Digital Commons Network^™

Healthy Dietary Patterns Are Associated With Exposure To Environmental Chemicals In A Pregnancy Cohort, Guoqi Yu, Ruijin Lu, Jiaxi Yang, Mohammad L Rahman, Ling-Jun Li, Dong D Wang, Qi Sun, Wei Wei Pang, Claire Guivarch, Anna Birukov, Jagteshwar Grewal, Zhen Chen, Cuilin Zhang

2020-Current year OA Pubs

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory …

Plasmacytoid Dendritic Cells Control Homeostasis Of Megakaryopoiesis, Florian Gaertner, Marco Colonna, Et Al.

2020-Current year OA Pubs

Platelet homeostasis is essential for vascular integrity and immune defence

Integrating Multisector Molecular Characterization Into Personalized Peptide Vaccine Design For Patients With Newly Diagnosed Glioblastoma, Tanner M Johanns, Elizabeth A R Garfinkle, Katherine E Miller, Alexandra J Livingstone, Kaleigh F Roberts, Lakshmi P Rao Venkata, Joshua L Dowling, Michael R Chicoine, Ralph G Dacey, Gregory J Zipfel, Albert H Kim, Elaine R Mardis, Gavin P Dunn

2020-Current year OA Pubs

PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax.

PATIENTS AND METHODS: In this …

Il2 Targeted To Cd8+ T Cells Promotes Robust Effector T-Cell Responses And Potent Antitumor Immunity, Kelly D Moynihan, Hussein Sultan, Robert D Schreiber, Et Al.

2020-Current year OA Pubs

IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2's effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells …

Epigenetic Developmental Mechanisms Underlying Sex Differences In Cancer, Joshua B. Rubin, Tamara Abou-Antoun, Joseph E. Ippolito, Lorida Llaci, Camryn T. Marquez, Jason P. Wong, Lihua Yang

2020-Current year OA Pubs

Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, …

Tumor-Immune Signatures Of Treatment Resistance To Brentuximab Vedotin With Ipilimumab And/Or Nivolumab In Hodgkin Lymphoma, Edgar Gonzalez-Kozlova, Brad S Kahl, Et Al.

2020-Current year OA Pubs

UNLABELLED: To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed …

Suicide In Us Preteens Aged 8 To 12 Years, 2001 To 2022, Donna A Ruch, Lisa M Horowitz, Jennifer L Hughes, Katherine Sarkisian, Joan L Luby, Cynthia A Fontanella, Jeffrey A Bridge

2020-Current year OA Pubs

No abstract provided.

Pharmacokinetic Modeling Of The Effect Of Tariquidar On Ondansetron Disposition Into The Central Nervous System, Manting Chiang, Hyunmoon Back, Jong Bong Lee, Sarah Oh, Tiffany Guo, Simone Girgis, Celine Park, Simon Haroutounian, Leonid Kagan

2020-Current year OA Pubs

PURPOSE: Serotonin (5-HT

METHODS: Ondansetron (10 mg/kg) and tariquidar (7.5 mg/kg) were administered intravenously, plasma and tissue samples were collected and analyzed by HPLC. A mathematical model with brain, spinal cord, cerebrospinal fluid and two systemic disposition compartments was developed to describe the data.

RESULTS: The results demonstrate that tariquidar at 7.5 mg/kg resulted in a complete inhibition of Pgp efflux of ondansetron in the brain and spinal cord. The compartmental model successfully captured pharmacokinetics of ondansetron in wild type and Pgp knockout (KO) animals receiving the drug alone or in wild type animals receiving the ondansetron and tariquidar combination. …

Implementation Strategies To Improve Hiv Care Cascade Outcomes In Low- And Middle-Income Countries: A Systematic Review From 2014 To 2021, Sita Lujintanon, Ingrid Eshun-Wilson, Noelle Le Tourneau, Laura Beres, Sheree Schwartz, Stefan Baral, Ryan Thompson, Ashley Underwood, Branson Fox, Elvin H Geng, Christopher G Kemp

2020-Current year OA Pubs

INTRODUCTION: In low- and middle-income countries (LMICs), which are disproportionately affected by the HIV epidemic and manage limited resources, optimized implementation strategies are needed to enhance the efficiency of the HIV response. Assessing strategy usage to date could identify research gaps and inform future implementation efforts. We conducted a systematic review to describe the features and distributions of published implementation strategies attempting to improve HIV treatment service delivery and outcomes.

