Digital Commons Network^™

Protein Proximity Networks And Functional Evaluation Of The Casein Kinase 1 Gamma Family Reveal Unique Roles For Ck1Γ3 In Wnt Signaling, Megan J. Agajanian, Frances M. Potjewyd, Brittany M. Bowman, Smaranda Solomon, Kyle M. Lapak, Dhaval P. Bhatt, Jeffery L. Smith, Dennis Goldfarb, Alison D. Axtman, Michael B. Major

2020-Current year OA Pubs

Aberrant activation or suppression of WNT/β-catenin signaling contributes to cancer initiation and progression, neurodegeneration, and bone disease. However, despite great need and more than 40 years of research, targeted therapies for the WNT pathway have yet to be fully realized. Kinases are considered exceptionally druggable and occupy key nodes within the WNT signaling network, but several pathway-relevant kinases remain understudied and "dark." Here, we studied the function of the casein kinase 1γ (CSNK1γ) subfamily of human kinases and their roles in WNT signaling. miniTurbo-based proximity biotinylation and mass spectrometry analysis of CSNK1γ1, CSNK1γ2, and CSNK1γ3 revealed numerous components of the …

Pdxnet Portal: Patient-Derived Xenograft Model, Data, Workflow And Tool Discovery, Soner Koc, Ramaswamy Govindan, Li Ding, Shunqiang Li, Et Al.

2020-Current year OA Pubs

We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI's Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples …

Horizontal Gene Transfer Provides Insights Into The Deep Evolutionary History And Biology Of Trichinella, Dante Zarlenga, Peter Thompson, Makedonka Mitreva, Bruce A Rosa, Eric Hoberg

2020-Current year OA Pubs

Evolution involves temporal changes in the characteristics of a species that are subsequently propagated or rejected through natural selection. In the case of parasites, host switching also plays a prominent role in the evolutionary process. These changes are rooted in genetic variation and gene flow where genes may be deleted, mutated (sequence), duplicated, rearranged and/or translocated and then transmitted through vertical gene transfer. However, the introduction of new genes is not driven only by Mendelian inheritance and mutation but also by the introduction of DNA from outside a lineage in the form of horizontal gene transfer between donor and recipient …

Rationale Of Using The Dual Chemokine Receptor Ccr2/Ccr5 Inhibitor Cenicriviroc For The Treatment Of Covid-19, Daniel Clark Files, Frank Tacke, Alexandra O'Sullivan, Patrick Dorr, William G. Ferguson, William G. Powderly

2020-Current year OA Pubs

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created a global pandemic infecting over 230 million people and costing millions of lives. Therapies to attenuate severe disease are desperately needed. Cenicriviroc (CVC), a C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) antagonist, an agent previously studied in advanced clinical trials for patients with HIV or nonalcoholic steatohepatitis (NASH), may have the potential to reduce respiratory and cardiovascular organ failures related to COVID-19. Inhibiting the CCR2 and CCR5 pathways could attenuate or prevent inflammation or fibrosis in both early and …

Bespoke Io Protocol: A Multicentre, Prospective Observational Study Evaluating The Utility Of Ctdna In Guiding Immunotherapy In Patients With Advanced Solid Tumours, Pashtoon Murtaza Kasi, Sakti Chakrabarti, Sarah Sawyer, Michael Krainock, Andrew Poklepovic, George Ansstas, Minu Maninder, Meenakshi Malhotra, Joe Ensor, Ling Gao, Zeynep Eroglu, Sascha Ellers, Paul Billings, Angel Rodriguez, Alexey Aleshin

Open Access Publications

INTRODUCTION: Immunotherapy (IO) has transformed the treatment paradigm for a wide variety of solid tumours. However, assessment of response can be challenging with conventional radiological imaging (eg, iRECIST), which do not precisely capture the unique response patterns of tumours treated with IO. Emerging data suggest that circulating tumour DNA (ctDNA) can aid in response assessment in patients with solid tumours receiving IO. The short half-life of ctDNA puts it in a unique position for early treatment response monitoring. The BESPOKE IO study is designed to investigate the clinical utility of serial ctDNA testing to assess treatment response using a tumour-informed, …

The H3k27m Mutation Alters Stem Cell Growth, Epigenetic Regulation, And Differentiation Potential, N Kfoury-Beaumont, R Prakasam, S Pondugula, J S Lagas, S Matkovich, P Gontarz, L Yang, H Yano, A H Kim, J B Rubin, K L Kroll

