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Swi/Snf Senses Carbon Starvation With A Ph-Sensitive Low-Complexity Sequence, J. Ignacio Gutierrez, Gregory P. Brittingham, Yonca Karadeniz, Kathleen D. Tran, Arnob Dutta, Alex S. Holehouse, Craig L. Peterson, Liam J. Holt Jan 2022

Swi/Snf Senses Carbon Starvation With A Ph-Sensitive Low-Complexity Sequence, J. Ignacio Gutierrez, Gregory P. Brittingham, Yonca Karadeniz, Kathleen D. Tran, Arnob Dutta, Alex S. Holehouse, Craig L. Peterson, Liam J. Holt

Open Access Publications

It is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation in


An Immuno-Enrichment Free, Validated Quantification Of Tau Protein In Human Csf By Lc-Ms/Ms, Wade Self, Khader Awwad, John Paul Savaryn, Michael Schulz Jan 2022

An Immuno-Enrichment Free, Validated Quantification Of Tau Protein In Human Csf By Lc-Ms/Ms, Wade Self, Khader Awwad, John Paul Savaryn, Michael Schulz

Open Access Publications

Tau protein is a key target of interest in developing therapeutics for neurodegenerative diseases. Here, we sought to develop a method that quantifies extracellular tau protein concentrations in human cerebrospinal fluid (CSF) without antibody-based enrichment strategies. We demonstrate that the fit-for-purpose validated method in Alzheimer's Disease CSF is limited to quasi quantitative measures of tau surrogate peptides. We also provide evidence that CSF total Tau measures by LC-MS are feasible in the presence of monoclonal therapeutic antibodies in human CSF. Our Tau LC-MS/MS method is a translational bioanalytical tool for assaying target engagement and pharmacodynamics for anti-tau antibody drug development …


Pleiotropic Effects Of Simvastatin And Losartan In Preclinical Models Of Post-Traumatic Elbow Contracture, Michael A David, Alex J Reiter, Chelsey L Dunham, Ryan M Castile, James A Abraham, Leanne E Iannucci, Ishani D Shah, Necat Havlioglu, Aaron M Chamberlain, Spencer P Lake Jan 2022

Pleiotropic Effects Of Simvastatin And Losartan In Preclinical Models Of Post-Traumatic Elbow Contracture, Michael A David, Alex J Reiter, Chelsey L Dunham, Ryan M Castile, James A Abraham, Leanne E Iannucci, Ishani D Shah, Necat Havlioglu, Aaron M Chamberlain, Spencer P Lake

Open Access Publications

Elbow trauma can lead to post-traumatic joint contracture (PTJC), which is characterized by loss of motion associated with capsule/ligament fibrosis and cartilage damage. Unfortunately, current therapies are often unsuccessful or cause complications. This study aimed to determine the effects of prophylactically administered simvastatin (SV) and losartan (LS) in two preclinical models of elbow PTJC: an


Amigo1 Promotes Axon Growth And Territory Matching In The Retina, Florentina Soto, Ning Shen, Daniel Kerschensteiner Jan 2022

Amigo1 Promotes Axon Growth And Territory Matching In The Retina, Florentina Soto, Ning Shen, Daniel Kerschensteiner

Open Access Publications

Dendrite and axon arbor sizes are critical to neuronal function and vary widely between different neuron types. The relative dendrite and axon sizes of synaptic partners control signal convergence and divergence in neural circuits. The developmental mechanisms that determine cell-type-specific dendrite and axon size and match synaptic partners' arbor territories remain obscure. Here, we discover that retinal horizontal cells express the leucine-rich repeat domain cell adhesion molecule AMIGO1. Horizontal cells provide pathway-specific feedback to photoreceptors-horizontal cell axons to rods and horizontal cell dendrites to cones. AMIGO1 selectively expands the size of horizontal cell axons. When


Economic Choices Under Simultaneous Or Sequential Offers Rely On The Same Neural Circuit, Weikang Shi, Sébastien Ballesta, Camillo Padoa-Schioppa Jan 2022

