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Playing for half the deck: the molecular biology of meiosis

Mia D. Champion, R. Scott Hawley
2002 Nature Cell Biology  
Figure 2 2 Directionality of the meiotic process -D. melanogaster versus S. cerevisiae. a, In D. melanogaster, synapsis of homologues is required for exchange to occur. b, Conversely, in S. cerevisiae,  ... 
doi:10.1038/ncb-nm-fertilitys50 pmid:12479615 fatcat:vfwpqsgspvbfvcroztni5tgpie

Host-Pathogen O-Methyltransferase Similarity and Its Specific Presence in Highly Virulent Strains of Francisella tularensis Suggests Molecular Mimicry

Mia D. Champion, Olivier Lespinet
2011 PLoS ONE  
In Mycobacterium avium 104, methyltransferase D mediates the methylation of highly antigenic glycopeptidolipids (GPLs) found densely distributed on the cell surface [36] .  ...  Combined p-values for the motif profiles are shown next to each sequence. doi:10.1371/journal.pone.0020295.g005 Figure 6 . 6 Motif conservation profiles and polymorphic sites map proximal to a 3-D region  ... 
doi:10.1371/journal.pone.0020295 pmid:21637805 pmcid:PMC3102702 fatcat:y2ro5iz2u5ckpbk4zksvwipl2q

The Evolutionary History of Amino Acid Variations Mediating Increased Resistance of S. aureus Identifies Reversion Mutations in Metabolic Regulators

Mia D. Champion, Vanessa Gray, Carl Eberhard, Sudhir Kumar, Ramy K. Aziz
2013 PLoS ONE  
D G D benign 0.439 benign 0.235 Tolerated 1.000 Neutral 0.235 purD 389 A A V A benign Not Scored benign Not Scored Tolerated 1.000 0 0.000 A9635 Vancomycin  ...  The accuracy statistics of three methods in predicting StaphRAMs (A-C) is compared to the known accuracy of the same methods for predicting Human DAMs [21] (D) Maximum likelihood estimation of a binormal  ... 
doi:10.1371/journal.pone.0056466 pmid:23424663 pmcid:PMC3570469 fatcat:sjxjaeincfemxocipoa6fxvaka

IL-33 facilitates oncogene-induced cholangiocarcinoma in mice by an interleukin-6-sensitive mechanism

Daisaku Yamada, Sumera Rizvi, Nataliya Razumilava, Steven F. Bronk, Jaime I. Davila, Mia D. Champion, Mitesh J. Borad, Jorge A. Bezerra, Xin Chen, Gregory J. Gores
2015 Hepatology  
Furthermore, immunohistochemistry and immunofluorescence also demonstrated abundant ST2 expression in murine tumors (Fig. 5C,D) .  ...  (D) Immunofluorescence was used to detect ST2 in murine CCA cells (CK19-positive) compared to cancer-associated fibroblasts (a-SMApositive) (left panel).  ... 
doi:10.1002/hep.27687 pmid:25580681 pmcid:PMC4406813 fatcat:x7jwyhecireuvcufm7svvdhwbq

When Outgroups Fail; Phylogenomics of Rooting the Emerging Pathogen, Coxiella burnetii

Talima Pearson, Heidie M. Hornstra, Jason W. Sahl, Sarah Schaack, James M. Schupp, Stephen M. Beckstrom-Sternberg, Matthew W. O'Neill, Rachael A. Priestley, Mia D. Champion, James S. Beckstrom-Sternberg, Gilbert J. Kersh, James E. Samuel (+2 others)
2013 Systematic Biology  
C G*A* Q321 A A C A T G C A C G G T C C G T A T T A C G G A C T C C T T C G A G C A G G G A G C T T D G D G A D D D D D G T C T A A A G C G A A' RSA 493 G G T A C*G*T* C C*G G T C T G T A T C G C G A A  ...  D D D G C A A A A A A A A Q212 A* A* T* A* C G T A C T* G*D C T A C C G C G T A A G T C T T C C T C G A C A A A A G G T T C G*T* A*G*G G C A A A A G C G*A* Dugway A A C A C G T A C G G C C T A C C G C  ... 
doi:10.1093/sysbio/syt038 pmid:23736103 pmcid:PMC3739886 fatcat:cjyz6kyvczgthngxhkdciz7mnm

