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Mitochondrial Dysfunction And Pharmacodynamics Of Mitofusin Activation In Murine Charcot-Marie-Tooth Disease Type 2a, Antonietta Franco, Xiawei Dang, Lihong Zhang, Perry B Molinoff, Gerald W Dorn 2nd

2020-Current year OA Pubs

Mitofusin (MFN) 1 and MFN2 are dynamin GTPase family mitochondrial proteins that mediate mitochondrial fusion requiring MFN conformational shifts, formation of macromolecular complexes on and between mitochondria, and GTP hydrolysis. Damaging MFN2 mutations cause an untreatable, largely pediatric progressive peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease type 2A. We used small molecule allosteric mitofusin activators that promote MFN conformations favoring fusion to interrogate the effects of MFN2 conformation and GTPase activity on MFN2-mediated mitochondrial fusion and motility in vitro. We translated these findings in vivo by defining dose-dependent pharmacodynamic and disease-modifying effects of mitofusin activators in murine CMT2A. MFN2 catalytic GTPase activity …

Distinct Stimulus-Dependent Neutrophil Dynamics Revealed By Real-Time Imaging Of Intestinal Mucosa After Acute Injury, Veronica Azcutia, Matthias Kelm, Seonyoung Kim, Anny-Claude Luissint, Sven Flemming, Lisa Abernathy-Close, Vincent B Young, Asma Nusrat, Mark J Miller, Charles A Parkos

2020-Current year OA Pubs

Clinical symptoms in many inflammatory diseases of the intestine are directly related to neutrophil (PMN) migration across colonic mucosa and into the intestinal lumen, yet in-vivo studies detailing this process are lacking. Using real-time intravital microscopy and a new distal colon loop model, we report distinct PMN migratory dynamics in response to several models of acute colonic injury. PMNs exhibited rapid swarming responses after mechanically induced intestinal wounds. Similar numbers of PMNs infiltrated colonic mucosa after wounding in germ-free mice, suggesting microbiota-independent mechanisms. By contrast, acute mucosal injury secondary to either a treatment of mice with dextran sodium sulfate or …

A New Mouse Model Of Charcot-Marie-Tooth 2j Neuropathy Replicates Human Axonopathy And Suggest Alteration In Axo-Glia Communication, Ghjuvan'ghjacumu Shackleford, Yo Sasaki, Et Al.

2020-Current year OA Pubs

Myelin is essential for rapid nerve impulse propagation and axon protection. Accordingly, defects in myelination or myelin maintenance lead to secondary axonal damage and subsequent degeneration. Studies utilizing genetic (CNPase-, MAG-, and PLP-null mice) and naturally occurring neuropathy models suggest that myelinating glia also support axons independently from myelin. Myelin protein zero (MPZ or P0), which is expressed only by Schwann cells, is critical for myelin formation and maintenance in the peripheral nervous system. Many mutations in MPZ are associated with demyelinating neuropathies (Charcot-Marie-Tooth disease type 1B [CMT1B]). Surprisingly, the substitution of threonine by methionine at position 124 of P0 …

Inositol Phosphorylceramide Synthase Null Leishmania Are Viable And Virulent In Animal Infections Where Salvage Of Host Sphingomyelin Predominates, F Matthew Kuhlmann, Phillip N Key, Suzanne M Hickerson, John Turk, Fong-Fu Hsu, Stephen M Beverley

2020-Current year OA Pubs

Many pathogens synthesize inositol phosphorylceramide (IPC) as the major sphingolipid (SL), differing from the mammalian host where sphingomyelin (SM) or more complex SLs predominate. The divergence between IPC synthase and mammalian SL synthases has prompted interest as a potential drug target. However, in the trypanosomatid protozoan Leishmania, cultured insect stage promastigotes lack de novo SL synthesis (Δspt2

Trim-Nhl Protein, Nhl-2, Modulates Cell Fate Choices In The C. Elegans Germ Line, John L. Brenner, Erin M. Jyo, Ariz Mohammad, Paul Fox, Vovanti Jones, Elaine Mardis, Tim Schedl, Eleanor M. Maine

2020-Current year OA Pubs

Many tissues contain multipotent stem cells that are critical for maintaining tissue function. In Caenorhabditis elegans, germline stem cells allow gamete production to continue in adulthood. In the gonad, GLP-1/Notch signaling from the distal tip cell niche to neighboring germ cells activates a complex regulatory network to maintain a stem cell population. GLP-1/Notch signaling positively regulates production of LST-1 and SYGL-1 proteins that, in turn, interact with a set of PUF/FBF proteins to positively regulate the stem cell fate. We previously described sog (suppressor of glp-1 loss of function) and teg (tumorous enhancer of glp-1 gain of function) genes that …

A Phase I First-In-Human Study Of Abbv-383, A B-Cell Maturation Antigen × Cd3 Bispecific T-Cell Redirecting Antibody, In Patients With Relapsed/Refractory Multiple Myeloma, Anita D'Souza, Ravi Vij, Et Al.

