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Acetate Coordinates Neutrophil And Ilc3 Responses Against C. Difficile Through Ffar2, José Luís Fachi, Cristiane Sécca, Blanda Di Luccia, Marco Colonna, Et Al
Acetate Coordinates Neutrophil And Ilc3 Responses Against C. Difficile Through Ffar2, José Luís Fachi, Cristiane Sécca, Blanda Di Luccia, Marco Colonna, Et Al
Open Access Publications
Antibiotic-induced dysbiosis is a key predisposing factor for Clostridium difficile infections (CDIs), which cause intestinal disease ranging from mild diarrhea to pseudomembranous colitis. Here, we examined the impact of a microbiota-derived metabolite, short-chain fatty acid acetate, on an acute mouse model of CDI. We found that administration of acetate is remarkably beneficial in ameliorating disease. Mechanistically, we show that acetate enhances innate immune responses by acting on both neutrophils and ILC3s through its cognate receptor free fatty acid receptor 2 (FFAR2). In neutrophils, acetate-FFAR2 signaling accelerates their recruitment to the inflammatory sites, facilitates inflammasome activation, and promotes the release of …
The Struggling Infectious Diseases Fellow: Remediation Challenges And Opportunities, Michael T. Melia, Gerome Escota, Et Al
The Struggling Infectious Diseases Fellow: Remediation Challenges And Opportunities, Michael T. Melia, Gerome Escota, Et Al
Open Access Publications
Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with …
Glp-1 Notch-Lag-1 Csl Control Of The Germline Stem Cell Fate Is Mediated By Transcriptional Targets Lst-1 And Sygl-1, Jian Chen, Ariz Mohammad, Nanette Pazdernik, Huiyan Huang, Beth Bowman, Eric Tycksen, Tim Schedl
Glp-1 Notch-Lag-1 Csl Control Of The Germline Stem Cell Fate Is Mediated By Transcriptional Targets Lst-1 And Sygl-1, Jian Chen, Ariz Mohammad, Nanette Pazdernik, Huiyan Huang, Beth Bowman, Eric Tycksen, Tim Schedl
Open Access Publications
Stem cell systems are essential for the development and maintenance of polarized tissues. Intercellular signaling pathways control stem cell systems, where niche cells signal stem cells to maintain the stem cell fate/self-renewal and inhibit differentiation. In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. We undertook a comprehensive genome-wide approach to identify transcriptional targets of GLP-1 signaling. We expected primary response target genes to be evident at the intersection of genes identified as directly bound by LAG-1, from ChIP-seq experiments, with genes identified as …
Modular Analysis Of The Control Of Flagellar Ca2+-Spike Trains Produced By Catsper And Cav Channels In Sea Urchin Sperm, Daniel A. Priego-Espinosa, Alberto Darszon, Adán Guerrero, Ana Laura González-Cota, Takuya Nishigaki, Gustavo Martínez-Mekler, Jorge Carneiro
Modular Analysis Of The Control Of Flagellar Ca2+-Spike Trains Produced By Catsper And Cav Channels In Sea Urchin Sperm, Daniel A. Priego-Espinosa, Alberto Darszon, Adán Guerrero, Ana Laura González-Cota, Takuya Nishigaki, Gustavo Martínez-Mekler, Jorge Carneiro
Open Access Publications
Intracellular calcium ([Ca2+]i) is a basic and ubiquitous cellular signal controlling a wide variety of biological processes. A remarkable example is the steering of sea urchin spermatozoa towards the conspecific egg by a spatially and temporally orchestrated series of [Ca2+]i spikes. Although this process has been an experimental paradigm for reproduction and sperm chemotaxis studies, the composition and regulation of the signalling network underlying the cytosolic calcium fluctuations are hitherto not fully understood. Here, we used a differential equations model of the signalling network to assess which set of channels can explain the characteristic envelope and temporal organisation of the …
Second-Line Lenvatinib In Patients With Recurrent Endometrial Cancer, Ignace Vergote, Matthew A Powell, Michael G Teneriello, David S Miller, Agustin A Garcia, Olga N Mikheeva, Mariusz Bidzinski, Cristina Ligia Cebotaru, Corina E Dutcus, Min Ren, Tadashi Kadowaki, Yasuhiro Funahashi, Richard T Penson
Second-Line Lenvatinib In Patients With Recurrent Endometrial Cancer, Ignace Vergote, Matthew A Powell, Michael G Teneriello, David S Miller, Agustin A Garcia, Olga N Mikheeva, Mariusz Bidzinski, Cristina Ligia Cebotaru, Corina E Dutcus, Min Ren, Tadashi Kadowaki, Yasuhiro Funahashi, Richard T Penson
Open Access Publications
OBJECTIVE: This study assessed the efficacy of lenvatinib, a multitargeted tyrosine kinase inhibitor, as second-line therapy in patients with unresectable endometrial cancer. The primary end point was the objective response rate (ORR) as assessed by independent radiologic review (IRR). Secondary end points included median progression-free survival (PFS), overall survival (OS), and clinical benefit rate. Exploratory end points examined the association of baseline levels of plasma biomarkers (50 circulating cytokine and/or angiogenic factors measured by immunoassays) with efficacy outcomes.
