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  1. Article ; Online: TALEN-mediated intron editing of HSPCs enables transgene expression restricted to the myeloid lineage.

    Seclen, Eduardo / Jang, Jessica C / Lawal, Aminah O / Pulicani, Sylvain / Boyne, Alex / Tkach, Diane / Juillerat, Alexandre / Duchateau, Philippe / Valton, Julien

    Molecular therapy : the journal of the American Society of Gene Therapy

    2024  

    Abstract: Gene therapy in hematopoietic stem and progenitor cells (HSPCs) shows great potential for the treatment of inborn metabolic diseases. Typical HSPC gene therapy approaches rely on constitutive promoters to express a therapeutic transgene, which is ... ...

    Abstract Gene therapy in hematopoietic stem and progenitor cells (HSPCs) shows great potential for the treatment of inborn metabolic diseases. Typical HSPC gene therapy approaches rely on constitutive promoters to express a therapeutic transgene, which is associated with multiple disadvantages. Here, we propose a novel promoterless intronic gene editing approach that triggers transgene expression only after cellular differentiation into the myeloid lineage. We integrated a splicing-competent eGFP cassette into the first intron of CD11b and observed expression of eGFP in the myeloid lineage but minimal to no expression in HSPCs or differentiated non-myeloid lineages. In vivo, edited HSPCs successfully engrafted in immunodeficient mice and displayed transgene expression in the myeloid compartment of multiple tissues. Using the same approach, we expressed alpha-L-iduronidase (IDUA), the defective enzyme in Mucopolysaccharidosis type I, and observed a 10-fold supraendogenous IDUA expression exclusively after myeloid differentiation. Edited cells efficiently populated bone marrow, blood, and spleen of immunodeficient mice, and retained the capacity to secrete IDUA ex vivo. Importantly, cells edited with the eGFP and IDUA transgenes were also found in the brain. This approach may unlock new therapeutic strategies for inborn metabolic and neurological diseases that require the delivery of therapeutics in brain.
    Language English
    Publishing date 2024-04-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2024.04.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Deletion of monoamine oxidase A in a prostate cancer model enhances anti-tumor immunity through reduced immune suppression.

    Lapierre, Jessica A / Geary, Lauren A / Jang, Julie K / Epstein, Alan L / Hong, Frank / Shih, Jean C

    Biochemical and biophysical research communications

    2022  Volume 634, Page(s) 100–107

    Abstract: We have previously shown that monoamine oxidase A (MAO A) mediates prostate cancer growth and metastasis. Further, MAO A/Pten double knockout (DKO) mice were generated and demonstrated that the deletion of MAO A delayed prostate tumor development in the ... ...

    Abstract We have previously shown that monoamine oxidase A (MAO A) mediates prostate cancer growth and metastasis. Further, MAO A/Pten double knockout (DKO) mice were generated and demonstrated that the deletion of MAO A delayed prostate tumor development in the Pten knockout mouse model of prostate adenocarcinoma. Here, we investigated its effect on immune cells in the tumor microenvironment in MAO A/Pten DKO mouse model. Our results shows that Paraffin embedded prostate tissues from MAO A/Pten DKO mice had elevated markers of immune stimulation (CD8
    MeSH term(s) Humans ; Male ; Mice ; Animals ; Prostate/pathology ; Monoamine Oxidase/genetics ; Prostatic Neoplasms/pathology ; Immunosuppression Therapy ; Tumor Microenvironment ; Cell Line, Tumor
    Chemical Substances Monoamine Oxidase (EC 1.4.3.4)
    Language English
    Publishing date 2022-10-06
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2022.10.016
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  3. Article ; Online: Pathogenesis and Transmission Assessment of 3 Swine-Origin Influenza A(H3N2) Viruses With Zoonotic Risk to Humans Isolated in the United States, 2017-2020.