2020-Current year OA Pubs

PURPOSE: ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study.

METHODS: Patients with RRMM (≥ three prior lines including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody) were eligible. ABBV-383 was administered intravenously over 1-2 hours once every 3 weeks, without any step dosing. A 3 + 3 design with backfilling for dose escalation was used (intrapatient escalation to highest …

An Assessment Of Pediatric Residency Applicant Perceptions Of "Fit" During The Virtual Interview Era, Jason D. Vadhan, Jorge G. Zarate Rodriguez, Michael Wallendorf, Michael M. Awad, Andrew J. White

2020-Current year OA Pubs

PURPOSE: Residency recruitment events and interviews are widely considered an integral component of the residency match experience. Due to the COVID-19 pandemic, residency recruitment and interviewing throughout the 2020-2021 academic year were performed virtually, which created challenges for applicants' ability to discern "fit" to a program. Given this change, it is reasonable to suspect that applicants would be less able to discern program fit. Therefore, this study evaluated how virtual interviews impacted pediatric residency applicants' ability to assess factors contributing to fit and subsequently how applicants assessed their self-perceived fit to their top-ranked programs.

METHODS: An online, anonymous survey was …

Transgenic Force Sensors And Software To Measure Force Transmission Across The Mammalian Nuclear Envelope In Vivo, Kelli D Fenelon, Evan Thomas, Mohammad Samani, Min Zhu, Hirotaka Tao, Yu Sun, Helen Mcneill, Sevan Hopyan

2020-Current year OA Pubs

Nuclear mechanotransduction is a growing field with exciting implications for the regulation of gene expression and cellular function. Mechanical signals may be transduced to the nuclear interior biochemically or physically through connections between the cell surface and chromatin. To define mechanical stresses upon the nucleus in physiological settings, we generated transgenic mouse strains that harbour FRET-based tension sensors or control constructs in the outer and inner aspects of the nuclear envelope. We knocked-in a published esprin-2G sensor to measure tensions across the LINC complex and generated a new sensor that links the inner nuclear membrane to chromatin. To mitigate challenges …

Associations Between Transcranial Doppler Vasospasm And Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study, Abhijit V. Lele, Rafael Wabl, Sarah Wahlster, Jade Keen, Andrew M. Walters, Christine T. Fong, Vasu B. Dhulipala, Umeshkumar Athiraman, Anne Moore, Monica S. Vavilala, Louis J. Kim, Michael R. Levitt

2020-Current year OA Pubs

OBJECTIVE: The objective is to examine the relationship between transcranial Doppler cerebral vasospasm (TCD-vasospasm), and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH).

METHODS: In a retrospective cohort study, using univariate and multivariate analysis, we examined the association between TCD-vasospasm (defined as Lindegaard ratio >3) and patient's ability to ambulate without assistance, the need for tracheostomy and gastrostomy tube placement, and the likelihood of being discharged home from the hospital.

RESULTS: We studied 346 patients with aSAH; median age 55 years (Interquartile range IQR 46,64), median Hunt and Hess 3 [IQR 1-5]. Overall, 68.6% (n=238) had TCD-vasospasm, and 28% (n=97) had …

High-Speed, Scanned Laser Structuring Of Multi-Layered Eco/Bioresorbable Materials For Advanced Electronic Systems, Quansan Yang, Yameng Xu, Ying Yan, Wilson Z Ray, Mitchell A Pet, Matthew R Macewan, Et Al.

2020-Current year OA Pubs

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin …

Identification Of Novel Genes And Proteoforms In Angiostrongylus Costaricensis Through A Proteogenomic Approach, Esdras Matheus Gomes Da Silva, Karina Mastropasqua Rebello, Young-Jun Choi, Vitor Gregorio, Alexandre Rossi Paschoal, Makedonka Mitreva, James H Mckerrow, Ana Gisele Da Costa Neves-Ferreira, Fabio Passetti

2020-Current year OA Pubs

RNA sequencing (RNA-Seq) and mass-spectrometry-based proteomics data are often integrated in proteogenomic studies to assist in the prediction of eukaryote genome features, such as genes, splicing, single-nucleotide (SNVs), and single-amino-acid variants (SAAVs). Most genomes of parasite nematodes are draft versions that lack transcript- and protein-level information and whose gene annotations rely only on computational predictions.