METHODS: An international, open-label, single-arm, multicenter, phase 2 trial was conducted. Eligible patients had histologically confirmed unresectable endometrial cancer that relapsed after …
Microbiome Restoration By Rbx2660 Does Not Preclude Recurrence Of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report, Eric C. Keen, Preston Tasoff, Tiffany Hink, Kimberly A. Reske, Carey-Ann D. Burnham, Gautam Dantas, Jennie H. Kwon, Erik R. Dubberke
Microbiome Restoration By Rbx2660 Does Not Preclude Recurrence Of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report, Eric C. Keen, Preston Tasoff, Tiffany Hink, Kimberly A. Reske, Carey-Ann D. Burnham, Gautam Dantas, Jennie H. Kwon, Erik R. Dubberke
Open Access Publications
A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.
Tgfβ1 Orchestrates Renal Fibrosis Following Escherichia Coli Pyelonephritis, Teri N Hreha, Christina A Collins, Allyssa L Daugherty, Joy Twentyman, Nitin Paluri, David A Hunstad
Tgfβ1 Orchestrates Renal Fibrosis Following Escherichia Coli Pyelonephritis, Teri N Hreha, Christina A Collins, Allyssa L Daugherty, Joy Twentyman, Nitin Paluri, David A Hunstad
Open Access Publications
Renal scarring after pyelonephritis is linked to long-term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenic Escherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti-androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/6 mice to elucidate the molecular mechanisms of post-infectious renal fibrosis and to determine how these pathways are altered by the presence of androgens. We found that elevated circulating testosterone levels primed the kidney for fibrosis by increasing local production of TGFβ1 before …
Operative Versus Nonoperative Treatment Of Acute Achilles Tendon Ruptures: A Pilot Economic Decision Analysis, Alvin W Su, Ljiljana Bogunovic, Jeffrey Johnson, Sandra Klein, Matthew J Matava, Jeremy Mccormick, Matthew V Smith, Rick W Wright, Robert H Brophy
Operative Versus Nonoperative Treatment Of Acute Achilles Tendon Ruptures: A Pilot Economic Decision Analysis, Alvin W Su, Ljiljana Bogunovic, Jeffrey Johnson, Sandra Klein, Matthew J Matava, Jeremy Mccormick, Matthew V Smith, Rick W Wright, Robert H Brophy
Open Access Publications
Background: The operative treatment of Achilles tendon ruptures has been associated with lower rerupture rates and better function but also a risk of surgery-related complications compared with nonoperative treatment, which may provide improved outcomes with accelerated rehabilitation protocols. However, economic decision analyses integrating the updated costs of both treatment options are limited in the literature.
Purpose: To compare the cost-effectiveness of operative and nonoperative treatment of acute Achilles tendon tears.
Study Design: Economic and decision analysis; Level of evidence, 2.
Methods: An economic decision model was built to assess the cost-utility ratio (CUR) of open primary repair versus nonoperative treatment …
5 Challenges In Understanding The Role Of The Virome In Health And Disease, David Wang
5 Challenges In Understanding The Role Of The Virome In Health And Disease, David Wang
Open Access Publications
No abstract provided.
