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Long Runs Of Homozygosity Are Associated With Alzheimer’S Disease, Sonia Moreno-Grau, Maria Victoria Fernández, Fabiana Farias, John P. Budde, Carlos Cruchaga, O. Maroñas, Et Al. Jan 2021

Long Runs Of Homozygosity Are Associated With Alzheimer’S Disease, Sonia Moreno-Grau, Maria Victoria Fernández, Fabiana Farias, John P. Budde, Carlos Cruchaga, O. Maroñas, Et Al.

Open Access Publications

No abstract provided.


Single Cell Transcriptomic Analysis Of Human Pluripotent Stem Cell Chondrogenesis, Chia-Lung Wu, Amanda Dicks, Nancy Steward, Ruhang Tang, Dakota B. Katz, Yun-Rak Choi, Farshid Guilak Jan 2021

Single Cell Transcriptomic Analysis Of Human Pluripotent Stem Cell Chondrogenesis, Chia-Lung Wu, Amanda Dicks, Nancy Steward, Ruhang Tang, Dakota B. Katz, Yun-Rak Choi, Farshid Guilak

Open Access Publications

No abstract provided.


A Casz1–Nurd Complex Regulates Temporal Identity Transitions In Neural Progenitors, Pierre Mattar, Christine Jolicoeur, Thanh Dang, Sujay Shah, Brian S. Clark, Michel Cayouette Jan 2021

A Casz1–Nurd Complex Regulates Temporal Identity Transitions In Neural Progenitors, Pierre Mattar, Christine Jolicoeur, Thanh Dang, Sujay Shah, Brian S. Clark, Michel Cayouette

Open Access Publications

No abstract provided.


Anti-Inflammatory Dopamine- And Serotonin-Based Endocannabinoid Epoxides Reciprocally Regulate Cannabinoid Receptors And The Trpv1 Channel, William R. Arnold, Lauren N. Carnevale, Zili Xie, Javier L. Baylon, Emad Tajkhorshid, Hongzhen Hu, Aditi Das Jan 2021

Anti-Inflammatory Dopamine- And Serotonin-Based Endocannabinoid Epoxides Reciprocally Regulate Cannabinoid Receptors And The Trpv1 Channel, William R. Arnold, Lauren N. Carnevale, Zili Xie, Javier L. Baylon, Emad Tajkhorshid, Hongzhen Hu, Aditi Das

Open Access Publications

No abstract provided.


Choroid Plexus Nkcc1 Mediates Cerebrospinal Fluid Clearance During Mouse Early Postnatal Development, Huixin Xu, Yong Zhang, Michael J. Holtzman, Et Al. Jan 2021

Choroid Plexus Nkcc1 Mediates Cerebrospinal Fluid Clearance During Mouse Early Postnatal Development, Huixin Xu, Yong Zhang, Michael J. Holtzman, Et Al.

Open Access Publications

No abstract provided.


Redox-Responsive Hyaluronic Acid-Based Nanogels For The Topical Delivery Of The Visual Chromophore To Retinal Photoreceptors, Amine M. Laradji, Alexander V. Kolesnikov, Bedia B. Karakoçak, Vladimir J. Kefalov, Nathan Ravi Jan 2021

Redox-Responsive Hyaluronic Acid-Based Nanogels For The Topical Delivery Of The Visual Chromophore To Retinal Photoreceptors, Amine M. Laradji, Alexander V. Kolesnikov, Bedia B. Karakoçak, Vladimir J. Kefalov, Nathan Ravi

Open Access Publications

No abstract provided.


