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Medicine and Health Sciences

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2012

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Full-Text Articles in Genetics and Genomics

Draft Genome Sequence For Pseudomonas Aeruginosa Strain Pao579, A Mucoid Derivative Of Pao381, T. Ryan Withers, Shannon L. Johnson, Hongwei D. Yu Dec 2012

Draft Genome Sequence For Pseudomonas Aeruginosa Strain Pao579, A Mucoid Derivative Of Pao381, T. Ryan Withers, Shannon L. Johnson, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is an opportunistic pathogen that establishes a chronic lung infection in individuals afflicted with cystic fibrosis. Here, we announce the draft genome of P. aeruginosa strain PAO579, an alginate-overproducing derivative of strain PAO381.


Chapter 11: Genome-Wide Association Studies, William S. Bush, Jason H. Moore Dec 2012

Chapter 11: Genome-Wide Association Studies, William S. Bush, Jason H. Moore

Dartmouth Scholarship

Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.


The Principal Genetic Determinants For Nasopharyngeal Carcinoma In China Involve The Hla Class I Antigen Recognition Groove, Minzhong Tang, J. A. Lautenberger, Xiaojiang Gao, Efe Sezgin, Sher L. Hendrickson, Jennifer L. Troyer, Victor A. David, Li Guan, Carl Mcintosh, Xiuchan Guo, Yuming Zheng, Jian Liao, Hong Deng, Michael Malasky, Bailey Kessing, Cheryl Winkler, Mary Carrington, Guy De The, Yi Zeng, Stephen J. O'Brien Nov 2012

The Principal Genetic Determinants For Nasopharyngeal Carcinoma In China Involve The Hla Class I Antigen Recognition Groove, Minzhong Tang, J. A. Lautenberger, Xiaojiang Gao, Efe Sezgin, Sher L. Hendrickson, Jennifer L. Troyer, Victor A. David, Li Guan, Carl Mcintosh, Xiuchan Guo, Yuming Zheng, Jian Liao, Hong Deng, Michael Malasky, Bailey Kessing, Cheryl Winkler, Mary Carrington, Guy De The, Yi Zeng, Stephen J. O'Brien

Biology Faculty Articles

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4×10−29; P HLA-B-aa-site-116 = 6.5×10−19; P HLA-C-aa-site-156 = 6.8×10 …


Inla Promotes Dissemination Of Listeria Monocytogenes To The Mesenteric Lymph Nodes During Food Borne Infection Of Mice, Elsa N. Bou Ghanem, Grant S. Jones, Tanya Myers-Morales, Pooja D. Patil, Achmad N. Hidayatullah, Sarah E. F. D'Orazio Nov 2012

Inla Promotes Dissemination Of Listeria Monocytogenes To The Mesenteric Lymph Nodes During Food Borne Infection Of Mice, Elsa N. Bou Ghanem, Grant S. Jones, Tanya Myers-Morales, Pooja D. Patil, Achmad N. Hidayatullah, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Intestinal Listeria monocytogenes infection is not efficient in mice and this has been attributed to a low affinity interaction between the bacterial surface protein InlA and E-cadherin on murine intestinal epithelial cells. Previous studies using either transgenic mice expressing human E-cadherin or mouse-adapted L. monocytogenes expressing a modified InlA protein (InlA(m)) with high affinity for murine E-cadherin showed increased efficiency of intragastric infection. However, the large inocula used in these studies disseminated to the spleen and liver rapidly, resulting in a lethal systemic infection that made it difficult to define the natural course of intestinal infection. We describe here a …


Multifactorial Patterns Of Gene Expression In Colonic Epithelial Cells Predict Disease Phenotypes In Experimental Colitis, Aubrey Leigh Frantz, Maria E. C. Bruno, Eric William Rogier, Halide Tuna, Donald A. Cohen, Subbarao Bondada, Ralph Lakshman Chelvarajan, J. Anthony Brandon, C. Darrell Jennings, Charlotte S. Kaetzel Nov 2012

Multifactorial Patterns Of Gene Expression In Colonic Epithelial Cells Predict Disease Phenotypes In Experimental Colitis, Aubrey Leigh Frantz, Maria E. C. Bruno, Eric William Rogier, Halide Tuna, Donald A. Cohen, Subbarao Bondada, Ralph Lakshman Chelvarajan, J. Anthony Brandon, C. Darrell Jennings, Charlotte S. Kaetzel

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background— The pathogenesis of inflammatory bowel disease (IBD) is complex and the need to identify molecular biomarkers is critical. Epithelial cells play a central role in maintaining intestinal homeostasis. We previously identified five “signature” biomarkers in colonic epithelial cells (CEC) that are predictive of disease phenotype in Crohn's disease. Here we investigate the ability of CEC biomarkers to define the mechanism and severity of intestinal inflammation.

