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Myo/Nog Cells Give Rise To Myofibroblasts During Epiretinal Membrane Formation In A Mouse Model Of Proliferative Vitreoretinopathy., Mara Crispin, Jacquelyn Gerhart, Alison Heffer, Mark Martin, Fathma Abdalla, Arturo Bravo Nuevo, Nancy J Philp, Ajay E Kuriyan, Mindy George-Weinstein Feb 2023

Myo/Nog Cells Give Rise To Myofibroblasts During Epiretinal Membrane Formation In A Mouse Model Of Proliferative Vitreoretinopathy., Mara Crispin, Jacquelyn Gerhart, Alison Heffer, Mark Martin, Fathma Abdalla, Arturo Bravo Nuevo, Nancy J Philp, Ajay E Kuriyan, Mindy George-Weinstein

PCOM Scholarly Works

PURPOSE: Myo/Nog cells are the source of myofibroblasts in the lens and synthesize muscle proteins in human epiretinal membranes (ERMs). In the current study, we examined the response of Myo/Nog cells during ERM formation in a mouse model of proliferative vitreoretinopathy (PVR).

METHODS: PVR was induced by intravitreal injections of gas and ARPE-19 cells. PVR grade was scored by fundus imaging, optical coherence tomography, and histology. Double label immunofluorescence localization was performed to quantify Myo/Nog cells, myofibroblasts, and leukocytes.

RESULTS: Myo/Nog cells, identified by co-labeling with antibodies to brain-specific angiogenesis inhibitor 1 (BAI1) and Noggin, increased throughout the eye with …


Genomic Or Non-Genomic? A Question About The Pleiotropic Roles Of Vitamin D In Inflammatory-Based Diseases, Michael F. Holick, Luciana Mazzei, Sebastián García Menéndez, Virna Margarita Martín Giménez, Fatme Al Anouti, Walter Manucha Feb 2023

Genomic Or Non-Genomic? A Question About The Pleiotropic Roles Of Vitamin D In Inflammatory-Based Diseases, Michael F. Holick, Luciana Mazzei, Sebastián García Menéndez, Virna Margarita Martín Giménez, Fatme Al Anouti, Walter Manucha

All Works

Vitamin D (vit D) is widely known for its role in calcium metabolism and its importance for the bone system. However, various studies have revealed a myriad of extra-skeletal functions, including cell differentiation and proliferation, antibacterial, antioxidant, immunomodulatory, and anti-inflammatory properties in various cells and tissues. Vit D mediates its function via regulation of gene expression by binding to its receptor (VDR) which is expressed in almost all cells within the body. This review summarizes the pleiotropic effects of vit D, emphasizing its anti-inflammatory effect on different organ systems. It also provides a comprehensive overview of the genetic and epigenetic …


Carla+: An Evolution Of The Carla Simulator For Complex Environment Using A Probabilistic Graphical Model, Sumbal Malik, Manzoor Ahmed Khan, Aadam, Hesham El-Sayed, Farkhund Iqbal, Jalal Khan, Obaid Ullah Feb 2023

Carla+: An Evolution Of The Carla Simulator For Complex Environment Using A Probabilistic Graphical Model, Sumbal Malik, Manzoor Ahmed Khan, Aadam, Hesham El-Sayed, Farkhund Iqbal, Jalal Khan, Obaid Ullah

All Works

In an urban and uncontrolled environment, the presence of mixed traffic of autonomous vehicles, classical vehicles, vulnerable road users, e.g., pedestrians, and unprecedented dynamic events makes it challenging for the classical autonomous vehicle to navigate the traffic safely. Therefore, the realization of collaborative autonomous driving has the potential to improve road safety and traffic efficiency. However, an obvious challenge in this regard is how to define, model, and simulate the environment that captures the dynamics of a complex and urban environment. Therefore, in this research, we first define the dynamics of the envisioned environment, where we capture the dynamics relevant …


Allelic Discrimination Of Vitamin D Receptor Polymorphisms And Risk Of Type 2 Diabetes Mellitus: A Case-Controlled Study, Amal Ahmed Mohammed, Dina M.Abo El-Matty, Rola Abdel-Azeem, Khaled Raafat, Mona A. Hussein, Amira R. El-Ansary, Wael Hafez, Hatem Ahmed Hassan, Nourelhuda Ahmed Nassar, Nora Mahmoud Selim, Doaa Ghaith, Amal A.El Kholy, Soha M. Abd El Salam, Fatme Al Anouti, Alaa S. Wahba Feb 2023