A Priori Activation Of Apoptosis Pathways Of Tumor (Aaapt) Technology: Development Of Targeted Apoptosis Initiators For Cancer Treatment, Raghu S. Pandurangi, Marco Tomasetti, Sekar T. Verapazham, Ramasamy Paulmurugan, Cynthia Ma, Sandeep Rajput, Manjushree Anjanappa, Harikrishna Nakshatri Jan 2021

A Priori Activation Of Apoptosis Pathways Of Tumor (Aaapt) Technology: Development Of Targeted Apoptosis Initiators For Cancer Treatment, Raghu S. Pandurangi, Marco Tomasetti, Sekar T. Verapazham, Ramasamy Paulmurugan, Cynthia Ma, Sandeep Rajput, Manjushree Anjanappa, Harikrishna Nakshatri

Open Access Publications

Cancer cells develop tactics to circumvent the interventions by desensitizing themselves to interventions. Amongst many, the principle routes of desensitization include a) activation of survival pathways (e.g. NF-kB, PARP) and b) downregulation of cell death pathways (e.g. CD95/CD95L). As a result, it requires high therapeutic dose to achieve tumor regression which, in turn damages normal cells through the collateral effects. Methods are needed to sensitize the low and non-responsive resistant tumor cells including cancer stem cells (CSCs) in order to evoke a better response from the current treatments. Current treatments including chemotherapy can induce cell death only in bulk cancer …


Multistage And Transmission-Blocking Targeted Antimalarials Discovered From The Open-Source Mmv Pandemic Response Box, Janette Reader, Natalie J. Spillman, Eva S. Istvan, Daniel E. Goldberg, Et Al. Jan 2021

Multistage And Transmission-Blocking Targeted Antimalarials Discovered From The Open-Source Mmv Pandemic Response Box, Janette Reader, Natalie J. Spillman, Eva S. Istvan, Daniel E. Goldberg, Et Al.

Open Access Publications

No abstract provided.


Proteomic And Functional Mapping Of Cardiac Nav1.5 Channel Phosphorylation Sites, Maxime Lorenzini, Emily Wagner, Kiersten M. Ruff, Rohit V. Pappu, Jeanne M. Nerbonne, Jonathan R. Silva, R. Reid Townsend, Et Al Jan 2021

Proteomic And Functional Mapping Of Cardiac Nav1.5 Channel Phosphorylation Sites, Maxime Lorenzini, Emily Wagner, Kiersten M. Ruff, Rohit V. Pappu, Jeanne M. Nerbonne, Jonathan R. Silva, R. Reid Townsend, Et Al

Open Access Publications

Phosphorylation of the voltage-gated Na+ (NaV) channel NaV1.5 regulates cardiac excitability, yet the phosphorylation sites regulating its function and the underlying mechanisms remain largely unknown. Using a systematic, quantitative phosphoproteomic approach, we analyzed NaV1.5 channel complexes purified from nonfailing and failing mouse left ventricles, and we identified 42 phosphorylation sites on NaV1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic NaV1.5 mutants revealed the roles of three phosphosites in regulating NaV1.5 channel expression and gating. The phosphorylated serines S664 and S667 regulate the voltage dependence of channel activation in a cumulative …


Acupuncture And Oxytocinergic System: The Promising Treatment For Autism, Tangfeng Su, Lei Pei Jan 2021

Acupuncture And Oxytocinergic System: The Promising Treatment For Autism, Tangfeng Su, Lei Pei

Open Access Publications

No abstract provided.


Tumor-Associated Neutrophils (Tans) In Human Carcinoma-Draining Lymph Nodes: A Novel Tan Compartment, Silvia Lonardi, William Vermi, Et Al. Jan 2021

Tumor-Associated Neutrophils (Tans) In Human Carcinoma-Draining Lymph Nodes: A Novel Tan Compartment, Silvia Lonardi, William Vermi, Et Al.

Open Access Publications

No abstract provided.


Pore-Forming Transmembrane Domains Control Ion Selectivity And Selectivity Filter Conformation In The Kirbac1.1 Potassium Channel, Marcos Matamoros, Colin G. Nichols Jan 2021

Pore-Forming Transmembrane Domains Control Ion Selectivity And Selectivity Filter Conformation In The Kirbac1.1 Potassium Channel, Marcos Matamoros, Colin G. Nichols