Methods We analyzed the expression of RelA, A20, pIgR, tumor necrosis factor (TNF), and macrophage inflammatory protein (MIP)-2 in CEC of mice with dextran sodium sulfate (DSS) acute colitis or T-cell-mediated chronic colitis. …


Escherichia Coli Recg Functionally Suppresses Human Bloom Syndrome Phenotypes, Michael W. Killen, Dawn M. Stults, William A. Wilson, Andrew J. Pierce Oct 2012

Escherichia Coli Recg Functionally Suppresses Human Bloom Syndrome Phenotypes, Michael W. Killen, Dawn M. Stults, William A. Wilson, Andrew J. Pierce

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Defects in the human BLM gene cause Bloom syndrome, notable for early development of tumors in a broad variety of tissues. On the basis of sequence similarity, BLM has been identified as one of the five human homologs of RecQ from Escherichia coli. Nevertheless, biochemical characterization of the BLM protein indicates far greater functional similarity to the E. coli RecG protein and there is no known RecG homolog in human cells. To explore the possibility that the shared biochemistries of BLM and RecG may represent an example of convergent evolution of cellular function where in humans BLM has evolved to …


Gene Expression Analysis Of A Murine Model With Pulmonary Vascular Remodeling Compared To End-Stage Ipah Lungs, Kayoko Shimodaira, Yoichiro Okubo, Eri Ochiai, Haruo Nakayama, Harutaka Katano, Megumi Wakayama, Minoru Shinozaki, Takao Ishiwatari, Daisuke Sasai, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Katsuhiko Kamei, Kazutoshi Shibuya Oct 2012

Gene Expression Analysis Of A Murine Model With Pulmonary Vascular Remodeling Compared To End-Stage Ipah Lungs, Kayoko Shimodaira, Yoichiro Okubo, Eri Ochiai, Haruo Nakayama, Harutaka Katano, Megumi Wakayama, Minoru Shinozaki, Takao Ishiwatari, Daisuke Sasai, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Katsuhiko Kamei, Kazutoshi Shibuya

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our …


Borrelia Burgdorferi Cp32 Bpab Modulates Expression Of The Prophage Nucp Nuclease And Ssbp Single-Stranded Dna-Binding Protein, Alicia M. Chenail, Brandon L. Jutras, Claire A. Adams, Logan H. Burns, Amy Bowman, Ashutosh Verma, Brian Stevenson Sep 2012

Borrelia Burgdorferi Cp32 Bpab Modulates Expression Of The Prophage Nucp Nuclease And Ssbp Single-Stranded Dna-Binding Protein, Alicia M. Chenail, Brandon L. Jutras, Claire A. Adams, Logan H. Burns, Amy Bowman, Ashutosh Verma, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Borrelia burgdorferi BpaB proteins of the spirochete's ubiquitous cp32 prophages are DNA-binding proteins, required both for maintenance of the bacteriophage episomes and for transcriptional regulation of the cp32 erp operons. Through use of DNase I footprinting, we demonstrate that BpaB binds the erp operator initially at the sequence 5′-TTATA-3′. Electrophoretic mobility shift assays indicated that BpaB also binds with high affinity to sites located in the 5′ noncoding regions of two additional cp32 genes. Characterization of the proteins encoded by those genes indicated that they are a single-stranded DNA-binding protein and a nuclease, which we named SsbP and NucP, …


Mutations In Dmrt3 Affect Locomotion In Horses And Spinal Circuit Function In Mice, Lisa S. Andersson, Martin Larhammar, Fatima Memic, Hanna Wootz, Doreen Schwochow, Carl-Johan Rubin, Kalicharan Patra, Thorvaldur Arnason, Lisbeth Wellbring, Göran Hjälm, Freyja Imsland, Jessica Lynn Petersen, Molly E. Mccue, James R. Mickelson, Gus Cothran, Nadav Ahituv, Lars Roepstorff, Sofia Mikko, Anna Vallstedt, Gabriella Lindgren, Leif Andersson, Klas Kullander Aug 2012

