Scholars@Duke
Wei Yang

Wei Yang

Professor in Anesthesiology
Anesthesiology
wei.yang@duke.edu
Box 3094 Med Ctr, Durham, NC 27710
132 Sands Bldg, Durham, NC 27710

Selected Publications

Vagal stimulation ameliorates murine colitis by regulating SUMOylation.

Journal Article Sci Transl Med · November 20, 2024 Inflammatory bowel diseases (IBDs) are chronic debilitating conditions without cure, the etiologies of which are unknown, that shorten the lifespans of 7 million patients worldwide by nearly 10%. Here, we found that decreased autonomic parasympathetic tone ... Full text Link to item Cite

Microglial heterogeneity in the ischemic stroke mouse brain of both sexes.

Journal Article Genome Med · August 2, 2024 BACKGROUND: Ischemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving stroke outcomes, yet none have succeeded in the clinical setting. This lack of success is largely due ... Full text Link to item Cite

Isolating Immune Cells from Mouse Brain and Skull.

Journal Article J Vis Exp · July 26, 2024 Mounting evidence indicates that the immune response triggered by brain disorders (e.g., brain ischemia and autoimmune encephalomyelitis) occurs not only in the brain, but also in the skull. A key step toward analyzing changes in immune cell populations in ... Full text Link to item Cite

Therapeutic Potential of Targeting the PERK Signaling Pathway in Ischemic Stroke.

Journal Article Pharmaceuticals (Basel) · March 8, 2024 Many pathologic states can lead to the accumulation of unfolded/misfolded proteins in cells. This causes endoplasmic reticulum (ER) stress and triggers the unfolded protein response (UPR), which encompasses three main adaptive branches. One of these UPR br ... Full text Link to item Cite

Epinephrine-induced Effects on Cerebral Microcirculation and Oxygenation Dynamics Using Multimodal Monitoring and Functional Photoacoustic Microscopy.

Journal Article Anesthesiology · August 1, 2023 BACKGROUND: The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction ... Full text Link to item Cite

Non-invasive Deep-Brain Imaging with 3D Integrated Photoacoustic Tomography and Ultrasound Localization Microscopy (3D-PAULM).

Journal Article ArXiv · July 27, 2023 Photoacoustic computed tomography (PACT) is a proven technology for imaging hemodynamics in deep brain of small animal models. PACT is inherently compatible with ultrasound (US) imaging, providing complementary contrast mechanisms. While PACT can quantify ... Link to item Cite

Integrated Photoacoustic, Ultrasound, and Angiographic Tomography (PAUSAT) for NonInvasive Whole-Brain Imaging of Ischemic Stroke.

Journal Article J Vis Exp · June 2, 2023 Presented here is an experimental ischemic stroke study using our newly developed noninvasive imaging system that integrates three acoustic-based imaging technologies: photoacoustic, ultrasound, and angiographic tomography (PAUSAT). Combining these three m ... Full text Link to item Cite

A Modified Transcranial Middle Cerebral Artery Occlusion Model to Study Stroke Outcomes in Aged Mice.

Journal Article J Vis Exp · May 5, 2023 In experimental stroke research, middle cerebral artery occlusion (MCAO) with an intraluminal filament is widely used to model ischemic stroke in mice. The filament MCAO model typically exhibits a massive cerebral infarction in C57Bl/6 mice that sometimes ... Full text Link to item Cite

Mouse Cardiac Arrest Model for Brain Imaging and Brain Physiology Monitoring During Ischemia and Resuscitation.

Journal Article J Vis Exp · April 14, 2023 Most cardiac arrest (CA) survivors experience varying degrees of neurologic deficits. To understand the mechanisms that underpin CA-induced brain injury and, subsequently, develop effective treatments, experimental CA research is essential. To this end, a ... Full text Link to item Cite

Sustained overexpression of spliced X-box-binding protein-1 in neurons leads to spontaneous seizures and sudden death in mice.