2020-Current year OA Pubs

BACKGROUND: Neurodevelopmental disorders increase brain tumor risk, suggesting that normal brain development may have protective properties. Mutations in epigenetic regulators are common in pediatric brain tumors, highlighting a potentially central role for disrupted epigenetic regulation of normal brain development in tumorigenesis. For example, lysine 27 to methionine mutation (H3K27M) in the H3F3A gene occurs frequently in Diffuse Intrinsic Pontine Gliomas (DIPGs), the most aggressive pediatric glioma. As H3K27M mutation is necessary but insufficient to cause DIPGs, it is accompanied by additional mutations in tumors. However, how H3K27M alone increases vulnerability to DIPG tumorigenesis remains unclear.

RESULTS: Here, we used human …

Wireless Implantable Optical Probe For Continuous Monitoring Of Oxygen Saturation In Flaps And Organ Grafts, Hexia Guo, Yameng Xu, Lauren Jacobson, Amanda M Westman, Matthew R Macewan, Mitchell A Pet, Et Al.

2020-Current year OA Pubs

Continuous, real-time monitoring of perfusion after microsurgical free tissue transfer or solid organ allotransplantation procedures can facilitate early diagnosis of and intervention for anastomotic thrombosis. Current technologies including Doppler systems, cutaneous O

Beyond Inhibition: A Novel Strategy Of Targeting Hiv-1 Protease To Eliminate Viral Reservoirs, Josh G Kim, Liang Shan

2020-Current year OA Pubs

HIV-1 protease (PR) is a viral enzyme that cleaves the Gag and Gag-Pol polyprotein precursors to convert them into their functional forms, a process which is essential to generate infectious viral particles. Due to its broad substrate specificity, HIV-1 PR can also cleave certain host cell proteins. Several studies have identified host cell substrates of HIV-1 PR and described the potential impact of their cleavage on HIV-1-infected cells. Of particular interest is the interaction between PR and the caspase recruitment domain-containing protein 8 (CARD8) inflammasome. A recent study demonstrated that CARD8 can sense HIV-1 PR activity and induce cell death. …

Multisystem Proteinopathy Due To Vcp Mutations: A Review Of Clinical Heterogeneity And Genetic Diagnosis, Gerald Pfeffer, Grace Lee, Carly S Pontifex, Roberto D Fanganiello, Allison Peck, Conrad C Weihl, Virginia Kimonis

2020-Current year OA Pubs

In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in

Synthetic Gene Circuits For Preventing Disruption Of The Circadian Clock Due To Interleukin-1-Induced Inflammation, Lara Pferdehirt, Anna R Damato, Michal Dudek, Qing-Jun Meng, Erik D Herzog, Farshid Guilak

Open Access Publications

The circadian clock regulates tissue homeostasis through temporal control of tissue-specific clock-controlled genes. In articular cartilage, disruptions in the circadian clock are linked to a procatabolic state. In the presence of inflammation, the cartilage circadian clock is disrupted, which further contributes to the pathogenesis of diseases such as osteoarthritis. Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 …

Shiny Gatom: Omics-Based Identification Of Regulated Metabolic Modules In Atom Transition Networks, Mariia Emelianova, Anastasiia Gainullina, Nikolay Poperechnyi, Alexander Loboda, Maxim Artyomov, Alexey Sergushichev

2020-Current year OA Pubs

Multiple high-throughput omics techniques provide different angles on systematically quantifying and studying metabolic regulation of cellular processes. However, an unbiased analysis of such data and, in particular, integration of multiple types of data remains a challenge. Previously, for this purpose we developed GAM web-service for integrative metabolic network analysis. Here we describe an updated pipeline GATOM and the corresponding web-service Shiny GATOM, which takes as input transcriptional and/or metabolomic data and finds a metabolic subnetwork most regulated between the two conditions of interest. GATOM features a new metabolic network topology based on atom transition, which significantly improves interpretability of the …

Sars-Cov-2 Accessory Proteins Reveal Distinct Serological Signatures In Children, Asmaa Hachim, Gaya K Amarasinghe, Abraham J Qavi, Et Al