Mutations In Dmrt3 Affect Locomotion In Horses And Spinal Circuit Function In Mice, Lisa S. Andersson, Martin Larhammar, Fatima Memic, Hanna Wootz, Doreen Schwochow, Carl-Johan Rubin, Kalicharan Patra, Thorvaldur Arnason, Lisbeth Wellbring, Göran Hjälm, Freyja Imsland, Jessica Lynn Petersen, Molly E. Mccue, James R. Mickelson, Gus Cothran, Nadav Ahituv, Lars Roepstorff, Sofia Mikko, Anna Vallstedt, Gabriella Lindgren, Leif Andersson, Klas Kullander

Department of Animal Science: Faculty Publications

Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left–right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favorable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes …


Atlas-Based White Matter Analysis In Individuals With Velo-Cardio-Facial Syndrome (22q11.2 Deletion Syndrome) And Unaffected Siblings, Petya D. Radoeva, Ioana L. Coman, Kevin M. Antshel, Wanda Fremont, Christopher Mccarthy, Ashwini Kotkar, Dongliang Wang, Robert J. Shprintzen, Wendy R. Kates Aug 2012

Atlas-Based White Matter Analysis In Individuals With Velo-Cardio-Facial Syndrome (22q11.2 Deletion Syndrome) And Unaffected Siblings, Petya D. Radoeva, Ioana L. Coman, Kevin M. Antshel, Wanda Fremont, Christopher Mccarthy, Ashwini Kotkar, Dongliang Wang, Robert J. Shprintzen, Wendy R. Kates

Communication Disorders Faculty Publications

Background: Velo-cardio-facial syndrome (VCFS, MIM#192430, 22q11.2 Deletion Syndrome) is a genetic disorder caused by a deletion of about 40 genes at the q11.2 band of one copy of chromosome 22. Individuals with VCFS present with deficits in cognition and social functioning, high risk of psychiatric disorders, volumetric reductions in gray and white matter (WM) and some alterations of the WM microstructure. The goal of the current study was to characterize the WM microstructural differences in individuals with VCFS and unaffected siblings, and the correlation of WM microstructure with neuropsychological performance. We hypothesized that individuals with VCFS would have decreased indices …


Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen Jun 2012

Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen

Dartmouth Scholarship

Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s …


Technical Desiderata For The Integration Of Genomic Data Into Electronic Health Records., Daniel R Masys, Gail P Jarvik, Neil F Abernethy, Nicholas R Anderson, George J Papanicolaou, Dina N Paltoo, Mark A Hoffman, Isaac S Kohane, Howard P Levy Jun 2012

Technical Desiderata For The Integration Of Genomic Data Into Electronic Health Records., Daniel R Masys, Gail P Jarvik, Neil F Abernethy, Nicholas R Anderson, George J Papanicolaou, Dina N Paltoo, Mark A Hoffman, Isaac S Kohane, Howard P Levy

Manuscripts, Articles, Book Chapters and Other Papers

The era of "Personalized Medicine," guided by individual molecular variation in DNA, RNA, expressed proteins and other forms of high volume molecular data brings new requirements and challenges to the design and implementation of Electronic Health Records (EHRs). In this article we describe the characteristics of biomolecular data that differentiate it from other classes of data commonly found in EHRs, enumerate a set of technical desiderata for its management in healthcare settings, and offer a candidate technical approach to its compact and efficient representation in operational systems.


Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit May 2012

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.


An Integrated Bioinformatics And Computational Biology Approach Identifies New Bh3-Only Protein Candidates, Robert G. Hawley, Yuzhong Chen, Irene Riz, Chen Zeng May 2012

An Integrated Bioinformatics And Computational Biology Approach Identifies New Bh3-Only Protein Candidates, Robert G. Hawley, Yuzhong Chen, Irene Riz, Chen Zeng

Anatomy and Regenerative Biology Faculty Publications

FoxD4L1 is a forkhead transcription factor that expands the neural ectoderm by down-regulating genes that promote the onset of neural differentiation and up-regulating genes that maintain proliferative neural precursors in an immature state. We previously demonstrated that binding of Grg4 to an Eh-1 motif enhances the ability of FoxD4L1 to down-regulate target neural genes but does not account for all of its repressive activity. Herein we analyzed the protein sequence for additional interaction motifs and secondary structure. Eight conserved motifs were identified in the C-terminal region of fish and frog proteins. Extending the analysis to mammals identified a high scoring …


Heterotopic Ossification: Cellular Basis, Symptoms, And Treatment, Brian Wolfe Apr 2012

