Life Sciences Commons^™

Sodium Bicarbonate Cotransporter Nbce2 Gene Variants Increase Sodium And Bicarbonate Transport In Human Renal Proximal Tubule Cells., John J Gildea, Peng Xu, Brandon A Kemp, Julia M Carlson, Hanh T Tran, Dora Bigler Wang, Christophe J Langouët-Astrié, Helen E Mcgrath, Robert M Carey, Pedro A Jose, Robin A Felder

Medicine Faculty Publications

RATIONALE: Salt sensitivity of blood pressure affects >30% of the hypertensive and >15% of the normotensive population. Variants of the electrogenic sodium bicarbonate cotransporter NBCe2 gene, SLC4A5, are associated with increased blood pressure in several ethnic groups. SLC4A5 variants are also highly associated with salt sensitivity, independent of hypertension. However, little is known about how NBCe2 contributes to salt sensitivity, although NBCe2 regulates renal tubular sodium bicarbonate transport. We hypothesized that SLC4A5 rs10177833 and rs7571842 increase NBCe2 expression and human renal proximal tubule cell (hRPTC) sodium transport and may be a cause of salt sensitivity of blood pressure.

OBJECTIVE: To …

Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley

Genomics and Precision Medicine Faculty Publications

Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM. By disruption of phosphofurin acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 (Drp1), …

Leukocyte Telomere Length, T Cell Composition And Dna Methylation Age., Brian H Chen, Cara L Carty, Masayuki Kimura, Jeremy D Kark, Wei Chen, Shengxu Li, Tao Zhang, Charles Kooperberg, Daniel Levy, Themistocles Assimes, Devin Absher, Steve Horvath, Alexander P Reiner, Abraham Aviv

Clinical Research and Leadership Faculty Publications

Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age-the extrinsic epigenetic age acceleration (EEAA)-is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. LTL was measured by Southern blots and leukocyte DNA methylation was determined using Illumina Infinium HumanMethylation450 BeadChip in participants in the Women's Health Initiative (WHI; n=804), the Framingham Heart Study (FHS; n=909) and the Bogalusa Heart study (BHS; n=826). EEAA was computed using 71 DNA methylation sites, further weighted by proportions of naïve CD8+ T cells, memory CD8+ T cells, and …

Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Accumulating evidence implicates Zika virus (ZIKV) in pathogenesis of microcephaly in newborns and Guillain-Barré syndrome in adults. However, it remains unclear which viral proteins are responsible for these effects and what are the underlying mechanisms of their pathogenic activity. A recent paper by Drs. Zhao and Gallo, and their colleagues at University of Maryland in Baltimore used fission yeast for genome-wide analysis of ZIKV proteins. They demonstrated cytopathogenic activity for seven ZIKV proteins, anaC, C, prM, M, E, NS2B and NS4A. This activity was shown to be dependent on oxidative stress, and for NS4A they demonstrated involvement of the TOR …

An Amphipathic Trans-Acting Phosphorothioate Rna Element Delivers An Uncharged Phosphorodiamidate Morpholino Sequence In Mdx Mouse Myotube, H. Jain, J. Boehler, D. Verthelyi, Kanneboyina Nagaraju, S. Beaucage

Genomics and Precision Medicine Faculty Publications

An efficient method for the delivery of uncharged polyA-tailed phosphorodiamidate morpholino sequences (PMO) in mammalian cells consists of employing a synthetic 8-mer amphipathic trans-acting poly-2′-O-methyluridylic thiophosphate triester element (2′-OMeUtaPS) as a transfection reagent. Unlike the dTtaPS DNA-based element, this RNA element is potent at delivering polyA-tailed PMO sequences to HeLa pLuc 705 cells or to myotube muscle cells. However, much like dTtaPS, the 2′-OMeUtaPS-mediated internalization of PMO sequences occurs through an energy-dependent mechanism; macropinocytosis appears to be the predominant endocytic pathway used for cellular uptake. The transfected PMO sequences induce alternate splicing of either the pre-mRNA encoding luciferase in HeLa …

Lysosomal Storage Diseases, Carlos Ferreira, William Gahl

Pediatrics Faculty Publications

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency …

Sirt1 Regulates Glial Progenitor Proliferation And Regeneration In White Matter After Neonatal Brain Injury., Beata Jablonska, Marcin Gierdalski, Li-Jin Chew, Teresa Hawley, Mackenzie Catron, Arturo Lichauco, Juan Cabrera-Luque, Tracy Yuen, David Rowitch, Vittorio Gallo