    Sun, Xiangjie / Belser, Jessica A / Pulit-Penaloza, Joanna A / Brock, Nicole / Pappas, Claudia / Zanders, Natosha / Jang, Yunho / Jones, Joyce / Tumpey, Terrence M / Davis, C Todd / Maines, Taronna R

    The Journal of infectious diseases

    2023  Volume 229, Issue 4, Page(s) 1107–1111

    Abstract: The sporadic occurrence of human infections with swine-origin influenza A(H3N2) viruses and the continual emergence of novel A(H3N2) viruses in swine herds underscore the necessity for ongoing assessment of the pandemic risk posed by these viruses. Here, ...

    Abstract The sporadic occurrence of human infections with swine-origin influenza A(H3N2) viruses and the continual emergence of novel A(H3N2) viruses in swine herds underscore the necessity for ongoing assessment of the pandemic risk posed by these viruses. Here, we selected 3 recent novel swine-origin A(H3N2) viruses isolated between 2017 to 2020, bearing hemagglutinins from the 1990.1, 2010.1, or 2010.2 clades, and evaluated their ability to cause disease and transmit in a ferret model. We conclude that despite considerable genetic variances, all 3 contemporary swine-origin A(H3N2) viruses displayed a capacity for robust replication in the ferret respiratory tract and were also capable of limited airborne transmission. These findings highlight the continued public health risk of swine-origin A(H3N2) strains, especially in human populations with low cross-reactive immunity.
    MeSH term(s) Humans ; Animals ; United States/epidemiology ; Swine ; Influenza, Human ; Orthomyxoviridae Infections ; Influenza A Virus, H3N2 Subtype/genetics ; Ferrets ; Influenza A virus ; Swine Diseases
    Language English
    Publishing date 2023-08-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad359
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  4. Article ; Online: Author Correction: Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis.

    Jourdon, Alexandre / Wu, Feinan / Mariani, Jessica / Capauto, Davide / Norton, Scott / Tomasini, Livia / Amiri, Anahita / Suvakov, Milovan / Schreiner, Jeremy D / Jang, Yeongjun / Panda, Arijit / Nguyen, Cindy Khanh / Cummings, Elise M / Han, Gloria / Powell, Kelly / Szekely, Anna / McPartland, James C / Pelphrey, Kevin / Chawarska, Katarzyna /
    Ventola, Pamela / Abyzov, Alexej / Vaccarino, Flora M

    Nature neuroscience

    2023  Volume 26, Issue 11, Page(s) 2035

    Language English
    Publishing date 2023-09-06
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/s41593-023-01447-9
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  5. Article ; Online: Pathogenesis and transmission of human seasonal and swine-origin A(H1) influenza viruses in the ferret model.

    Pulit-Penaloza, Joanna A / Brock, Nicole / Jones, Joyce / Belser, Jessica A / Jang, Yunho / Sun, Xiangjie / Thor, Sharmi / Pappas, Claudia / Zanders, Natosha / Tumpey, Terrence M / Davis, C Todd / Maines, Taronna R

    Emerging microbes & infections

    2022  Volume 11, Issue 1, Page(s) 1452–1459

    Abstract: Influenza A viruses (IAVs) in the swine reservoir constantly evolve, resulting in expanding genetic and antigenic diversity of strains that occasionally cause infections in humans and pose a threat of emerging as a strain capable of human-to-human ... ...

    Abstract Influenza A viruses (IAVs) in the swine reservoir constantly evolve, resulting in expanding genetic and antigenic diversity of strains that occasionally cause infections in humans and pose a threat of emerging as a strain capable of human-to-human transmission. For these reasons, there is an ongoing need for surveillance and characterization of newly emerging strains to aid pandemic preparedness efforts, particularly for the selection of candidate vaccine viruses and conducting risk assessments. Here, we performed a parallel comparison of the pathogenesis and transmission of genetically and antigenically diverse swine-origin A(H1N1) variant (v) and A(H1N2)v, and human seasonal A(H1N1)pdm09 IAVs using the ferret model. Both groups of viruses were capable of replication in the ferret upper respiratory tract; however, variant viruses were more frequently isolated from the lower respiratory tract as compared to the human-adapted viruses. Regardless of virus origin, observed clinical signs of infection differed greatly between strains, with some viruses causing nasal discharge, sneezing and, in some instances, diarrhea in ferrets. The most striking difference between the viruses was the ability to transmit through the air. Human-adapted viruses were capable of airborne transmission between all ferret pairs. In contrast, only one out of the four tested variant viruses was able to transmit via the air as efficiently as the human-adapted viruses. Overall, this work highlights the need for sustained monitoring of emerging swine IAVs to identify strains of concern such as those that are antigenically different from vaccine strains and that possess adaptations required for efficient respiratory droplet transmission in mammals.
    MeSH term(s) Animals ; Ferrets ; Humans ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza A virus ; Influenza, Human ; Orthomyxoviridae Infections ; Seasons ; Swine
    Language English
    Publishing date 2022-05-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2681359-2
    ISSN 2222-1751 ; 2222-1751
    ISSN (online) 2222-1751
    ISSN 2222-1751
    DOI 10.1080/22221751.2022.2076615
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  6. Article ; Online: An Unusual Presentation of Syphilis in the Context of Child Sexual Abuse.