Heterotopic Ossification: Cellular Basis, Symptoms, And Treatment, Brian Wolfe

Senior Honors Theses

Heterotopic ossification (HO) is the process by which calcified bone develops in soft tissues. Because of the abnormal calcification, complications such as bone deformation, loss of range of motion, and joint immobility adversely affect patients. There are many genetic types of heterotopic ossification, namely fibrodysplasia ossificans progressiva, progressive osseous heteroplasia, and Albright hereditary osteodystrophy. However, this condition can also arise from surgery, burns, or traumatic injuries, so it is seen as an important area for research in the future. There are various treatments available such as non-steroidal anti-inflammatory drugs and radiation therapy, as well as combinations of the two. The …


Resource Availability, Mortality And Fertility: A Path Analytic Approach To Global Life History Variation, Mark A. Caudell, Robert J. Quinlan Apr 2012

Resource Availability, Mortality And Fertility: A Path Analytic Approach To Global Life History Variation, Mark A. Caudell, Robert J. Quinlan

Human Biology Open Access Pre-Prints

Humans exhibit considerable diversity in timing and rate of reproduction. Life history theory suggests that ecological cues of resource richness and survival probabilities shape human phenotypes across populations. Populations experiencing high extrinsic mortality due to uncertainty in resources should exhibit faster life histories. Here we use a path analytic approach informed by life history theory to model the multiple pathways between resources, mortality rates, and reproductive behavior in 191 countries. Resources that account for the most variance in population mortality rates are predicted to explain the most variance in total fertility rates. Results indicate that resources (e.g., calories, sanitation, education, …


Association Among Obesity-Related Anthropometric Phenotypes: Analyzing Genetic And Environmental Contribution, Aline Jelenkovic, Esther Rebato Apr 2012

Association Among Obesity-Related Anthropometric Phenotypes: Analyzing Genetic And Environmental Contribution, Aline Jelenkovic, Esther Rebato

Human Biology Open Access Pre-Prints

Obesity has become a public health and policy problem in many parts of the world. Epidemiological and population studies in this field are usually based on different anthropometric measures, however, common genetic and environmental factors between these phenotypes have been scarcely studied. The objective of this work is to assess the strength of these factors on the covariation among a large set of obesity-related traits. The subject group consisted of 533 nuclear families living in the Greater Bilbao (Spain), and included 1702 individuals aged 2-61 years. Detailed anthropometric measurements (stature, breadths, circumferences and skinfolds) were carried out in each subject. …


Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry Mar 2012

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …


Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Poland, Michael A. Barry, Karl A. Nath, Andrew D. Badley Mar 2012

Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Poland, Michael A. Barry, Karl A. Nath, Andrew D. Badley

Nebraska Center for Virology: Faculty Publications

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median …


Dialogues, Dilemmas, And Disclosures: Genomic Research And Incidental Findings, Lynn W. Bush, Karen H. Rothenberg Mar 2012

Dialogues, Dilemmas, And Disclosures: Genomic Research And Incidental Findings, Lynn W. Bush, Karen H. Rothenberg

Faculty Scholarship

No abstract provided.


Genes And Plays: Bringing Elsi Issues To Life, Karen H. Rothenberg, Lynn W. Bush Feb 2012

Genes And Plays: Bringing Elsi Issues To Life, Karen H. Rothenberg, Lynn W. Bush

Faculty Scholarship

Ethical complexities surround the promise of genomic technology and the power of genetic information as they alter conceptions of identity and dynamics within personal and professional relationships. Creative approaches such as dramatic vignettes offer a unique analytical stage for imagining the bioethical past and future. Dramatic narratives can bring to life images of differing perspectives and values when experiencing innovations in medicine. Although the scientific landscape shifts, concerns expressed in theatre from 50 years ago parallel many contemporary ELSI (ethical, legal and social implications) issues, highlighting the ongoing struggle to appreciate the impact of emerging genetic technologies on relationships. To …


Emerging Viruses In The Felidae: Shifting Paradigms, Stephen J. O'Brien, Jennifer L. Troyer, Meredith Brown, Warren E. Johnson, Agostinho Antunes, Melody E. Roelke, Jill Pecon-Slattery Feb 2012

Emerging Viruses In The Felidae: Shifting Paradigms, Stephen J. O'Brien, Jennifer L. Troyer, Meredith Brown, Warren E. Johnson, Agostinho Antunes, Melody E. Roelke, Jill Pecon-Slattery