Economic Choices Under Simultaneous Or Sequential Offers Rely On The Same Neural Circuit, Weikang Shi, Sébastien Ballesta, Camillo Padoa-Schioppa

Open Access Publications

A series of studies in which monkeys chose between two juices offered in variable amounts identified in the orbitofrontal cortex (OFC) different groups of neurons encoding the value of individual options (offer value), the binary choice outcome (chosen juice), and the chosen value. These variables capture both the input and the output of the choice process, suggesting that the cell groups identified in OFC constitute the building blocks of a decision circuit. Several lines of evidence support this hypothesis. However, in previous experiments offers were presented simultaneously, raising the question of whether current notions generalize to when goods are presented …


Contralateral Limb Specificity For Movement Preparation In The Parietal Reach Region, Eric Mooshagian, Eric A. Yttri, Arthur D. Loewy, Lawrence H. Snyder Jan 2022

Contralateral Limb Specificity For Movement Preparation In The Parietal Reach Region, Eric Mooshagian, Eric A. Yttri, Arthur D. Loewy, Lawrence H. Snyder

Open Access Publications

The canonical view of motor control is that distal musculature is controlled primarily by the contralateral cerebral hemisphere; unilateral brain lesions typically affect contralateral but not ipsilateral musculature. Contralateral-only limb deficits following a unilateral lesion suggest but do not prove that control is strictly contralateral: the loss of a contribution of the lesioned hemisphere to the control of the ipsilesional limb could be masked by the intact contralateral drive from the nonlesioned hemisphere. To distinguish between these possibilities, we serially inactivated the parietal reach region, comprising the posterior portion of medial intraparietal area, the anterior portion of V6a, and portions …


Essential Functions Of Mll1 And Mll2 In Retinal Development And Cone Cell Maintenance, Chi Sun, Xiaodong Zhang, Philip A Ruzycki, Shiming Chen Jan 2022

Essential Functions Of Mll1 And Mll2 In Retinal Development And Cone Cell Maintenance, Chi Sun, Xiaodong Zhang, Philip A Ruzycki, Shiming Chen

Open Access Publications

MLL1 (KMT2A) and MLL2 (KMT2B) are homologous members of the mixed-lineage leukemia (MLL) family of histone methyltransferases involved in epigenomic transcriptional regulation. Their sequence variants have been associated with neurological and psychological disorders, but little is known about their roles and mechanism of action in CNS development. Using mouse retina as a model, we previously reported MLL1's role in retinal neurogenesis and horizontal cell maintenance. Here we determine roles of MLL2 and MLL1/MLL2 together in retinal development using conditional knockout (CKO) mice. Deleting


Homeostatic Interferon-Lambda Response To Bacterial Microbiota Stimulates Preemptive Antiviral Defense Within Discrete Pockets Of Intestinal Epithelium, Jacob A. Van Winkle, Stefan T. Peterson, Elizabeth A. Kennedy, Michael J. Wheadon, Harshad Ingle, Chandni Desai, Rachel Rodgers, David A. Constant, Austin P. Wright, Lena Li, Maxim N. Artyomov, Sanghyun Lee, Megan T. Baldridge, Timothy J. Nice Jan 2022

Homeostatic Interferon-Lambda Response To Bacterial Microbiota Stimulates Preemptive Antiviral Defense Within Discrete Pockets Of Intestinal Epithelium, Jacob A. Van Winkle, Stefan T. Peterson, Elizabeth A. Kennedy, Michael J. Wheadon, Harshad Ingle, Chandni Desai, Rachel Rodgers, David A. Constant, Austin P. Wright, Lena Li, Maxim N. Artyomov, Sanghyun Lee, Megan T. Baldridge, Timothy J. Nice

Open Access Publications

Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-λ receptor (


Wormbase In 2022-Data, Processes, And Tools For Analyzing Caenorhabditis Elegans, Paul Davis, Tim Schedl, Et Al Jan 2022

Wormbase In 2022-Data, Processes, And Tools For Analyzing Caenorhabditis Elegans, Paul Davis, Tim Schedl, Et Al