Myocardial Infarction Size As An Independent Predictor Of Intramyocardial Haemorrhage In Acute Reperfused Myocardial Ischaemic Rats, Rui Xia, Tong Zhu, Yu Zhang, Bo He, Yushu Chen, Lei Wang, Yang Zhou, Jichun Liao, Jie Zheng, Yongmei Li, Fajin Lv, Fabao Gao

2020-Current year OA Pubs

BACKGROUND: In previous studies, haemorrhage occurred only with large infarct sizes, and studies found a moderate correlation between the extent of necrosis and haemorrhage, but the extent of infarction size in these studies was limited. This study aimed to find the correlations between intramyocardial haemorrhage (IMH), myocardial infarction (MI), and myocardial oedema (ME) from small to large sizes of MI in a 7.0-T MR scanner.

METHODS: Different sizes of myocardial infarction were induced by occluding different sections of the proximal left anterior descending coronary artery (1-3 mm under the left auricle). T2*-mapping, T2-mapping and late gadolinium enhancement (LGE) sequences were …

Genetic Addiction Risk And Psychological Profiling Analyses For "Preaddiction" Severity Index, Kenneth Blum, Mark S Gold, Et Al.

2020-Current year OA Pubs

Since 1990, when our laboratory published the association of the

Discovery And Characterization Of Potent, Efficacious, Orally Available Antimalarial Plasmepsin X Inhibitors And Preclinical Safety Assessment Of Ucb7362, Martin A Lowe, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Plasmepsin X (PMX) is an essential aspartyl protease controlling malaria parasite egress and invasion of erythrocytes, development of functional liver merozoites (prophylactic activity), and blocking transmission to mosquitoes, making it a potential multistage drug target. We report the optimization of an aspartyl protease binding scaffold and the discovery of potent, orally active PMX inhibitors with in vivo antimalarial efficacy. Incorporation of safety evaluation early in the characterization of PMX inhibitors precluded compounds with a long human half-life (

Risk Factors And Treatment Strategy For Retinal Vascular Occlusive Diseases, Ryo Terao, Ryosuke Fujino, Tazbir Ahmed

2020-Current year OA Pubs

Retinal occlusive diseases are common diseases that can lead to visual impairment. Retinal artery occlusion and retinal vein occlusion are included in the clinical entity, but they have quite different pathophysiologies. Retinal artery occlusion is an emergent eye disorder. Retinal artery occlusion is mainly caused by thromboembolism, which frequently occurs in conjunction with life-threatening stroke and cardiovascular diseases. Therefore, prompt examinations and interventions for systemic vascular diseases are often necessary for these patients. Retinal vein occlusion is characterized by retinal hemorrhage and ischemia, which may impair visual function via several complications such as macular edema, macular ischemia, vitreous hemorrhage, and …

Self-Renewal Of Macrophages: Tumor-Released Factors And Signaling Pathways, Serena Filiberti, Mariapia Russo, Silvia Lonardi, Mattia Bugatti, William Vermi, Cathy Tournier, Emanuele Giurisato

2020-Current year OA Pubs

Macrophages are the most abundant immune cells of the tumor microenvironment (TME) and have multiple important functions in cancer. During tumor growth, both tissue-resident macrophages and newly recruited monocyte-derived macrophages can give rise to tumor-associated macrophages (TAMs), which have been associated with poor prognosis in most cancers. Compelling evidence indicate that the high degree of plasticity of macrophages and their ability to self-renew majorly impact tumor progression and resistance to therapy. In addition, the microenvironmental factors largely affect the metabolism of macrophages and may have a major influence on TAMs proliferation and subsets functions. Thus, understanding the signaling pathways regulating …

Epidemiology Of Plasmid Lineages Mediating The Spread Of Extended-Spectrum Beta-Lactamases Among Clinical Escherichia Coli, Bejan Mahmud, Meghan A Wallace, Kimberly A Reske, Kelly Alvarado, Carol E Muenks, David A Rasmussen, Carey-Ann D Burnham, Cristina Lanzas, Erik R Dubberke, Gautam Dantas

2020-Current year OA Pubs

The prevalence of extended-spectrum beta-lactamases (ESBLs) among clinical isolates of Escherichia coli has been increasing, with this spread driven by ESBL-encoding plasmids. However, the epidemiology of ESBL-disseminating plasmids remains understudied, obscuring the roles of individual plasmid lineages in ESBL spread. To address this, we performed an in-depth genomic investigation of 149 clinical ESBL-like E. coli isolates from a tertiary care hospital. We obtained high-quality assemblies for 446 plasmids, revealing an extensive map of plasmid sharing that crosses time, space, and bacterial sequence type boundaries. Through a sequence-based network, we identified specific plasmid lineages that are responsible for the dissemination of …