Open Access Publications

The antibody response magnitude and kinetics may impact clinical severity, serological diagnosis and long-term protection of COVID-19, which may play a role in why children experience lower morbidity. We therefore tested samples from 122 children in Hong Kong with symptomatic (n = 78) and asymptomatic (n = 44) SARS-CoV-2 infections up to 200 days post infection, relative to 71 infected adults (symptomatic n = 61, and asymptomatic n = 10), and negative controls (n = 48). We assessed serum IgG antibodies to a 14-wide antigen panel of structural and accessory proteins by Luciferase Immuno-Precipitation System (LIPS) assay and circulating cytokines. …

Multivalent Designed Proteins Neutralize Sars-Cov-2 Variants Of Concern And Confer Protection Against Infection In Mice, Andrew C Hunt, James Brett Case, Rita E Chen, Baoling Ying, Adam L Bailey, Natasha M Kafai, Michael S Diamond, Et Al

Open Access Publications

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. …

Cardiovascular Tropism And Sequelae Of Sars-Cov-2 Infection, Oleksandr Dmytrenko, Kory J Lavine

2020-Current year OA Pubs

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline …

A Genetically Distinct Pediatric Subtype Of Primary Cns Large B-Cell Lymphoma Is Associated With Favorable Clinical Outcome, Ekin Güney, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

No abstract provided.

Surprise And Recency In Novelty Detection In The Primate Brain, Kaining Zhang, Ethan S Bromberg-Martin, Fatih Sogukpinar, Kim Kocher, Ilya E Monosov

2020-Current year OA Pubs

Primates and other animals must detect novel objects. However, the neuronal mechanisms of novelty detection remain unclear. Prominent theories propose that visual object novelty is either derived from the computation of recency (how long ago a stimulus was experienced) or is a form of sensory surprise (stimulus unpredictability). Here, we use high-channel electrophysiology in primates to show that in many primate prefrontal, temporal, and subcortical brain areas, object novelty detection is intertwined with the computations of recency and sensory surprise. Also, distinct circuits could be engaged by expected versus unexpected sensory surprise. Finally, we studied neuronal novelty-to-familiarity transformations during learning …

Integrative Genomic Analysis Reveals Low T-Cell Infiltration As The Primary Feature Of Tobacco Use In Hpv-Positive Oropharyngeal Cancer, Benjamin M Wahle, Paul Zolkind, Ricardo J Ramirez, Zachary L Skidmore, Sydney R Anderson, Angela Mazul, D Neil Hayes, Vlad C Sandulache, Wade L Thorstad, Douglas Adkins, Obi L Griffith, Malachi Griffith, Jose P Zevallos

2020-Current year OA Pubs

Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T > C substitutions and a lower proportion of expected mutational signatures, but not with …

Belimumab For Systemic Lupus Erythematosus - Focus On Lupus Nephritis, Marlene Plüß, Silvia Piantoni, Björn Tampe, Alfred H J Kim, Peter Korsten

2020-Current year OA Pubs

In recent years, advances in the treatment and management of patients with systemic lupus erythematosus (SLE) have improved their life expectancy and quality of life. However, lupus nephritis (LN) still represents a major life-threatening complication of the disease. Belimumab (BEL), a fully human monoclonal IgG1λ antibody neutralizing soluble B cell activating factor, was approved more than ten years ago as add-on therapy in adults and pediatric patients with a highly active, autoantibody-positive disease despite standard of care (SoC). Recently, the superiority of the addition of BEL to SoC was also demonstrated in LN. In this review, we provide a comprehensive …

The Plasmodium Falciparum Abc Transporter Abci3 Confers Parasite Strain-Dependent Pleiotropic Antimalarial Drug Resistance, James M Murithi, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital need to develop compounds with novel modes of action and identify new druggable targets. Here, we profile five compounds that potently inhibit P. falciparum asexual blood stages. Resistance selection studies with three carboxamide-containing compounds, confirmed by gene editing and conditional knockdowns, identify point mutations in the parasite transporter ABCI3 as the primary mediator of resistance. Selection studies with imidazopyridine or quinoline-carboxamide compounds also yield changes in ABCI3, this time through gene amplification. Imidazopyridine mode of action is attributed to inhibition of heme detoxification, as evidenced by cellular accumulation and heme …

Temporal Trend Of Opioid And Nonopioid Pain Medications: Results From A National In-Home Survey, 2001 To 2018, Yun Wang, Dan Wu, Alexandre Chan, Chih-Hung Chang, Vivian W Y Lee, Michael B Nichol

Open Access Publications

Introduction: The opioid epidemic persists in the United States. The use of opioid medications is often assessed by claims data but potentially underestimated.

