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Article ; Online: Creating truly radical change in autism research: A response to Frith and Mottron.

Pearson, Amy / Woods, Richard / Morgan, Hayley / Botha, Monique

Autism research : official journal of the International Society for Autism Research

2021 Volume 14, Issue 10, Page(s) 2243–2244

MeSH term(s)	Autism Spectrum Disorder ; Autistic Disorder ; Humans
Language	English
Publishing date	2021-09-08
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2481338-2
ISSN	1939-3806 ; 1939-3792
ISSN (online)	1939-3806
ISSN	1939-3792
DOI	10.1002/aur.2605
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Zs.A 6785: Show issues

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Article ; Online: Mucus clears from the trachea in a helix: a new twist to understanding airway diseases.

Abelson, David / Di Michiel, James / Frater, Clayton / Pearson, Mark / Russo, Robert / Wechselberger, Martin / Cottee, Alice / Morgan, Lucy

Thorax

2024

Abstract: Background: Mucociliary clearance (MCC) is critical to lung health and is impaired in many diseases. The path of MCC may have an important impact on clearance but has never been rigorously studied. The objective of this study is to assess the three- ... ...

Abstract	Background: Mucociliary clearance (MCC) is critical to lung health and is impaired in many diseases. The path of MCC may have an important impact on clearance but has never been rigorously studied. The objective of this study is to assess the three-dimensional path of human tracheal MCC in disease and health. Methods: Tracheal MCC was imaged in 12 ex-smokers, 3 non-smokers (1 opportunistically imaged during acute influenza and repeated after recovery) and 5 individuals with primary ciliary dyskinesia (PCD). Radiolabelled macroaggregated albumin droplets were injected into the trachea via the cricothyroid membrane. Droplet movement was tracked via scintigraphy, the path of movement mapped and helical and axial models of tracheal MCC were compared. Measurements and main results: In 5/5 participants with PCD and 1 healthy participant with acute influenza, radiolabelled albumin coated the trachea and did not move. In all others (15/15), mucus coalesced into globules. Globule movement was negligible in 3 ex-smokers, but in all others (12/15) ascended the trachea in a helical path. Median cephalad tracheal MCC was 2.7 mm/min ex-smokers vs 8.4 mm/min non-smokers (p=0.02) and correlated strongly to helical angle (r=0.92 (p=0.00002); median 18 Conclusion: For the first time, we show that human tracheal MCC is helical, and impairment in ex-smokers is often caused by flattened helical transit, not slower movement. Our methodology provides a simple method to map tracheal MCC and speed in vivo.
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thorax-2023-221052
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Article ; Online: Spontaneous Disseminated Histiocytic Sarcoma in a Bengal Tiger (Panthera tigris tigris).

Matthews, Morgan / Hilliard, Berkeley / Pearson, Merten / Waggoner, Aubrey

Journal of comparative pathology

2021 Volume 188, Page(s) 32–36

Abstract: A 16-year-old, female, captive Bengal tiger (Panthera tigris tigris) had a history of a recurrent subcutaneous mass. After two attempts at surgical removal, euthanasia was elected during the third surgical attempt due to the degree of neoplastic ... ...

Abstract	A 16-year-old, female, captive Bengal tiger (Panthera tigris tigris) had a history of a recurrent subcutaneous mass. After two attempts at surgical removal, euthanasia was elected during the third surgical attempt due to the degree of neoplastic infiltration. At necropsy, a large subcutaneous mass infiltrated the dermis, subcutis and abdominal wall with metastasis to the lungs, spleen and adrenal glands. Microscopically, the neoplasm formed nodules comprising sheets of round cells with large irregular nuclei. Toluidine blue and Giemsa stains were negative. An immunohistochemistry panel revealed membranous and cytoplasmic labelling with ionized calcium-binding adaptor molecule 1 (IBA1), cytoplasmic labelling with vimentin but no labelling with multiple myeloma oncogene 1 (MUM1), CD20 or pancytokeratin markers. Based on the gross distribution and histological and immunohistochemistry features, a diagnosis of disseminated histiocytic sarcoma was made. To the best of our knowledge, this is the first record of disseminated histiocytic sarcoma in a captive Bengal tiger.
MeSH term(s)	Adrenal Glands ; Animals ; Animals, Zoo ; Female ; Histiocytic Sarcoma/veterinary ; Lung ; Neoplasm Metastasis ; Spleen ; Tigers
Language	English
Publishing date	2021-09-22
Publishing country	England
Document type	Journal Article
ZDB-ID	390920-7
ISSN	1532-3129 ; 0021-9975
ISSN (online)	1532-3129
ISSN	0021-9975
DOI	10.1016/j.jcpa.2021.08.007
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Ud II Zs.195: Show issues