Journal Article Commun Biol · March 9, 2023 The underlying etiologies of seizures are highly heterogeneous and remain incompletely understood. While studying the unfolded protein response (UPR) pathways in the brain, we unexpectedly discovered that transgenic mice (XBP1s-TG) expressing spliced X-box ... Full text Link to item Cite

Three-dimensional non-invasive brain imaging of ischemic stroke by integrated photoacoustic, ultrasound and angiographic tomography (PAUSAT).

Journal Article Photoacoustics · February 2023 We present an ischemic stroke study using our newly-developed PAUSAT system that integrates photoacoustic computed tomography (PACT), high-frequency ultrasound imaging, and acoustic angiographic tomography. PAUSAT is capable of three-dimensional (3D) imagi ... Full text Link to item Cite

Splenic SUMO1 controls systemic inflammation in experimental sepsis.

Journal Article Front Immunol · 2023 INTRODUCTION: The recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials to potentiate immunotherapy in metastatic tumors and hematologic malignanc ... Full text Link to item Cite

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma.

Journal Article Front Cell Dev Biol · 2023 Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, effi ... Full text Link to item Cite

High-speed wide-field photoacoustic microscopy using a cylindrically focused transparent high-frequency ultrasound transducer.

Journal Article Photoacoustics · December 2022 Combining focused optical excitation and high-frequency ultrasound detection, optical-resolution photoacoustic microscopy (OR-PAM) can provide micrometer-level spatial resolution with millimeter-level penetration depth and has been employed in a variety of ... Full text Link to item Cite

Targeting O-GlcNAcylation in ischemic stroke.

Journal Article Neural regeneration research · November 2022 Full text Cite

Stroke Proteomics: From Discovery to Diagnostic and Therapeutic Applications.

Journal Article Circ Res · April 15, 2022 Stroke remains a leading cause of death and disability, with limited therapeutic options and suboptimal tools for diagnosis and prognosis. High throughput technologies such as proteomics generate large volumes of experimental data at once, thus providing a ... Full text Link to item Cite

Cervical Vagus Nerve Stimulation Improves Neurologic Outcome After Cardiac Arrest in Mice by Attenuating Oxidative Stress and Excessive Autophagy.

Journal Article Neuromodulation · April 2022 BACKGROUND: Cerebral ischemia and reperfusion (I/R) induces oxidative stress and activates autophagy, leading to brain injury and neurologic deficits. Cervical vagus nerve stimulation (VNS) increases cerebral blood flow (CBF). In this study, we investigate ... Full text Open Access Link to item Cite

Single-cell transcriptomic analysis of the immune cell landscape in the aged mouse brain after ischemic stroke.

Journal Article Journal of neuroinflammation · April 2022 BackgroundIschemic stroke is a medical emergency that primarily affects the elderly. A complex immune response in the post-stroke brain constitutes a key component of stroke pathophysiology. This study aimed to determine how stroke affects immune ... Full text Open Access Cite

Beneficial effects of neuronal ATF6 activation in permanent ischemic stroke.

Journal Article Front Cell Neurosci · 2022 Objective: Brain ischemia leads to the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) lumen and consequently, ER stress. To help cells restore ER function, a series of adaptive stress response pathways, collectively termed th ... Full text Link to item Cite

Sound out the impaired perfusion: Photoacoustic imaging in preclinical ischemic stroke.

Journal Article Frontiers in neuroscience · January 2022 Acoustically detecting the optical absorption contrast, photoacoustic imaging (PAI) is a highly versatile imaging modality that can provide anatomical, functional, molecular, and metabolic information of biological tissues. PAI is highly scalable and can p ... Full text Cite

High-speed functional photoacoustic microscopy using a water-immersible two-axis torsion-bending scanner.

Journal Article Photoacoustics · December 2021 Optical-resolution photoacoustic microscopy (OR-PAM) can provide functional, anatomical, and molecular images at micrometer level resolution with an imaging depth of less than 1 mm in tissue. However, the imaging speed of traditional OR-PAM is often low du ... Full text Link to item Cite

An update on the unfolded protein response in brain ischemia: Experimental evidence and therapeutic opportunities.