Biology Faculty Articles

The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important …


Contribution Of The Infection-Associated Complement Regulator-Acquiring Surface Protein 4 (Erpc) To Complement Resistance Of Borrelia Burgdorferi, Claudia Hammerschmidt, Teresia Hallström, Christine Skerka, Reinhard Wallich, Brian Stevenson, Peter F Zipfel, Peter Kraiczy Jan 2012

Contribution Of The Infection-Associated Complement Regulator-Acquiring Surface Protein 4 (Erpc) To Complement Resistance Of Borrelia Burgdorferi, Claudia Hammerschmidt, Teresia Hallström, Christine Skerka, Reinhard Wallich, Brian Stevenson, Peter F Zipfel, Peter Kraiczy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi evades complement-mediated killing by interacting with complement regulators through distinct complement regulator-acquiring surface proteins (CRASPs). Here, we extend our analyses to the contribution of CRASP-4 in mediating complement resistance of B. burgdorferi and its interaction with human complement regulators. CRASP-4 (also known as ErpC) was immobilized onto magnetic beads and used to capture proteins from human serum. Following Western blotting, factor H (CFH), CFH-related protein 1 (CFHR1), CFHR2, and CFHR5 were identified as ligands of CRASP-4. To analyze the impact of native CRASP-4 on mediating survival of serum-sensitive cells in human serum, a B. garinii strain was generated …


Genetics And Cancer, Sachin Puri Jan 2012

Genetics And Cancer, Sachin Puri

A with Honors Projects

Genes' effect in body and relationship with cancer. Role in cell cycle and angiogenesis.


Tissue Sampling Methods And Standards For Vertebrate Genomics, Pamela B. Y. Wong, Edward O. Wiley, Warren E. Johnson, Oliver A. Ryder, Stephen J. O'Brien, David Haussler, Klaus-Peter Koepfli, Marlys L. Houck, Polina L. Perelman, Gabriela Mastromonaco, Andrew C. Bentley, Byrappa Venkatesh, Ya-Ping Zhang, Robert W. Murphy, Genome 10k Project Community Of Scientists Jan 2012

Tissue Sampling Methods And Standards For Vertebrate Genomics, Pamela B. Y. Wong, Edward O. Wiley, Warren E. Johnson, Oliver A. Ryder, Stephen J. O'Brien, David Haussler, Klaus-Peter Koepfli, Marlys L. Houck, Polina L. Perelman, Gabriela Mastromonaco, Andrew C. Bentley, Byrappa Venkatesh, Ya-Ping Zhang, Robert W. Murphy, Genome 10k Project Community Of Scientists

Biology Faculty Articles

The recent rise in speed and efficiency of new sequencing technologies have facilitated high-throughput sequencing, assembly and analyses of genomes, advancing ongoing efforts to analyze genetic sequences across major vertebrate groups. Standardized procedures in acquiring high quality DNA and RNA and establishing cell lines from target species will facilitate these initiatives. We provide a legal and methodological guide according to four standards of acquiring and storing tissue for the Genome 10K Project and similar initiatives as follows: four-star (banked tissue/cell cultures, RNA from multiple types of tissue for transcriptomes, and sufficient flash-frozen tissue for 1 mg of DNA, all from …


Cell-Free Circulating Mirna Biomarkers In Cancer., Meng-Hsuan Mo, Liang Chen, Yebo Fu, Wendy Wang, Sidney W. Fu Jan 2012

Cell-Free Circulating Mirna Biomarkers In Cancer., Meng-Hsuan Mo, Liang Chen, Yebo Fu, Wendy Wang, Sidney W. Fu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Considerable attention and an enormous amount of resources have been dedicated to cancer biomarker discovery and validation. However, there are still a limited number of useful biomarkers available for clinical use. An ideal biomarker should be easily assayed with minimally invasive medical procedures but possess high sensitivity and specificity. Commonly used circulating biomarkers are proteins in serum, most of which require labor-intensive analysis hindered by low sensitivity in early tumor detection. Since the deregulation of microRNA (miRNA) is associated with cancer development and progression, profiling of circulating miRNAs has been used in a number of studies to identify novel minimally …


Development And Validation Of A Novel Reporter Assay For Human Papillomavirus Type 16 Late Gene Expression, Beatrice Orru, Ciaran Cunniffe, Fergus Ryan, Stefan Schwartz Jan 2012

Development And Validation Of A Novel Reporter Assay For Human Papillomavirus Type 16 Late Gene Expression, Beatrice Orru, Ciaran Cunniffe, Fergus Ryan, Stefan Schwartz