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Article ; Online: Potentiating the radiation-induced type I interferon antitumoral immune response by ATM inhibition in pancreatic cancer.

Zhang, Qiang / Jiang, Long / Wang, Weiwei / Huber, Amanda K / Valvo, Victoria M / Jungles, Kassidy M / Holcomb, Erin A / Pearson, Ashley N / The, Stephanie / Wang, Zhuwen / Parsels, Leslie A / Parsels, Joshua D / Wahl, Daniel R / Rao, Arvind / Sahai, Vaibhav / Lawrence, Theodore S / Green, Michael D / Morgan, Meredith A

JCI insight

2024 Volume 9, Issue 6

Abstract: Radiotherapy induces a type I interferon-mediated (T1IFN-mediated) antitumoral immune response that we hypothesized could be potentiated by a first-in-class ataxia telangiectasia mutated (ATM) inhibitor, leading to enhanced innate immune signaling, T1IFN ...

Abstract	Radiotherapy induces a type I interferon-mediated (T1IFN-mediated) antitumoral immune response that we hypothesized could be potentiated by a first-in-class ataxia telangiectasia mutated (ATM) inhibitor, leading to enhanced innate immune signaling, T1IFN expression, and sensitization to immunotherapy in pancreatic cancer. We evaluated the effects of AZD1390 or a structurally related compound, AZD0156, on innate immune signaling and found that both inhibitors enhanced radiation-induced T1IFN expression via the POLIII/RIG-I/MAVS pathway. In immunocompetent syngeneic mouse models of pancreatic cancer, ATM inhibitor enhanced radiation-induced antitumoral immune responses and sensitized tumors to anti-PD-L1, producing immunogenic memory and durable tumor control. Therapeutic responses were associated with increased intratumoral CD8+ T cell frequency and effector function. Tumor control was dependent on CD8+ T cells, as therapeutic efficacy was blunted in CD8+ T cell-depleted mice. Adaptive immune responses to combination therapy provided systemic control of contralateral tumors outside of the radiation field. Taken together, we show that a clinical candidate ATM inhibitor enhances radiation-induced T1IFN, leading to both innate and subsequent adaptive antitumoral immune responses and sensitization of otherwise resistant pancreatic cancer to immunotherapy.
MeSH term(s)	Animals ; Mice ; Interferon Type I ; Ataxia Telangiectasia ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/radiotherapy ; Pancreatic Neoplasms/pathology ; Immunity ; Pyridines ; Quinolones
Chemical Substances	Interferon Type I ; AZD1390 ; Pyridines ; Quinolones
Language	English
Publishing date	2024-02-20
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.168824
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Article ; Online: Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes.

Boldison, Joanne / Hopkinson, Jessica R / Davies, Joanne / Pearson, James A / Leete, Pia / Richardson, Sarah / Morgan, Noel G / Wong, F Susan

Diabetologia

2022 Volume 66, Issue 3, Page(s) 551–566

Abstract: Aims/hypothesis: B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell ... ...

Abstract	Aims/hypothesis: B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes. Methods: Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice. Results: B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph nodes. We identified both a discrete and a core shared gene expression profile in islet CD19 Conclusions/interpretation: Our study provides a detailed transcriptional analysis of islet B cells. Specific gene signatures and interaction networks have been identified that point towards a functional role for B cells in driving autoimmune diabetes.
MeSH term(s)	Mice ; Animals ; Diabetes Mellitus, Type 1/metabolism ; Mice, Inbred NOD ; Pancreas/metabolism ; Islets of Langerhans/metabolism ; Gene Expression Profiling
Language	English
Publishing date	2022-12-12
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-022-05839-7
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Zs.A 279: Show issues

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Article ; Online: Emotion Regulation Mediates the Relationship Between Therapeutic Alliance and Anxiety in Emerging Adults During Inpatient Psychiatric Treatment.

