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Articles 91 - 120 of 501
Full-Text Articles in Cell and Developmental Biology
Primary Cilium-Dependent Signaling Mechanisms, Rajasekharreddy Pala, Nedaa Alomari, Surya M. Nauli
Primary Cilium-Dependent Signaling Mechanisms, Rajasekharreddy Pala, Nedaa Alomari, Surya M. Nauli
Pharmacy Faculty Articles and Research
Primary cilia are hair-like organelles and play crucial roles in vertebrate development, organogenesis, health, and many genetic disorders. A primary cilium is a mechano-sensory organelle that responds to mechanical stimuli in the micro-environment. A cilium is also a chemosensor that senses chemical signals surrounding a cell. The overall function of a cilium is therefore to act as a communication hub to transfer extracellular signals into intracellular responses. Although intracellular calcium has been one of the most studied signaling messengers that transmit extracellular signals into the cells, calcium signaling by various ion channels remains a topic of interest in the field. …
Cyclic Peptide Conjugate Of Curcumin And Doxorubicin As An Anticancer Agent, Shaban Darwish, Saghar Mozaffari, Keykavous Parang, Rakesh Tiwari
Cyclic Peptide Conjugate Of Curcumin And Doxorubicin As An Anticancer Agent, Shaban Darwish, Saghar Mozaffari, Keykavous Parang, Rakesh Tiwari
Pharmacy Faculty Articles and Research
The hydrophobicity of curcumin creates hurdle towards its use in the anticancer therapy. Herein, we synthesized a curcumin-doxorubicin conjugated cyclic peptide scaffold to improve the solubility of curcumin and create a conjugate containing two anticancer agents. A solid-phase Fmoc/tBu solid phase methodology was used to synthesize a cell-penetrating nuclear targeting peptide with free thiol and amine groups, which was coupled with the activated doxorubicin (Dox) and curcumin, affording Dox-peptide-curcumin conjugate (DPCC) (10). The antiproliferative activity of the conjugate was evaluated in human leukemia carcinoma cell (CCRF-CEM), human ovarian carcinoma cell (SKOV-3), and normal kidney cell line (LLCPK). Cyclic peptide-doxorubicin conjugate …
Inhibition Of Cholesterol Biosynthesis Through Rnf145-Dependent Ubiquitination Of Scap, Li Zhang, Prashant Rajbhandari, Christina Priest, Jaspreet Sandhu, Xiaohui Wu, Ryan E. Temel, Antonio Castrillo, Thomas Q. De Aguiar Vallim, Tamer Sallam, Peter Tontonoz
Inhibition Of Cholesterol Biosynthesis Through Rnf145-Dependent Ubiquitination Of Scap, Li Zhang, Prashant Rajbhandari, Christina Priest, Jaspreet Sandhu, Xiaohui Wu, Ryan E. Temel, Antonio Castrillo, Thomas Q. De Aguiar Vallim, Tamer Sallam, Peter Tontonoz
Saha Cardiovascular Research Center Faculty Publications
Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show …
Alcohol Consumption Impairs The Ependymal Cilia Motility In The Brain Ventricles, Alzahra J. Al Omran, Hannah C. Saternos, Yusuf S. Althobaiti, Alexander Wisner, Youssef Sari, Surya M. Nauli, Wissam A. Aboualaiwi
Alcohol Consumption Impairs The Ependymal Cilia Motility In The Brain Ventricles, Alzahra J. Al Omran, Hannah C. Saternos, Yusuf S. Althobaiti, Alexander Wisner, Youssef Sari, Surya M. Nauli, Wissam A. Aboualaiwi
Pharmacy Faculty Articles and Research
Ependymal cilia protrude into the central canal of the brain ventricles and spinal cord to circulate the cerebral spinal fluid (CSF). Ependymal cilia dysfunction can hinder the movement of CSF leading to an abnormal accumulation of CSF within the brain known as hydrocephalus. Although the etiology of hydrocephalus was studied before, the effects of ethanol ingestion on ependymal cilia function have not been investigated in vivo. Here, we report three distinct types of ependymal cilia, type-I, type-II and type-III classified based upon their beating frequency, their beating angle, and their distinct localization within the mouse brain-lateral ventricle. Our studies …