Pediatrics Faculty Publications

Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture …

Leukocyte Telomere Length In Relation To 17 Biomarkers Of Cardiovascular Disease Risk: A Cross-Sectional Study Of Us Adults, David Rehkopf, Belinda L. Needham, Jue Lin, Elizabeth Blackburn, Ami R. Zota, Janet Wojcicki, Elissa Epel

Environmental and Occupational Health Faculty Publications

Background

Leukocyte telomere length (LTL) is a putative biological marker of immune system age, and there are demonstrated associations between LTL and cardiovascular disease. This may be due in part to the relationship of LTL with other biomarkers associated with cardiovascular disease risk. However, the strength of associations between LTL and adiposity, metabolic, proinflammatory, and cardiovascular biomarkers has not been systematically evaluated in a United States nationally representative population.

Methods and Findings

We examined associations between LTL and 17 cardiovascular biomarkers, including lipoproteins, blood sugar, circulatory pressure, proinflammatory markers, kidney function, and adiposity measures, in adults ages 20 to 84 …

Sulfatase 2 Facilitates Lymphangiogenesis In Breast Cancer By Regulating Vegf-D., Chenfang Zhu, Xiaoliang Qi, Xin Zhou, Xin Nie, Yan Gu

Surgery Faculty Publications

In our previous studies, sulfatase 2 (Sulf2) was found to upregulate vascular endothelial growth factor-D (VEGF-D) expression in breast cancer. As VEGF-D plays an important role in lymphangiogenesis, we hypothesized that Sulf2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. To evaluate the functions of Sulf2 on lymphangiogenesis in breast cancer, proliferation, apoptosis, cell cycle, cell mobility and tube-formation of lymphatic endothelial cells (LECs) were measured in vitro. Lymphangiogenesis in nude mouse ears and breast cancer xenografts were examined in vivo. Furthermore, the expression levels of related signaling pathway genes were screened and verified in LECs. We found that Sulf2 …

The Clinical, Biochemical And Genetic Features Associated With Rmnd1-Related Mitochondrial Disease., Yi Shiau Ng, Charlotte L Alston, Daria Diodato, Andrew A Morris, Nicole Ulrick, Stanislav Kmoch, +Several Additional Authors

Neurology Faculty Publications

BACKGROUND: Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects.

METHODS: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors.

RESULTS: We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, …

Fbxo30 Regulates Mammopoiesis By Targeting The Bipolar Mitotic Kinesin Eg5., Yan Liu, Yin Wang, Zhanwen Du, Xiaoli Yan, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Fbxo30 is an orphan member of the F-box protein family with no known substrate or function. Here we report that, while Fbxo30^−/− mice exhibit normal development, growth, lifespan, and fertility, the females fail to nurture their offspring as a result of defective mammopoiesis. Mass spectrometry analysis of Fbxo30-associated proteins revealed that Fbxo30 specifically interacts with the bipolar spindle kinesin EG5 (encoded byKif11). As a result, Fbxo30 targets Eg5 for ubiquitinylation and controls its oscillation during the cell cycle. Correlated with EG5 dysregulation, Fbxo30^−/− mammary epithelial cells exhibit multiple defects in centrosome homeostasis, mitotic spindle …

Hypertonicity: Pathophysiologic Concept And Experimental Studies, Christos Argyropoulos, Helbert Rondon-Berrios, Dominic S. Raj, Deepak Malhotra, Emmanuel I. Agaba, +5 Additional Authors

Medicine Faculty Publications

Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted …

The Glucose Metabolite Methylglyoxal Inhibits Expression Of The Glucose Transport Genes By Inactivating The Cell Surface Glucose Sensors Rgt2 And Snf3 In Yeast, Adhiraj Roy, Salman Hashmi, Zerui Li, Angela Dement, Kyu Hong Cho, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Methylglyoxal (MG) is a cytotoxic by-product of glycolysis. MG has inhibitory effect on the growth of cells ranging from microorganisms to higher eukaryotes, but its molecular targets are largely unknown. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of expression of genes encoding glucose transporters (HXTs). Here we provide evidence that these glucose sensors are primary targets of MG in yeast. MG inhibits the growth of glucose-fermenting yeast cells by inducing endocytosis and degradation of the glucose sensors. However, the glucose sensors with mutations …