Shepard, Christopher A / Rufino, Katrina A / Daza, Patricia / Pearson, Alexandra / Cuenod, Morgan / Patriquin, Michelle A

Journal of psychiatric practice

2022 Volume 28, Issue 5, Page(s) 383–390

Abstract: Emerging adulthood is a critical developmental period characterized by emotional growth and unstructured living. To date, there is little research on emerging adults-defined as those 18 to 25 years old-with serious mental illnesses and even less on ... ...

Abstract	Emerging adulthood is a critical developmental period characterized by emotional growth and unstructured living. To date, there is little research on emerging adults-defined as those 18 to 25 years old-with serious mental illnesses and even less on emerging adults in psychiatric hospitals. This study analyzed therapeutic alliance with the clinical team and change in anxiety symptoms in emerging adult psychiatric inpatients with the goal of establishing whether emotion regulation could serve as a mediator between these 2 constructs. Participants were 913 emerging adults (46.7% female; 18 to 25 y of age) who were voluntarily admitted to an intermediate length-of-stay (6 to 8 wk) inpatient psychiatric hospital. Each patient completed measures assessing anxiety symptoms, emotion regulation strategies, and working alliance as an assessment of therapeutic alliance. The results indicated that working alliance had significant indirect effects on change in anxiety symptoms through emotion dysregulation and lack of awareness, limited access to emotion regulation strategies, and lack of emotional clarity. This study emphasizes the need to understand emerging adults and the difficulties characteristic of this developmental period, and that clinicians should be aware that cognitive factors involved in emotion regulation may impact anxiety symptoms in emerging adult populations.
MeSH term(s)	Adolescent ; Adult ; Anxiety/psychology ; Anxiety/therapy ; Anxiety Disorders/psychology ; Anxiety Disorders/therapy ; Emotional Regulation ; Female ; Humans ; Inpatients/psychology ; Male ; Therapeutic Alliance ; Young Adult
Language	English
Publishing date	2022-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2022726-7
ISSN	1538-1145 ; 1527-4160
ISSN (online)	1538-1145
ISSN	1527-4160
DOI	10.1097/PRA.0000000000000656
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Zs.A 4753: Show issues

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Article: Spontaneous Disseminated Histiocytic Sarcoma in a Bengal Tiger (Panthera tigris tigris)

Matthews, Morgan / Hilliard, Berkeley / Pearson, Merten / Waggoner, Aubrey

Journal of comparative pathology. 2021 Oct., v. 188

2021

Abstract	A 16-year-old, female, captive Bengal tiger (Panthera tigris tigris) had a history of a recurrent subcutaneous mass. After two attempts at surgical removal, euthanasia was elected during the third surgical attempt due to the degree of neoplastic infiltration. At necropsy, a large subcutaneous mass infiltrated the dermis, subcutis and abdominal wall with metastasis to the lungs, spleen and adrenal glands. Microscopically, the neoplasm formed nodules comprising sheets of round cells with large irregular nuclei. Toluidine blue and Giemsa stains were negative. An immunohistochemistry panel revealed membranous and cytoplasmic labelling with ionized calcium-binding adaptor molecule 1 (IBA1), cytoplasmic labelling with vimentin but no labelling with multiple myeloma oncogene 1 (MUM1), CD20 or pancytokeratin markers. Based on the gross distribution and histological and immunohistochemistry features, a diagnosis of disseminated histiocytic sarcoma was made. To the best of our knowledge, this is the first record of disseminated histiocytic sarcoma in a captive Bengal tiger.
Keywords	Panthera tigris tigris ; dermis ; euthanasia ; females ; immunohistochemistry ; ionization ; metastasis ; myeloma ; necropsy ; oncogenes ; sarcoma ; spleen ; toluidine blue ; vimentin
Language	English
Dates of publication	2021-10
Size	p. 32-36.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	390920-7
ISSN	1532-3129 ; 0021-9975
ISSN (online)	1532-3129
ISSN	0021-9975
DOI	10.1016/j.jcpa.2021.08.007
Database	NAL-Catalogue (AGRICOLA)

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Ud II Zs.195: Show issues

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Article ; Online: Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups along the US/Mexico border.