Journal Article Neurochem Int · December 2021 After ischemic stroke or cardiac arrest, brain ischemia occurs. Currently, no pharmacologic intervention that targets cellular processes has proven effective in improving neurologic outcome in patients after brain ischemia. Recent experimental research has ... Full text Link to item Cite

Activation of the XBP1s/O-GlcNAcylation Pathway Improves Functional Outcome After Cardiac Arrest and Resuscitation in Young and Aged Mice.

Journal Article Shock · November 1, 2021 After cardiac arrest (CA) and resuscitation, the unfolded protein response (UPR) is activated in various organs including the brain. However, the role of the UPR in CA outcome remains largely unknown. One UPR branch involves spliced X-box-binding protein-1 ... Full text Open Access Link to item Cite

SUMO1 Deficiency Exacerbates Neurological and Cardiac Dysfunction after Intracerebral Hemorrhage in Aged Mice.

Journal Article Transl Stroke Res · August 2021 Small ubiquitin-like modifier 1 (SUMO1) reduces cardiac hypertrophy and induces neuroprotective effects. Previous studies have found that intracerebral hemorrhage (ICH) provokes cardiac deficit in the absence of primary cardiac diseases in mice. In this st ... Full text Link to item Cite

Photoacoustic imaging of in vivo hemodynamic responses to sodium nitroprusside.

Journal Article J Biophotonics · July 2021 The in vivo hemodynamic impact of sodium nitroprusside (SNP), a widely used antihypertensive agent, has not been well studied. Here, we applied functional optical-resolution photoacoustic microscopy (OR-PAM) to study the hemodynamic responses to SNP in mic ... Full text Open Access Link to item Cite

Activation of the ATF6 (Activating Transcription Factor 6) Signaling Pathway in Neurons Improves Outcome After Cardiac Arrest in Mice.

Journal Article J Am Heart Assoc · June 15, 2021 Background Ischemia/reperfusion injury impairs proteostasis, and triggers adaptive cellular responses, such as the unfolded protein response (UPR), which functions to restore endoplasmic reticulum homeostasis. After cardiac arrest (CA) and resuscitation, t ... Full text Open Access Link to item Cite

Development and Evaluation of a Novel Mouse Model of Asphyxial Cardiac Arrest Revealed Severely Impaired Lymphopoiesis After Resuscitation.

Journal Article J Am Heart Assoc · June 2021 Background Animal disease models represent the cornerstone in basic cardiac arrest (CA) research. However, current experimental models of CA and resuscitation in mice are limited. In this study, we aimed to develop a mouse model of asphyxial CA followed by ... Full text Open Access Link to item Cite

Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression.

Journal Article J Cereb Blood Flow Metab · May 2021 In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two c ... Full text Open Access Link to item Cite

Increasing O-GlcNAcylation is neuroprotective in young and aged brains after ischemic stroke.

Journal Article Exp Neurol · May 2021 Spliced X-box binding protein-1 (XBP1s) together with the hexosamine biosynthetic pathway (HBP) and O-GlcNAcylation forms the XBP1s/HBP/O-GlcNAc axis. Our previous studies have provided evidence that activation of this axis is neuroprotective after ischemi ... Full text Open Access Link to item Cite

A near-infrared genetically encoded calcium indicator for in vivo imaging.

Journal Article Nat Biotechnol · March 2021 While calcium imaging has become a mainstay of modern neuroscience, the spectral properties of current fluorescent calcium indicators limit deep-tissue imaging as well as simultaneous use with other probes. Using two monomeric near-infrared (NIR) fluoresce ... Full text Link to item Cite

SUMOylation Connects Cell Stress Responses and Inflammatory Control: Lessons From the Gut as a Model Organ.

Journal Article Front Immunol · 2021 Conjugation with the small ubiquitin-like modifier (SUMO) constitutes a key post-translational modification regulating the stability, activity, and subcellular localization of its target proteins. However, the vast numbers of identified SUMO substrates obs ... Full text Link to item Cite

Linking proteostasis, aging, and brain ischemia

Chapter · January 1, 2021 Cardiac arrest and ischemic stroke can lead to severe brain dysfunction, due to metabolic stress and loss of protein homeostasis (proteostasis). Further, both metabolic resilience and proteostasis deteriorate with aging, which renders cells inefficient in ... Full text Cite

Small ubiquitin-like modifier 2 (SUMO2) is critical for memory processes in mice.