Comparative Transcriptomics Reveal Developmental Turning Points During Embryogenesis Of A Hemimetabolous Insect, The Damselfly Ischnura Elegans, Sabrina Simon, Sven Sagasser, Edoardo Saccenti, Mercer R. Brugler, M. Eric Schranz, Heike Hadrys, George Amato, Rob Desalle
Comparative Transcriptomics Reveal Developmental Turning Points During Embryogenesis Of A Hemimetabolous Insect, The Damselfly Ischnura Elegans, Sabrina Simon, Sven Sagasser, Edoardo Saccenti, Mercer R. Brugler, M. Eric Schranz, Heike Hadrys, George Amato, Rob Desalle
Publications and Research
Identifying transcriptional changes during embryogenesis is of crucial importance for unravelling evolutionary, molecular and cellular mechanisms that underpin patterning and morphogenesis. However, comparative studies focusing on early/embryonic stages during insect development are limited to a few taxa. Drosophila melanogaster is the paradigm for insect development, whereas comparative transcriptomic studies of embryonic stages of hemimetabolous insects are completely lacking. We reconstructed the first comparative transcriptome covering the daily embryonic developmental progression of the blue-tailed damselfly Ischnura elegans (Odonata), an ancient hemimetabolous representative. We identified a “core” set of 6,794 transcripts – shared by all embryonic stages – which are mainly involved …
Substitutions In Conserved Regions Preceding And Within The Linker Affect Activity And Flexibility Of Trnase Zl, The Long Form Of Trnase Z, Makensie Saoura, Kyla Pinnock, Maria Pujantell-Graell, Louis Levinger
Substitutions In Conserved Regions Preceding And Within The Linker Affect Activity And Flexibility Of Trnase Zl, The Long Form Of Trnase Z, Makensie Saoura, Kyla Pinnock, Maria Pujantell-Graell, Louis Levinger
Publications and Research
The enzyme tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions as a homodimer and is found in all prokaryotes and some eukaryotes. The long form, tRNase ZL, related to tRNase ZS through tandem duplication and found only in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS. tRNase ZL consists of related but diverged amino and carboxy domains connected by a flexible linker (also referred to as a flexible tether) and functions as a monomer. The amino …
Cd80 Expressed By Cd8+ T Cells Contributes To Pd-L1-Induced Apoptosis Of Activated Cd8+ T Cells, Meagan R. Rollins, Rachel M. Gibbons Johnson
Cd80 Expressed By Cd8+ T Cells Contributes To Pd-L1-Induced Apoptosis Of Activated Cd8+ T Cells, Meagan R. Rollins, Rachel M. Gibbons Johnson
Biology Publications
Tumor cells are capable of limiting antitumor CD8+ T cell responses through their cell surface expression of PD-L1. In addition to PD-1 expressed by CD8+ T cells, PD-L1 also binds to CD80 expressed by CD8+ T cells. The influence of the PD-L1/CD80 interaction on CD8+ T cell function has not been fully characterized, so we sought to investigate the impact of the PD-L1/CD80 interaction on PD-L1-induced apoptosis of activated CD8+ T cells. We found that CD8+ T cells that lacked CD80 expression got activated to the same extent as wild-type CD8+ T cells, but when cultured with anti-CD3 and PD-L1/Fc …
Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie
Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie
Molecular and Cellular Biochemistry Faculty Publications
Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning …
Myoblasts And Macrophages Are Required For Therapeutic Morpholino Antisense Oligonucleotide Delivery To Dystrophic Muscle., James S Novak, Marshall W Hogarth, Jessica F Boehler, Marie Nearing, Maria C Vila, Raul Heredia, Alyson A Fiorillo, Aiping Zhang, Yetrib Hathout, Eric P Hoffman, Jyoti K Jaiswal, Kanneboyina Nagaraju, Sebahattin Cirak, Terence A Partridge
Myoblasts And Macrophages Are Required For Therapeutic Morpholino Antisense Oligonucleotide Delivery To Dystrophic Muscle., James S Novak, Marshall W Hogarth, Jessica F Boehler, Marie Nearing, Maria C Vila, Raul Heredia, Alyson A Fiorillo, Aiping Zhang, Yetrib Hathout, Eric P Hoffman, Jyoti K Jaiswal, Kanneboyina Nagaraju, Sebahattin Cirak, Terence A Partridge
Pediatrics Faculty Publications
Exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), employing morpholino antisense oligonucleotides (PMO-AO) to exclude disruptive exons from the mutant DMD transcript and elicit production of truncated dystrophin protein. Clinical trials for PMO show variable and sporadic dystrophin rescue. Here, we show that robust PMO uptake and efficient production of dystrophin following PMO administration coincide with areas of myofiber regeneration and inflammation. PMO localization is sustained in inflammatory foci where it enters macrophages, actively differentiating myoblasts and newly forming myotubes. We conclude that efficient PMO delivery into muscle requires two concomitant events: first, accumulation and retention …
Diverse Amide Analogs Of Sulindac For Cancer Treatment And Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds
Diverse Amide Analogs Of Sulindac For Cancer Treatment And Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds
Pharmaceutical Sciences Faculty Publications
Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivoantitumor activity that was comparable to sulindac in a human colon tumorxenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good …
Glycolytic Reprogramming Through Pck2 Regulates Tumor Initiation Of Prostate Cancer Cells, Jiangsha Zhao, Jieran Li, Teresa W.M. Fan, Steven X. Hou
Glycolytic Reprogramming Through Pck2 Regulates Tumor Initiation Of Prostate Cancer Cells, Jiangsha Zhao, Jieran Li, Teresa W.M. Fan, Steven X. Hou
Toxicology and Cancer Biology Faculty Publications
Tumor-initiating cells (TICs) play important roles in tumor progression and metastasis. Identifying the factors regulating TICs may open new avenues in cancer therapy. Here, we show that TIC-enriched prostate cancer cell clones use more glucose and secrete more lactate than TIC-low clones. We determined that elevated levels of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) are critical for the metabolic switch and the maintenance of TICs in prostate cancer. Information from prostate cancer patient databases revealed that higher PCK2 levels correlated with more aggressive tumors and lower survival rates. PCK2 knockdown resulted in low TIC numbers, increased cytosolic acetyl-CoA and cellular protein …
The Pulse Vision & Change Rubrics, Version 1.0: A Valid And Equitable Tool To Measure Transformation Of Life Sciences Departments At All Institution Types, Loretta Brancaccio-Taras, Pamela Pape-Lindstrom, Marcy Peteroy-Kelly, Karen Aguirre, Judy Awong-Taylor, Teri Balser, Michael J. Cahill, Regina F. Frey, Thomas Jack, Michael Kelrick, Kate Marley, Kathryn G. Miller, Marcy Osgood, Sandra Romano, J. Akif Uzman, Jiuqing Zhao