Impaired Tumor Necrosis Factor-Α Secretion By Cd4 T Cells During Respiratory Syncytial Virus Bronchiolitis Associated With Recurrent Wheeze, Maleewan Kitcharoensakkul, Leonard B Bacharier, Huiqing Yin-Declue, Jonathan S Boomer, Geneline Sajol, Marilyn K Leung, Brad Wilson, Kenneth B Schechtman, John P Atkinson, Jonathan M Green, Mario Castro
Impaired Tumor Necrosis Factor-Α Secretion By Cd4 T Cells During Respiratory Syncytial Virus Bronchiolitis Associated With Recurrent Wheeze, Maleewan Kitcharoensakkul, Leonard B Bacharier, Huiqing Yin-Declue, Jonathan S Boomer, Geneline Sajol, Marilyn K Leung, Brad Wilson, Kenneth B Schechtman, John P Atkinson, Jonathan M Green, Mario Castro
Open Access Publications
BACKGROUND: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life.
METHODS: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin-10, interferon-γ, tumor necrosis factor-α (TNF-α), IL-4, and IL-5 production by in vitro anti-CD3/CD28- and anti-CD3/CD46-activated CD4+ T cells, and percentage of peripheral Treg …
The Safety Of Combined Triple Drug Therapy With Ivermectin, Diethylcarbamazine And Albendazole In The Neglected Tropical Diseases Co-Endemic Setting Of Fiji: A Cluster Randomised Trial, Myra Hardy, Josaia Samuela, Mike Kama, Meciusela Tuicakau, Lucia Romani, Margot J. Whitfeld, Christopher L. King, Gary J. Weil, Anneke C. Grobler, Leanne J. Robinson, John M. Kaldor, Andrew C. Steer
The Safety Of Combined Triple Drug Therapy With Ivermectin, Diethylcarbamazine And Albendazole In The Neglected Tropical Diseases Co-Endemic Setting Of Fiji: A Cluster Randomised Trial, Myra Hardy, Josaia Samuela, Mike Kama, Meciusela Tuicakau, Lucia Romani, Margot J. Whitfeld, Christopher L. King, Gary J. Weil, Anneke C. Grobler, Leanne J. Robinson, John M. Kaldor, Andrew C. Steer
Open Access Publications
Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days …
Civicpy: A Python Software Evelopment And Analysis Toolkit For The Civic Knowledgebase, Alex H Wagner, Susanna Kiwala, Adam C Coffman, Joshua F Mcmichael, Kelsy C Cotto, Thomas B Mooney, Erica K Barnell, Kilannin Krysiak, Arpad M Danos, Jason Walker, Obi L Griffith, Malachi Griffith
Civicpy: A Python Software Evelopment And Analysis Toolkit For The Civic Knowledgebase, Alex H Wagner, Susanna Kiwala, Adam C Coffman, Joshua F Mcmichael, Kelsy C Cotto, Thomas B Mooney, Erica K Barnell, Kilannin Krysiak, Arpad M Danos, Jason Walker, Obi L Griffith, Malachi Griffith
Open Access Publications
PURPOSE: Precision oncology depends on the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, and open-access knowledgebase. CIViC provides a structured framework for evaluating genomic variants of various types (eg, fusions, single-nucleotide variants) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented application programming interface for accessing CIViC records: assertions, evidence, variants, and genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this application programming interface, often reimplementing redundant functionality …
Disease-Modifying Therapy Adherence And Associated Factors In A National Sample Of Medicare Patients With Multiple Sclerosis, Pengxiang Li, Vrushabh P Ladage, Joseph Berger, Salim Chahin, Mehul Jhaveri, Caroline Geremakis, Jalpa A Doshi
Disease-Modifying Therapy Adherence And Associated Factors In A National Sample Of Medicare Patients With Multiple Sclerosis, Pengxiang Li, Vrushabh P Ladage, Joseph Berger, Salim Chahin, Mehul Jhaveri, Caroline Geremakis, Jalpa A Doshi
Open Access Publications
OBJECTIVES: Disease-modifying therapies (DMTs) reduce relapse rates and disability progression for relapsing multiple sclerosis (MS). Although 25% to 30% of all US patients with MS are Medicare beneficiaries, limited information exists on this population. This is the first study using national Medicare data to (1) describe characteristics of patients with MS using DMTs, (2) estimate adherence to DMTs over a 1-year and 3-year follow-up, and (3) examine factors associated with DMT adherence.