Allelic Discrimination Of Vitamin D Receptor Polymorphisms And Risk Of Type 2 Diabetes Mellitus: A Case-Controlled Study, Amal Ahmed Mohammed, Dina M.Abo El-Matty, Rola Abdel-Azeem, Khaled Raafat, Mona A. Hussein, Amira R. El-Ansary, Wael Hafez, Hatem Ahmed Hassan, Nourelhuda Ahmed Nassar, Nora Mahmoud Selim, Doaa Ghaith, Amal A.El Kholy, Soha M. Abd El Salam, Fatme Al Anouti, Alaa S. Wahba

All Works

(1) Background: Type 2 diabetes mellitus (T2DM) is one of the rapidly growing healthcare problems, and several vitamin D receptor (VDR) polymorphisms seem to modulate the risk of T2DM. Our research was designed to investigate the allelic discrimination of VDR polymorphisms and T2DM occurrence risk. (2) Methods: This case-control research included 156 patients with T2DM and 145 healthy control subjects. Most of the study population were males 56.6% vs. 62.8% in the case and control groups, respectively. Genotyping for VDR single nucleotide polymorphisms (SNPs), rs228570 (Fok1), rs7975232 (Apa1), and rs1544410 (Bsm1) was compared between both groups. (3) Results: There was …


4-H Volunteer Conference Workshop Descriptions, Extension Feb 2023

4-H Volunteer Conference Workshop Descriptions, Extension

UNH Cooperative Extension

No abstract provided.


Dairy Knowledge Bowl Packet, Extension Feb 2023

Dairy Knowledge Bowl Packet, Extension

UNH Cooperative Extension

No abstract provided.


Legal Dispositionism And Artificially-Intelligent Attributions, Jerrold Soh Feb 2023

Legal Dispositionism And Artificially-Intelligent Attributions, Jerrold Soh

Research Collection Yong Pung How School Of Law

It is conventionally argued that because an artificially-intelligent (AI) system acts autonomously, its makers cannot easily be held liable should the system's actions harm. Since the system cannot be liable on its own account either, existing laws expose victims to accountability gaps and need to be reformed. Recent legal instruments have nonetheless established obligations against AI developers and providers. Drawing on attribution theory, this paper examines how these seemingly opposing positions are shaped by the ways in which AI systems are conceptualised. Specifically, folk dispositionism underpins conventional legal discourse on AI liability, personality, publications, and inventions and leads us towards …


Colorblind Nationalism And The Limits Of Citizenship, Ming Hsu Chen Feb 2023

Colorblind Nationalism And The Limits Of Citizenship, Ming Hsu Chen

Cardozo Law Review

Policymakers and lawyers posit formal citizenship as the key to inclusion. Rather than presume that formal citizenship will necessarily promote equality, this Article examines the relationship between citizenship, racial equality, and nationalism. It asks: What role does formal citizenship play in excluding noncitizens and Asian, Latinx, and Muslim citizens racialized as foreigners? What effects does it have on the meaning of being American as a non-White citizen? The Article argues that commitments to colorblind equality and democratic self-governance of the nation stand in contradiction to aspirations to protect all persons within the nation. Consequently, individual rights designed to remedy racial …


Foreseeability Conventions, John Fabian Witt, Morgan Savige Feb 2023

Foreseeability Conventions, John Fabian Witt, Morgan Savige

Cardozo Law Review

How has the foreseeability standard survived its critics? Law relies on foreseeability to solve hard legal problems in a vast array of doctrinal fields. But for a century and more, critics have pilloried the standard as hopelessly indeterminate. Decisionmakers, observe the critics, can characterize virtually any consequence as either foreseeable or unforeseeable. It all depends on how one tells the story. This Article explains the conundrum of foreseeability’s puzzling persistence by offering a novel account of how foreseeability has flourished in fields like tort, contract, and crime. Foreseeability has survived and flourished, the Article proposes, not because it carries determinate …


Transeuntis Mundi, A Nomadic Artistic Practice, Cândida Luiza Borges Da Silva Feb 2023

