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Full-Text Articles in Medicine and Health Sciences

Vitamin D Treatment Prevents Uremia-Induced Reductions In Aortic Microrna-145 Attenuating Osteogenic Differentiation Despite Hyperphosphatemia, Natalia Carrillo-López, Sara Panizo, Maria Vittoria Arcidiacono, Sandra De La Fuente, Laura Martínez-Arias, Emerenziana Ottaviano, Catalina Ulloa, María Piedad Ruiz-Torres, Isabel Rodríguez, Jorge B Cannata-Andía, Manuel Naves-Díaz, Adriana S Dusso Jun 2022

Vitamin D Treatment Prevents Uremia-Induced Reductions In Aortic Microrna-145 Attenuating Osteogenic Differentiation Despite Hyperphosphatemia, Natalia Carrillo-López, Sara Panizo, Maria Vittoria Arcidiacono, Sandra De La Fuente, Laura Martínez-Arias, Emerenziana Ottaviano, Catalina Ulloa, María Piedad Ruiz-Torres, Isabel Rodríguez, Jorge B Cannata-Andía, Manuel Naves-Díaz, Adriana S Dusso

2020-Current year OA Pubs

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 …


Antigenic Landscapes On Staphylococcus Aureus Pore-Forming Toxins Reveal Insights Into Specificity And Cross-Neutralization, Shweta Kailasan, Ravi Kant, Madeleine Noonan-Shueh, Tulasikumari Kanipakala, Grant Liao, Sergey Shulenin, Daisy W Leung, Richard A Alm, Rajan P Adhikari, Gaya K Amarasinghe, Michael L Gross, M Javad Aman Jun 2022

Antigenic Landscapes On Staphylococcus Aureus Pore-Forming Toxins Reveal Insights Into Specificity And Cross-Neutralization, Shweta Kailasan, Ravi Kant, Madeleine Noonan-Shueh, Tulasikumari Kanipakala, Grant Liao, Sergey Shulenin, Daisy W Leung, Richard A Alm, Rajan P Adhikari, Gaya K Amarasinghe, Michael L Gross, M Javad Aman

2020-Current year OA Pubs

No abstract provided.


Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling To Promote Health And Longevity, Mahmoud Abdellatif, Tobias Pendl, Sebastian J Hofer, Moydul Islam, Abhinav Diwan, Tobias Eisenberg, Frank Madeo, Et Al Jun 2022

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling To Promote Health And Longevity, Mahmoud Abdellatif, Tobias Pendl, Sebastian J Hofer, Moydul Islam, Abhinav Diwan, Tobias Eisenberg, Frank Madeo, Et Al

2020-Current year OA Pubs

BACKGROUND: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial.

METHODS: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic …


Mechanism Of Voltage Sensing In Ca2+- And Voltage-Activated K + (Bk) Channels, Willy Carrasquel-Ursulaez, Ignacio Segura, Ignacio Díaz-Franulic, Felipe Echeverría, Yenisleidy Lorenzo-Ceballos, Nicolás Espinoza, Maximiliano Rojas, Jose Antonio Garate, Eduardo Perozo, Osvaldo Alvarez, Fernando D Gonzalez-Nilo, Ramón Latorre, Valeria Marquez-Miranda Jun 2022

Mechanism Of Voltage Sensing In Ca2+- And Voltage-Activated K + (Bk) Channels, Willy Carrasquel-Ursulaez, Ignacio Segura, Ignacio Díaz-Franulic, Felipe Echeverría, Yenisleidy Lorenzo-Ceballos, Nicolás Espinoza, Maximiliano Rojas, Jose Antonio Garate, Eduardo Perozo, Osvaldo Alvarez, Fernando D Gonzalez-Nilo, Ramón Latorre, Valeria Marquez-Miranda

2020-Current year OA Pubs

In neurosecretion, allosteric communication between voltage sensors and Ca


Activation Of The Rat Α1Β2Ε Gabaa Receptor By Orthosteric And Allosteric Agonists, Allison L Germann, Ariel B Burbridge, Spencer R Pierce, Gustav Akk Jun 2022

Activation Of The Rat Α1Β2Ε Gabaa Receptor By Orthosteric And Allosteric Agonists, Allison L Germann, Ariel B Burbridge, Spencer R Pierce, Gustav Akk

2020-Current year OA Pubs

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Mitochondrial Cyclophilin D Promotes Disease Tolerance By Licensing Nk Cell Development And Il-22 Production Against Influenza Virus, Jeffrey Downey, Haley E Randolph, Erwan Pernet, Kim A Tran, Shabaana A Khader, Irah L King, Luis B Barreiro, Maziar Divangahi Jun 2022

Mitochondrial Cyclophilin D Promotes Disease Tolerance By Licensing Nk Cell Development And Il-22 Production Against Influenza Virus, Jeffrey Downey, Haley E Randolph, Erwan Pernet, Kim A Tran, Shabaana A Khader, Irah L King, Luis B Barreiro, Maziar Divangahi

2020-Current year OA Pubs

Severity of pulmonary viral infections, including influenza A virus (IAV), is linked to excessive immunopathology, which impairs lung function. Thus, the same immune responses that limit viral replication can concomitantly cause lung damage that must be countered by largely uncharacterized disease tolerance mechanisms. Here, we show that mitochondrial cyclophilin D (CypD) protects against IAV via disease tolerance. CypD