Open Access Publications

Potassium (K+) channels are membrane proteins with the remarkable ability to very selectively conduct K+ ions across the membrane. High-resolution structures have revealed that dehydrated K+ ions permeate through the narrowest region of the pore, formed by the backbone carbonyls of the signature selectivity filter (SF) sequence TxGYG. However, the existence of nonselective channels with similar SF sequences, as well as effects of mutations in other regions on selectivity, suggest that the SF is not the sole determinant of selectivity. We changed the selectivity of the KirBac1.1 channel by introducing mutations at residue I131 in transmembrane helix 2 (TM2). These …


Microglia Control Small Vessel Calcification Via Trem2, Yvette Zarb, Sucheta Sridhar, Sina Nassiri, Sebastian Guido Utz, Johanna Schaffenrath, Upasana Maheshwari, Elisabeth J Rushing, K Peter R Nilsson, Mauro Delorenzi, Marco Colonna, Melanie Greter, Annika Keller Jan 2021

Microglia Control Small Vessel Calcification Via Trem2, Yvette Zarb, Sucheta Sridhar, Sina Nassiri, Sebastian Guido Utz, Johanna Schaffenrath, Upasana Maheshwari, Elisabeth J Rushing, K Peter R Nilsson, Mauro Delorenzi, Marco Colonna, Melanie Greter, Annika Keller

Open Access Publications

Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification,


Task-Generic And Task-Specific Connectivity Modulations In The Adhd Brain: An Integrated Analysis Across Multiple Tasks, Roselyne J. Chauvin, Jan K. Buitelaar, Emma Sprooten, Marianne Oldehinkel, Barbara Franke, Catharina Hartman, Dirk J. Heslenfeld, Pieter J. Hoekstra, Jaap Oosterlaan, Christian F. Beckmann, Maarten Mennes Jan 2021

Task-Generic And Task-Specific Connectivity Modulations In The Adhd Brain: An Integrated Analysis Across Multiple Tasks, Roselyne J. Chauvin, Jan K. Buitelaar, Emma Sprooten, Marianne Oldehinkel, Barbara Franke, Catharina Hartman, Dirk J. Heslenfeld, Pieter J. Hoekstra, Jaap Oosterlaan, Christian F. Beckmann, Maarten Mennes

Open Access Publications

No abstract provided.


A Chromosome-Level Genome Of Astyanax Mexicanus Surface Fish For Comparing Population-Specific Genetic Differences Contributing To Trait Evolution, Wesley C. Warren, Chad Tomlinson, Milinn Kremitzki, Tina Graves-Lindsay, Et Al. Jan 2021

A Chromosome-Level Genome Of Astyanax Mexicanus Surface Fish For Comparing Population-Specific Genetic Differences Contributing To Trait Evolution, Wesley C. Warren, Chad Tomlinson, Milinn Kremitzki, Tina Graves-Lindsay, Et Al.

Open Access Publications

No abstract provided.


The Dark Side Of The Gut: Virome-Host Interactions In Intestinal Homeostasis And Disease, Yuhao Li, Scott A. Handley, Megan T. Baldridge Jan 2021

The Dark Side Of The Gut: Virome-Host Interactions In Intestinal Homeostasis And Disease, Yuhao Li, Scott A. Handley, Megan T. Baldridge

Open Access Publications

The diverse enteric viral communities that infect microbes and the animal host collectively constitute the gut virome. Although recent advances in sequencing and analysis of metaviromes have revealed the complexity of the virome and facilitated discovery of new viruses, our understanding of the enteric virome is still incomplete. Recent studies have uncovered how virome-host interactions can contribute to beneficial or detrimental outcomes for the host. Understanding the complex interactions between enteric viruses and the intestinal immune system is a prerequisite for elucidating their role in intestinal diseases. In this review, we provide an overview of the enteric virome composition and …


Integrating Imaging And Rna-Seq Improves Outcome Prediction In Cervical Cancer, Jin Zhang, Ramachandran Rashmi, Matthew Inkman, Kay Jayachandran, Fiona Ruiz, Michael R Waters, Perry W Grigsby, Stephanie Markovina, Julie K Schwarz Jan 2021