Transeuntis Mundi, A Nomadic Artistic Practice, Cândida Luiza Borges Da Silva

School of Law, Humanities and Social Sciences Theses

In this practice-led Ph.D. research, I investigate how an artistic practice can respond to the migration phenomena performed by human beings across the planet over millennia ¬– what I refer to as the millennial global human journey. Based on the idea of mobility, I chose to frame this research in the articulation of concepts deriving from the prefix trans: transculture, transhumance and transmediality. This research contributes to studies in art composition by developing the processes and concept of transmedial composition, mainly contributing to the field of New Media Art. This investigation resulted in the work Transeuntis Mundi (TM) Project – …


Phenomics Enables Measurement Of Complex Responses Of Developing Animals To Global Environmental Drivers, Oliver Tills, Luke A. Holmes, Elliot Quinn, Tony Everett, Manuela Truebano, John I. Spicer Feb 2023

Phenomics Enables Measurement Of Complex Responses Of Developing Animals To Global Environmental Drivers, Oliver Tills, Luke A. Holmes, Elliot Quinn, Tony Everett, Manuela Truebano, John I. Spicer

School of Biological and Marine Sciences

Phenomics offers technological advances for high-dimensional phenotyping, facilitating rapid, high-throughput assessment of physiological performance and has proven invaluable in global research challenges including drug discovery and food security. However, this rapidly growing discipline has remained largely inaccessible to the increasingly urgent challenge of assessing organismal functional sensitivity to global change drivers. Here, we investigate the response of an ecologically important marine invertebrate to multiple environmental drivers using Energy Proxy Traits (EPTs), a new approach for measuring complex phenotypes captured on video as a spectrum of energy levels across different temporal frequencies in fluctuating pixel values. We imaged three developmental stages …


Natural Disasters And Corporate Philanthropy: A Double Movement Perspective, Guoguang Wan, Heli Wang, Xuesong Geng, Kenneth G. Huang Feb 2023

Natural Disasters And Corporate Philanthropy: A Double Movement Perspective, Guoguang Wan, Heli Wang, Xuesong Geng, Kenneth G. Huang

Research Collection Lee Kong Chian School Of Business

This study examines Chinese corporations’ responses to a sudden natural disaster in terms of their philanthropic donations. We apply Polanyi’s double movement perspective to argue that rapid market expansion in an emerging economy causes social problems such as large-income disparities and environmental degradation. This calls forth counterforces advocating social responsibility and sustainability. Such countermovements can be strengthened by a major disaster, especially in the domain of corporate philanthropy. The resulting increase in corporate philanthropy persists long after the disaster, especially for those firms with large intra-firm pay disparities, operating in socially contested industries and located in regions with more social …


Using Virtual Simulations Of Future Extreme Weather Events To Communicate Climate Change Risk, Terry Van Gevelt, Brian G. Mcadoo, Jie Yang, Linlin Li, Fiona Williamson, Alex Scollay, Aileen Lam, Kwan Nok Chan, Adam D. Switzer Feb 2023

Using Virtual Simulations Of Future Extreme Weather Events To Communicate Climate Change Risk, Terry Van Gevelt, Brian G. Mcadoo, Jie Yang, Linlin Li, Fiona Williamson, Alex Scollay, Aileen Lam, Kwan Nok Chan, Adam D. Switzer

Research Collection College of Integrative Studies

Virtual simulations of future extreme weather events may prove an effective vehicle for climate change risk communication. To test this, we created a 3D virtual simulation of a future tropical cyclone amplified by climate change. Using an experimental framework, we isolated the effect of our simulation on risk perceptions and individual mitigation behaviour for a representative sample (n = 1507) of the general public in Hong Kong. We find that exposure to our simulation is systematically associated with a relatively small decrease in risk perceptions and individual mitigation behaviour. We suggest that this is likely due to climate change scepticism, …


Biallelic Variants In Ogdh Encoding Oxoglutarate Dehydrogenase Lead To A Neurodevelopmental Disorder Characterized By Global Developmental Delay, Movement Disorder, And Metabolic Abnormalities, Ella F Whittle, Madison Chilian, Ehsan Ghayoor Karimiani, Helga Progri, Daniela Buhas, Melis Kose, Rebecca D Ganetzky, Mehran Beiraghi Toosi, Paria Najarzadeh Torbati, Reza Shervin Badv, Ivan Shelihan, Hui Yang, Houda Zghal Elloumi, Sukyeong Lee, Yalda Jamshidi, Alan M Pittman, Henry Houlden, Erika Ignatius, Shamima Rahman, Reza Maroofian, Wan Hee Yoon, Christopher J Carroll Feb 2023