METHODS: We searched PubMed, Embase, and CINAHL and screened abstracts and full texts published between 1 January 2014 and 27 August 2021, for English-language studies conducted in LMICs that described …

Liver Disease And Transplantation In Telomere Biology Disorders: An International Multicenter Cohort, Yunzu Michele Wang, Steven K Brennan, Sakil Kulkarni, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes.

METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study.

RESULTS: Group A ("Advanced") included 40 patients with advanced liver disease. Of …

Evaluation Of Markers Of Immunity In Different Metastatic Immune Microenvironments Suggests More Suppression Within Breast To Liver Metastases In Breast Cancer, Robert Hsu, Foluso O Ademuyiwa, Et Al.

2020-Current year OA Pubs

PURPOSE: Programmed death receptor ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are approved screening biomarkers for immune checkpoint inhibition (ICI) in advanced triple negative breast cancer. We examined these biomarkers along with characterization of the tumor microenvironment (TME) between breast tumors (BrTs), axillary metastases (AxMs), liver metastases (LvMs), non-axillary lymph node metastases, and non-liver metastases to determine differences related to site of metastatic disease.

METHODS: 3076 unpaired biopsies from breast cancer patients were analyzed using whole transcriptome sequencing and NextGen DNA depicting TMB within tumor sites. The PD-L1 positivity was determined with VENTANA PD-L1 (SP142) assay. The immune cell …

Origins Of Cancer: Ain't It Just Mature Cells Misbehaving?, Charles J Cho, Jeffrey W Brown, Jason C Mills

2020-Current year OA Pubs

A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain …

Feasibility Of Simulation Free Abdominal Stereotactic Adaptive Radiotherapy Using An Expedited Pre-Plan Workflow, Alex T Price, Joshua P Schiff, Alice Silberstein, Robbie Beckert, Tianyu Zhao, Geoffrey D Hugo, Pamela P Samson, Eric Laugeman, Lauren E Henke

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: Improved hounsfield-unit accuracy of on-board imaging may lead to direct-to-unit treatment approaches We aimed to demonstrate the feasibility of using only a diagnostic (dx) computed tomography (CT)-defined target pre-plan in an

MATERIALS AND METHODS: Eight patients with abdominal treatment sites (five pancreatic cancer, three oligometastases) were treated using an integrated adaptive O-Ring gantry system. Each patient's target was delineated on a dxCT. The target only pre-plan served primarily to seed the ART process. During the ART session, all structures were delineated. All simulated cases were treated to 50 Gy in 5 fractions to a planning target optimization …

Dlg1 Functions Upstream Of Sdccag3 And Ift20 To Control Ciliary Targeting Of Polycystin-2, Csenge K Rezi, Tao Cheng, Jeffrey H Miner, Moe R Mahjoub, Et Al.

2020-Current year OA Pubs

Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20, and polycystin-2 (PC2) are reduced in the cilia of DLG1-deficient cells compared to control cells. This phenotype is recapitulated in vivo and …

Tumor-Informed Deep Sequencing Of Ctdna Detects Minimal Residual Disease And Predicts Relapse In Osteosarcoma, Yiwei Fu, Albert H Kim, Dimitrios Mathios, Et Al.

2020-Current year OA Pubs

BACKGROUND: Current surveillance modalities of osteosarcoma relapse exhibit limited sensitivity and specificity. Although circulating tumor DNA (ctDNA) has been established as a biomarker of minimal residual disease (MRD) in many solid tumors, a sensitive ctDNA detection technique has not been thoroughly explored for longitudinal MRD detection in osteosarcoma.

METHODS: From August 2019 to June 2023, 59 patients diagnosed with osteosarcoma at the First Affiliated Hospital of Sun Yat-sen University were evaluated in this study. Tumor-informed MRD panels were developed through whole exome sequencing (WES) of tumor tissues. Longitudinal blood samples were collected during treatment and subjected to multiplex PCR-based next-generation …

A Personalized Semi-Automatic Sleep Spindle Detection (Psasd) Framework, Mohammadmehdi Kafashan, Gaurang Gupte, Paul Kang, Orlandrea Hyche, Anhthi H Luong, G V Prateek, Yo-El S Ju, Ben Julian A Palanca

2020-Current year OA Pubs

BACKGROUND: Sleep spindles are distinct electroencephalogram (EEG) patterns of brain activity that have been posited to play a critical role in development, learning, and neurological disorders. Manual scoring for sleep spindles is labor-intensive and tedious but could supplement automated algorithms to resolve challenges posed with either approaches alone.