Integrating Imaging And Rna-Seq Improves Outcome Prediction In Cervical Cancer, Jin Zhang, Ramachandran Rashmi, Matthew Inkman, Kay Jayachandran, Fiona Ruiz, Michael R Waters, Perry W Grigsby, Stephanie Markovina, Julie K Schwarz

Open Access Publications

Approaches using a single type of data have been applied to classify human tumors. Here we integrate imaging features and transcriptomic data using a prospectively collected tumor bank. We demonstrate that increased maximum standardized uptake value on pretreatment 18F-fluorodeoxyglucose-positron emission tomography correlates with epithelial-to-mesenchymal transition (EMT) gene expression. We derived and validated 3 major molecular groups, namely squamous epithelial, squamous mesenchymal, and adenocarcinoma, using prospectively collected institutional (n = 67) and publicly available (n = 304) data sets. Patients with tumors of the squamous mesenchymal subtype showed inferior survival outcomes compared with the other 2 molecular groups. High mesenchymal gene …


Trem2 Sustains Macrophage-Hepatocyte Metabolic Coordination In Nonalcoholic Fatty Liver Disease And Sepsis, Jinchao Hou, Yingyue Zhou, Marco Colonna, Et Al Jan 2021

Trem2 Sustains Macrophage-Hepatocyte Metabolic Coordination In Nonalcoholic Fatty Liver Disease And Sepsis, Jinchao Hou, Yingyue Zhou, Marco Colonna, Et Al

Open Access Publications

Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of …


Autophagy Buffers Ras-Induced Genotoxic Stress Enabling Malignant Transformation In Keratinocytes Primed By Human Papillomavirus, Eduardo Cararo-Lopes, Matheus H. Dias, Marcelo S. Da Silva, Julianna D. Zeidler, Alexandre T. Vessoni, Marcelo S. Reis, Enrique Boccardo, Hugo A. Armelin Jan 2021

Autophagy Buffers Ras-Induced Genotoxic Stress Enabling Malignant Transformation In Keratinocytes Primed By Human Papillomavirus, Eduardo Cararo-Lopes, Matheus H. Dias, Marcelo S. Da Silva, Julianna D. Zeidler, Alexandre T. Vessoni, Marcelo S. Reis, Enrique Boccardo, Hugo A. Armelin

Open Access Publications

No abstract provided.


Atoh7-Independent Specification Of Retinal Ganglion Cell Identity, Justin Brodie-Kommit, Brian S Clark, Fion Shiau, Philip A Ruzycki, Et Al Jan 2021

Atoh7-Independent Specification Of Retinal Ganglion Cell Identity, Justin Brodie-Kommit, Brian S Clark, Fion Shiau, Philip A Ruzycki, Et Al

Open Access Publications

Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor


Loss Of Quaking Rna Binding Protein Disrupts The Expression Of Genes Associated With Astrocyte Maturation In Mouse Brain, Kristina Sakers, Yating Liu, Lorida Llaci, Scott M. Lee, Michael J. Vasek, Michael A. Rieger, Sean Brophy, Eric Tycksen, Renate Lewis, Susan E. Maloney, Joseph D. Dougherty Jan 2021

Loss Of Quaking Rna Binding Protein Disrupts The Expression Of Genes Associated With Astrocyte Maturation In Mouse Brain, Kristina Sakers, Yating Liu, Lorida Llaci, Scott M. Lee, Michael J. Vasek, Michael A. Rieger, Sean Brophy, Eric Tycksen, Renate Lewis, Susan E. Maloney, Joseph D. Dougherty

Open Access Publications

No abstract provided.