Biallelic Variants In Ogdh Encoding Oxoglutarate Dehydrogenase Lead To A Neurodevelopmental Disorder Characterized By Global Developmental Delay, Movement Disorder, And Metabolic Abnormalities, Ella F Whittle, Madison Chilian, Ehsan Ghayoor Karimiani, Helga Progri, Daniela Buhas, Melis Kose, Rebecca D Ganetzky, Mehran Beiraghi Toosi, Paria Najarzadeh Torbati, Reza Shervin Badv, Ivan Shelihan, Hui Yang, Houda Zghal Elloumi, Sukyeong Lee, Yalda Jamshidi, Alan M Pittman, Henry Houlden, Erika Ignatius, Shamima Rahman, Reza Maroofian, Wan Hee Yoon, Christopher J Carroll

Faculty, Staff and Students Publications

PURPOSE: This study aimed to establish the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.

METHODS: We performed a detailed clinical characterization of 4 unrelated individuals from consanguineous families with a neurodevelopmental disorder. We used exome sequencing or targeted-exome sequencing, cosegregation, in silico protein modeling, and functional analyses of variants in HEK293 cells and Drosophila melanogaster, as well as in proband-derived fibroblast cells.

RESULTS: In the 4 individuals, we identified 3 novel homozygous variants in oxoglutarate dehydrogenase (OGDH) (NM_002541.3), which encodes a subunit of the tricarboxylic acid cycle enzyme …


Serial Recombineering Cloning To Build Selectable And Tagged Genomic P[Acman] Bac Clones For Selection Transgenesis And Functional Gene Analysis Using Drosophila Melanogaste, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick Feb 2023

Serial Recombineering Cloning To Build Selectable And Tagged Genomic P[Acman] Bac Clones For Selection Transgenesis And Functional Gene Analysis Using Drosophila Melanogaste, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick

Faculty, Staff and Students Publications

Transgenes with genomic DNA fragments that encompass genes of interest are the gold standard for complementing null alleles in rescue experiments in the fruit fly Drosophila melanogaster. Of particular interest are genomic DNA clones available as bacterial artificial chromosomes (BACs) or fosmids from publicly available genomic DNA libraries. Genes contained within BAC and fosmid clones can be easily modified by recombineering cloning to insert peptide or protein tags to localize, visualize, or manipulate gene products, and to create point mutations or deletions for structure-function analysis of the inserted genes. However, since transgenesis efficiency is inversely correlated with transgene size, obtaining …


Maternal Western Diet Is Associated With Distinct Preclinical Pediatric Nafld Phenotypes In Juvenile Nonhuman Primate Offspring, Michael J Nash, Evgenia Dobrinskikh, Rachel C Janssen, Mark A Lovell, Deborah A Schady, Claire Levek, Kenneth L Jones, Angelo D'Alessandro, Paul Kievit, Kjersti M Aagaard, Carrie E Mccurdy, Maureen Gannon, Jacob E Friedman, Stephanie R Wesolowski Feb 2023

Maternal Western Diet Is Associated With Distinct Preclinical Pediatric Nafld Phenotypes In Juvenile Nonhuman Primate Offspring, Michael J Nash, Evgenia Dobrinskikh, Rachel C Janssen, Mark A Lovell, Deborah A Schady, Claire Levek, Kenneth L Jones, Angelo D'Alessandro, Paul Kievit, Kjersti M Aagaard, Carrie E Mccurdy, Maureen Gannon, Jacob E Friedman, Stephanie R Wesolowski

Faculty, Staff and Students Publications

Pediatric NAFLD has distinct and variable pathology, yet causation remains unclear. We have shown that maternal Western-style diet (mWSD) compared with maternal chow diet (CD) consumption in nonhuman primates produces hepatic injury and steatosis in fetal offspring. Here, we define the role of mWSD and postweaning Western-style diet (pwWSD) exposures on molecular mechanisms linked to NAFLD development in a cohort of 3-year-old juvenile nonhuman primates offspring exposed to maternal CD or mWSD followed by CD or Western-style diet after weaning. We used histologic, transcriptomic, and metabolomic analyses to identify hepatic pathways regulating NAFLD. Offspring exposed to mWSD showed increased hepatic …