    Edward, Heather L / Moore, Jessica / Jang, Eun Ji / Rogo, Tanya / Barron, Christine

    Journal of pediatric and adolescent gynecology

    2023  Volume 37, Issue 2, Page(s) 209–212

    Abstract: A 13-year-old presented with a genital lesion, which helped in guiding a diagnosis of child sexual abuse. The patient disclosed unprotected penile-vaginal penetration by a 20-year-old male neighbor. On exam, her left labia minora had a single 2-cm ... ...

    Abstract A 13-year-old presented with a genital lesion, which helped in guiding a diagnosis of child sexual abuse. The patient disclosed unprotected penile-vaginal penetration by a 20-year-old male neighbor. On exam, her left labia minora had a single 2-cm hypopigmented fleshy non-tender mass, and laboratory studies revealed positive Treponemal IgG IgM antibody (>8) and rapid plasma reagin titer of 1:128, indicating syphilis infection. Given the resolution of the labial mass with treatment of syphilis, this lesion was most consistent with condyloma lata. Genital exams are an important component of pediatric evaluations. Condyloma lata can vary in appearance (papules, nodules, or wart-like lesions) and color and may present as a single lesion or multiple lesions. Our patient had one 2-cm lesion, and therefore, clinicians should assume that an anogenital lesion is condyloma lata in the setting of positive syphilis testing.
    MeSH term(s) Male ; Female ; Humans ; Child ; Young Adult ; Adult ; Adolescent ; Syphilis/complications ; Syphilis/diagnosis ; Syphilis/drug therapy ; Child Abuse, Sexual/diagnosis ; Skin Neoplasms
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Case Reports
    ZDB-ID 1325079-6
    ISSN 1873-4332 ; 1083-3188
    ISSN (online) 1873-4332
    ISSN 1083-3188
    DOI 10.1016/j.jpag.2023.09.012
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  7. Article ; Online: SNOT-22 Quality of Life Scores Improve After Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Rhinorrhea.

    Liu, Matthew Y / Woodworth, Bradford A / Kanaan, Alissa / Jang, David W / Yao, William C / Radabaugh, Jeffrey Paul / Gardner, James Reed / Goros, Martin / Grayson, Jessica W / Wang, Zhu / Chen, Philip G

    The Annals of otology, rhinology, and laryngology

    2022  Volume 132, Issue 9, Page(s) 1077–1084

    Abstract: Objectives: Patients with spontaneous cerebrospinal fluid (CSF) rhinorrhea can experience significant sinonasal symptom burden, leading to poor quality of life (QOL). The objective of this study was to investigate sinonasal outcome test-22 (SNOT-22) ... ...