The Pulse Vision & Change Rubrics, Version 1.0: A Valid And Equitable Tool To Measure Transformation Of Life Sciences Departments At All Institution Types, Loretta Brancaccio-Taras, Pamela Pape-Lindstrom, Marcy Peteroy-Kelly, Karen Aguirre, Judy Awong-Taylor, Teri Balser, Michael J. Cahill, Regina F. Frey, Thomas Jack, Michael Kelrick, Kate Marley, Kathryn G. Miller, Marcy Osgood, Sandra Romano, J. Akif Uzman, Jiuqing Zhao
Publications and Research
The PULSE Vision & Change Rubrics, version 1.0, assess life sciences departments’ progress toward implementation of the principles of the Vision and Change report. This paper reports on the development of the rubrics, their validation, and their reliability in measuring departmental change aligned with the Vision and Change recommendations. The rubrics assess 66 different criteria across five areas: Curriculum Alignment, Assessment, Faculty Practice/Faculty Support, Infrastructure, and Climate for Change. The results from this work demonstrate the rubrics can be used to evaluate departmental transformation equitably across institution types and represent baseline data about the adoption of the Vision and Change …
The Molecular Mechanism Of N-Acetylglucosamine Side-Chain Attachment To The Lancefield Group A Carbohydrate In Streptococcus Pyogenes, Jeffrey Rush, Rebecca J. Edgar, Pan Deng, Jing Chen, Haining Zhu, Nina M. Van Sorge, Andrew J. Morris, Konstantin V. Korotkov, Natalia Korotkova
The Molecular Mechanism Of N-Acetylglucosamine Side-Chain Attachment To The Lancefield Group A Carbohydrate In Streptococcus Pyogenes, Jeffrey Rush, Rebecca J. Edgar, Pan Deng, Jing Chen, Haining Zhu, Nina M. Van Sorge, Andrew J. Morris, Konstantin V. Korotkov, Natalia Korotkova
Molecular and Cellular Biochemistry Faculty Publications
In many Lactobacillales species (i.e. lactic acid bacteria), peptidoglycan is decorated by polyrhamnose polysaccharides that are critical for cell envelope integrity and cell shape and also represent key antigenic determinants. Despite the biological importance of these polysaccharides, their biosynthetic pathways have received limited attention. The important human pathogen, Streptococcus pyogenes, synthesizes a key antigenic surface polymer, the Lancefield group A carbohydrate (GAC). GAC is covalently attached to peptidoglycan and consists of a polyrhamnose polymer, with N-acetylglucosamine (GlcNAc) side chains, which is an essential virulence determinant. The molecular details of the mechanism of polyrhamnose modification with GlcNAc are …
Heads And Tails, Julie Simons
Heads And Tails, Julie Simons
Annual Symposium on Biomathematics and Ecology Education and Research
No abstract provided.
Modeling Cdc42 Oscillation In Fission Yeast, Bin Xu
Modeling Cdc42 Oscillation In Fission Yeast, Bin Xu
Annual Symposium on Biomathematics and Ecology Education and Research
No abstract provided.
Modeling Microtubule-Based Transport In The Frog Egg Cell, Maria-Veronica Ciocanel
Modeling Microtubule-Based Transport In The Frog Egg Cell, Maria-Veronica Ciocanel
Annual Symposium on Biomathematics and Ecology Education and Research
No abstract provided.
Development Of Epithelial Tissues: How Are Cleavage Planes Chosen?, Ying Xin
Development Of Epithelial Tissues: How Are Cleavage Planes Chosen?, Ying Xin
Annual Symposium on Biomathematics and Ecology Education and Research
No abstract provided.
Mathematical Medicine: Modeling Disease And Treatment, Lisette Depillis
Mathematical Medicine: Modeling Disease And Treatment, Lisette Depillis
Annual Symposium on Biomathematics and Ecology Education and Research
No abstract provided.