K14+ Compound Niches Are Present On The Mouse Cornea Early After Birth And Expand After Debridement Wounds., Ahdeah Pajoohesh-Ganji, Sonali Pal-Ghosh, Gauri Tadvalkar, Mary Ann Stepp

Anatomy and Regenerative Biology Faculty Publications

Background: We previously identified compound niches (CNs) at the limbal:corneal border of the mouse cornea that contain corneal epithelial progenitor cells, express Keratin 8 (K8), and goblet cell mucin Muc5AC. During re-epithelialization after 2.5 mm epithelial debridement wounds, CNs migrate onto the cornea and expand in number mimicking conjunctivalization. When CNs form during development and whether they express corneal epithelial progenitor cell enriched K14 was not known.

Results: To provide insight into corneal epithelial homeostasis, we quantify changes in expression of simple (K8, K18, K19) and stratified squamous epithelial keratins (K5, K12, K14, and K15) during postnatal development and in …

Low-Ω3 Fatty Acid And Soy Protein Attenuate Alcohol-Induced Fatty Liver And Injury By Regulating The Opposing Lipid Oxidation And Lipogenic Signaling Pathways., Karina Reyes-Gordillo, Ruchi Shah, Ravi Varatharajalu, Mamatha Garige, Leslie C. Leckey, M. Raj Lakshman

Biochemistry and Molecular Medicine Faculty Publications

Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β) affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA) that primarily regulates PGC1α and soy protein (SP) that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with …

Endothelin-B Receptor Activation In Astrocytes Regulates The Rate Of Oligodendrocyte Regeneration During Remyelination., Timothy R. Hammond, Brian Mcellin, Paul D Morton, Matthew Raymond, Jeff Dupree, Vittorio Gallo

Medicine Faculty Publications

Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multiple sclerosis (MS) lesions and limits repair by delaying oligodendrocyte progenitor cell (OPC) maturation. However, as ET receptors are widely expressed on neural cells, the cell- and receptor-specific mechanisms of OPC inhibition by ET-1 action remain undefined. Using pharmacological approaches and cell-specific endothelin receptor (EDNR) ablation, …

Age-Associated Methylation Suppresses Spry1, Leading To A Failure Of Re-Quiescence And Loss Of The Reserve Stem Cell Pool In Elderly Muscle., Anne Bigot, William J Duddy, Zamalou G Ouandaogo, Elisa Negroni, Virginie Mariot, Svetlana Ghimbovschi, Brennan Harmon, Aurore Wielgosik, Camille Loiseau, Joseph Devaney, Julie Dumonceaux, Gillian Butler-Browne, Vincent Mouly, Stéphanie Duguez

Genomics and Precision Medicine Faculty Publications

The molecular mechanisms by which aging affects stem cell number and function are poorly understood. Murine data have implicated cellular senescence in the loss of muscle stem cells with aging. Here, using human cells and by carrying out experiments within a strictly pre-senescent division count, we demonstrate an impaired capacity for stem cell self-renewal in elderly muscle. We link aging to an increased methylation of the SPRY1 gene, a known regulator of muscle stem cell quiescence. Replenishment of the reserve cell pool was modulated experimentally by demethylation or siRNA knockdown of SPRY1. We propose that suppression of SPRY1 by age-associated …

The Role Of The Pleckstrin Homology Domain-Containing Protein Ckip-1 In Activation Of P21-Activated Kinase 1 (Pak1), Yong-Bae Kim, Yong Jae Shin, Adhiraj Roy, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Upon growth factor stimulation, PAK1 is recruited to the plasma membrane and activated by a mechanism that requires its phosphorylation at S223 by the protein kinase CK2. However, the upstream signaling molecules that regulate this phosphorylation event are not clearly defined. Here, we demonstrate a major role of the CK2α-interacting protein CKIP-1 in activation of PAK1. CK2α, CKIP-1 and PAK1 are translocated to membrane ruffles in response to the epidermal growth factor (EGF), where CKIP-1 mediates the interaction between CK2α, and PAK1 in a PI3K-dependent manner. Consistently, we observe that PAK1 mediates phosphorylation and modulation of the activity of p41-Arc, …