Open Access Publications

WormBase (www.wormbase.org) is the central repository for the genetics and genomics of the nematode Caenorhabditis elegans. We provide the research community with data and tools to facilitate the use of C. elegans and related nematodes as model organisms for studying human health, development, and many aspects of fundamental biology. Throughout our 22-year history, we have continued to evolve to reflect progress and innovation in the science and technologies involved in the study of C. elegans. We strive to incorporate new data types and richer data sets, and to provide integrated displays and services that avail the knowledge generated by the …


High Temporal Resolution Measurements Of Movement Reveal Novel Early-Life Physiological Decline In C. Elegans, Drew Benjamin Sinha, Zachary Scott Pincus Jan 2022

High Temporal Resolution Measurements Of Movement Reveal Novel Early-Life Physiological Decline In C. Elegans, Drew Benjamin Sinha, Zachary Scott Pincus

Open Access Publications

Age-related physiological changes are most notable and best-studied late in life, while the nature of aging in early- or middle-aged individuals has not been explored as thoroughly. In C. elegans, many studies of movement vs. age generally focus on three distinct phases: sustained, youthful movement; onset of rapidly progressing impairment; and gross immobility. We investigated whether this first period of early-life adult movement is a sustained "healthy" level of high function followed by a discrete "movement catastrophe"-or whether there are early-life changes in movement that precede future physiological declines. To determine how movement varies during early adult life, we followed …


Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al Jan 2022

Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al

Open Access Publications

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to …


Disruption Of Thymic Central Tolerance By Infection With Murine Roseolovirus Induces Autoimmune Gastritis, Tarin M. Bigley, Liping Yang, Liang-I Kang, Jose B. Saenz, Francisco Victorino, Wayne M. Yokoyama Jan 2022

Disruption Of Thymic Central Tolerance By Infection With Murine Roseolovirus Induces Autoimmune Gastritis, Tarin M. Bigley, Liping Yang, Liang-I Kang, Jose B. Saenz, Francisco Victorino, Wayne M. Yokoyama

Open Access Publications

Infections with herpesviruses, including human roseoloviruses, have been proposed to cause autoimmune disease, but defining a causal relationship and mechanism has been difficult due to the ubiquitous nature of infection and development of autoimmunity long after acute infection. Murine roseolovirus (MRV) is highly related to human roseoloviruses. Herein we show that neonatal MRV infection induced autoimmune gastritis (AIG) in adult mice in the absence of ongoing infection. MRV-induced AIG was dependent on replication during the neonatal period and was CD4+ T cell and IL-17 dependent. Moreover, neonatal MRV infection was associated with development of a wide array of autoantibodies in …


Sonobiopsy For Minimally Invasive, Spatiotemporally-Controlled, And Sensitive Detection Of Glioblastoma-Derived Circulating Tumor Dna, Christopher Pacia, Jinyun Yuan, Yimei Yue, Lu Xu, Arash Nazeri, Rupen Desai, H. Michael Gach, Xiaowei Wang, Michael Talcott, Aadel Chaudhuri, Gavin Dunn, Eric Leuthardt, Hong Chen Jan 2022

Sonobiopsy For Minimally Invasive, Spatiotemporally-Controlled, And Sensitive Detection Of Glioblastoma-Derived Circulating Tumor Dna, Christopher Pacia, Jinyun Yuan, Yimei Yue, Lu Xu, Arash Nazeri, Rupen Desai, H. Michael Gach, Xiaowei Wang, Michael Talcott, Aadel Chaudhuri, Gavin Dunn, Eric Leuthardt, Hong Chen

Open Access Publications

No abstract provided.