Insights Into Land Plant Evolution Garnered From The Marchantia Polymorpha Genome, John L. Bowman, Takayuki Kohchi, Katsuyuki T. Yamato, Jerry Jenkins, Shengqiang Shu, Kimitsune Ishizaki, Shohei Yamaoka, Ryuichi Nishihama, Yasukazu Nakamura, Frédéric Berger, Catherine Adam, Shiori Sugamata Aki, Felix Althoff, Takashi Araki, Mario A. Arteaga-Vazquez, Sureshkumar Balasubrmanian, Kerrie Barry, Diane Bauer, Christian R. Boehm, Liam Briginshaw, Juan Caballero-Perez, Bruno Catarino, Feng Chen, Shota Chiyoda, Mansi Chovatia, Kevin M. Davies, Mihails Delmans, Taku Demura, Tom Dierschke, Liam Dolan, Tomokazu Kawashima
Insights Into Land Plant Evolution Garnered From The Marchantia Polymorpha Genome, John L. Bowman, Takayuki Kohchi, Katsuyuki T. Yamato, Jerry Jenkins, Shengqiang Shu, Kimitsune Ishizaki, Shohei Yamaoka, Ryuichi Nishihama, Yasukazu Nakamura, Frédéric Berger, Catherine Adam, Shiori Sugamata Aki, Felix Althoff, Takashi Araki, Mario A. Arteaga-Vazquez, Sureshkumar Balasubrmanian, Kerrie Barry, Diane Bauer, Christian R. Boehm, Liam Briginshaw, Juan Caballero-Perez, Bruno Catarino, Feng Chen, Shota Chiyoda, Mansi Chovatia, Kevin M. Davies, Mihails Delmans, Taku Demura, Tom Dierschke, Liam Dolan, Tomokazu Kawashima
Plant and Soil Sciences Faculty Publications
The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), …
Temporal Transcriptomic Profiling Of The Ant-Feeding Assassin Bug Acanthaspis Cincticrus Reveals A Biased Expression Of Genes Associated With Predation In Nymphs, Fei Kou, Hu Li, Shujuan Li, Huaizhu Xun, Yinqiao Zhang, Ziqiang Sun, Xuguo Zhou, Wanzhi Cai
Temporal Transcriptomic Profiling Of The Ant-Feeding Assassin Bug Acanthaspis Cincticrus Reveals A Biased Expression Of Genes Associated With Predation In Nymphs, Fei Kou, Hu Li, Shujuan Li, Huaizhu Xun, Yinqiao Zhang, Ziqiang Sun, Xuguo Zhou, Wanzhi Cai
Entomology Faculty Publications
Acanthaspis cincticrus (Stål) is an assassin bug with a specialized camouflaging behavior to ambush ants in the nymphal stages. In this study, we comprehensively sequenced all the life stages of A. cincticrus, including the eggs, five nymph instars, female and male adults using Illumina HiSeq technology. We obtained 176 million clean sequence reads. The assembled 84,055 unigenes were annotated and classified functionally based on protein databases. Among the unigenes, 29.03% were annotated by one or more databases, suggesting their well-conserved functions. Comparison of the gene expression profiles in the egg, nymph and adult stages revealed certain bias. Functional enrichment …
Development Of Novel Alkaloid Derivatives For The Treatment Of Chronic Myeloid Leukemia, Lindsay Michelle Renn
Development Of Novel Alkaloid Derivatives For The Treatment Of Chronic Myeloid Leukemia, Lindsay Michelle Renn
Theses and Dissertations
The majority of chronic myeloid leukemia (CML) patients can be treated with and respond to imatinib mesylate (Gleevec). Imatinib is known to inhibit BCR-ABLl kinase activity, and is effective for the treatment of the majority of CML patients. Multiple mutations have been found in patients resistant to imatinib treatment, including many located in the BCR-ABLl tyrosine kinase domain (e.g. E255K and T315I). Matrine is a bioactive alkaloid from Sophora flavescens and has been shown to inhibit several types of cancers and is used in Chinese medicine. The goal of this study is to develop new matrine derivatives that inhibit growth …
Microstructure Of Attachment Mechanisms Of Newly Hatched Larvae Of Four Cyprinid Species With Comments On Terminology, George E. Maurakis, Eugene G. Maurakis
Microstructure Of Attachment Mechanisms Of Newly Hatched Larvae Of Four Cyprinid Species With Comments On Terminology, George E. Maurakis, Eugene G. Maurakis
Virginia Journal of Science