Microbiota Signals Suppress B Lymphopoiesis With Aging In Mice, Joseph R Krambs, Darlene A Monlish, Feng Gao, Laura G Schuettpelz, Daniel C Link Jan 2021

Microbiota Signals Suppress B Lymphopoiesis With Aging In Mice, Joseph R Krambs, Darlene A Monlish, Feng Gao, Laura G Schuettpelz, Daniel C Link

Open Access Publications

Aging is associated with significant changes in hematopoiesis that include a shift from lymphopoiesis to myelopoiesis and an expansion of phenotypic hematopoietic stem cells (HSCs) with impaired self-renewal capacity and myeloid-skewed lineage differentiation. Signals from commensal flora support basal myelopoiesis in young mice; however, their contribution to hematopoietic aging is largely unknown. Here, we characterize hematopoiesis in young and middle-aged mice housed under specific pathogen free (SPF) and germ-free (GF) conditions. The marked shift from lymphopoiesis to myelopoiesis that develops during aging of SPF mice is mostly abrogated in GF mice. Compared with aged SPF mice, there is a marked …


Noninvasive Immuno-Pet Imaging Of Cd8 + T Cell Behavior In Influenza A Virus-Infected Mice, Paul W Rothlauf, Zeyang Li, Novalia Pishesha, Yushu Joy Xie, Andrew W Woodham, Djenet Bousbaine, Stephen C Kolifrath, Vincent L Verschoor, Hidde L Ploegh Jan 2021

Noninvasive Immuno-Pet Imaging Of Cd8 + T Cell Behavior In Influenza A Virus-Infected Mice, Paul W Rothlauf, Zeyang Li, Novalia Pishesha, Yushu Joy Xie, Andrew W Woodham, Djenet Bousbaine, Stephen C Kolifrath, Vincent L Verschoor, Hidde L Ploegh

Open Access Publications

Immuno-positron emission tomography (immuno-PET) is a noninvasive imaging method that enables tracking of immune cells in living animals. We used a nanobody that recognizes mouse CD8α and labeled it with


Endocannabinoid System Unlocks The Puzzle Of Autism Treatment, Tangfeng Su, Yu Yan, Qiang Li, Jiacai Ye, Lei Pei Jan 2021

Endocannabinoid System Unlocks The Puzzle Of Autism Treatment, Tangfeng Su, Yu Yan, Qiang Li, Jiacai Ye, Lei Pei

Open Access Publications

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder and characterized by early childhood-onset impairments in social interaction and communication, restricted and repetitive patterns of behavior or interests. So far there is no effective treatment for ASD, and the pathogenesis of ASD remains unclear. Genetic and epigenetic factors have been considered to be the main cause of ASD. It is known that endocannabinoid and its receptors are widely distributed in the central nervous system, and provide a positive and irreversible change toward a more physiological neurodevelopment. Recently, the endocannabinoid system (ECS) has been found to participate in the regulation of …


High Affinity Associations With Α-Snap Enable Calcium Entry Via Orai1 Channels, Ramanagouda Ramanagoudr-Bhojappa, Yong Miao, Monika Vig Jan 2021

High Affinity Associations With Α-Snap Enable Calcium Entry Via Orai1 Channels, Ramanagouda Ramanagoudr-Bhojappa, Yong Miao, Monika Vig

Open Access Publications

Molecular steps that activate store-operated calcium entry (SOCE) via Orai channel supramolecular complex remain incompletely defined. We have earlier shown that α-SNAP regulates the on-site functional assembly and calcium selectivity of Orai1 channels. Here we investigate the molecular basis of its association with Orai, Stim and find that the affinity of α-SNAP for Orai and Stim is substantially higher than previously reported affinities between Stim and Orai sub-domains. α-SNAP binds the coiled-coil 3 (CC3) sub-domain of Stim1. Mutations of Tryptophan 430 in Stim1-CC3 disrupted α-SNAP association and SOCE, demonstrating a novel α-SNAP dependent function for this crucial subdomain. Further, α-SNAP …


Successful Treatment Of Noise-Induced Hearing Loss By Mesenchymal Stromal Cells: An Rnaseq Analysis Of Protective/Repair Pathways, Athanasia Warnecke, Jennifer Harre, Matthew Shew, Adam J Mellott, Igor Majewski, Martin Durisin, Hinrich Staecker Jan 2021

Successful Treatment Of Noise-Induced Hearing Loss By Mesenchymal Stromal Cells: An Rnaseq Analysis Of Protective/Repair Pathways, Athanasia Warnecke, Jennifer Harre, Matthew Shew, Adam J Mellott, Igor Majewski, Martin Durisin, Hinrich Staecker