Broad Protective Vaccination Against Systemic Escherichia Coli With Autotransporter Antigens, Yikun Xing, Justin R Clark, James D Chang, Dylan M Chirman, Sabrina Green, Jacob J Zulk, Joseph Jelinski, Kathryn A Patras, Anthony W Maresso Feb 2023

Broad Protective Vaccination Against Systemic Escherichia Coli With Autotransporter Antigens, Yikun Xing, Justin R Clark, James D Chang, Dylan M Chirman, Sabrina Green, Jacob J Zulk, Joseph Jelinski, Kathryn A Patras, Anthony W Maresso

Faculty, Staff and Students Publications

Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause of adult life-threatening sepsis and urinary tract infections (UTI). The emergence and spread of multidrug-resistant (MDR) ExPEC strains result in a considerable amount of treatment failure and hospitalization costs, and contribute to the spread of drug resistance amongst the human microbiome. Thus, an effective vaccine against ExPEC would reduce morbidity and mortality and possibly decrease carriage in healthy or diseased populations. A comparative genomic analysis demonstrated a gene encoding an invasin-like protein, termed sinH, annotated as an autotransporter protein, shows high prevalence in various invasive ExPEC phylogroups, especially those associated with …


Early Life Reprogramming-Based Treatment Promotes Longevity, Patrizia Pessina, Bruno Di Stefano Feb 2023

Early Life Reprogramming-Based Treatment Promotes Longevity, Patrizia Pessina, Bruno Di Stefano

Faculty, Staff and Students Publications

Short-term expression of Yamanaka factors early in life promotes epigenetic reprogramming and an increased healthy lifespan in a mouse model of accelerated aging.


A Retrospective Study Of The Relationship Between Hypertension And Vestibular Disorders In Middle-Aged Women With And Without Hiv, Helen S Cohen, Michael W Plankey, Deanna Ware Feb 2023

A Retrospective Study Of The Relationship Between Hypertension And Vestibular Disorders In Middle-Aged Women With And Without Hiv, Helen S Cohen, Michael W Plankey, Deanna Ware

Faculty, Staff and Students Publications

BACKGROUND: Patients often conflate the problem of lightheadedness from hypertension (HTN) and vertigo from a vestibular impairment, describing both problems as dizziness. The goal of the study was to learn if there is a relationship between measures of vestibular function and blood pressure.

METHODS: This retrospective study consisted of women who participated in a longitudinal study of the human immunodeficiency virus (HIV) and a control cohort of age-matched women without HIV. We used data from the point in time when participants were tested for vestibular functions with bi-thermal caloric tests and cervical vestibular evoked myogenic potentials; the data also included …


Regulation Of Skeletal Muscle Protein Synthesis In The Preterm Pig By Intermittent Leucine Pulses During Continuous Parenteral Feeding, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis Feb 2023

Regulation Of Skeletal Muscle Protein Synthesis In The Preterm Pig By Intermittent Leucine Pulses During Continuous Parenteral Feeding, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition.

METHODS: Following preterm delivery (on day 105 of 115 gestation), …


Reduction In Junctophilin 2 Expression In Cardiac Nodal Tissue Results In Intracellular Calcium-Driven Increase In Nodal Cell Automaticity, Andrew P Landstrom, Qixin Yang, Bo Sun, Robin M Perelli, Minu-Tshyeto Bidzimou, Zhushan Zhang, Yuriana Aguilar-Sanchez, Katherina M Alsina, Shuyi Cao, Julia O Reynolds, Tarah A Word, Niels M R Van Der Sangen, Quinn Wells, Prince J Kannankeril, Andreas Ludwig, Jeffrey J Kim, Xander H T Wehrens Feb 2023

