《Journal of Equine Veterinary Science》2012

Several selective androgen receptor modulators (SARMs) have been synthesized and investigated in humans, rats, and dogs in the past, but no data are yet available concerning the metabolism of SARMs in horses. The aryl-propionamide-derived drug candidates S24 and S4 (andarine) have a strong androgen receptor binding affinity and show distinctive specific cell answers. Although no SARM drug candidate (aiming for testosterone replacement therapy) has completed clinical trials yet, S4 has been illicitly available via the Internet. These facts led to the prohibition of SARMs by the German equestrian federation, and the (mis)use of such compounds would further represent a doping rule violation in horse racing. In this study, the drug candidates S24 and S4 were subjected to in vitro metabolism experiments with equine liver microsomal preparations from a female Quarter Horse to obtain information about potential target analytes in equine doping control analysis. The enzymatically synthesized metabolites were characterized by liquid chromatography–tandem mass spectrometry and –high-resolution/high-accuracy mass spectrometry. All observed S24 and S4 equine metabolites are in agreement with earlier in vitro and in vivo studies in humans and dogs. Nevertheless, the relative percentage of generated equine metabolites (as determined from the analytes’ response in full-scan chromatography–tandem mass spectrometry and –high-resolution/high-accuracy mass spectrometry measurements) differs considerably from the reported profiles. Although the S24 metabolite pattern is comparably balanced concerning glucuronidated and sulfonated conjugates, the major S4 metabolite was found to be the unconjugated dephenylated compound, with a proportion of more than 90%.  相似文献