Articles

To facilitate the investigations of HPV-16 late gene expression HPV-16 reporter plasmids were generated using previously described sub-genomic HPV-16 plasmids, named pBEL and pBELM, that, similar to the full viral genome, produce primarily HPV-16 early mRNAs and very little, if any, late mRNAs in cervical cancer cells. The HPV-16 late L1 gene was replaced by the chloramphenicol acetyltransferase (CAT) reporter gene, or green fluorescent protein (GFP), preceded by the poliovirus internal ribosome entry site (IRES). Results show that the reporter genes mimic the expression of L1 from these plasmids. For example, overexpression of adenovirus E4orf4 protein (E4orf4), polypyrimidine tract binding …


Evolution Of Starvation Resistance In Drosophila Melanogaster: Measurement Of Direct And Correlated Responses To Artificial Selection, Tiffany E. Schwasinger-Schmidt, Stephen D. Kachman, Lawrence G. Harshman Jan 2012

Evolution Of Starvation Resistance In Drosophila Melanogaster: Measurement Of Direct And Correlated Responses To Artificial Selection, Tiffany E. Schwasinger-Schmidt, Stephen D. Kachman, Lawrence G. Harshman

Lawrence G. Harshman Publications

Laboratory selection for resistance to starvation has been conducted under relatively controlled conditions to investigate direct and correlated responses to artificial selection. With regard to starvation resistance, there are three physiological routes by which the trait can evolve: resource accumulation, energy conservation and starvation tolerance. A majority of energetic compounds and macromolecules including triglycerides, trehalose and other sugars, and soluble protein increased in abundance as a result of selection. Movement was additionally investigated with selected males moving less than control males and selected females exhibiting a similar response to selection. Results obtained from this study supported two of the possible …


Epigenetic Variation May Compensate For Decreased Genetic Variation With Introductions: A Case Study Using House Sparrows (Passer Domesticus) On Two Continents, Aaron W. Schrey, Courtney A. C. Coon, Michael T. Grispo, Mohammed Awad, Titus Imboma, Earl D. Mccoy, Henry R. Mushinsky, Christina L. Richards, Lynn B. Martin Jan 2012

Epigenetic Variation May Compensate For Decreased Genetic Variation With Introductions: A Case Study Using House Sparrows (Passer Domesticus) On Two Continents, Aaron W. Schrey, Courtney A. C. Coon, Michael T. Grispo, Mohammed Awad, Titus Imboma, Earl D. Mccoy, Henry R. Mushinsky, Christina L. Richards, Lynn B. Martin

Integrative Biology Faculty and Staff Publications

Epigenetic mechanisms impact several phenotypic traits and may be important for ecology and evolution. The introduced house sparrow (Passer domesticus) exhibits extensive phenotypic variation among and within populations. We screened methylation in populations from Kenya and Florida to determine if methylation varied among populations, varied with introduction history (Kenyan invasion < 50 years old, Florida invasion ~150 years old), and could potentially compensate for decrease genetic variation with introductions. While recent literature has speculated on the importance of epigenetic effects for biological invasions, this is the first such study among wild vertebrates. Methylation was more frequent in Nairobi, and outlier loci suggest that populations may be differentiated. Methylation diversity was similar between populations, in spite of known lower genetic diversity in Nairobi, which suggests that epigenetic variation may compensate for decreased genetic diversity as a source of phenotypic variation during introduction. Our results suggest that methylation differences may be common among house sparrows, but research is needed to discern whether methylation impacts phenotypic variation.


Novel Report Of Expression And Function Of Cd97 In Malignant Gliomas: Correlation With Wilms Tumor 1 Expression And Glioma Cell Invasiveness Laboratory Investigation, Archana Chidambaram, Helen L. Fillmore, Timothy E. Van Meter, Catherine I. Dumur, William C. Broaddus Jan 2012

Novel Report Of Expression And Function Of Cd97 In Malignant Gliomas: Correlation With Wilms Tumor 1 Expression And Glioma Cell Invasiveness Laboratory Investigation, Archana Chidambaram, Helen L. Fillmore, Timothy E. Van Meter, Catherine I. Dumur, William C. Broaddus

Office of Research Faculty & Staff Publications

Object. The Wilms tumor 1 (WT1) protein—a developmentally regulated transcription factor—is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells.

Methods. The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness. Gene expression analysis was then used to identify the candidate genes that were altered as a result of WT1 silencing. One candidate target, CD97, was then selected for further investigation into its role by suppressing …