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

  相似文献   

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   

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   

Prostatic Masses in Geldings: Two Cases     

Marc KnobbeDavid Levine  DVM  DACVS  Perry HabeckerLiberty Getman  DVM  DACVS  Jill BeechRegina Turner  VMD  PhD  DACT 《Journal of Equine Veterinary Science》2012

Prostatic masses were detected in two geldings that were presented to our referral hospital for evaluation of dysuria. The masses were detected during transrectal palpation and ultrasonography of the prostate gland and were further evaluated using urethral endoscopy. A 10-year-old gelding underwent intraurethral debulking of the prostatic mass. Histopathological diagnosis was prostatic cystadenoma. The mass regrew within 9 months, and the horse was euthanized due to deteriorating clinical control of urinary continence. In another case, a 12-year-old gelding was scheduled for transurethral debulking; however, the owners decided against treatment and the horse was euthanized due to progression of clinical disease. Postmortem examination revealed the prostate to be nearly completely obliterated by the mass. Histopathological diagnosis was adenocarcinoma incorporated into a spindle cell population of unknown histogenesis. To our knowledge, these represent the first reported cases of equine prostatic cystadenoma and adenocarcinoma. In both horses, referring complaint was dysuria, and identification of the prostatic mass was made on palpation and ultrasonographic examination per rectum. Treatment options for prostatic masses in horses are limited because of the difficulty of obtaining prostatic tissue via biopsy, the surgical inaccessibility of the gland, and the apparent low incidence of occurrence. We have subsequently identified prostatic masses in two additional geldings, both also presenting for dysuria. However, the exact nature of these two apparent prostatic masses has not been definitively diagnosed with histopathological examinations to date. The prostate should be evaluated in male horses presenting for dysuria.  相似文献   

Gliomatosis cerebri in two dogs     

BL Plattner  M Kent  B Summers  SR Platt  AC Freeman  U Blas-Machado  J Clemans  NF Cheville  D Garcia-Tapia 《Journal of the American Animal Hospital Association》2012,48(5):359-365

A 3.5 yr old Saint Bernard was evaluated for nonambulatory tetraparesis and cranial nerve dysfunction, and a 7 yr old rottweiler was evaluated for progressive paraparesis. Clinical signs of left-sided vestibular and general proprioceptive ataxia and cranial nerve VII dysfunction in the Saint Bernard suggested a lesion affecting the brain stem. Signs in the rottweiler consisted of general proprioceptive/upper motor neuron paraparesis, suggesting a lesion involving the third thoracic (T3) to third lumbar (L3) spinal cord segments. MRI was normal in the Saint Bernard, but an intra-axial lesion involving the T13-L2 spinal cord segments was observed in the rottweiler. In both dogs, the central nervous system (CNS) contained neoplastic cells with features consistent with gliomatosis cerebri (GC). In the Saint Bernard, neoplastic cells were present in the medulla oblongata and cranial cervical spinal cord. In the rottweiler, neoplastic cells were only present in the spinal cord. Immunohistochemistry disclosed two distinct patterns of CD18, nestin, and vimentin staining. GC is a rarely reported tumor of the CNS. Although GC typically involves the cerebrum, clinical signs in these two dogs reflected caudal brainstem and spinal cord involvement.  相似文献