Sarm1 Activation Produces Cadpr To Increase Intra-Axonal Ca++ And Promote Axon Degeneration In Pipn, Yihang Li, Maria F. Pazyra-Murphy, Daina Avizonis, Mariana De Sá Tavares Russo, Sophia Tang, Chiung-Ya Chen, Yi-Ping Hsueh, Johann S. Bergholz, Tao Jiang, Jean J. Zhao, Jian Zhu, Kwang Woo Ko, Jeffrey Milbrandt, Aaron Diantonio, Rosalind A. Segal Jan 2022

Sarm1 Activation Produces Cadpr To Increase Intra-Axonal Ca++ And Promote Axon Degeneration In Pipn, Yihang Li, Maria F. Pazyra-Murphy, Daina Avizonis, Mariana De Sá Tavares Russo, Sophia Tang, Chiung-Ya Chen, Yi-Ping Hsueh, Johann S. Bergholz, Tao Jiang, Jean J. Zhao, Jian Zhu, Kwang Woo Ko, Jeffrey Milbrandt, Aaron Diantonio, Rosalind A. Segal

Open Access Publications

Cancer patients frequently develop chemotherapy-induced peripheral neuropathy (CIPN), a painful and long-lasting disorder with profound somatosensory deficits. There are no effective therapies to prevent or treat this disorder. Pathologically, CIPN is characterized by a "dying-back" axonopathy that begins at intra-epidermal nerve terminals of sensory neurons and progresses in a retrograde fashion. Calcium dysregulation constitutes a critical event in CIPN, but it is not known how chemotherapies such as paclitaxel alter intra-axonal calcium and cause degeneration. Here, we demonstrate that paclitaxel triggers Sarm1-dependent cADPR production in distal axons, promoting intra-axonal calcium flux from both intracellular and extracellular calcium stores. Genetic or …


The 2021 Faseb Science Research Conference On Nad Metabolism And Signaling, Vera Gorbunova, Shin-Ichiro Imai, Et Al Jan 2022

The 2021 Faseb Science Research Conference On Nad Metabolism And Signaling, Vera Gorbunova, Shin-Ichiro Imai, Et Al

Open Access Publications

No abstract provided.


Epigenetic Regulation Of Human T‐Cell Leukemia Virus Gene Expression, Lee Ratner Jan 2022

Epigenetic Regulation Of Human T‐Cell Leukemia Virus Gene Expression, Lee Ratner

Open Access Publications

No abstract provided.


Dopamine D4 Receptor Is A Regulator Of Morphine-Induced Plasticity In The Rat Dorsal Striatum, Alicia Rivera, Diana Suarez-Boomgard, Cristina Miguelez, Alejandra Valderrama-Carvajal, Jerome Baufreton, Kirill Shumilov, Anne Taupignon, Belen Gago, M.Angeles Real Jan 2022

Dopamine D4 Receptor Is A Regulator Of Morphine-Induced Plasticity In The Rat Dorsal Striatum, Alicia Rivera, Diana Suarez-Boomgard, Cristina Miguelez, Alejandra Valderrama-Carvajal, Jerome Baufreton, Kirill Shumilov, Anne Taupignon, Belen Gago, M.Angeles Real

Open Access Publications

No abstract provided.


Transition From Cmyc To L-Myc During Dendritic Cell Development Coordinated By Rising Levels Of Irf8, David A. Anderson, Feiya Ou, Sunkyung Kim, Theresa L. Murphy, Kenneth M. Murphy Jan 2022

Transition From Cmyc To L-Myc During Dendritic Cell Development Coordinated By Rising Levels Of Irf8, David A. Anderson, Feiya Ou, Sunkyung Kim, Theresa L. Murphy, Kenneth M. Murphy

Open Access Publications

During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL …


M6a Modifications Regulate Intestinal Immunity And Rotavirus Infection, Anmin Wang, Gaopeng Hou, Siyuan Ding, Et Al Jan 2022

M6a Modifications Regulate Intestinal Immunity And Rotavirus Infection, Anmin Wang, Gaopeng Hou, Siyuan Ding, Et Al

Open Access Publications

N6-methyladenosine (m6A) is an abundant mRNA modification and affects many biological processes. However, how m6A levels are regulated during physiological or pathological processes such as virus infections, and the in vivo function of m6A in the intestinal immune defense against virus infections are largely unknown. Here, we uncover a novel antiviral function of m6A modification during rotavirus (RV) infection in small bowel intestinal epithelial cells (IECs). We found that rotavirus infection induced global m6A modifications on mRNA transcripts by down-regulating the m6a eraser ALKBH5. Mice lacking the m6A writer enzymes METTL3 in IECs (