NEW METHODS: A Personalized Semi-Automatic Sleep Spindle Detection (PSASD) framework was developed to combine the strength of automated detection algorithms and visual expertise of human scorers. The underlying model in the PSASD framework assumes a generative model for EEG sleep spindles as oscillatory components, optimized to EEG amplitude, with remaining signals distributed …

Gene Expression Networks Regulated By Human Personality, Coral Del Val, Elisa Díaz De La Guardia-Bolívar, Igor Zwir, Pashupati P Mishra, Alberto Mesa, Ramiro Salas, Guillermo F Poblete, Gabriel De Erausquin, Emma Raitoharju, Mika Kähönen, Olli Raitakari, Liisa Keltikangas-Järvinen, Terho Lehtimäki, Claude Robert Cloninger

2020-Current year OA Pubs

Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic …

Alcohol Milestones And Internalizing, Externalizing, And Executive Function: Longitudinal And Polygenic Score Associations, Sarah E Paul, David A A Baranger, Joshua J Jackson, Aaron J Gorelik, Alexander S Hatoum, Michael Strube, Andrey P Anokhin, Arpana Agrawal, Kathleen K Bucholz, Ryan Bogdan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (

RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe …

Survival Disparities In Rural Versus Urban Patients With Pancreatic Neuroendocrine Tumor: A Multi-Institutional Study From The Us Neuroendocrine Tumor Study Group, Muhammad Bilal Mirza, Jordan J Baechle, Paula Marincola Smith, Mary Dillhoff, George Poultsides, Flavio G Rocha, Clifford S Cho, Emily R Winslow, Ryan C Fields, Shishir K Maithel, Kamran Idrees

2020-Current year OA Pubs

BACKGROUND: Pancreatic Neuroendocrine Tumors (PNETs) are indolent malignancies that often have a prolonged clinical course. This study assesses disparities in outcomes between PNET patients who live in urban (UA) and rural areas (RA).

METHODS: A retrospective cohort study was performed using the US Neuroendocrine Tumor Study Group database. PNET patients with a home zip code recorded were included and categorized as RA or UA according to the Federal Office of Rural Health Policy. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and logistical regression.

RESULTS: Of the 1176 PNET patients in the database, 1126 (96%) had zip code …

Modulation Of Tmem16b Channel Activity By The Calcium-Activated Chloride Channel Regulator 4 (Clca4) In Human Cells, Monica Sala-Rabanal, Zeynep Yurtsever, Kayla N Berry, Conor Mcclenaghan, Alyssa J Foy, Alex Hanson, Deborah F Steinberg, Jessica A Greven, Colin E Kluender, Jennifer M Alexander-Brett, Colin G Nichols, Tom J Brett

2020-Current year OA Pubs

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Diagnostic Efficacy And Clinical Impact Of Image-Guided Core Needle Biopsy Of Suspected Vertebral Osteomyelitis, Winston L Winkler, Ige A George, Sumanth Gandra, Jonathan C Baker, Anderanik Tomasian, Benjamin Northrup, Theodore L Vander Velde, Travis J Hillen, Chongliang Luo, Resten Imaoka, Gino M Dettorre, Jack W Jennings

2020-Current year OA Pubs

OBJECTIVES: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected vertebral osteomyelitis in adults is heterogenous in published studies owing to small sample sizes, indicating the need for large cohort studies.

METHODS: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with imaging findings consistent with vertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. In addition, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. A multivariate statistical analysis …

Aqueous Macrophages Contribute To Conserved Ccl2 And Cxcl10 Gradients In Uveitis, Joseph B Lin, Kathryn L Pepple, Christian Concepcion, Yulia Korshunova, Michael A Paley, Grace L Paley, Jennifer Laurent, Rajendra S Apte, Lynn M Hassman

2020-Current year OA Pubs

PURPOSE: Uveitis is a heterogenous group of inflammatory eye disease for which current cytokine-targeted immune therapies are effective for only a subset of patients. We hypothesized that despite pathophysiologic nuances that differentiate individual disease states, all forms of eye inflammation might share common mechanisms for immune cell recruitment. Identifying these mechanisms is critical for developing novel, broadly acting therapeutic strategies.

DESIGN: Experimental study.

SUBJECTS: Biospecimens from patients with active or inactive uveitis and healthy controls.

METHODS: Protein concentration and single cell gene expression were assessed in aqueous fluid biopsies and plasma samples from deidentified patients with uveitis or healthy controls. …

Matching-Adjusted Indirect Comparison From The Lymphoma Epidemiology Of Outcomes Consortium For Real World Evidence (Leo Crewe) Study To A Clinical Trial Of Mosunetuzumab In Relapsed Or Refractory Follicular Lymphoma, Matthew J. Maurer, Brad S. Kahl, Et Al.