    Abstract Objectives: Patients with spontaneous cerebrospinal fluid (CSF) rhinorrhea can experience significant sinonasal symptom burden, leading to poor quality of life (QOL). The objective of this study was to investigate sinonasal outcome test-22 (SNOT-22) scores in patients undergoing endoscopic endonasal surgery for spontaneous CSF rhinorrhea and compare them to patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis without nasal polyps (CRSsNP).
    Methods: A multi-institutional retrospective review of patients with spontaneous CSF rhinorrhea and CRSsNP was performed. Pre-surgery and post-surgery SNOT-22 scores and domains were compared within each group. Improvements in SNOT-22 scores after surgery were compared between the groups.
    Results: Ninety-one patients were in the CSF rhinorrhea group and 105 patients were in the CRSsNP group. Within each group, surgery significantly improved total SNOT-22 scores, domain scores, and most of the individual symptoms. Comparing the 2 groups revealed similar improvements in total SNOT-22 scores (
    Conclusions: Patients with spontaneous CSF rhinorrhea experience significant symptom burden. Those who undergo CSF leak repair should experience significant improvement in QOL similar to patients who undergo ESS for CRSsNP as measured by SNOT-22.
    MeSH term(s) Humans ; Sino-Nasal Outcome Test ; Cerebrospinal Fluid Rhinorrhea/surgery ; Quality of Life ; Rhinitis/complications ; Rhinitis/surgery ; Rhinitis/diagnosis ; Nose ; Endoscopy ; Nasal Polyps/surgery ; Sinusitis/complications ; Sinusitis/surgery ; Sinusitis/diagnosis ; Chronic Disease ; Treatment Outcome
    Language English
    Publishing date 2022-11-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120642-4
    ISSN 1943-572X ; 0003-4894
    ISSN (online) 1943-572X
    ISSN 0003-4894
    DOI 10.1177/00034894221133769
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  8. Article ; Online: Individual SNOT-22 Items Aid in Differentiating Between Spontaneous Cerebrospinal Fluid Rhinorrhea and Chronic Rhinosinusitis Without Nasal Polyps.

    Liu, Matthew Y / Gardner, James Reed / Woodworth, Bradford A / Jang, David W / Kanaan, Alissa / Radabaugh, Jeffrey Paul / Yao, William C / Goros, Martin / Challa, Megana / Grayson, Jessica W / Wang, Zhu / Chen, Philip G

    The Annals of otology, rhinology, and laryngology

    2022  Volume 132, Issue 6, Page(s) 698–704

    Abstract: Objectives: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)- ...

    Abstract Objectives: Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a diagnostic challenge due to its overlapping symptomatology with other sinonasal diseases. The objective of this study was to investigate whether items on the sinonasal outcome test (SNOT)-22 could suggest a diagnosis of spontaneous CSF rhinorrhea versus chronic rhinosinusitis without nasal polyps (CRSsNP).
    Methods: A multi-institutional retrospective chart review of patients with spontaneous CSF rhinorrhea and a control group of CRSsNP patients was performed. Individual SNOT-22 scores and domain scores were compared.
    Results: One hundred fifteen patients were included in both cohorts. Of the patients in the CSF rhinorrhea group, 48% were misdiagnosed as chronic rhinosinusitis (CRS) prior to the correct identification of a CSF leak. On bivariate analysis, the CSF rhinorrhea group scored significantly higher on the SNOT-22 for runny nose (
    Conclusions: Spontaneous CSF rhinorrhea is commonly misdiagnosed as other sinonasal pathologies. However, individual SNOT-22 items can help aid in suggesting a CSF leak. Spontaneous CSF rhinorrhea should be suspected in patients who have high SNOT-22 scores for runny nose and report this symptom as most important, but have lower scores related to the other cardinal symptoms of CRS.
    MeSH term(s) Humans ; Nasal Polyps/diagnosis ; Cerebrospinal Fluid Rhinorrhea/diagnosis ; Sino-Nasal Outcome Test ; Nasal Obstruction ; Retrospective Studies ; Rhinitis/complications ; Rhinitis/diagnosis ; Chronic Disease ; Sinusitis/complications ; Sinusitis/diagnosis ; Facial Pain ; Rhinorrhea ; Quality of Life
    Language English
    Publishing date 2022-07-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120642-4
    ISSN 1943-572X ; 0003-4894
    ISSN (online) 1943-572X
    ISSN 0003-4894
    DOI 10.1177/00034894221111256
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  9. Article: Alternatively Activated Macrophages Revisited: New Insights into the Regulation of Immunity, Inflammation and Metabolic Function following Parasite Infection.