Reduction In Junctophilin 2 Expression In Cardiac Nodal Tissue Results In Intracellular Calcium-Driven Increase In Nodal Cell Automaticity, Andrew P Landstrom, Qixin Yang, Bo Sun, Robin M Perelli, Minu-Tshyeto Bidzimou, Zhushan Zhang, Yuriana Aguilar-Sanchez, Katherina M Alsina, Shuyi Cao, Julia O Reynolds, Tarah A Word, Niels M R Van Der Sangen, Quinn Wells, Prince J Kannankeril, Andreas Ludwig, Jeffrey J Kim, Xander H T Wehrens

Faculty, Staff and Students Publications

Background: Spontaneously depolarizing nodal cells comprise the pacemaker of the heart. Intracellular calcium (Ca2+) plays a critical role in mediating nodal cell automaticity and understanding this so-called Ca2+ clock is critical to understanding nodal arrhythmias. We previously demonstrated a role for Jph2 (junctophilin 2) in regulating Ca2+-signaling through inhibition of RyR2 (ryanodine receptor 2) Ca2+ leak in cardiac myocytes; however, its role in pacemaker function and nodal arrhythmias remains unknown. We sought to determine whether nodal Jph2 expression silencing causes increased sinoatrial and atrioventricular nodal cell automaticity due to aberrant RyR2 Ca2+ leak.

Methods: A tamoxifen-inducible, nodal tissue-specific, knockdown mouse …


Genetic Variants In Arhgef6 Cause Congenital Anomalies Of The Kidneys And Urinary Tract In Humans, Mice, And Frogs, Verena Klämbt, Florian Buerger, Chunyan Wang, Thomas Naert, Karin Richter, Theresa Nauth, Anna-Carina Weiss, Tobias Sieckmann, Ethan Lai, Dervla M Connaughton, Steve Seltzsam, Nina Mann, Amar J Majmundar, Chen-Han W Wu, Ana C Onuchic-Whitford, Shirlee Shril, Sophia Schneider, Luca Schierbaum, Rufeng Dai, Mir Reza Bekheirnia, Marieke Joosten, Omer Shlomovitz, Asaf Vivante, Ehud Banne, Shrikant Mane, Richard P Lifton, Karin M Kirschner, Andreas Kispert, Georg Rosenberger, Klaus-Dieter Fischer, Soeren S Lienkamp, Mirjam M P Zegers, Friedhelm Hildebrandt Feb 2023

Genetic Variants In Arhgef6 Cause Congenital Anomalies Of The Kidneys And Urinary Tract In Humans, Mice, And Frogs, Verena Klämbt, Florian Buerger, Chunyan Wang, Thomas Naert, Karin Richter, Theresa Nauth, Anna-Carina Weiss, Tobias Sieckmann, Ethan Lai, Dervla M Connaughton, Steve Seltzsam, Nina Mann, Amar J Majmundar, Chen-Han W Wu, Ana C Onuchic-Whitford, Shirlee Shril, Sophia Schneider, Luca Schierbaum, Rufeng Dai, Mir Reza Bekheirnia, Marieke Joosten, Omer Shlomovitz, Asaf Vivante, Ehud Banne, Shrikant Mane, Richard P Lifton, Karin M Kirschner, Andreas Kispert, Georg Rosenberger, Klaus-Dieter Fischer, Soeren S Lienkamp, Mirjam M P Zegers, Friedhelm Hildebrandt

Faculty, Staff and Students Publications

Background: About 40 disease genes have been described to date for isolated CAKUT, the most common cause of childhood CKD. However, these genes account for only 20% of cases. ARHGEF6, a guanine nucleotide exchange factor that is implicated in biologic processes such as cell migration and focal adhesion, acts downstream of integrin-linked kinase (ILK) and parvin proteins. A genetic variant of ILK that causes murine renal agenesis abrogates the interaction of ILK with a murine focal adhesion protein encoded by Parva , leading to CAKUT in mice with this variant.