Journal Article FASEB J · November 2020 Small ubiquitin-like modifier (SUMO1-3) conjugation (SUMOylation), a posttranslational modification, modulates almost all major cellular processes. Mounting evidence indicates that SUMOylation plays a crucial role in maintaining and regulating neural funct ... Full text Open Access Link to item Cite

MCC950, a selective NLPR3 inflammasome inhibitor, improves neurologic function and survival after cardiac arrest and resuscitation.

Journal Article J Neuroinflammation · August 31, 2020 BACKGROUND: Cardiac arrest (CA) is associated with high morbidity and mortality, even after spontaneous circulation is re-established. This dire situation is partly due to post-CA syndrome for which no specific and effective intervention is available. One ... Full text Open Access Link to item Cite

PERK (Protein Kinase RNA-Like ER Kinase) Branch of the Unfolded Protein Response Confers Neuroprotection in Ischemic Stroke by Suppressing Protein Synthesis.

Journal Article Stroke · May 2020 Background and Purpose- Ischemic stroke impairs endoplasmic reticulum (ER) function, causes ER stress, and activates the unfolded protein response. The unfolded protein response consists of 3 branches controlled by ER stress sensor proteins, which include ... Full text Open Access Link to item Cite

Chemogenetics-mediated acute inhibition of excitatory neuronal activity improves stroke outcome.

Journal Article Exp Neurol · April 2020 BACKGROUND AND PURPOSE: Ischemic stroke significantly perturbs neuronal homeostasis leading to a cascade of pathologic events causing brain damage. In this study, we assessed acute stroke outcome after chemogenetic inhibition of forebrain excitatory neuron ... Full text Open Access Link to item Cite

The requirement of SUMO2/3 for SENP2 mediated extraembryonic and embryonic development.

Journal Article Dev Dyn · February 2020 Small ubiquitin-related modifier (SUMO)-specific protease 2 (SENP2) is essential for the development of healthy placenta. The loss of SENP2 causes severe placental deficiencies and leads to embryonic death that is associated with heart and brain deformitie ... Full text Link to item Cite

The Role of SUMOylation and Ubiquitination in Brain Ischaemia: Critical Concepts and Clinical Implications.

Journal Article Curr Issues Mol Biol · 2020 Brain ischaemia is a severe form of metabolic stress that activates a cascade of pathological events involving many signalling pathways. Modulation of these pathways is largely mediated by post-translational modifications (PTMs). Indeed, PTMs can rapidly m ... Full text Link to item Cite

Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome.

Journal Article Crit Care Med · August 2019 OBJECTIVES: We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days. DESIGN: Controlled, randomized, ... Full text Open Access Link to item Cite

Impaired capacity to restore proteostasis in the aged brain after ischemia: Implications for translational brain ischemia research.

Journal Article Neurochem Int · July 2019 Brain ischemia induced by cardiac arrest or ischemic stroke is a severe form of metabolic stress that substantially disrupts cellular homeostasis, especially protein homeostasis (proteostasis). As proteostasis is fundamental for cellular and organismal hea ... Full text Link to item Cite

High-speed widefield photoacoustic microscopy of small-animal hemodynamics.

Journal Article Biomed Opt Express · October 1, 2018 Optical-resolution photoacoustic microscopy (OR-PAM) has become a popular tool in small-animal hemodynamic studies. However, previous OR-PAM techniques variously lacked a high imaging speed and/or a large field of view, impeding the study of highly dynamic ... Full text Open Access Link to item Cite

Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.

Journal Article J Am Heart Assoc · September 4, 2018 Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood. Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , ... Full text Open Access Link to item Cite

Ubc9 overexpression and SUMO1 deficiency blunt inflammation after intestinal ischemia/reperfusion.

