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81.
82.
Susan M. Gribble Frances K. Wiseman Stephen Clayton Elena Prigmore Elizabeth Langley Fengtang Yang Sean Maguire Beiyuan Fu Diana Rajan Olivia Sheppard Carol Scott Heidi Hauser Philip J. Stephens Lucy A. Stebbings Bee Ling Ng Tomas Fitzgerald Michael A. Quail Ruby Banerjee Kai Rothkamm Victor L. J. Tybulewicz Elizabeth M. C. Fisher Nigel P. Carter 《PloS one》2013,8(4)
Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype – phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439. 相似文献
83.
Gregory V. Stark James P. Long Diana I. Ortiz Melicia Gainey Benjamin A. Carper Jingyu Feng Stephen M. Miller John E. Bigger Eric M. Vela 《PloS one》2013,8(3)
Influenza A viruses continue to pose a threat to human health; thus, various vaccines and prophylaxis continue to be developed. Testing of these products requires various animal models including mice, guinea pigs, and ferrets. However, because ferrets are naturally susceptible to infection with human influenza viruses and because the disease state resembles that of human influenza, these animals have been widely used as a model to study influenza virus pathogenesis. In this report, a statistical analysis was performed to evaluate data involving 269 ferrets infected with seasonal influenza, swine influenza, and highly pathogenic avian influenza (HPAI) from 16 different studies over a five year period. The aim of the analyses was to better qualify the ferret model by identifying relationships among important animal model parameters (endpoints) and variables of interest, which include survival, time-to-death, changes in body temperature and weight, and nasal wash samples containing virus, in addition to significant changes from baseline in selected hematology and clinical chemistry parameters. The results demonstrate that a disease clinical profile, consisting of various changes in the biological parameters tested, is associated with various influenza A infections in ferrets. Additionally, the analysis yielded correlates of protection associated with HPAI disease in ferrets. In all, the results from this study further validate the use of the ferret as a model to study influenza A pathology and to evaluate product efficacy. 相似文献
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85.
Kateel G. Shetty Diana V. Rivadeneira Krish Jayachandran Donald M. Walker 《Mycological Progress》2016,15(9):977-986
Fungal endophytes are the most ubiquitous and highly diverse microorganisms that inhabit the interior of healthy plants. They are important in plant ecology and offer untapped potential to improve plant health and productivity in agroecosystems. The endophytic assemblage of avocado is poorly understood; therefore, surveys of fungal endophytes of Persea americana Mill. (Avocado) in South Florida organic and conventional orchards were conducted. A total of 17 endophytic fungal species were recovered from healthy avocado terminal branches. Endophytic fungal species were identified by rDNA sequencing of the internal transcribed spacer (ITS) region, using UNITE Species Hypotheses to reliably assign a taxon name, and determined as belonging to the genera Alternaria, Cladosporium, Colletotrichum, Corynespora, Diaporthe, Lasiodiplodia, Neofusicoccum, Neopestalotiopsis, Phyllosticta, and Strelitziana. Endophyte community assemblage differed between organic and conventional agroecosystems. This is the first report of Alternaria eichhorniae, Cladosporium tenuissimum, Corynespora cassiicola, Colletotrichum alatae, Diaporthe fraxini-angustifoliae, Lasiodiplodia gonubiensis, Neofusicoccum algeriense, Neofusicoccum andinum, Neopestalotiopsis foedans, Phyllosticta capitalensis, and Strelitziana africana as endophytes of avocado. Evaluation using pathogenicity tests on avocado leaves and terminal branches showed that endophytic fungal isolates did not cause disease symptoms. 相似文献
86.
Werner Scheuer Markus Thomas Petra Hanke Johannes Sam Franz Osl Diana Weininger 《MABS-AUSTIN》2016,8(3):562-573
Vascular endothelial growth factor (VEGF)-A blockade has been validated clinically as a treatment for human cancers. Angiopoietin-2 (Ang-2) is a key regulator of blood vessel remodeling and maturation. In tumors, Ang-2 is up-regulated and an unfavorable prognostic factor. Recent data demonstrated that Ang-2 inhibition mediates anti-tumoral effects. We generated a tetravalent bispecific antibody (Ang-2-VEGF-TAvi6) targeting VEGF-A with 2 arms based on bevacizumab (Avastin®), and targeting Ang-2 with 2 arms based on a novel anti-Ang-2 antibody (LC06). The two Ang-2-targeting single-chain variable fragments are disulfide-stabilized and fused to the C-terminus of the heavy chain of bevacizumab. Treatment with Ang-2-VEGF-A-TAvi6 led to a complete abrogation of angiogenesis in the cornea micropocket assay. Metastatic spread and tumor growth of subcutaneous, orthotopic and anti-VEGF-A resistant tumors were also efficiently inhibited. These data further establish Ang-2-VEGF bispecific antibodies as a promising anti-angiogenic, anti-metastatic and anti-tumor agent for the treatment of cancer. 相似文献
87.
Daniel Stern Diana Pauly Martin Zydek Lilija Miller Janett Piesker Michael Laue Fred Lisdat Martin B. Dorner Brigitte G. Dorner Andreas Nitsche 《PloS one》2016,11(3)
Orthopoxvirus species like cowpox, vaccinia and monkeypox virus cause zoonotic infections in humans worldwide. Infections often occur in rural areas lacking proper diagnostic infrastructure as exemplified by monkeypox, which is endemic in Western and Central Africa. While PCR detection requires demanding equipment and is restricted to genome detection, the evidence of virus particles can complement or replace PCR. Therefore, an easily distributable and manageable antigen capture enzyme-linked immunosorbent assay (ELISA) for the detection of orthopoxviruses was developed to facilitate particle detection. By comparing the virus particle binding properties of polyclonal antibodies developed against surface-exposed attachment or fusion proteins, the surface protein A27 was found to be a well-bound, highly immunogenic and exposed target for antibodies aiming at virus particle detection. Subsequently, eight monoclonal anti-A27 antibodies were generated and characterized by peptide epitope mapping and surface plasmon resonance measurements. All antibodies were found to bind with high affinity to two epitopes at the heparin binding site of A27, toward either the N- or C-terminal of the crucial KKEP-segment of A27. Two antibodies recognizing different epitopes were implemented in an antigen capture ELISA. Validation showed robust detection of virus particles from 11 different orthopoxvirus isolates pathogenic to humans, with the exception of MVA, which is apathogenic to humans. Most orthopoxviruses could be detected reliably for viral loads above 1 × 103 PFU/mL. To our knowledge, this is the first solely monoclonal and therefore reproducible antibody-based antigen capture ELISA able to detect all human pathogenic orthopoxviruses including monkeypox virus, except variola virus which was not included. Therefore, the newly developed antibody-based assay represents important progress towards feasible particle detection of this important genus of viruses. 相似文献
88.
Enrico Munari Alcides Chaux Ajay M. Vaghasia Diana Taheri Sarah Karram Stephania M. Bezerra Nilda Gonzalez Roibon William G. Nelson Srinivasan Yegnasubramanian George J. Netto Michael C. Haffner 《PloS one》2016,11(1)
Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment. 相似文献
89.