METHODS: This retrospective claims analysis used 2011-2014 100% Medicare files. Monthly adherence to MS DMTs was defined as the proportion of days covered ≥0.80 with any DMT in …
Decision-Making Based On 3d Printed Models In Laparoscopic Liver Resections With Intraoperative Ultrasound: A Prospective Observational Study, Jan Witowski, Andrzej Budzyński, Anna Grochowska, David H Ballard, Piotr Major, Mateusz Rubinkiewicz, Adriana Złahoda-Huzior, Tadeusz J Popiela, Mateusz Wierdak, Michał Pędziwiatr
Decision-Making Based On 3d Printed Models In Laparoscopic Liver Resections With Intraoperative Ultrasound: A Prospective Observational Study, Jan Witowski, Andrzej Budzyński, Anna Grochowska, David H Ballard, Piotr Major, Mateusz Rubinkiewicz, Adriana Złahoda-Huzior, Tadeusz J Popiela, Mateusz Wierdak, Michał Pędziwiatr
Open Access Publications
OBJECTIVES: The aim of this study was to evaluate impact of 3D printed models on decision-making in context of laparoscopic liver resections (LLR) performed with intraoperative ultrasound (IOUS) guidance.
METHODS: Nineteen patients with liver malignances (74% were colorectal cancer metastases) were prospectively qualified for LLR or radiofrequency ablation in a single center from April 2017 to December 2018. Models were 3DP in all cases based on CT and facilitated optical visualization of tumors' relationships with portal and hepatic veins. Planned surgical extent and its changes were tracked after CT analysis and 3D model inspection, as well as intraoperatively using IOUS. …
The Dual-Specificity Kinase Dyrk1a Modulates The Levels Of Cyclin L2 To Control Hiv Replication In Macrophages, Javan K. Kisaka, Lee Ratner, George B. Kyei
The Dual-Specificity Kinase Dyrk1a Modulates The Levels Of Cyclin L2 To Control Hiv Replication In Macrophages, Javan K. Kisaka, Lee Ratner, George B. Kyei
Open Access Publications
HIV replication in macrophages contributes to the latent viral reservoirs, which are considered the main barrier to HIV eradication. Few cellular factors that facilitate HIV replication in latently infected cells are known. We previously identified cyclin L2 as a critical factor required by HIV-1 and found that depletion of cyclin L2 attenuates HIV-1 replication in macrophages. Here we demonstrate that cyclin L2 promotes HIV-1 replication through interactions with the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Cyclin L2 and DYRK1A were colocalized in the nucleus and were found together in immunoprecipitation experiments. Knockdown or inhibition of DYRK1A increased HIV-1 replication in …
Improving Characterization Of Understudied Human Microbiomes Using Targeted Phylogenetics, Bruce A Rosa, Kathie Mihindukulasuriya, Kymberlie Hallsworth-Pepin, Aye Wollam, John Martin, Caroline Snowden, William Michael Dunne Jr., George M Weinstock, Carey-Ann D. Burnham, Makedonka Mitreva
Improving Characterization Of Understudied Human Microbiomes Using Targeted Phylogenetics, Bruce A Rosa, Kathie Mihindukulasuriya, Kymberlie Hallsworth-Pepin, Aye Wollam, John Martin, Caroline Snowden, William Michael Dunne Jr., George M Weinstock, Carey-Ann D. Burnham, Makedonka Mitreva
Open Access Publications
Whole-genome bacterial sequences are required to better understand microbial functions, niche-specific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g., feces), as few as 13% of bacterium-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from underrepresented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full-length 16S rRNA gene sequences, clustered the sequences to ensure that no individual taxonomic group was …
The Plasmodium Falciparum Artemisinin Susceptibility-Associated Ap-2 Adaptin Μ Subunit Is Clathrin Independent And Essential For Schizont Maturation, Ryan C Henrici, Rachel L Edwards, Martin Zoltner, Donelly A Van Schalkwyk, Melissa N Hart, Franziska Mohring, Robert W Moon, Stephanie D Nofal, Avnish Patel, Christian Flueck, David A Baker, Audrey R Odom John, Mark C Field, Colin J Sutherland
The Plasmodium Falciparum Artemisinin Susceptibility-Associated Ap-2 Adaptin Μ Subunit Is Clathrin Independent And Essential For Schizont Maturation, Ryan C Henrici, Rachel L Edwards, Martin Zoltner, Donelly A Van Schalkwyk, Melissa N Hart, Franziska Mohring, Robert W Moon, Stephanie D Nofal, Avnish Patel, Christian Flueck, David A Baker, Audrey R Odom John, Mark C Field, Colin J Sutherland