Journal Article Lab Invest · June 2018 The intestinal epithelium constitutes a crucial defense to the potentially life-threatening effects of gut microbiota. However, due to a complex underlying vasculature, hypoperfusion and resultant tissue ischemia pose a particular risk to function and inte ... Full text Open Access Link to item Cite

Quantitative high-throughput screening identifies cytoprotective molecules that enhance SUMO conjugation via the inhibition of SUMO-specific protease (SENP)2.

Journal Article FASEB J · March 2018 The development of novel neuroprotective treatments for acute stroke has been fraught with failures, which supports the view of ischemic brain damage as a highly complex multifactorial process. Post-translational modifications such as small ubiquitin-like ... Full text Link to item Cite

Novel Modification of Potassium Chloride Induced Cardiac Arrest Model for Aged Mice.

Journal Article Aging Dis · February 2018 Experimental cardiac arrest (CA) in aging research is infrequently studied in part due to the limitation of animal models. We aimed to develop an easily performed mouse CA model to meet this need. A standard mouse KCl-induced CA model using chest compressi ... Full text Open Access Link to item Cite

SUMOylation in brain ischemia: Patterns, targets, and translational implications.

Journal Article J Cereb Blood Flow Metab · January 2018 Post-translational protein modification by small ubiquitin-like modifier (SUMO) regulates a myriad of homeostatic and stress responses. The SUMOylation pathway has been extensively studied in brain ischemia. Convincing evidence is now at hand to support th ... Full text Link to item Cite

Is age a key factor contributing to the disparity between success of neuroprotective strategies in young animals and limited success in elderly stroke patients? Focus on protein homeostasis.

Journal Article J Cereb Blood Flow Metab · October 2017 Neuroprotection strategies to improve stroke outcome have been successful in the laboratory but not in clinical stroke trials, and thus have come under scrutiny by the medical community. Experimental stroke investigators are therefore under increased press ... Full text Link to item Cite

Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming.

Journal Article Sci Rep · August 7, 2017 Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is gliob ... Full text Link to item Cite

XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.

Journal Article Stroke · June 2017 BACKGROUND AND PURPOSE: Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded prote ... Full text Open Access Link to item Cite

Activation of the ATF6 branch of the unfolded protein response in neurons improves stroke outcome.

Journal Article J Cereb Blood Flow Metab · March 2017 Impaired function of the endoplasmic reticulum (ER stress) is a hallmark of many human diseases including stroke. To restore ER function in stressed cells, the unfolded protein response (UPR) is induced, which activates 3 ER stress sensor proteins includin ... Full text Open Access Link to item Cite

Neuron-specific SUMO knockdown suppresses global gene expression response and worsens functional outcome after transient forebrain ischemia in mice.

Journal Article Neuroscience · February 20, 2017 Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) plays key roles in neurologic function in health and disease. Neuronal SUMOylation is essential for emotionality and cognition, and this pathway is dramatically activated in post-ischemic neuro ... Full text Open Access Link to item Cite

Proteomic analysis of SUMOylation in the post-ischemic brain

Chapter · January 1, 2017 Post-translational protein modification by small ubiquitin-like modifier (SUMO) is increasingly recognized as a key modulator in many cellular processes including DNA repair, cell-cycle regulation, gene transcription, RNA processing, and protein quality co ... Full text Cite

Unfolded protein response in brain ischemia: A timely update.

Journal Article J Cereb Blood Flow Metab · December 2016 Folding and processing newly synthesized proteins are vital functions of the endoplasmic reticulum that are sensitive to a variety of stress conditions. The unfolded protein response is activated to restore endoplasmic reticulum function impaired by stress ... Full text Link to item Cite

Targeting the SUMO pathway for neuroprotection in brain ischaemia.

Journal Article Stroke Vasc Neurol · September 2016 Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) is a post-translational protein modification that modulates almost all major cellular processes, and has been implicated in many human diseases. A growing body of evidence from in vitro and in ... Full text Open Access Link to item Cite

O-linked β-N-acetylglucosamine modification of proteins is activated in post-ischemic brains of young but not aged mice: Implications for impaired functional recovery from ischemic stress.