The Use Of Stem Cells In Burn Wound Healing: A Review, Fadi Ghieh, Rosalyn A. Jurjus, Amir Ibrahim, Alice Gerges Geagea, Hisham Daouk, Bassel El Baba, Sana Cham, Michel Matar, Wadih Zein, Abdo Jurjus

Anatomy and Regenerative Biology Faculty Publications

Burn wound healing involves a series of complex processes which are subject to intensive investigations to improve the outcomes, in particular, the healing time and the quality of the scar. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. Stem cells have been recently applied in the field to promote superior healing of the wounds. Not only have stem cells been shown to promote better and faster healing of the burn wounds, but also they have decreased the inflammation levels with less scar progression and fibrosis. This review aims to highlight the beneficial therapeutic …

Once Upon A Microscopic Slide: The Story Of Histology, Inaya Hussein, Mohamad Raad, Rawan Safa, Rosalyn A. Jurjus, Abdo Jurjus

Anatomy and Regenerative Biology Faculty Publications

For centuries, histology has maintained its remarkable place in the medical curriculum. However, its teaching has been influenced by the new technological advancement that has reshaped medicine teaching into a more modern student-friendly form. Since its inception in the 18th century, the discipline of histology has progressed hand in hand with the advancements in microscopy and microscopic technologies, including immunohistochemistry. In the traditional curriculum of USA medical schools, especially after the first Flexner’s report of 1910, histology was considered as very essential topic for a physician studying the “Art and Science” of medicine. In this era, the teaching relied more …

Subcellular Metabolite And Lipid Analysis Of Xenopus Laevis Eggs By Laesi Mass Spectrometry, Bindesh Shrestha, Prabhakar Sripadi, Brent R. Reschke, Holly D. Henderson, Matthew J. Powell, Sally Ann Moody, Akos Vertes

Anatomy and Regenerative Biology Faculty Publications

Xenopus laevis eggs are used as a biological model system for studying fertilization and early embryonic development in vertebrates. Most methods used for their molecular analysis require elaborate sample preparation including separate protocols for the water soluble and lipid components. In this study, laser ablation electrospray ionization (LAESI), an ambient ionization technique, was used for direct mass spectrometric analysis of X. laevis eggs and early stage embryos up to five cleavage cycles. Single unfertilized and fertilized eggs, their animal and vegetal poles, and embryos through the 32-cell stage were analyzed. Fifty two small metabolite ions, including glutathione, GABA and amino …

Asynchronous Remodeling Is A Driver Of Failed Regeneration In Duchenne Muscular Dystrophy, Sherry Dadgar, Zuyi Wang, Helen Johnston, Akanchha Kesari, Kanneboyina Nagaraju, Yi-Wen Chen, D. Ashley Hill, Terence A. Partridge, Robert J. Freishtat, Javad Nazarian, Jianhua Xuan, Yue Wang, Eric P. Hoffman

Genomics and Precision Medicine Faculty Publications

We sought to determine the mechanisms underlying failure of muscle regeneration that is observed in dystrophic muscle through hypothesis generation using muscle profiling data (human dystrophy and murine regeneration). We found that transforming growth factor β-centered networks strongly associated with pathological fibrosis and failed regeneration were also induced during normal regeneration but at distinct time points. We hypothesized that asynchronously regenerating microenvironments are an underlying driver of fibrosis and failed regeneration. We validated this hypothesis using an experimental model of focal asynchronous bouts of muscle regeneration in wild-type (WT) mice. A chronic inflammatory state and reduced mitochondrial oxidative capacity are …

Neural Transcription Factors: From Embryos To Neural Stem Cells, Hyun-Kyung Lee, Hyun-Shik Lee, Sally Ann Moody

Anatomy and Regenerative Biology Faculty Publications

The early steps of neural development in the vertebrate embryo are regulated by sets of transcription factors that control the induction of proliferative, pluripotent neural precursors, the expansion of neural plate stem cells, and their transition to differentiating neural progenitors. These early events are critical for producing a pool of multipotent cells capable of giving rise to the multitude of neurons and glia that form the central nervous system. In this review we summarize findings from gain- and loss-of-function studies in embryos that detail the gene regulatory network responsible for these early events. We discuss whether this information is likely …