Open Access Publications

Mesenchymal stromal cells (MSCs) are an adult derived stem cell-like population that has been shown to mediate repair in a wide range of degenerative disorders. The protective effects of MSCs are mainly mediated by the release of growth factors and cytokines thereby modulating the diseased environment and the immune system. Within the inner ear, MSCs have been shown protective against tissue damage induced by sound and a variety of ototoxins. To better understand the mechanism of action of MSCs in the inner ear, mice were exposed to narrow band noise. After exposure, MSCs derived from human umbilical cord Wharton's jelly …


Tms-Eeg Biomarkers Of Amnestic Mild Cognitive Impairment Due To Alzheimer's Disease: A Proof-Of-Concept Six Years Prospective Study, Florinda Ferreri, Andrea Guerra, Luca Vollero, David Ponzo, Sara Määtta, Mervi Könönen, Fabrizio Vecchio, Patrizio Pasqualetti, Francesca Miraglia, Ilaria Simonelli, Maurizio Corbetta, Paolo Maria Rossini Jan 2021

Tms-Eeg Biomarkers Of Amnestic Mild Cognitive Impairment Due To Alzheimer's Disease: A Proof-Of-Concept Six Years Prospective Study, Florinda Ferreri, Andrea Guerra, Luca Vollero, David Ponzo, Sara Määtta, Mervi Könönen, Fabrizio Vecchio, Patrizio Pasqualetti, Francesca Miraglia, Ilaria Simonelli, Maurizio Corbetta, Paolo Maria Rossini

Open Access Publications

No abstract provided.


Zo-1 Intracellular Localization Organizes Immune Response In Non-Small Cell Lung Cancer, Déborah Neyrinck-Leglantier, Julien Lesage, Silvia Blacher, Arnaud Bonnomet, Walter Hunziker, Agnès Noël, Valérian Dormoy, Béatrice Nawrocki-Raby, Christine Gilles, Myriam Polette Jan 2021

Zo-1 Intracellular Localization Organizes Immune Response In Non-Small Cell Lung Cancer, Déborah Neyrinck-Leglantier, Julien Lesage, Silvia Blacher, Arnaud Bonnomet, Walter Hunziker, Agnès Noël, Valérian Dormoy, Béatrice Nawrocki-Raby, Christine Gilles, Myriam Polette

Open Access Publications

Delocalization of zonula occludens-1 (ZO-1) from tight junctions plays a substantial role in epithelial cell plasticity observed during tumor progression.


Bladder Exposure To Gardnerella Activates Host Pathways Necessary For Escherichia Coli Recurrent Uti, Valerie P O'Brien, Amanda L Lewis, Nicole M Gilbert Jan 2021

Bladder Exposure To Gardnerella Activates Host Pathways Necessary For Escherichia Coli Recurrent Uti, Valerie P O'Brien, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic


The Worldwide Alzheimer's Disease Neuroimaging Initiative: Adni-3 Updates And Global Perspectives, Christopher J Weber, Richard J Perrin, John C Morris, Et Al Jan 2021

The Worldwide Alzheimer's Disease Neuroimaging Initiative: Adni-3 Updates And Global Perspectives, Christopher J Weber, Richard J Perrin, John C Morris, Et Al

Open Access Publications

The Worldwide Alzheimer's Disease Neuroimaging Initiative (WW-ADNI) is a collaborative effort to investigate imaging and biofluid markers that can inform Alzheimer's disease treatment trials. It is a public-private partnership that spans North America, Argentina, Australia, Canada, China, Japan, Korea, Mexico, and Taiwan. In 2004, ADNI researchers began a naturalistic, longitudinal study that continues today around the globe. Through several successive phases (ADNI-1, ADNI-GO, ADNI-2, and ADNI-3), the study has fueled amyloid and tau phenotyping and refined neuroimaging methodologies. WW-ADNI researchers have successfully standardized analyses and openly share data without embargo, providing a rich data set for other investigators. On August …