Open Access Publications
The efficacy of current antimalarial drugs is threatened by reduced susceptibility of
How To Stop The Bleed: First Care Provider Model For Developing Public Trauma Response Beyond Basic Hemorrhage Control, Joshua P Bobko, Dylan J Badin, Leila Danishgar, Kate Bayhan, Kevin J Thompson, William J Harris, R. Todd Baldridge, Gerald R Fortuna
How To Stop The Bleed: First Care Provider Model For Developing Public Trauma Response Beyond Basic Hemorrhage Control, Joshua P Bobko, Dylan J Badin, Leila Danishgar, Kate Bayhan, Kevin J Thompson, William J Harris, R. Todd Baldridge, Gerald R Fortuna
Open Access Publications
INTRODUCTION: Since 2013, the First Care Provider (FCP) model has successfully educated the non-medical population on how to recognize life-threatening injuries and perform interventions recommended by the Committee for Tactical Emergency Casualty Care (C-TECC) and the Hartford Consensus in the disaster setting. Recent programs, such as the federal "Stop The Bleed" campaign, have placed the emphasis of public training on hemorrhage control. However, recent attacks demonstrate that access to wounded, recognition of injury, and rapid evacuation are equally as important as hemorrhage control in minimizing mortality. To date, no training programs have produced a validated study with regard to training …
Neural Mechanisms Of Economic Choices In Mice, Masaru Kuwabara, Ningdong Kang, Timothy E. Holy, Camillo Padoa-Schioppa
Neural Mechanisms Of Economic Choices In Mice, Masaru Kuwabara, Ningdong Kang, Timothy E. Holy, Camillo Padoa-Schioppa
Open Access Publications
Economic choices entail computing and comparing subjective values. Evidence from primates indicates that this behavior relies on the orbitofrontal cortex. Conversely, previous work in rodents provided conflicting results. Here we present a mouse model of economic choice behavior, and we show that the lateral orbital (LO) area is intimately related to the decision process. In the experiments, mice chose between different juices offered in variable amounts. Choice patterns closely resembled those measured in primates. Optogenetic inactivation of LO dramatically disrupted choices by inducing erratic changes of relative value and by increasing choice variability. Neuronal recordings revealed that different groups of …
Agonist-Selective Recruitment Of Engineered Protein Probes And Of Grk2 By Opioid Receptors In Living Cells, Miriam Stoeber, Damien Jullié, Joy Li, Soumen Chakraborty, Susruta Majumdar, Nevin A. Lambert, Aashish Manglik, Mark Von Zastrow
Agonist-Selective Recruitment Of Engineered Protein Probes And Of Grk2 By Opioid Receptors In Living Cells, Miriam Stoeber, Damien Jullié, Joy Li, Soumen Chakraborty, Susruta Majumdar, Nevin A. Lambert, Aashish Manglik, Mark Von Zastrow
Open Access Publications
G protein-coupled receptors (GPCRs) signal through allostery, and it is increasingly clear that chemically distinct agonists can produce different receptor-based effects. It has been proposed that agonists selectively promote receptors to recruit one cellular interacting partner over another, introducing allosteric 'bias' into the signaling system. However, the underlying hypothesis - that different agonists drive GPCRs to engage different cytoplasmic proteins in living cells - remains untested due to the complexity of readouts through which receptor-proximal interactions are typically inferred. We describe a cell-based assay to overcome this challenge, based on GPCR-interacting biosensors that are disconnected from endogenous transduction mechanisms. Focusing …
Pituitary Carcinoma: Two Case Reports And Review Of Literature, Lai Xu, Karam Khaddour, Jie Chen, Keith M. Rich, Richard J. Perrin, Jian Li Campian
Pituitary Carcinoma: Two Case Reports And Review Of Literature, Lai Xu, Karam Khaddour, Jie Chen, Keith M. Rich, Richard J. Perrin, Jian Li Campian
Open Access Publications
BACKGROUND: Pituitary carcinoma is a rare type of malignancy that can be very difficult to diagnose and treat. Many cases were diagnosed at autopsy. Delays in diagnosis often adversely impact patients' outcomes. Even with prompt diagnosis, treatment decisions remain challenging in the absence of randomized controlled trials.