Barger, Steven D / Lininger, Monica R / Trotter, Robert T / Mbegbu, Mimi / Kyman, Shari / Tucker-Morgan, Kara / Wood, Colin / Coyne, Briana / Russakoff, Benjamin / Ceniceros, Kathya / Padilla, Cristina / Maltinsky, Sara / Pearson, Talima

PloS one

2023 Volume 18, Issue 4, Page(s) e0284400

Abstract: Asymptomatic carriage of Staphylococcus aureus is a major risk factor for subsequent clinical infection. Diminishing returns from mitigation efforts emphasize the need to better understand colonization, spread, and transmission of this opportunistic ... ...

Abstract	Asymptomatic carriage of Staphylococcus aureus is a major risk factor for subsequent clinical infection. Diminishing returns from mitigation efforts emphasize the need to better understand colonization, spread, and transmission of this opportunistic pathogen. While contact with other people presents opportunities for pathogen exposure and transmission, diversity of social connections may be protective against pathogens such as the common cold. This study examined whether social relationship resources, including the amount and diversity of social contacts, are associated with S. aureus colonization. Participants were community members (N = 443; 68% Hispanic) in naturally occurring social groups in southwestern Arizona. Four types of social relationships and loneliness were assessed, and samples from the skin, nose and throat were obtained to ascertain S. aureus colonization. Overall S. aureus prevalence was 64.8%. Neither the amount nor the diversity of social contacts were associated with S. aureus colonization. The concurrent validity of the social relationship assessments was supported by their moderate intercorrelations and by their positive association with self-rated health. The results suggest that the association of social network diversity and susceptibility to the common cold does not extend to S. aureus colonization. Conversely, colonization prevalence was not higher among those with more social contacts. The latter pattern suggests that social transmission may be relatively infrequent or that more intimate forms of social interaction may drive transmission and colonization resulting in high community prevalence of S. aureus colonization. These data inform communicable disease control efforts.
MeSH term(s)	Humans ; Staphylococcus aureus ; Cross-Sectional Studies ; Common Cold ; Social Group ; Mexico/epidemiology ; Staphylococcal Infections/epidemiology ; Social Interaction ; Methicillin-Resistant Staphylococcus aureus ; Carrier State/epidemiology
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0284400
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Article ; Online: Short-term Assessment of Subfoveal Injection of Adeno-Associated Virus-Mediated hCHM Gene Augmentation in Choroideremia Using Adaptive Optics Ophthalmoscopy.

Morgan, Jessica I W / Jiang, Yu You / Vergilio, Grace K / Serrano, Leona W / Pearson, Denise J / Bennett, Jean / Maguire, Albert M / Aleman, Tomas S

JAMA ophthalmology

2022 Volume 140, Issue 4, Page(s) 411–420

Abstract: Importance: Subretinal injection for gene augmentation in retinal degenerations forcefully detaches the neural retina from the retinal pigment epithelium, potentially damaging photoreceptors and/or retinal pigment epithelium cells.: Objective: To use ...

