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Full-Text Articles in Genetics and Genomics
Highly Conserved Molecular Pathways, Including Wnt Signaling, Promote Functional Recovery From Spinal Cord Injury In Lampreys, Paige E. Herman, Angelos Papatheodorou, Stephanie A. Bryant, Courtney K. M. Waterbury, Joseph R. Herdy, Anthony A. Arcese, Joseph D. Buxbaum, Jeramiah J. Smith, Jennifer R. Morgan, Ona Bloom
Highly Conserved Molecular Pathways, Including Wnt Signaling, Promote Functional Recovery From Spinal Cord Injury In Lampreys, Paige E. Herman, Angelos Papatheodorou, Stephanie A. Bryant, Courtney K. M. Waterbury, Joseph R. Herdy, Anthony A. Arcese, Joseph D. Buxbaum, Jeramiah J. Smith, Jennifer R. Morgan, Ona Bloom
Biology Faculty Publications
In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery. We describe complex transcriptional responses in the injured spinal cord, and somewhat surprisingly, also in the brain. Transcriptional responses to SCI in lampreys included transcription factor networks …
Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus
Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus
Physiology Faculty Publications
Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer’s disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended …
Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray
Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray
Pharmacology and Nutritional Sciences Faculty Publications
Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.
Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …
A Therapeutic Approach For Senile Dementias: Neuroangiogenesis, Charles T. Ambrose
A Therapeutic Approach For Senile Dementias: Neuroangiogenesis, Charles T. Ambrose
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Alzheimer's disease (AD) and related senile dementias (SDs) represent a growing medical and economic crisis in this country. Apart from cautioning persons about risk factors, no practical, effective therapy is currently available. Much of the recent research in AD has been based on the amyloid cascade theory. Another approach assumes a vascular basis for SDs. This paper presents evidence from a score of studies that cerebral capillary density (CCD) declines during old age in animals and people as well as in AD. Neuroangiogenic (NAG) factors initiate and maintain capillaries in the brain. Thus a waning level of these factors and …
Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki
Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other …
Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist
Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …
A Brain-Specific Cytochrome P450 Responsible For The Majority Of Deltamethrin Resistance In The Qtc279 Strain Of Tribolium Castaneum, Fang Zhu, R. Parthasarathy, Hua Bai, Katharina Woithe, Martin Kaussmann, Ralf Nauen, Douglas A. Harrison, Subba R. Palli
A Brain-Specific Cytochrome P450 Responsible For The Majority Of Deltamethrin Resistance In The Qtc279 Strain Of Tribolium Castaneum, Fang Zhu, R. Parthasarathy, Hua Bai, Katharina Woithe, Martin Kaussmann, Ralf Nauen, Douglas A. Harrison, Subba R. Palli
Entomology Faculty Publications
Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. However, the molecular basis of this mechanism and the physiological functions of P450s associated with insecticide resistance remain largely unknown. Here, we exploited the functional genomics and reverse genetic approaches to identify and characterize a P450 gene responsible for the majority of deltamethrin resistance observed in the QTC279 strain of Tribolium castaneum. We used recently completed whole-genome sequence of T. castaneum to prepare custom microarrays and identified a P450 gene, CYP6BQ9, which showed more than a 200-fold higher expression in the deltamethrin-resistant QTC279 strain when compared …
Detection Of Sub-Clinical Cwd Infection In Conventional Test-Negative Deer Long After Oral Exposure To Urine And Feces From Cwd+ Deer, Nicholas J. Haley, Candace K. Mathiason, Mark D. Zabel, Glenn C. Telling, Edward A Hoover
Detection Of Sub-Clinical Cwd Infection In Conventional Test-Negative Deer Long After Oral Exposure To Urine And Feces From Cwd+ Deer, Nicholas J. Haley, Candace K. Mathiason, Mark D. Zabel, Glenn C. Telling, Edward A Hoover
Microbiology, Immunology, and Molecular Genetics Faculty Publications
BACKGROUND: Chronic wasting disease (CWD) of cervids is a prion disease distinguished by high levels of transmissibility, wherein bodily fluids and excretions are thought to play an important role. Using cervid bioassay and established CWD detection methods, we have previously identified infectious prions in saliva and blood but not urine or feces of CWD+ donors. More recently, we identified very low concentrations of CWD prions in urine of deer by cervid PrP transgenic (Tg[CerPrP]) mouse bioassay and serial protein misfolding cyclic amplification (sPMCA). This finding led us to examine further our initial cervid bioassay experiments using sPMCA.
OBJECTIVES: We sought …