Objectives: We evaluated the temporal trend in the use of opioid and nonopioid pain medications from a national survey.

Methods: Using data from the 2001 to 2018 National Health and Nutrition Examination Survey (NHANES), we examined the current use of prescription analgesics in the past 30 days among 50,201 respondents aged 20 years or older. Joinpoint regressions were used to test statistically meaningful trends of opioid vs nonopioid analgesics.

Results: The mean percentage of people who had …

An Approach For Evaluating The Effects Of Dietary Fiber Polysaccharides On The Human Gut Microbiome And Plasma Proteome, Omar Delannoy-Bruno, Chandani Desai, Ruteja A Barve, Jiye Cheng, Nathan Han, Stacey Marion, Andrew C Heath, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

Increases in snack consumption associated with Westernized lifestyles provide an opportunity to introduce nutritious foods into poor diets. We describe two 10-wk-long open label, single group assignment human studies that measured the effects of two snack prototypes containing fiber preparations from two sustainable and scalable sources; the byproducts remaining after isolation of protein from the endosperm of peas and the vesicular pulp remaining after processing oranges for the manufacture of juices. The normal diets of study participants were supplemented with either a pea- or orange fiber-containing snack. We focused our analysis on quantifying the abundances of genes encoding carbohydrate-active enzymes …

Metasquare: An Integrated Metadatabase Of 16s Rrna Gene Amplicon For Microbiome Taxonomic Classification, Chun-Chieh Liao, Po-Ying Fu, Chih-Wei Huang, Chia-Hsien Chuang, Yun Yen, Chung-Yen Lin, Shu-Hwa Chen

2020-Current year OA Pubs

MOTIVATION: Taxonomic classification of 16S ribosomal RNA gene amplicon is an efficient and economic approach in microbiome analysis. 16S rRNA sequence databases like SILVA, RDP, EzBioCloud and HOMD used in downstream bioinformatic pipelines have limitations on either the sequence redundancy or the delay on new sequence recruitment. To improve the 16S rRNA gene-based taxonomic classification, we merged these widely used databases and a collection of novel sequences systemically into an integrated resource.

RESULTS: MetaSquare version 1.0 is an integrated 16S rRNA sequence database. It is composed of more than 6 million sequences and improves taxonomic classification resolution on both long-read …

Country Reports On Practical Aspects Of Conducting Large-Scale Community Studies Of The Tolerability Of Mass Drug Administration With Ivermectin/Diethylcarbamazine/Albendazole For Lymphatic Filariasis, Purushothaman Jambulingam, Swaminathan Subramanian, Kaliannagounder Krishnamoorthy, Taniawati Supali, Peter Fischer, Christine Dubray, Carl Fayette, Jean Frantz Lemoine, Moses Laman, Christopher King, Josaia Samuela, Myra Hardy, Gary J Weil

2020-Current year OA Pubs

This article is a compilation of summaries prepared by lead investigators for large-scale safety and efficacy studies on mass drug administration of IDA (ivermectin, diethylcarbamazine, and albendazole) for lymphatic filariasis. The summaries highlight the experiences of study teams that assessed the safety and efficacy of IDA in five countries: India, Indonesia, Haiti, Papua New Guinea, and Fiji. They also highlight significant challenges encountered during these community studies and responses to those challenges that contributed to success.

Phase Ii Trial Of Cdx-3379 And Cetuximab In Recurrent/Metastatic, Hpv-Negative, Cetuximab-Resistant Head And Neck Cancer, Julie E Bauman, Ricklie Julian, Nabil F Saba, Trisha M Wise-Draper, Douglas R Adkins, Paul O'Brien, Mary Jo Fidler, Michael K Gibson, Umamaheswar Duvvuri, Margo Heath-Chiozzi, Diego Alvarado, Richard Gedrich, Philip Golden, Roger B Cohen

Open Access Publications

In phase I development, CDX-3379, an anti-ErbB3 monoclonal antibody, showed promising molecular and antitumor activity in head and neck squamous cell carcinoma (HNSCC), alone or in combination with cetuximab. Preliminary biomarker data raised the hypothesis of enhanced response in tumors harboring

A Genome-Wide Crispr-Cas9 Knockout Screen Identifies Essential And Growth-Restricting Genes In Human Trophoblast Stem Cells, Chen Dong, Shuhua Fu, Rowan M Karvas, Brian Chew, Laura A Fischer, Xiaoyun Xing, Jessica K Harrison, Pooja Popli, Ramakrishna Kommagani, Ting Wang, Bo Zhang, Thorold W Theunissen