Abstract	Importance: Subretinal injection for gene augmentation in retinal degenerations forcefully detaches the neural retina from the retinal pigment epithelium, potentially damaging photoreceptors and/or retinal pigment epithelium cells. Objective: To use adaptive optics scanning light ophthalmoscopy (AOSLO) to assess the short-term integrity of the cone mosaic following subretinal injections of adeno-associated virus vector designed to deliver a functional version of the CHM gene (AAV2-hCHM) in patients with choroideremia. Design, setting, and participants: This longitudinal case series study enrolled adult patients with choroideremia from February 2015 to January 2016 in the US. To be included in the study, study participants must have received uniocular subfoveal injections of low-dose (5 × 1010 vector genome per eye) or high-dose (1 × 1011 vector genome per eye) AAV2-hCHM. Analysis began February 2015. Main outcomes and measures: The macular regions of both eyes were imaged before and 1 month after injection using a custom-built multimodal AOSLO. Postinjection cone inner segment mosaics were compared with preinjection mosaics at multiple regions of interest. Colocalized spectral-domain optical coherence tomography and dark-adapted cone sensitivity was also acquired at each time point. Results: Nine study participants ranged in age from 26 to 50 years at the time of enrollment, and all were White men. Postinjection AOSLO images showed preservation of the cone mosaic in all 9 AAV2-hCHM-injected eyes. Mosaics appeared intact and contiguous 1 month postinjection, with the exception of foveal disruption in 1 patient. Optical coherence tomography showed foveal cone outer segment shortening postinjection. Cone-mediated sensitivities were unchanged in 8 of 9 injected and 9 of 9 uninjected eyes. One participant showed acute loss of foveal optical coherence tomography cone outer segment-related signals along with cone sensitivity loss that colocalized with disruption of the mosaic on AOSLO. Conclusions and relevance: Integrity of the cone mosaic is maintained following subretinal delivery of AAV2-hCHM, providing strong evidence in support of the safety of the injections. Minor foveal thinning observed following surgery corresponds with short-term cone outer segment shortening rather than cone cell loss. Foveal cone loss in 1 participant raises the possibility of individual vulnerability to the subretinal injection.
MeSH term(s)	Adult ; Choroideremia/diagnosis ; Choroideremia/genetics ; Choroideremia/therapy ; Dependovirus/genetics ; Humans ; Male ; Middle Aged ; Ophthalmoscopy/methods ; Retinal Cone Photoreceptor Cells ; Tomography, Optical Coherence/methods
Language	English
Publishing date	2022-03-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701705-9
ISSN	2168-6173 ; 2168-6165
ISSN (online)	2168-6173
ISSN	2168-6165
DOI	10.1001/jamaophthalmol.2022.0158
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Article ; Online: The SON RNA splicing factor is required for intracellular trafficking structures that promote centriole assembly and ciliogenesis.

Stemm-Wolf, Alexander J / O'Toole, Eileen T / Sheridan, Ryan M / Morgan, Jacob T / Pearson, Chad G

Molecular biology of the cell

2021 Volume 32, Issue 20, Page(s) ar4

Abstract: Control of centrosome assembly is critical for cell division, intracellular trafficking, and cilia. Regulation of centrosome number occurs through the precise duplication of centrioles that reside in centrosomes. Here we explored transcriptional control ... ...

Abstract	Control of centrosome assembly is critical for cell division, intracellular trafficking, and cilia. Regulation of centrosome number occurs through the precise duplication of centrioles that reside in centrosomes. Here we explored transcriptional control of centriole assembly and find that the RNA splicing factor SON is specifically required for completing procentriole assembly. Whole genome mRNA sequencing identified genes whose splicing and expression are affected by the reduction of SON, with an enrichment in genes involved in the microtubule (MT) cytoskeleton, centrosome, and centriolar satellites. SON is required for the proper splicing and expression of
MeSH term(s)	Cell Cycle Proteins/metabolism ; Cell Line ; Centrioles/metabolism ; Centrioles/physiology ; Centrosome/metabolism ; Centrosome/physiology ; Cilia/metabolism ; Cilia/physiology ; Cytoskeletal Proteins/metabolism ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/physiology ; Gene Expression ; Humans ; Microtubules/metabolism ; Minor Histocompatibility Antigens/metabolism ; Minor Histocompatibility Antigens/physiology ; Protein Transport/physiology ; RNA/metabolism ; RNA Splicing Factors/genetics ; RNA Splicing Factors/physiology
Chemical Substances	CEP131 protein, human ; Cell Cycle Proteins ; Cytoskeletal Proteins ; DNA-Binding Proteins ; Minor Histocompatibility Antigens ; RNA Splicing Factors ; SON protein, human ; RNA (63231-63-0)
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E21-06-0305
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