Journal Article J Cereb Blood Flow Metab · February 2016 To evaluate the effect of age on the response of brains to an ischemic challenge, we subjected young and aged mice to transient forebrain ischemia, and analyzed the heat shock response and unfolded protein response, ubiquitin conjugation and SUMO conjugati ... Full text Open Access Link to item Cite

SUMO proteomics to decipher the SUMO-modified proteome regulated by various diseases.

Journal Article Proteomics · March 2015 Small ubiquitin-like modifier (SUMO1-3) conjugation is a posttranslational protein modification whereby SUMOs are conjugated to lysine residues of target proteins. SUMO conjugation can alter the activity, stability, and function of target proteins, and the ... Full text Link to item Cite

SUMO2 is essential while SUMO3 is dispensable for mouse embryonic development.

Journal Article EMBO Rep · August 2014 Small ubiquitin-like modifier (SUMO1-3) conjugation plays a critical role in embryogenesis. Embryos deficient in the SUMO-conjugating enzyme Ubc9 die at the early postimplantation stage. Sumo1(-/-) mice are viable, as SUMO2/3 can compensate for most SUMO1 ... Full text Link to item Cite

Neuron-specific Sumo1-3 knockdown in mice impairs episodic and fear memories.

Journal Article J Psychiatry Neurosci · July 2014 BACKGROUND: Growing evidence suggests that small ubiquitin-like modifier (SUMO) conjugation plays a key role in brain plasticity by modulating activity-dependent synaptic transmission. However, these observations are based largely on cell culture experimen ... Full text Open Access Link to item Cite

Small ubiquitin-like modifier 3-modified proteome regulated by brain ischemia in novel small ubiquitin-like modifier transgenic mice: putative protective proteins/pathways.

Journal Article Stroke · April 2014 BACKGROUND AND PURPOSE: Small ubiquitin-like modifier (SUMO) conjugation is a post-translational modification associated with many human diseases. Characterization of the SUMO-modified proteome is pivotal to define the mechanistic link between SUMO conjuga ... Full text Open Access Link to item Cite

Characterization of the ubiquitin-modified proteome regulated by transient forebrain ischemia.

Journal Article J Cereb Blood Flow Metab · March 2014 Ubiquitylation is a posttranslational protein modification that modulates various cellular processes of key significance, including protein degradation and DNA damage repair. In animals subjected to transient cerebral ischemia, ubiquitin-conjugated protein ... Full text Open Access Link to item Cite

Characterization of the interleukin 1 receptor-associated kinase 4 (IRAK4)-encoding gene in salmonid fish: the functional copy is rearranged in Oncorhynchus mykiss and that factor can impair TLR signaling in mammalian cells.

Journal Article Fish Shellfish Immunol · January 2014 The interleukin 1 receptor-associated kinase 4 (IRAK4) is an essential factor for TLR-mediated activation of the host's immune functions subsequent to pathogen contact. We have characterized the respective cDNA and gene sequences from three salmonid specie ... Full text Link to item Cite

Development of a high-throughput screening assay for inhibitors of small ubiquitin-like modifier proteases.

Journal Article J Biomol Screen · June 2013 Small ubiquitin-like modifier (SUMO1-3) is a small group of proteins that are ligated to lysine residues in target proteins. SUMO conjugation is a highly dynamic process, as SUMOylated proteins are rapidly deconjugated by SUMO proteases. SUMO conjugation/d ... Full text Link to item Cite

Transient ischemia induces massive nuclear accumulation of SUMO2/3-conjugated proteins in spinal cord neurons.

Journal Article Spinal Cord · February 2013 OBJECTIVES: The objective of this study is to determine whether transient spinal cord ischemia activates small ubiquitin-like modifier (SUMO1-3) conjugation, a post-translational protein modification that protects neurons from ischemia-like conditions. MET ... Full text Open Access Link to item Cite

Small ubiquitin-like modifier 1-3 conjugation [corrected] is activated in human astrocytic brain tumors and is required for glioblastoma cell survival.