A Central Role For Vimentin In Regulating Repair Function During Healing Of The Lens Epithelium, A. S. Menko, B. M. Bleaken, A. A. Libowitz, L. Zhang, Mary Ann Stepp, J. L. Walker

Anatomy and Regenerative Biology Faculty Publications

Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by an innate mesenchymal subpopulation of vimentin-rich repair cells. We report that vimentin is essential to the function of repair cells as the directors of the wound-healing process. Vimentin and not actin filaments are the predominant cytoskeletal elements in the lamellipodial extensions of the repair cells at the wound edge. These vimentin filaments link to paxillin-containing focal adhesions at the lamellipodial tips. Microtubules are involved …

Protein Kinase Ck2 Phosphorylates And Activates P21-Activated Kinase 1, Yong Jae Shin, Yong-Bae Kim, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Activation of the p21-activated kinase 1 (PAK1) is achieved through a conformational change that converts an inactive PAK1 dimer to an active monomer. In this paper, we show that this change is necessary but not sufficient to activate PAK1 and that it is, rather, required for CK2-dependent PAK1S223 phosphorylation that converts a monomeric PAK1 into a catalytically active form. This phosphorylation appears to be essential for autophosphorylation at specific residues and overall activity of PAK1. A phosphomimetic mutation (S223E) bypasses the requirement for GTPases in PAK1 activation, whereas the constitutive activity of the PAK1 mutant (PAK1H83,86L), postulated to mimic GTPase-induced …

The Dn2 Myeloid-T (Dn2mt) Progenitor Is A Target Cell For Leukemic Transformation By The Tlx1 Oncogene, Lynnsey A. Zweier-Renn, Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Introduction: Inappropriate activation of the TLX1 (T-cell leukemia homeobox 1) gene by chromosomal translocation is a recurrent event in human T-cell Acute Lymphoblastic Leukemia (T-ALL). Ectopic expression of TLX1 in murine bone marrow progenitor cells using a conventional retroviral vector efficiently yields immortalized cell lines and induces T-ALL-like tumors in mice after long latency.

Methods: To eliminate a potential contribution of retroviral insertional mutagenesis to TLX1 immortalizing and transforming function, we incorporated the TLX1 gene into an insulated self-inactivating retroviral vector.

Results: Retrovirally transduced TLX1-expressing murine bone marrow progenitor cells had a growth/survival advantage and readily gave rise to immortalized …

Alloreactivity-Based Medical Conditions, Stanislav Vukmanovic, Margaret G. Petroff, Anne M. Stevens, Daniel Rukavina

Pediatrics Faculty Publications

No abstract provided.

Delayed Expression Of Cell Cycle Proteins Contributes To Astroglial Scar Formation And Chronic Inflammation After Rat Spinal Cord Contusion, Junfang Wu, Ahdeah Pajoohesh-Ganji, Bogdan A. Stoica, Michael Dinizo, Kelsey Guanciale, Alan I. Faden

Anatomy and Regenerative Biology Faculty Publications

Background

Traumatic spinal cord injury (SCI) induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs) inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model.

Methods

Adult male rats were …

Basic Concepts In Understanding Recovery Of Function In Vestibular Reflex Networks During Vestibular Compensation, Kenna D. Peusner, Mei Shao, Rebecca Reddaway, June C. Hirsch

Anatomy and Regenerative Biology Faculty Publications

Unilateral peripheral vestibular lesions produce a syndrome of oculomotor and postural deficits with the symptoms at rest, the static symptoms, partially or completely normalizing shortly after the lesion due to a process known as vestibular compensation. The symptoms are thought to result from changes in the activity of vestibular sensorimotor reflexes. Since the vestibular nuclei must be intact for recovery to occur, many investigations have focused on studying these neurons after lesions. At present, the neuronal plasticity underlying early recovery from the static symptoms is not fully understood. Here we propose that knowledge of the reflex identity and input–output connections …

Transgenic C. Elegans Dauer Larvae Expressing Hookworm Phospho Null Daf-16/Foxo Exit Dauer, Verena Gelmedin, Thomas Brodigan, Xin Gao, Michael Krause, Zhu Wang, John M. Hawdon

Research Center for Neglected Diseases of Poverty

Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3) in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from …