    Jang, Jessica C / Nair, Meera G

    Current immunology reviews

    2013  Volume 9, Issue 3, Page(s) 147–156

    Abstract: The role of macrophages in homeostatic conditions and the immune system range from clearing debris to recognizing and killing pathogens. While classically activated macrophages (CAMacs) are induced by T helper type 1 (Th1) cytokines and exhibit ... ...

    Abstract The role of macrophages in homeostatic conditions and the immune system range from clearing debris to recognizing and killing pathogens. While classically activated macrophages (CAMacs) are induced by T helper type 1 (Th1) cytokines and exhibit microbicidal properties, Th2 cytokines promote alternative activation of macrophages (AAMacs). AAMacs contribute to the killing of helminth parasites and mediate additional host-protective processes such as regulating inflammation and wound healing. Yet, other parasites susceptible to Th1 type responses can exploit alternative activation of macrophages to diminish Th1 immune responses and prolong infection. In this review, we will delineate the factors that mediate alternative activation (e.g. Th2 cytokines and chitin) and the resulting downstream signaling events (e.g. STAT6 signaling). Next, the specific AAMac-derived factors (e.g. Arginase1) that contribute to resistance or susceptibility to parasitic infections will be summarized. Finally, we will conclude with the discussion of additional AAMac functions beyond immunity to parasites, including the regulation of inflammation, wound healing and the regulation of metabolic disorders.
    Language English
    Publishing date 2013-10-13
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2274820-9
    ISSN 1875-631X ; 1573-3955
    ISSN (online) 1875-631X
    ISSN 1573-3955
    DOI 10.2174/1573395509666131210232548
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  10. Article ; Online: Development and Benchmarking of Open Force Field 2.0.0: The Sage Small Molecule Force Field.

    Boothroyd, Simon / Behara, Pavan Kumar / Madin, Owen C / Hahn, David F / Jang, Hyesu / Gapsys, Vytautas / Wagner, Jeffrey R / Horton, Joshua T / Dotson, David L / Thompson, Matthew W / Maat, Jessica / Gokey, Trevor / Wang, Lee-Ping / Cole, Daniel J / Gilson, Michael K / Chodera, John D / Bayly, Christopher I / Shirts, Michael R / Mobley, David L

    Journal of chemical theory and computation

    2023  Volume 19, Issue 11, Page(s) 3251–3275

    Abstract: We introduce the Open Force Field (OpenFF) 2.0.0 small molecule force field for drug-like molecules, code-named Sage, which builds upon our previous iteration, Parsley. OpenFF force fields are based on direct chemical perception, which generalizes easily ...

    Abstract We introduce the Open Force Field (OpenFF) 2.0.0 small molecule force field for drug-like molecules, code-named Sage, which builds upon our previous iteration, Parsley. OpenFF force fields are based on direct chemical perception, which generalizes easily to highly diverse sets of chemistries based on substructure queries. Like the previous OpenFF iterations, the Sage generation of OpenFF force fields was validated in protein-ligand simulations to be compatible with AMBER biopolymer force fields. In this work, we detail the methodology used to develop this force field, as well as the innovations and improvements introduced since the release of Parsley 1.0.0. One particularly significant feature of Sage is a set of improved Lennard-Jones (LJ) parameters retrained against condensed phase mixture data, the first refit of LJ parameters in the OpenFF small molecule force field line. Sage also includes valence parameters refit to a larger database of quantum chemical calculations than previous versions, as well as improvements in how this fitting is performed. Force field benchmarks show improvements in general metrics of performance against quantum chemistry reference data such as root-mean-square deviations (RMSD) of optimized conformer geometries, torsion fingerprint deviations (TFD), and improved relative conformer energetics (ΔΔ
    MeSH term(s) Benchmarking ; Ligands ; Proteins/chemistry ; Thermodynamics ; Entropy
    Chemical Substances Ligands ; Proteins
    Language English
    Publishing date 2023-05-11
    Publishing country United States
    Document type Journal Article
    ISSN 1549-9626
    ISSN (online) 1549-9626
    DOI 10.1021/acs.jctc.3c00039
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