Novel Chelating Agents For Zirconium-89-Positron Emission Tomography (Pet) Imaging: Synthesis, Dft Calculation, Radiolabeling, And In Vitro And In Vivo Complex Stability, Chi Soo Kang, Shuyuan Zhang, Haixing Wang, Yujie Liu, Siyuan Ren, Yanda Chen, Jingbai Li, Nilantha Bandara, Andrey Yu Rogachev, Buck E Rogers, Hyun-Soon Chong

2020-Current year OA Pubs

We report the synthesis and evaluation of novel chelating agents for zirconium-89 (

Human Neutrophil Development And Functionality Are Enabled In A Humanized Mouse Model, Yunjiang Zheng, Esen Sefik, John Astle, Kutay Karatepe, Hasan H Öz, Angel G Solis, Ruaidhrí Jackson, Hongbo R Luo, Emanuela M Bruscia, Stephanie Halene, Liang Shan, Richard A Flavell

2020-Current year OA Pubs

Mice with a functional human immune system serve as an invaluable tool to study the development and function of the human immune system in vivo. A major technological limitation of all current humanized mouse models is the lack of mature and functional human neutrophils in circulation and tissues. To overcome this, we generated a humanized mouse model named MISTRGGR, in which the mouse granulocyte colony-stimulating factor (G-CSF) was replaced with human G-CSF and the mouse G-CSF receptor gene was deleted in existing MISTRG mice. By targeting the G-CSF cytokine-receptor axis, we dramatically improved the reconstitution of mature circulating and tissue-infiltrating …

Integrated Host-Microbe Plasma Metagenomics For Sepsis Diagnosis In A Prospective Cohort Of Critically Ill Adults, Katrina L Kalantar, Pratik Sinha, Et Al.

2020-Current year OA Pubs

We carried out integrated host and pathogen metagenomic RNA and DNA next generation sequencing (mNGS) of whole blood (n = 221) and plasma (n = 138) from critically ill patients following hospital admission. We assigned patients into sepsis groups on the basis of clinical and microbiological criteria. From whole-blood gene expression data, we distinguished patients with sepsis from patients with non-infectious systemic inflammatory conditions using a trained bagged support vector machine (bSVM) classifier (area under the receiver operating characteristic curve (AUC) = 0.81 in the training set; AUC = 0.82 in a held-out validation set). Plasma RNA also yielded a …

Cross-Species Efficacy Of Enzyme Replacement Therapy For Cln1 Disease In Mice And Sheep, Hemanth R. Nelvagal, Sophie H. Wang, Elizabeth M. Eultgen, Keigo Takashash, Steven Q. Le, Rachel Nesbitt, Joshua T. Dearborn, Patricia I. Dickson, Mark S. Sands, Jonathan D. Cooper, Et Al.

2020-Current year OA Pubs

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient …

Il-1Β-Dependent Extravasation Of Preexisting Lung-Restricted Autoantibodies During Lung Transplantation Activates Complement And Mediates Primary Graft Dysfunction, Wenbin Yang, Daniel Kreisel, Et Al.

2020-Current year OA Pubs

Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and …

Amyloid Β, Lipid Metabolism, Basal Cholinergic System, And Therapeutics In Alzheimer's Disease, Victoria Campos-Peña, Pavel Pichardo-Rojas, Talía Sánchez-Barbosa, Emma Ortíz-Islas, Citlali Ekaterina Rodríguez-Pérez, Pedro Montes, Gerardo Ramos-Palacios, Daniela Silva-Adaya, Rafael Valencia-Quintana, Jorge Francisco Cerna-Cortes, Danira Toral-Rios

2020-Current year OA Pubs

The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each …

Cellular Sources And Neuroprotective Roles Of Interleukin-10 In The Facial Motor Nucleus After Axotomy, Elizabeth M Runge, Deborah O Setter, Abhirami K Iyer, Eric J Regele, Felicia M Kennedy, Virginia M Sanders, Kathryn J Jones

2020-Current year OA Pubs

Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA.

A Bioresorbable Peripheral Nerve Stimulator For Electronic Pain Block, Geumbee Lee, Emily Ray, Sabrina Genovese, Ying Yan, Arman Odabas, Umang Khandpur, Wilson Z Ray, Matthew R Macewan, Et Al.