Methods: To identify novel genes that, when mutated, result in …


In Vivo Editing Of The Pan-Endothelium By Immunity Evading Simian Adenoviral Vector, Reka Lorincz, Aluet Borrego Alvarez, Christopher J Walkey, Samir A Mendonça, Zhi Hong Lu, Alexa E Martinez, Cecilia Ljungberg, Jason D Heaney, William R Lagor, David T Curiel Feb 2023

In Vivo Editing Of The Pan-Endothelium By Immunity Evading Simian Adenoviral Vector, Reka Lorincz, Aluet Borrego Alvarez, Christopher J Walkey, Samir A Mendonça, Zhi Hong Lu, Alexa E Martinez, Cecilia Ljungberg, Jason D Heaney, William R Lagor, David T Curiel

Faculty, Staff and Students Publications

Biological applications deriving from the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 site-specific nuclease system continue to impact and accelerate gene therapy strategies. Safe and effective in vivo co-delivery of the CRISPR/Cas9 system to target somatic cells is essential in the clinical therapeutic context. Both non-viral and viral vector systems have been applied for this delivery matter. Despite elegant proof-of-principle studies, available vector technologies still face challenges that restrict the application of CRISPR/Cas9-facilitated gene therapy. Of note, the mandated co-delivery of the gene-editing components must be accomplished in the potential presence of pre-formed anti-vector immunity. Additionally, methods must be sought …


The Roles Of Cyp1a2 And Cyp2d In Pharmacokinetic Profiles Of Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine And Its Metabolites In Mice, Xuan Qin, Cen Xie, John M Hakenjos, Kevin R Mackenzie, Shelton R Boyd, Mercedes Barzi, Karl-Dimiter Bissig, Damian W Young, Feng Li Feb 2023

The Roles Of Cyp1a2 And Cyp2d In Pharmacokinetic Profiles Of Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine And Its Metabolites In Mice, Xuan Qin, Cen Xie, John M Hakenjos, Kevin R Mackenzie, Shelton R Boyd, Mercedes Barzi, Karl-Dimiter Bissig, Damian W Young, Feng Li

Faculty, Staff and Students Publications

Duloxetine (DLX) is widely used to treat major depressive disorder. Little is known about the mechanistic basis for DLX-related adverse effects (e.g., liver injury). Human CYP1A2 and CYP2D6 mainly contributes to DLX metabolism, which was proposed to be involved in its adverse effects. Here, we investigated the roles of Cyp1a2 and Cyp2d on DLX pharmacokinetic profile and tissue distribution using a Cyp1a2 knockout (Cyp1a2-KO) mouse model together with a Cyp2d inhibitor (propranolol). Cyp1a2-KO has the few effects on the systematic exposure (area under the plasma concentration-time curve, AUC) and tissue disposition of DLX and its primary metabolites. Propranolol dramatically increased …


Magel2 Truncation Alters Select Behavioral And Physiological Outcomes In A Rat Model Of Schaaf-Yang Syndrome, Derek L Reznik, Mingxiao V Yang, Pedro Albelda De La Haza, Antrix Jain, Melanie Spanjaard, Susanne Theiss, Christian P Schaaf, Anna Malovannaya, Theresa V Strong, Surabi Veeraragavan, Rodney C Samaco Feb 2023

Magel2 Truncation Alters Select Behavioral And Physiological Outcomes In A Rat Model Of Schaaf-Yang Syndrome, Derek L Reznik, Mingxiao V Yang, Pedro Albelda De La Haza, Antrix Jain, Melanie Spanjaard, Susanne Theiss, Christian P Schaaf, Anna Malovannaya, Theresa V Strong, Surabi Veeraragavan, Rodney C Samaco

Faculty, Staff and Students Publications

Previous studies in mice have utilized Magel2 gene deletion models to examine the consequences of its absence. We report the generation, molecular validation and phenotypic characterization of a novel rat model with a truncating Magel2 mutation modeling variants associated with Schaaf-Yang syndrome-causing mutations. Within the hypothalamus, a brain region in which human MAGEL2 is paternally expressed, we demonstrated, at the level of transcript and peptide detection, that rat Magel2 exhibits a paternal, parent-of-origin effect. In evaluations of behavioral features across several domains, juvenile Magel2 mutant rats displayed alterations in anxiety-like behavior and sociability measures. Moreover, the analysis of peripheral organ …


Sumoylation Regulates Functional Properties Of The Oocyte Transcription Factors Sohlh1 And Nobox, Bethany K Patton, Surabhi Madadi, Shawn M Briley, Avery A Ahmed, Stephanie A Pangas Feb 2023

Sumoylation Regulates Functional Properties Of The Oocyte Transcription Factors Sohlh1 And Nobox, Bethany K Patton, Surabhi Madadi, Shawn M Briley, Avery A Ahmed, Stephanie A Pangas