Journal Article Cancer Sci · January 2013 Small ubiquitin-like modifier (SUMO1-3) constitutes a group of proteins that conjugate to lysine residues of target proteins thereby modifying their activity, stability, and subcellular localization. A large number of SUMO target proteins are transcription ... Full text Link to item Cite

Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons.

Journal Article J Neurochem · November 2012 Deep hypothermia protects the brain from ischemic damage and is therefore used during major cardiovascular surgeries requiring cardiopulmonary bypass and a period of circulatory arrest. Here, we demonstrated that small ubiquitin-like modifier (SUMO1-3) con ... Full text Link to item Cite

Analysis of oxygen/glucose-deprivation-induced changes in SUMO3 conjugation using SILAC-based quantitative proteomics.

Journal Article J Proteome Res · February 3, 2012 Transient cerebral ischemia dramatically activates small ubiquitin-like modifier (SUMO2/3) conjugation. In cells exposed to 6 h of transient oxygen/glucose deprivation (OGD), a model of ischemia, SUMOylation increases profoundly between 0 and 30 min follow ... Full text Open Access Link to item Cite

SUMO2/3 conjugation is an endogenous neuroprotective mechanism.

Journal Article J Cereb Blood Flow Metab · November 2011 Small ubiquitin-like modifier (SUMO)2/3 but not SUMO1 conjugation is activated after transient cerebral ischemia. To investigate its function, we blocked neuronal SUMO2/3 translation through lentiviral microRNA delivery in primary cortical neurons. Viabili ... Full text Link to item Cite

Development of a simplified spinal cord ischemia model in mice.

Journal Article J Neurosci Methods · June 15, 2010 Use of genetically manipulated mice facilitates understanding pathological mechanisms in many diseases and contributes to therapy development. However, there is no practical and clinically relevant mouse model available for spinal cord ischemia. This repor ... Full text Open Access Link to item Cite

Long-term neuroprotection from a potent redox-modulating metalloporphyrin in the rat.

Journal Article Free Radic Biol Med · October 1, 2009 Sustained oxidative stress is a known sequel to focal cerebral ischemia. This study examined the effects of treatment with a single dose or sustained infusion of the redox-modulating MnPorphyrin Mn(III)TDE-2-ImP(5+) on outcome from middle cerebral artery o ... Full text Link to item Cite

Deep hypothermia markedly activates the small ubiquitin-like modifier conjugation pathway; implications for the fate of cells exposed to transient deep hypothermic cardiopulmonary bypass.

Journal Article J Cereb Blood Flow Metab · May 2009 Various cardiovascular operations are performed during conditions of deep hypothermic circulatory arrest. Here we investigated the effects of deep hypothermia on the small ubiquitin-like modifier (SUMO) conjugation pathway using a clinically relevant anima ... Full text Link to item Cite

Gene expression and cell growth are modified by silencing SUMO2 and SUMO3 expression.

Journal Article Biochem Biophys Res Commun · April 24, 2009 Small ubiquitin-like modifier (SUMO) is a group of proteins binding to lysine residues of target proteins and thereby modifying their stability, activity and subcellular localization. Here we report that blocking SUMO2 and SUMO3 conjugation by silencing th ... Full text Link to item Cite

Assessment of the immune capacity of mammary epithelial cells: comparison with mammary tissue after challenge with Escherichia coli.

Journal Article Vet Res · 2009 We examined the repertoire and extent of inflammation dependent gene regulation in a bovine mammary epithelial cell (MEC) model, to better understand the contribution of the MEC in the immune defence of the udder. We challenged primary cultures of MEC from ... Full text Link to item Cite

Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation--a new target for therapeutic intervention?

Journal Article J Neurochem · August 2008 Transient cerebral ischemia/stroke activates various post-translational protein modifications such as phosphorylation and ubiquitin conjugation that are believed to play a major role in the pathological process triggered by an interruption of blood supply ... Full text Link to item Cite

Transient focal cerebral ischemia induces a dramatic activation of small ubiquitin-like modifier conjugation.