An adhesive organ is a prominent, protruding mucus secreting gland that is used by newly hatched tadpoles and larvae of some fishes to attach to aquatic vegetation. The objective of this research is to test the hypothesis that newly hatched cyprinid larvae of Hybognathus hankinsoni, Notemigonus crysoleucas, Cyprinus carpio and Gila atraria contain cephalic adhesive organs. Newly hatched larvae of Semotilus atromaculatus, which do not attach to submerged aquatic vegetation, were used as the control. SEM examination of newly hatched larvae indicate there were no adhesive organs on the control species (S. atromaculatus) or test species …
The Trophic Life Cycle Stage Of The Opportunistic Fungal Pathogen Pneumocystis Murina Hinders The Ability Of Dendritic Cells To Stimulate Cd4+ T Cell Responses, Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy
The Trophic Life Cycle Stage Of The Opportunistic Fungal Pathogen Pneumocystis Murina Hinders The Ability Of Dendritic Cells To Stimulate Cd4+ T Cell Responses, Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy
Microbiology, Immunology, and Molecular Genetics Faculty Publications
The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding …
Targeting Mitochondrial Dysfunction In Cns Injury Using Methylene Blue; Still A Magic Bullet?, Hemendra J. Vekaria, Lora Talley Watts, Ai-Ling Lin, Patrick G. Sullivan
Targeting Mitochondrial Dysfunction In Cns Injury Using Methylene Blue; Still A Magic Bullet?, Hemendra J. Vekaria, Lora Talley Watts, Ai-Ling Lin, Patrick G. Sullivan
Spinal Cord and Brain Injury Research Center Faculty Publications
Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. Mitochondria are complex organelles found within the cell, which act as powerhouses within all cells by supplying ATP. These organelles are also necessary for calcium cycling, redox signaling and play a major role in the initiation of cell death pathways. When mitochondria become dysfunctional, there is a tendency for the cell to loose …
Lim Protein Ajuba Directly Interacts With Replication Protein A To Prevent Atr Dna Damage Response, Sandy Wan Shan Fowler
Lim Protein Ajuba Directly Interacts With Replication Protein A To Prevent Atr Dna Damage Response, Sandy Wan Shan Fowler
Dissertations, Theses, and Capstone Projects
Integrity of the human genome is essential for viability and proliferation of human cells. Intrinsic (endogenous replication stress) or extrinsic (UV, chemotherapy drugs) agents threaten the stability of the genome by generation of single stranded (ss) DNA or double stranded (ds) DNA breaks. The DNA damage response (DDR) pathways are conserved in evolution and constitute systems that perform the surveillance, signaling, and repair of the damage in the nucleus. Unchecked and accumulation of DNA damage can lead to deleterious effects such as replication fork collapse, chromosome fusion and breakage. The dysregulations of DNA damage response pathways are hallmarks of tumorigenesis. …
The Role Of Pitx Proteins In Early Xenopus Development, Ye Jin
The Role Of Pitx Proteins In Early Xenopus Development, Ye Jin
Dissertations, Theses, and Capstone Projects
Embryos of the African clawed frog Xenopus laevis are widely used for the study of early vertebrate development. The cement gland, which secrets mucus to help tadpoles attach to solid supports and live in relative safety, has long been used as a model to study the interplay between cell signaling pathways and transcription factors. It has been proposed that an intermediate level of Bone Morphogenetic Protein (BMP) signaling is essential for cement gland formation. In addition, several transcription factors have been linked to cement gland development. Among them, the homeodomain proteins Pitx1 and the closely related Pitx2c can generate ectopic …
Pleiotropy Of Genetic Variants On Obesity And Smoking Phenotypes: Results From The Oncoarray Project Of The International Lung Cancer Consortium, Tao Wang, Jee-Young Moon, Yiqun Wu, Christopher I. Amos, Rayjean J. Hung, Adonina Tardon, Angeline Andrew, Chu Chen, David C. Christiani, Demetrios Albanes, Erik H. F. M. Van Der Heijden, Eric Duell, Gadi Rennert, Gary Goodman, Geoffrey Liu, James D. Mckay, Jian-Min Yuan, John K. Field, Jonas Manjer, Kjell Grankvist, Lambertus A. Kiemeney, Loic Le Marchand, M. Dawn Teare, Matthew B. Schabath, Mattias Johansson, Melinda C. Aldrich, Michael Davies, Mikael Johansson, Ming-Sound Tsao, Neil Caporaso, Susanne Arnold