Phylogeography of Francisella tularensis subspecies holarctica from the country of Georgia

Gvantsa Chanturia, Dawn N Birdsell, Merab Kekelidze, Ekaterine Zhgenti, George Babuadze, Nikoloz Tsertsvadze, Shota Tsanava, Paata Imnadze, Stephen M Beckstrom-Sternberg, James S Beckstrom-Sternberg, Mia D Champion, Shripad Sinari (+10 others)
2011 BMC Microbiology  
Department of Homeland Security S&T CB Division Bioforensics R&D Program.  ...  Table 1 1 Melt-MAMA primers targeting informative canSNPs SNP SCHU S4 position Genome SNP state (D/A) a Melt MAMA primer c Melt-MAMA primer sequences d Primer conc.  ...  c D: Derived; A: Ancestral; C: Common Primer d Primer tails and antepenultimate mismatch bases are in lower case Table 2 2 Francisella tularensis subsp. holarctica isolates from the country of Georgia  ... 
doi:10.1186/1471-2180-11-139 pmid:21682874 pmcid:PMC3224097 fatcat:sybi6ltlu5axdh6v3hifmgff34

Whole Genome Analyses of a Well-Differentiated Liposarcoma Reveals Novel SYT1 and DDR2 Rearrangements

Jan B. Egan, Michael T. Barrett, Mia D. Champion, Sumit Middha, Elizabeth Lenkiewicz, Lisa Evers, Princy Francis, Jessica Schmidt, Chang-Xin Shi, Scott Van Wier, Sandra Badar, Gregory Ahmann (+8 others)
2014 PLoS ONE  
Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has
more » ... y been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR) where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.
doi:10.1371/journal.pone.0087113 pmid:24505276 pmcid:PMC3914808 fatcat:2ry7r5koerc67nkzenjgfix6cm

Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies

Mia D. Champion, Qiandong Zeng, Eli B. Nix, Francis E. Nano, Paul Keim, Chinnappa D. Kodira, Mark Borowsky, Sarah Young, Michael Koehrsen, Reinhard Engels, Matthew Pearson, Clint Howarth (+11 others)
2009 PLoS Pathogens  
genes (and psuedogenes) that encode components of the Twin Arginine Translocation (TAT), and secretion systems of Type I (T1SS), Type II (T2SS), Type V (T5SS), and VI (T6SS) ( Tables 4-6 and Table S1c ,d,  ...  regulator of transcription (sspA) FTT0557 hypothetical protein ahpC/TSA family FTT0623 trigger factor (TF) protein (peptidyl-prolyl cis/trans isomerase) FTT0628 peptidyl-prolyl cis-trans isomerase D  ... 
doi:10.1371/journal.ppat.1000459 pmid:19478886 pmcid:PMC2682660 fatcat:76urr2746zbcte2ht2bugtfst4

Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers

Mitesh J. Borad, Jan B. Egan, Rachel M. Condjella, Winnie S. Liang, Rafael Fonseca, Nicole R. Ritacca, Ann E. McCullough, Michael T. Barrett, Katherine S. Hunt, Mia D. Champion, Maitray D. Patel, Scott W. Young (+25 others)
2016 Scientific Reports  
DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/ refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using
more » ... LIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1-3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCIeNTIfIC REPORts | 6: 25 | profiling. Eighteen of 66 treated patients (27%) were found to have progression-free survival (PFS) ≥1.3 times longer on the molecular profiling directed approach compared to their most recent empiric therapy (PFS ratio), allowing for rejection of the null hypothesis of <15% having PFS ratio ≥1.3. In a similar effort focused on patients treated on Phase I trials, Tsimberidou and colleagues assessed microdissected paraffin embedded tissue for somatic hot-spot exonal mutations in 10 genes (PIK3CA, BRAF, NRAS, KRAS, EGFR, KIT, GNAQ, MET, TP53 and RET), IHC for PTEN and FISH for ALK translocations in 1,144 patients 7 . They found that 460 (40.2%) of these patients had at least one genomic aberration. Notably, a higher response rate (27% vs. 5%; P < 0.0001), time-to-treatment failure (median 5.2 vs. 2.2 months; P < 0.0001) and longer survival (median 13.4 vs. 9.0 months; P = 0.017) were observed in patients who had matched therapy compared to those patients who had empiric therapy. While the scope of molecular profiling performed in these studies was limited compared to current NGS enabled approaches, they provide a contextual platform upon which clinical efforts utilising NGS could be implemented. NGS based approaches assaying a panel of genes 4 or a panel of genes in conjunction with array comparative genomic hybridisation (aCGH) 8 , provided further impetus towards more ambitious, comprehensive genomic characterisation in the clinical setting. More recently, a retrospective study by Jones and colleagues comparing whole exome sequencing to NGS panel based approaches, highlighted the high false positive rate and absence of germline analysis associated with NGS panels as major limitations 9 . Several other recent studies have further demonstrated the necessity of including germline analysis when evaluating somatic mutations 10-13 . Exploratory evaluations of whole exome, genome and transcriptome sequencing have demonstrated the technical feasibility of the approach. However, these efforts were limited (Weiss and colleagues [n = 9] 3 and Roychowdhury and colleagues [n = 4] 5 ) and identified numerous barriers that should be evaluated in future studies. These barriers include the ability to execute the workflow consistently in a Clinical Laboratory Improvement Amendments (CLIA) 14 environment and challenges in acquisition of sufficient, high-quality, NGS suitable tissue from prospectively collected samples. Furthermore, ethical, legal, and social implications (ELSI) are significant as these encompass the communication of incidental (unsolicited) findings from germline analysis, data custody and data privacy in the event of death prior to result availability. In addition, the delivery of results to treating physicians in a timeframe that is compatible with the opportunity to treat patients experiencing clinical decline while awaiting results and access to genome analysis guided therapeutics through on/off-label use of drugs or clinical studies, present very real barriers to implementation of comprehensive NGS technologies in the clinic. In response to these observed challenges, a study was designed to evaluate the effectiveness of implementation of comprehensive NGS technologies in a clinical setting. The study objectives were threefold. First, the study sought to estimate the time to completion of integrated whole exome/long insert whole genome/transcriptome sequencing. Second, the objective was to estimate time to reporting of results of therapeutically relevant drug targets derived from integrated whole exome/long-insert whole genome/whole transcriptome sequencing along with CLIA validation. Finally, the study sought to determine mechanisms of drug access.
doi:10.1038/s41598-016-0021-4 pmid:28003660 pmcid:PMC5431338 fatcat:myuvizoldjacfgcagctgt7lbey

The clinical significance of cereblon expression in multiple myeloma

Steven R. Schuster, K. Martin Kortuem, Yuan Xiao Zhu, Esteban Braggio, Chang-Xin Shi, Laura A. Bruins, Jessica E. Schmidt, Greg Ahmann, Shaji Kumar, S. Vincent Rajkumar, Joseph Mikhael, Betsy LaPlant (+7 others)
2014 Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis  
a)-(d) CRBN expression in MM and its precursors.  ...  This increase is not only explained by copy number dependency of CRBN expression (shown in D). Fig. 3 . 3 Fig. 3. Fig. 4 . 4 CRBN expression correlates with PFS (A+C) and OS (B+D).  ... 
doi:10.1016/j.leukres.2013.08.015 pmid:24129344 pmcid:PMC3905958 fatcat:ozz6nm2ipzatlpopwmznm7dizi

Targeted sequencing using a 47 gene multiple myeloma mutation panel (M3P) in -17p high risk disease