CASE SUMMARY: We report two cases of pituitary carcinoma in men with a history of pituitary adenoma. In the first case, a 55-year-old man was initially diagnosed with pituitary macroadenoma. He underwent subtotal debulking of the tumor followed by adjuvant radiotherapy. Subsequently, he developed relapsed disease and multifocal intracranial metastases and a diagnosis …
An Inducible Cre Mouse Line To Sparsely Target Nervous System Cells, Including Remak Schwann Cells, Darshan Sapkota, Joseph D Dougherty
An Inducible Cre Mouse Line To Sparsely Target Nervous System Cells, Including Remak Schwann Cells, Darshan Sapkota, Joseph D Dougherty
Open Access Publications
Nerves of the peripheral nervous system contain two classes of Schwann cells: myelinating Schwann cells that ensheath large caliber axons and generate the myelin sheath, and Remak Schwann cells that surround smaller axons and do not myelinate. While tools exist for genetic targeting of Schwann cell precursors and myelinating Schwann cells, such reagents have been challenging to generate specifically for the Remak population, in part because many of the genes that mark this population in maturity are also robustly expressed in Schwann cell precursors. To circumvent this challenge, we utilized BAC transgenesis to generate a mouse line expressing a tamoxifen-inducible …
Continuous Representations Of Speed By Striatal Medium Spiny Neurons, Wambura C. Fobbs, Sebastiano Bariselli, Julia A. Licholai, Nanami L. Miyazaki, Bridget A. Matikainen-Ankney, Meaghan C. Creed, Alexxai V. Kravitz
Continuous Representations Of Speed By Striatal Medium Spiny Neurons, Wambura C. Fobbs, Sebastiano Bariselli, Julia A. Licholai, Nanami L. Miyazaki, Bridget A. Matikainen-Ankney, Meaghan C. Creed, Alexxai V. Kravitz
Open Access Publications
The striatum is critical for controlling motor output. However, it remains unclear how striatal output neurons encode and facilitate movement. A prominent theory suggests that striatal units encode movements in bursts of activity near specific events, such as the start or end of actions. These bursts are theorized to gate or permit specific motor actions, thereby encoding and facilitating complex sequences of actions. An alternative theory has suggested that striatal neurons encode continuous changes in sensory or motor information with graded changes in firing rate. Supporting this theory, many striatal neurons exhibit such graded changes without bursting near specific actions. …
Clinical Care Recommendations For Cardiologists Treating Adults With Myotonic Dystrophy, Elizabeth M Mcnally, Douglas L Mann, Yigal Pinto, Deepak Bhakta, Gordon Tomaselli, Saman Nazarian, William J Groh, Takuhisa Tamura, Denis Duboc, Hideki Itoh, Leah Hellerstein, Pradeep P A Mammen
Clinical Care Recommendations For Cardiologists Treating Adults With Myotonic Dystrophy, Elizabeth M Mcnally, Douglas L Mann, Yigal Pinto, Deepak Bhakta, Gordon Tomaselli, Saman Nazarian, William J Groh, Takuhisa Tamura, Denis Duboc, Hideki Itoh, Leah Hellerstein, Pradeep P A Mammen
Open Access Publications
Myotonic dystrophy is an inherited systemic disorder affecting skeletal muscle and the heart. Genetic testing for myotonic dystrophy is diagnostic and identifies those at risk for cardiac complications. The 2 major genetic forms of myotonic dystrophy, type 1 and type 2, differ in genetic etiology yet share clinical features. The cardiac management of myotonic dystrophy should include surveillance for arrhythmias and left ventricular dysfunction, both of which occur in progressive manner and contribute to morbidity and mortality. To promote the development of care guidelines for myotonic dystrophy, the Myotonic Foundation solicited the input of care experts and organized the drafting …
Cryptococcus Neoformans Chitin Synthase 3 Plays A Critical Role In Dampening Host Inflammatory Responses, Camaron R Hole, Woei C Lam, Rajendra Upadhya, Jennifer K Lodge
Cryptococcus Neoformans Chitin Synthase 3 Plays A Critical Role In Dampening Host Inflammatory Responses, Camaron R Hole, Woei C Lam, Rajendra Upadhya, Jennifer K Lodge
Open Access Publications
No abstract provided.