2020-Current year OA Pubs

The recent derivation of human trophoblast stem cells (hTSCs) provides a scalable in vitro model system of human placental development, but the molecular regulators of hTSC identity have not been systematically explored thus far. Here, we utilize a genome-wide CRISPR-Cas9 knockout screen to comprehensively identify essential and growth-restricting genes in hTSCs. By cross-referencing our data to those from similar genetic screens performed in other cell types, as well as gene expression data from early human embryos, we define hTSC-specific and -enriched regulators. These include both well-established and previously uncharacterized trophoblast regulators, such as ARID3A, GATA2, and TEAD1 (essential), and GCM1, …

Benefits Of Newborn Screening And Hematopoietic Cell Transplant In Infantile Krabbe Disease, Kristin M Page, Margie A Ream, Hemalatha G Rangarajan, Rafael Galindo, Ali Y Mian, Mai-Lan Ho, James Provenzale, Kathryn E Gustafson, Jennifer Rubin, Shalini Shenoy, Joanne Kurtzberg

Open Access Publications

Infantile Krabbe disease (IKD) can be treated with hematopoietic cell transplantation (HCT) if done during the first weeks of life before symptoms develop. To facilitate this, newborn screening (NBS) has been instituted in 8 US states. An application to add IKD to the recommended NBS panel is currently under review. In this report, the outcomes of newborns with IKD diagnosed through NBS and treated with HCT are presented. The unique challenges associated with NBS for this disease are discussed, including opportunities for earlier diagnosis and streamlining treatment referrals. This is a retrospective review of six infants with IKD detected by …

Caveolin-1 Temporal Modulation Enhances Antibody Drug Efficacy In Heterogeneous Gastric Cancer, Patrícia M R Pereira, Komal Mandleywala, Sébastien Monette, Melissa Lumish, Kathryn M Tully, Sandeep Surendra Panikar, Mike Cornejo, Audrey Mauguen, Ashwin Ragupathi, Nai C Keltee, Marissa Mattar, Yelena Y Janjigian, Jason S Lewis

Open Access Publications

Resistance mechanisms and heterogeneity in HER2-positive gastric cancers (GC) limit Trastuzumab benefit in 32% of patients, and other targeted therapies have failed in clinical trials. Using patient samples, patient-derived xenografts (PDXs), partially humanized biological models, and HER2-targeted imaging technologies we demonstrate the role of caveolin-1 (CAV1) as a complementary biomarker in GC selection for Trastuzumab therapy. In retrospective analyses of samples from patients enrolled on Trastuzumab trials, the CAV1-high profile associates with low membrane HER2 density and low patient survival. We show a negative correlation between CAV1 tumoral protein levels - a major protein of cholesterol-rich membrane domains - and …

Cutting-Edge Imaging Of Cardiac Metastases From Neuroendocrine Tumors: Lesson From A Case Series, Soraya El Ghannudi, Eric Ouvrard, Nidaa Mikail, Benjamin Leroy Freschini, Thomas H Schindler, Alessio Imperiale

Open Access Publications

With the increasing availability of high-performance medical imaging for the management of patients with neuroendocrine tumors (NETs), a progressive growth of asymptomatic and incidentally detected cardiac metastases (CMs) has been observed in the recent years. In clinical practice, CMs of NENs are often incidentally detected by whole-body

Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin

Open Access Publications

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential …

Oxysterol Compounds In Mouse Mutant Αa- And Αb-Crystallin Lenses Can Improve The Optical Properties Of The Lens, Kehao Wang, Masato Hoshino, Kentaro Uesugi, Naoto Yagi, Barbara K Pierscionek, Usha P Andley

Open Access Publications

Purpose: To investigate how cataract-linked mutations affect the gradient refractive index (GRIN) and lens opacification in mouse lenses and whether there is any effect on the optics of the lens from treatment with an oxysterol compound.

Methods: A total of 35 mice including wild-type and knock-in mutants (Cryaa-R49C and Cryab-R120G) were used in these experiments: 26 mice were treated with topical VP1-001, an oxysterol, in one eye and vehicle in the other, and nine mice were untreated controls. Slit lamp biomicroscopy was used to analyze the lens in live animals and to provide apparent cataract grades. Refractive index in the …