2020-Current year OA Pubs

Local electrical stimulation of peripheral nerves can block the propagation of action potentials, as an attractive alternative to pharmacological agents for the treatment of acute pain. Traditional hardware for such purposes, however, involves interfaces that can damage nerve tissue and, when used for temporary pain relief, that impose costs and risks due to requirements for surgical extraction after a period of need. Here, we introduce a bioresorbable nerve stimulator that enables electrical nerve block and associated pain mitigation without these drawbacks. This platform combines a collection of bioresorbable materials in architectures that support stable blocking with minimal adverse mechanical, electrical, …

Continuous Npwt Regulates Fibrosis In Murine Diabetic Wound Healing, Mengfan Wu, Dany Y Matar, Zhen Yu, Ziyu Chen, Samuel Knoedler, Brian Ng, Oliver A Darwish, Sadaf Sohrabi, Leigh Friedman, Valentin Haug, George F Murphy, Yuval Rinkevich, Dennis P Orgill, Adriana C Panayi

2020-Current year OA Pubs

Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, -125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP (

Unravelling The Reservoirs For Colonisation Of Infants With Campylobacter Spp. In Rural Ethiopia: Protocol For A Longitudinal Study During A Global Pandemic And Political Tensions, Arie H Havelaar, Mark J Manary, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Undernutrition is an underlying cause of mortality in children under five (CU5) years of age. Animal-source foods have been shown to decrease malnutrition in CU5. Livestock are important reservoirs for

METHODS AND ANALYSIS: This longitudinal study involves 115 infants who are followed from birth to 12 months of age and are selected randomly from 10 kebeles of Haramaya woreda, East Hararghe zone, Oromia region, Ethiopia. Questionnaire-based information is obtained on demographics, livelihoods, wealth, health, nutrition and women empowerment; animal ownership/management and diseases; and water, sanitation and hygiene. Faecal samples are collected from infants, mothers, siblings and livestock, drinking water …

A Non-Canonical Retina-Iprgcs-Scn-Pvt Visual Pathway For Mediating Contagious Itch Behavior, Fang Gao, Jun Ma, Yao-Qing Yu, Xiao-Fei Gao, Yang Bai, Yi Sun, Juan Liu, Xianyu Liu, Devin M Barry, Steven Wilhelm, Tyler Piccinni-Ash, Na Wang, Dongyang Liu, Yan Hao, Jin-Jing Jia, Qianyi Yang, Johan Van Nispen, Zhou-Feng Chen, Et Al.

2020-Current year OA Pubs

Contagious itch behavior informs conspecifics of adverse environment and is crucial for the survival of social animals. Gastrin-releasing peptide (GRP) and its receptor (GRPR) in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates contagious itch behavior in mice. Here, we show that intrinsically photosensitive retina ganglion cells (ipRGCs) convey visual itch information, independently of melanopsin, from the retina to GRP neurons via PACAP-PAC1R signaling. Moreover, GRPR neurons relay itch information to the paraventricular nucleus of the thalamus (PVT). Surprisingly, neither the visual cortex nor superior colliculus is involved in contagious itch. In vivo calcium imaging and extracellular recordings reveal contagious …

Reprogramming Alveolar Macrophage Responses To Tgf-Β Reveals Ccr2+ Monocyte Activity That Promotes Bronchiolitis Obliterans Syndrome, Zhiyi Liu, Fuyi Liao, Jihong Zhu, Dequan Zhou, Gyu Seong Heo, Hannah P. Leuhmann, Davide Scozzi, Antanisha Parks, Ramsey Hachem, Derek E. Byers, Laneshia K. Tague, Hrishikesh S. Kulkarni, Marlene Cano, Brian W. Wong, Wenjun Li, Daniel Kreisel, Andrew E Gelman, Et Al.

2020-Current year OA Pubs

Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-β and reduce TGF-β bioavailability through secretion of the TGF-β antagonist decorin. In untreated recipients, high airway …

The Transcription Factor Bach2 Negatively Regulates Murine Natural Killer Cell Maturation And Function, Shasha Li, Michael D Bern, Benpeng Miao, Changxu Fan, Xiaoyun Xing, Takeshi Inoue, Sytse J Piersma, Ting Wang, Marco Colonna, Tomohiro Kurosaki, Wayne M Yokoyama

2020-Current year OA Pubs

BTB domain And CNC Homolog 2 (Bach2) is a transcription repressor that actively participates in T and B lymphocyte development, but it is unknown if Bach2 is also involved in the development of innate immune cells, such as natural killer (NK) cells. Here, we followed the expression of Bach2 during murine NK cell development, finding that it peaked in immature CD27