Proof-Of-Concept Study Of The Efficacy Of A Microbiota-Directed Complementary Food Formulation (Mdcf) For Treating Moderate Acute Malnutrition, Ishita Mostafa, Naila Nurun Nahar, Md Munirul Islam, Sayeeda Huq, Mahfuz Mustafa, Michael Barratt, Jeffrey I Gordon, Tahmeed Ahmed
Proof-Of-Concept Study Of The Efficacy Of A Microbiota-Directed Complementary Food Formulation (Mdcf) For Treating Moderate Acute Malnutrition, Ishita Mostafa, Naila Nurun Nahar, Md Munirul Islam, Sayeeda Huq, Mahfuz Mustafa, Michael Barratt, Jeffrey I Gordon, Tahmeed Ahmed
Open Access Publications
BACKGROUND: Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between - 2 and - 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy …
Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis At The Blood-Brain Barrier For Central Nervous System Entry, Hamid Salimi, Matthew D Cain, Xiaoping Jiang, Robyn A Roth, Wandy L Beatty, Chengqun Sun, William B Klimstra, Jianghui Hou, Robyn S Klein
Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis At The Blood-Brain Barrier For Central Nervous System Entry, Hamid Salimi, Matthew D Cain, Xiaoping Jiang, Robyn A Roth, Wandy L Beatty, Chengqun Sun, William B Klimstra, Jianghui Hou, Robyn S Klein
Open Access Publications
Venezuelan and western equine encephalitis viruses (VEEV and WEEV, respectively) invade the central nervous system (CNS) early during infection, via neuronal and hematogenous routes. While viral replication mediates host shutoff, including expression of type I interferons (IFN), few studies have addressed how alphaviruses gain access to the CNS during established infection or the mechanisms of viral crossing at the blood-brain barrier (BBB). Here, we show that hematogenous dissemination of VEEV and WEEV into the CNS occurs via caveolin-1 (Cav-1)-mediated transcytosis (Cav-MT) across an intact BBB, which is impeded by IFN and inhibitors of RhoA GTPase. Use of reporter and nonreplicative …
A Qualitative Study Of Physician Perspectives On Adaptation To Electronic Health Records, Cynthia J Sieck, Nicole Pearl, Tiffani J Bright, Po-Yin Yen
A Qualitative Study Of Physician Perspectives On Adaptation To Electronic Health Records, Cynthia J Sieck, Nicole Pearl, Tiffani J Bright, Po-Yin Yen
Open Access Publications
BACKGROUND: Electronic Health Records (EHRs) have the potential to improve many aspects of care and their use has increased in the last decade. Because of this, acceptance and adoption of EHRs is less of a concern than adaptation to use. To understand this issue more deeply, we conducted a qualitative study of physician perspectives on EHR use to identify factors that facilitate adaptation.
METHODS: We conducted semi-structured interviews with 9 physicians across a range of inpatient disciplines at a large Academic Medical Center. Interviews were conducted by phone, lasting approximately 30 min, and were transcribed verbatim for analysis. We utilized …
Spatiotemporal Dynamics Of Multi-Vesicular Release Is Determined By Heterogeneity Of Release Sites Within Central Synapses, Dario Maschi, Vitaly A. Klyachko
Spatiotemporal Dynamics Of Multi-Vesicular Release Is Determined By Heterogeneity Of Release Sites Within Central Synapses, Dario Maschi, Vitaly A. Klyachko
Open Access Publications
A synaptic active zone (AZ) can release multiple vesicles in response to an action potential. This multi-vesicular release (MVR) occurs at most synapses, but its spatiotemporal properties are unknown. Nanoscale-resolution detection of individual release events in hippocampal synapses revealed unprecedented heterogeneity among vesicle release sites within a single AZ, with a gradient of release probability decreasing from AZ center to periphery. Parallel to this organization, MVR events preferentially overlap with uni-vesicular release (UVR) events at sites closer to an AZ center. Pairs of fusion events comprising MVR are also not perfectly synchronized, and the earlier event tends to occur closer …
Neuronal Activity In The Primate Amygdala During Economic Choice, Ahmad Jezzini, Camillo Padoa-Schioppa
Neuronal Activity In The Primate Amygdala During Economic Choice, Ahmad Jezzini, Camillo Padoa-Schioppa
Open Access Publications
Multiple lines of evidence link economic choices to the orbitofrontal cortex (OFC), but other brain regions may contribute to the computation and comparison of economic values. A particularly strong candidate is the basolateral amygdala (BLA). Amygdala lesions impair performance in reinforcer devaluation tasks, suggesting that the BLA contributes to value computation. Furthermore, previous studies of the BLA have found neuronal activity consistent with a value representation. Here, we recorded from the BLA of two male rhesus macaques choosing between different juices. Offered quantities varied from trial to trial, and relative values were inferred from choices. Approximately one-third of BLA cells …