Journal Article J Cereb Blood Flow Metab · May 2008 This study was designed to investigate whether small ubiquitin-like modifier (SUMO) conjugation is activated after focal cerebral ischemia. Transient ischemia induced a dramatic increase in SUMO2/3 protein conjugates. The most pronounced changes were found ... Full text Link to item Cite

Bovine TLR2 and TLR4 properly transduce signals from Staphylococcus aureus and E. coli, but S. aureus fails to both activate NF-kappaB in mammary epithelial cells and to quickly induce TNFalpha and interleukin-8 (CXCL8) expression in the udder.

Journal Article Mol Immunol · March 2008 Staphylococcus aureus, but not E. coli pathogens frequently cause subclinical, chronic infections of the mammary gland. We examined here, if inadequate activation of the bovine TLR2 and TLR4 pathogen receptors by ligands derived from S. aureus pathogens mi ... Full text Link to item Cite

Transient global cerebral ischemia induces a massive increase in protein sumoylation.

Journal Article J Cereb Blood Flow Metab · February 2008 A new group of proteins, small ubiquitin-like modifier (SUMO) proteins, has recently been identified and protein sumoylation has been shown to play a major role in various signal transduction pathways. Here, we report that transient global cerebral ischemi ... Full text Link to item Cite

Conditional gene silencing in mammalian cells mediated by a stress-inducible promoter.

Journal Article Biochem Biophys Res Commun · January 18, 2008 MicroRNAs (miRNAs) are endogenous non-coding small RNAs, which negatively regulate gene expression in a sequence-specific manner through the RNA interference (RNAi) pathway. Here we describe a new miRNA-based conditional RNAi expression system that relies ... Full text Link to item Cite

Escherichia coli, but not Staphylococcus aureus triggers an early increased expression of factors contributing to the innate immune defense in the udder of the cow.

Journal Article Vet Res · 2008 The outcome of an udder infection is influenced by the pathogen species. We established a strictly defined infection model to better analyze the unknown molecular causes for these pathogen-specific effects, using Escherichia coli and Staphylococcus aureus ... Full text Link to item Cite

Endoplasmic reticulum stress.

Journal Article Ann N Y Acad Sci · October 2007 Stress is the imbalance of homeostasis, which can be sensed even at the subcellular level. The stress-sensing capability of various organelles including the endoplasmic reticulum (ER) has been described. It has become evident that acute or prolonged ER str ... Full text Link to item Cite

Analysis of the real EADGENE data set: comparison of methods and guidelines for data normalisation and selection of differentially expressed genes (open access publication).

Journal Article Genet Sel Evol · 2007 A large variety of methods has been proposed in the literature for microarray data analysis. The aim of this paper was to present techniques used by the EADGENE (European Animal Disease Genomics Network of Excellence) WP1.4 participants for data quality co ... Full text Link to item Cite

Analysis of the real EADGENE data set: multivariate approaches and post analysis (open access publication).

Journal Article Genet Sel Evol · 2007 The aim of this paper was to describe, and when possible compare, the multivariate methods used by the participants in the EADGENE WP1.4 workshop. The first approach was for class discovery and class prediction using evidence from the data at hand. Several ... Full text Link to item Cite

DNA-remethylation around a STAT5-binding enhancer in the alphaS1-casein promoter is associated with abrupt shutdown of alphaS1-casein synthesis during acute mastitis.

Journal Article J Mol Endocrinol · December 2006 Prolactin stimulates the expression of milk genes during lactation through the activation of STAT5 transcription factors, which subsequently bind to their cognate target sequence on the promoters. Demethylation of 5methylCpG dinucleotides permits the tissu ... Full text Link to item Cite

NF-kappaB factors are essential, but not the switch, for pathogen-related induction of the bovine beta-defensin 5-encoding gene in mammary epithelial cells.

Journal Article Mol Immunol · February 2006 Expression of the bactericidal peptide beta-defensin 5 (BNBD5) is strongly induced by bacterial infections of the udder (mastitis). In situ hybridizations showed that bacteria elicit a strong, locally restricted expression of BNBD5 in mammary epithelial ce ... Full text Link to item Cite