Klaus M. Kortüm, Christian Langer, Jorge Monge, Laura Bruins, Jan B. Egan, Yuan X. Zhu, Chang Xin Shi, Patrick Jedlowski, Jessica Schmidt, Juhi Ojha, Lars Bullinger, Peter Liebisch (+10 others)
2014 British Journal of Haematology  
We constructed a multiple myeloma (MM)-specific gene panel for targeted sequencing and investigated 72 untreated high-risk (del17p) MM patients. Mutations were identified in 78% of the patients. While the majority of studied genes were mutated at similar frequency to published literature, the prevalence of TP53 mutation was increased (28%) and no mutations were found in FAM46C. This study provides a comprehensive insight into the mutational landscape of del17p high-risk MM. Additionally, our
more » ... k demonstrates the practical use of a customized sequencing panel, as an easy, cheap and fast approach to characterize the mutational profile of MM.
doi:10.1111/bjh.13171 pmid:25302557 pmcid:PMC4314325 fatcat:vln4emku3vcrnihcs4zhml5vfa

A Multidisciplinary Biospecimen Bank of Renal Cell Carcinomas Compatible with Discovery Platforms at Mayo Clinic, Scottsdale, Arizona

Thai H. Ho, Rafael Nunez Nateras, Huihuang Yan, Jin G. Park, Sally Jensen, Chad Borges, Jeong Heon Lee, Mia D. Champion, Raoul Tibes, Alan H. Bryce, Estrella M. Carballido, Mark A. Todd (+6 others)
2015 PLoS ONE  
D, Gene-body coverage by H3K36me3-binding sites.  ... 
doi:10.1371/journal.pone.0132831 pmid:26181416 pmcid:PMC4504486 fatcat:yujszsknnzbqlnpmqdnbywqxs4

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

Mitesh J. Borad, Mia D. Champion, Jan B. Egan, Winnie S. Liang, Rafael Fonseca, Alan H. Bryce, Ann E. McCullough, Michael T. Barrett, Katherine Hunt, Maitray D. Patel, Scott W. Young, Joseph M. Collins (+38 others)
2014 PLoS Genetics  
D) Tumor stained with pEGFR showing membranous positivity (solid arrows) with negative background lymphocytes (empty arrows).  ...  Summaries by individual patients are shown as follows: A) Patient 1, B) Patient 2, C) Patient 3, D) Patient 4, E) Patient 5, and F) Patient 6.  ... 
doi:10.1371/journal.pgen.1004135 pmid:24550739 pmcid:PMC3923676 fatcat:gtjn2vzmwngmfguyyqurcxqbvy

Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis

Christopher A. Desjardins, Mia D. Champion, Jason W. Holder, Anna Muszewska, Jonathan Goldberg, Alexandre M. Bailão, Marcelo Macedo Brigido, Márcia Eliana da Silva Ferreira, Ana Maria Garcia, Marcin Grynberg, Sharvari Gujja, David I. Heiman (+31 others)
2011 PLoS Genetics  
Our analysis indicated that the Paracoccidioides genome encodes for the catabolic pathways necessary to break down plant cell wall derived monosaccharides D-glucose, D-xylose, and D-mannose, and D-galactose  ...  U. reesii grew well on monosaccharides Dglucose, D-mannose, and D-xylose in at least two of the three replicates.  ... 
doi:10.1371/journal.pgen.1002345 pmid:22046142 pmcid:PMC3203195 fatcat:gdxwoeboa5bodhpx3hmbwuscyu

Page 898 of Guernsey Breeders' Journal Vol. 98, Issue 6 [page]

1956 Guernsey Breeders' Journal  
Bom October 23, 1950 Mia liiiiii Mia Hin-'a Ditiii < Itl.ltSI'HINO'H II.  ...  D. No. 1 Pennsylvania Band's Kree 11923 .lOSKBH KKTHKROLK Manager Tel. Orwigsburg—Empire 6-5872 Guernsey Breeders' Journal \  ... 
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