2020-Current year OA Pubs

Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate (ORR) of 80%, complete response (CR) rate of 60%, and a median progression-free survival (PFS) of 17.9 months in patients with relapsed/refractory (R/R) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for R/R FL can provide some context …

A Phase Ii Trial Of The Wee1 Inhibitor Adavosertib In Setd2-Altered Advanced Solid Tumor Malignancies (Nci 10170), Edward Maldonado, Nikolaos A Trikalinos, Et Al.

2020-Current year OA Pubs

UNLABELLED: We sought to evaluate the efficacy of WEE1 inhibitor adavosertib in patients with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B). NCT03284385 was a parallel cohort, Simon two-stage, phase II study of adavosertib (300 mg QDAY by mouth on days 1-5 and 8-12 of each 21-day cycle) in patients with solid tumor malignancies harboring a pathogenic SETD2 mutation. The primary endpoint was the objective response rate. Correlative assays evaluated the loss of H3K36me3 by IHC, a downstream consequence of SETD2 loss, in archival tumor tissue. Eighteen patients were enrolled (9/cohort). The median age …

Ballc And Ballcools: Efficient Formatting And Operating For Single-Cell Dna Methylation Data, Wei Tian, Wubin Ding, Jiawei Shen, Daofeng Li, Ting Wang, Joseph R Ecker

2020-Current year OA Pubs

MOTIVATION: With single-cell DNA methylation studies yielding vast datasets, existing data formats struggle with the unique challenges of storage and efficient operations, highlighting a need for improved solutions.

RESULTS: BAllC (Binary All Cytosines) emerges as a tailored format for methylation data, addressing these challenges. BAllCools, its complementary software toolkit, enhances parsing, indexing, and querying capabilities, promising superior operational speeds and reduced storage needs.

AVAILABILITY AND IMPLEMENTATION: https://github.com/jksr/ballcools.

Clinical Mycology Today: Emerging Challenges And Opportunities, Jessica Little, Adriana M Rauseo, Julio C Zuniga-Moya, Andrej Spec, Peter Pappas, John Perfect, Todd Mccarthy, Ilan S Schwartz

2020-Current year OA Pubs

The Mycoses Study Group Education and Research Consortium is a collective of clinicians, researchers, and educators with the common goal to advance awareness, diagnosis, and management of invasive fungal diseases. Clinical Mycology Today, the Mycoses Study Group Education and Research Consortium's biennial meeting, is dedicated to discussing the most pressing contemporary issues facing the field of clinical mycology, promoting clinical, translational, and basic science collaborations, and mentoring the next generation of clinical mycologists. Here, we review the current opportunities and challenges facing the field of mycology that arose from discussions at the 2022 meeting, with emphasis on novel host risk …

A Survey Of Availability And Affordability Of Polypills For Cardiovascular Disease In Selected Countries, Gautam Satheesh, Bishal Gyawali, Marie France Chan Sun, Mark D Huffman, Amitava Banerjee, Pablo Perel, Adrianna Murphy

2020-Current year OA Pubs

BACKGROUND: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally.

METHODS: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised …

[18f]F-Arag Imaging Reveals Association Between Neuroinflammation And Brown- And Bone Marrow Adipose Tissue, Jelena Levi, Caroline Guglielmetti, Et Al.

2020-Current year OA Pubs

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [

Cognitive Control Training With Domain-General Response Inhibition Does Not Change Children's Brains Or Behavior, Keertana Ganesan, Abigail Thompson, Claire R Smid, Roser Cañigueral, Yongjing Li, Grace Revill, Vanessa Puetz, Boris C Bernhardt, Nico U F Dosenbach, Rogier Kievit, Nikolaus Steinbeis

2020-Current year OA Pubs

Cognitive control is required to organize thoughts and actions and is critical for the pursuit of long-term goals. Childhood cognitive control relates to other domains of cognitive functioning and predicts later-life success and well-being. In this study, we used a randomized controlled trial to test whether cognitive control can be improved through a pre-registered 8-week intervention in 235 children aged 6-13 years targeting response inhibition and whether this leads to changes in multiple behavioral and neural outcomes compared to a response speed training. We show long-lasting improvements of closely related measures of cognitive control at the 1-year follow-up; however, training …

A Bistable Inhibitory Optogpcr For Multiplexed Optogenetic Control Of Neural Circuits, Jonas Wietek, Bobbie J Brown, Bryan A Copits, Et Al.

2020-Current year OA Pubs

Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with …