Pleiotropy Of Genetic Variants On Obesity And Smoking Phenotypes: Results From The Oncoarray Project Of The International Lung Cancer Consortium, Tao Wang, Jee-Young Moon, Yiqun Wu, Christopher I. Amos, Rayjean J. Hung, Adonina Tardon, Angeline Andrew, Chu Chen, David C. Christiani, Demetrios Albanes, Erik H. F. M. Van Der Heijden, Eric Duell, Gadi Rennert, Gary Goodman, Geoffrey Liu, James D. Mckay, Jian-Min Yuan, John K. Field, Jonas Manjer, Kjell Grankvist, Lambertus A. Kiemeney, Loic Le Marchand, M. Dawn Teare, Matthew B. Schabath, Mattias Johansson, Melinda C. Aldrich, Michael Davies, Mikael Johansson, Ming-Sound Tsao, Neil Caporaso, Susanne Arnold
Internal Medicine Faculty Publications
Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively correlated with pack-years of smoking (p < 0.001) in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p < 0.05), respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF) …
Cellular Mechanisms Of Cortisol-Induced Changes In Mauthner-Cell Excitability In The Startle Circuit Of Goldfish, Daniel R. Bronson, Thomas Preuss
Cellular Mechanisms Of Cortisol-Induced Changes In Mauthner-Cell Excitability In The Startle Circuit Of Goldfish, Daniel R. Bronson, Thomas Preuss
Publications and Research
Predator pressure and olfactory cues (alarm substance) have been shown to modulate Mauthner cell (M-cell) initiated startle escape responses (C-starts) in teleost fish. The regulation of such adaptive responses to potential threats is thought to involve the release of steroid hormones such as cortisol. However, the mechanism by which cortisol may regulate M-cell excitability is not known. Here, we used intrasomatic, in vivo recordings to elucidate the acute effects of cortisol on M-cell membrane properties and sound evoked post-synaptic potentials (PSPs). Cortisol tonically decreased threshold current in the M-cell within 10 min before trending towards baseline excitability over an hour …
There’S More Than One Way To Climb A Tree: Limb Length And Microhabitat Use In Lizards With Toe Pads, Travis J. Hagey, Scott Hart, Matthew Vickers, Luke J. Harmon, Lin Schwarzkopf
There’S More Than One Way To Climb A Tree: Limb Length And Microhabitat Use In Lizards With Toe Pads, Travis J. Hagey, Scott Hart, Matthew Vickers, Luke J. Harmon, Lin Schwarzkopf
Biology
Ecomorphology links microhabitat and morphology. By comparing ecomorphological associations across clades, we can investigate the extent to which evolution can produce similar solutions in response to similar challenges. While Anolis lizards represent a well-studied example of repeated convergent evolution, very few studies have investigated the ecomorphology of geckos. Similar to anoles, gekkonid lizards have independently evolved adhesive toe pads and many species are scansorial. We quantified gecko and anole limb length and microhabitat use, finding that geckos tend to have shorter limbs than anoles. Combining these measurements with microhabitat observations of geckos in Queensland, Australia, we observed geckos using similar …
Cardiac-Specific Inactivation Of Lpp3 In Mice Leads To Myocardial Dysfunction And Heart Failure, Mini Chandra, Diana Escalante-Alcalde, Shenuarin Bhuiyan, Anthony Wayne Orr, Christopher Kevil, Andrew J. Morris, Hyung Nam, Paari Dominic, Kevin J. Mccarthy, Sumitra Miriyala, Manikandan Panchatcharam
Cardiac-Specific Inactivation Of Lpp3 In Mice Leads To Myocardial Dysfunction And Heart Failure, Mini Chandra, Diana Escalante-Alcalde, Shenuarin Bhuiyan, Anthony Wayne Orr, Christopher Kevil, Andrew J. Morris, Hyung Nam, Paari Dominic, Kevin J. Mccarthy, Sumitra Miriyala, Manikandan Panchatcharam
Internal Medicine Faculty Publications
Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates. We observed that lack of Lpp3 enhanced cardiomyocyte …