A Test Of The Pioneer Factor Hypothesis Using Ectopic Liver Gene Activation, Jeffrey L. Hansen, Kaiser J. Loell, Barak A. Cohen Jan 2022

A Test Of The Pioneer Factor Hypothesis Using Ectopic Liver Gene Activation, Jeffrey L. Hansen, Kaiser J. Loell, Barak A. Cohen

Open Access Publications

The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and non-PF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and …


The Mutationathon Highlights The Importance Of Reaching Standardization In Estimates Of Pedigree-Based Germline Mutation Rates, Lucie A. Bergeron, Tychele Turner, Et Al Jan 2022

The Mutationathon Highlights The Importance Of Reaching Standardization In Estimates Of Pedigree-Based Germline Mutation Rates, Lucie A. Bergeron, Tychele Turner, Et Al

Open Access Publications

In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a 'Mutationathon,' a …


Intrinsic Mechanisms In The Gating Of Resurgent Na+ Currents, Joseph L. Ransdell, Jonathan D. Moreno, Druv Bhagavan, Jonathan R. Silva, Jeanne M. Nerbonne Jan 2022

Intrinsic Mechanisms In The Gating Of Resurgent Na+ Currents, Joseph L. Ransdell, Jonathan D. Moreno, Druv Bhagavan, Jonathan R. Silva, Jeanne M. Nerbonne

Open Access Publications

The resurgent component of the voltage-gated sodium current (I


Tumor Lysis Syndrome In A Patient With Metastatic Endometrial Cancer Treated With Lattice Stereotactic Body Radiation Therapy, Joshua P Schiff, Matthew B Spraker, Sai Duriseti, Sana Shaikh, Haris F Murad, David G Mutch, Clifford G Robinson, James Kavanaugh, Alexander J Lin Jan 2022

Tumor Lysis Syndrome In A Patient With Metastatic Endometrial Cancer Treated With Lattice Stereotactic Body Radiation Therapy, Joshua P Schiff, Matthew B Spraker, Sai Duriseti, Sana Shaikh, Haris F Murad, David G Mutch, Clifford G Robinson, James Kavanaugh, Alexander J Lin

Open Access Publications

No abstract provided.


Loss Of Kmt2c Reprograms The Epigenomic Landscape In Hpscs Resulting In Nodal Overexpression And A Failure Of Hemogenic Endothelium Specification, Shailendra Maurya, Wei Yang, Minori Tamai, Qiang Zhang, Petra Erdmann-Gilmore, Amelia Bystry, Fernanda Martins Rodrigues, Mark C Valentine, Wing H Wong, Reid Townsend, Todd E Druley Jan 2022

Loss Of Kmt2c Reprograms The Epigenomic Landscape In Hpscs Resulting In Nodal Overexpression And A Failure Of Hemogenic Endothelium Specification, Shailendra Maurya, Wei Yang, Minori Tamai, Qiang Zhang, Petra Erdmann-Gilmore, Amelia Bystry, Fernanda Martins Rodrigues, Mark C Valentine, Wing H Wong, Reid Townsend, Todd E Druley

Open Access Publications

Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably,


Augmented Cardiac Growth Hormone Signaling Contributes To Cardiomyopathy Following Genetic Disruption Of The Cardiomyocyte Circadian Clock, Ravi Sonkar, Ryan Berry, Mary N Latimer, Sumanth D Prabhu, Martin E Young, Stuart J Frank Jan 2022

Augmented Cardiac Growth Hormone Signaling Contributes To Cardiomyopathy Following Genetic Disruption Of The Cardiomyocyte Circadian Clock, Ravi Sonkar, Ryan Berry, Mary N Latimer, Sumanth D Prabhu, Martin E Young, Stuart J Frank