Faculty, Staff and Students Publications

SOHLH1 and NOBOX are oocyte-expressed transcription factors with critical roles in ovary development and fertility. In mice, Sohlh1 and Nobox are essential for fertility through their regulation of the oocyte transcriptional network and cross-talk to somatic cells. Sumoylation is a posttranslational modification that regulates transcription factor function, and we previously showed that mouse oocytes deficient for sumoylation had an altered transcriptional landscape that included significant changes in NOBOX target genes. Here, we show that mouse SOHLH1 is modified by SUMO2/3 at lysine 345 and mutation of this residue alters SOHLH1 nuclear to cytoplasmic localization. In NOBOX, we identify a non-consensus …


Aortic Stress Activates An Adaptive Program In Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength And Protects Against Aneurysm And Dissection In Mice, Chen Zhang, Yanming Li, Abhijit Chakraborty, Yang Li, Kimberly R Rebello, Pingping Ren, Wei Luo, Lin Zhang, Hong S Lu, Lisa A Cassis, Joseph S Coselli, Alan Daugherty, Scott A Lemaire, Ying H Shen Feb 2023

Aortic Stress Activates An Adaptive Program In Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength And Protects Against Aneurysm And Dissection In Mice, Chen Zhang, Yanming Li, Abhijit Chakraborty, Yang Li, Kimberly R Rebello, Pingping Ren, Wei Luo, Lin Zhang, Hong S Lu, Lisa A Cassis, Joseph S Coselli, Alan Daugherty, Scott A Lemaire, Ying H Shen

Faculty, Staff and Students Publications

BACKGROUND:

When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to angiotensin II (AngII) infusion and determined its importance in protecting against aortic aneurysm and dissection (AAD).

METHODS:

We performed single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analyses in a mouse model of sporadic AAD induced by AngII infusion. We also examined the …


Ancillary Documents For Nih Grant Applications: The Pages Beyond The Scienceancillary Documents For Nih Grant Applications: The Pages Beyond The Science, Monica Fahrenholz, Lily S Cheng, Oluyinka Olutoye, Anjali A Degala, Sonya S Keswani, Taylor Lee, Allan M Goldstein, Sundeep G Keswani Feb 2023

Ancillary Documents For Nih Grant Applications: The Pages Beyond The Scienceancillary Documents For Nih Grant Applications: The Pages Beyond The Science, Monica Fahrenholz, Lily S Cheng, Oluyinka Olutoye, Anjali A Degala, Sonya S Keswani, Taylor Lee, Allan M Goldstein, Sundeep G Keswani

Faculty, Staff and Students Publications

Preparing a grant proposal is no small feat, especially for research (R-series) grants from the National Institutes of Health. The National Institutes of Health is the largest public funder of biomedical research in the world, and as such, procuring a research grant from the National Institutes of Health is one of the ultimate benchmarks of success for a surgeon-scientist. Most investigators are familiar with the page limits for most R-series grants (12 pages for an R01 and 6 pages for an R21), with the addition of a single page allotted for the specific aims. Interestingly, despite the usual focus on …


Lipid Overload – A Culprit For Hypertrophic Cardiomyopathy?, Lilei Zhang, Na Li Feb 2023

Lipid Overload – A Culprit For Hypertrophic Cardiomyopathy?, Lilei Zhang, Na Li

Faculty, Staff and Students Publications

No abstract provided.


Dynamics Of Gametes And Embryos In The Oviduct: What Can In Vivo Imaging Reveal?, Shang Wang, Irina V Larina Feb 2023

Dynamics Of Gametes And Embryos In The Oviduct: What Can In Vivo Imaging Reveal?, Shang Wang, Irina V Larina

Faculty, Staff and Students Publications

IN BRIEF: In vivo imaging of gametes and embryos in the oviduct enables new studies of the native processes that lead to fertilization and pregnancy. This review article discusses recent advancements in the in vivo imaging methods and insights which contribute to understanding the oviductal function.

ABSTRACT: Understanding the physiological dynamics of gametes and embryos in the fallopian tube (oviduct) has significant implications for managing reproductive disorders and improving assisted reproductive technologies. Recent advancements in imaging of the mouse oviduct in vivo uncovered fascinating dynamics of gametes and embryos in their native states. These new imaging approaches and observations are …