Open Access Publications

Circadian clocks regulate numerous biological processes, at whole body, organ, and cellular levels. This includes both hormone secretion and target tissue sensitivity. Although growth hormone (GH) secretion is time-of-day-dependent (increased pulse amplitude during the sleep period), little is known regarding whether circadian clocks modulate GH sensitivity in target tissues. GH acts in part through induction of insulin-like growth factor 1 (IGF1), and excess GH/IGF1 signaling has been linked to pathologies such as insulin resistance, acromegaly, and cardiomyopathy. Interestingly, genetic disruption of the cardiomyocyte circadian clock leads to cardiac adverse remodeling, contractile dysfunction, and reduced lifespan. These observations led to the …


Steroid Hormone Signaling Activates Thermal Nociception During Drosophila Peripheral Nervous System Development, Jacob S. Jaszczak, Laura Devault, Lily Yeh Jan, Yuh Nung Jan Jan 2022

Steroid Hormone Signaling Activates Thermal Nociception During Drosophila Peripheral Nervous System Development, Jacob S. Jaszczak, Laura Devault, Lily Yeh Jan, Yuh Nung Jan

Open Access Publications

Sensory neurons enable animals to detect environmental changes and avoid harm. An intriguing open question concerns how the various attributes of sensory neurons arise in development.


Fracture Healing Is Delayed In The Absence Of Gasdermin-Interleukin-1 Signaling, Kai Sun, Chun Wang, Jianqiu Xiao, Michael D. Brodt, Luorongxin Yuan, Tong Yang, Yael Alippe, Huimin Hu, Dingjun Hao, Yousef Abu-Amer, Matthew J. Silva, Jie Shen, Gabriel Mbalaviele Jan 2022

Fracture Healing Is Delayed In The Absence Of Gasdermin-Interleukin-1 Signaling, Kai Sun, Chun Wang, Jianqiu Xiao, Michael D. Brodt, Luorongxin Yuan, Tong Yang, Yael Alippe, Huimin Hu, Dingjun Hao, Yousef Abu-Amer, Matthew J. Silva, Jie Shen, Gabriel Mbalaviele

Open Access Publications

Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking …


Tourette Syndrome Research Highlights From 2020, Andreas Hartmann, Cyril Atkinson-Clement, Christel Depienne, Kevin Black Jan 2022

Tourette Syndrome Research Highlights From 2020, Andreas Hartmann, Cyril Atkinson-Clement, Christel Depienne, Kevin Black

Open Access Publications

We present here research from 2020 relevant to Tourette syndrome (TS). The authors briefly summarize a few reports they consider most important or interesting.


Sglt2 Inhibitors Therapy Protects Glucotoxicity-Induced Β-Cell Failure In A Mouse Model Of Human Katp-Induced Diabetes Through Mitigation Of Oxidative And Er Stress, Zeenat A. Shyr, Zihan Yan, Alessandro Ustione, Erin M. Egan, Maria S. Remedi Jan 2022

Sglt2 Inhibitors Therapy Protects Glucotoxicity-Induced Β-Cell Failure In A Mouse Model Of Human Katp-Induced Diabetes Through Mitigation Of Oxidative And Er Stress, Zeenat A. Shyr, Zihan Yan, Alessandro Ustione, Erin M. Egan, Maria S. Remedi

Open Access Publications

Progressive loss of pancreatic β-cell functional mass and anti-diabetic drug responsivity are classic findings in diabetes, frequently attributed to compensatory insulin hypersecretion and β-cell exhaustion. However, loss of β-cell mass and identity still occurs in mouse models of human KATP-gain-of-function induced Neonatal Diabetes Mellitus (NDM), in the absence of insulin secretion. Here we studied the temporal progression and mechanisms underlying glucotoxicity-induced loss of functional β-cell mass in NDM mice, and the effects of sodium-glucose transporter 2 inhibitors (SGLT2i) therapy. Upon tamoxifen induction of transgene expression, NDM mice rapidly developed severe diabetes followed by an unexpected loss of insulin content, decreased …


Impact Of Motile Ciliopathies On Human Development And Clinical Consequences In The Newborn, Rachael Hyland, Steven L. Brody Dec 2021

Impact Of Motile Ciliopathies On Human Development And Clinical Consequences In The Newborn, Rachael Hyland, Steven L. Brody

Open Access Publications

No abstract provided.