Mrna Vaccine Boosting Enhances Antibody Responses Against Sars-Cov-2 Omicron Variant In Individuals With Antibody Deficiency Syndromes, Ofer Zimmerman, Alexa Michelle Altman Doss, Paulina Kaplonek, Chieh-Yu Liang, Laura A. Vanblargan, Rita E. Chen, Jennifer Marie Monroy, H. James Wedner, Anthony Kulczycki, Tarisa L. Mantia, Caitlin C. O'Shaughnessy, Hannah G. Davis-Adams, Harry L. Bertera, Lucas J. Adams, Saravanan Raju, Fang R. Zhao, Christopher J. Rigell, Tiffany Biason Dy, Andrew L. Kau, Zhen Ren, Jackson S. Turner, Jane A. O'Halloran, Rachel M. Presti, Daved H. Fremont, Peggy L. Kendall, Ali H. Ellebedy, Galit Alter, Michael S. Diamond Jun 2022

Mrna Vaccine Boosting Enhances Antibody Responses Against Sars-Cov-2 Omicron Variant In Individuals With Antibody Deficiency Syndromes, Ofer Zimmerman, Alexa Michelle Altman Doss, Paulina Kaplonek, Chieh-Yu Liang, Laura A. Vanblargan, Rita E. Chen, Jennifer Marie Monroy, H. James Wedner, Anthony Kulczycki, Tarisa L. Mantia, Caitlin C. O'Shaughnessy, Hannah G. Davis-Adams, Harry L. Bertera, Lucas J. Adams, Saravanan Raju, Fang R. Zhao, Christopher J. Rigell, Tiffany Biason Dy, Andrew L. Kau, Zhen Ren, Jackson S. Turner, Jane A. O'Halloran, Rachel M. Presti, Daved H. Fremont, Peggy L. Kendall, Ali H. Ellebedy, Galit Alter, Michael S. Diamond

2020-Current year OA Pubs

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. …


Mechanisms Of Transcranial Doppler Ultrasound Phenotypes In Paediatric Cerebral Malaria Remain Elusive., Nicole F O'Brien, Yudy Fonseca, Hunter C Johnson, Douglas Postels, Gretchen L Birbeck, Yamikani Chimalizeni, Karl B Seydel, Montfort Bernard Gushu, Tusekile Phiri, Sylvester June, Karen Chetcuti, Lorenna Vidal, Manu S Goyal, Terrie E Taylor Jun 2022

Mechanisms Of Transcranial Doppler Ultrasound Phenotypes In Paediatric Cerebral Malaria Remain Elusive., Nicole F O'Brien, Yudy Fonseca, Hunter C Johnson, Douglas Postels, Gretchen L Birbeck, Yamikani Chimalizeni, Karl B Seydel, Montfort Bernard Gushu, Tusekile Phiri, Sylvester June, Karen Chetcuti, Lorenna Vidal, Manu S Goyal, Terrie E Taylor

2020-Current year OA Pubs

BACKGROUND: Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes.

METHODS: This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a …


Mycobacterium Tuberculosis Infection Drives A Type I Ifn Signature In Lung Lymphocytes, Sadia Akter, Kuldeep S Chauhan, Micah D Dunlap, José Alberto Choreño-Parra, Lan Lu, Ekaterina Esaulova, Joaquin Zúñiga, Maxim N Artyomov, Deepak Kaushal, Shabaana A Khader Jun 2022

Mycobacterium Tuberculosis Infection Drives A Type I Ifn Signature In Lung Lymphocytes, Sadia Akter, Kuldeep S Chauhan, Micah D Dunlap, José Alberto Choreño-Parra, Lan Lu, Ekaterina Esaulova, Joaquin Zúñiga, Maxim N Artyomov, Deepak Kaushal, Shabaana A Khader

2020-Current year OA Pubs

Mycobacterium tuberculosis (Mtb) infects 25% of the world's population and causes tuberculosis (TB), which is a leading cause of death globally. A clear understanding of the dynamics of immune response at the cellular level is crucial to design better strategies to control TB. We use the single-cell RNA sequencing approach on lung lymphocytes derived from healthy and Mtb-infected mice. Our results show the enrichment of the type I IFN signature among the lymphoid cell clusters, as well as heat shock responses in natural killer (NK) cells from Mtb-infected mice lungs. We identify Ly6A as a lymphoid cell activation marker and …


Impact Of Capsulectomy Type On Post-Explantation Systemic Symptom Improvement: Findings From The Aserf Systemic Symptoms In Women-Biospecimen Analysis Study: Part 1, Caroline Glicksman, Patricia Mcguire, Marshall Kadin, Marisa Lawrence, Melinda Haws, Jill Newby, Sarah Ferenz, James Sung, Roger Wixtrom Jun 2022

Impact Of Capsulectomy Type On Post-Explantation Systemic Symptom Improvement: Findings From The Aserf Systemic Symptoms In Women-Biospecimen Analysis Study: Part 1, Caroline Glicksman, Patricia Mcguire, Marshall Kadin, Marisa Lawrence, Melinda Haws, Jill Newby, Sarah Ferenz, James Sung, Roger Wixtrom

2020-Current year OA Pubs

BACKGROUND: Breast Implant Illness (BII) is a term used to describe a variety of symptoms by patients with breast implants for which there are no abnormal physical or laboratory findings to explain their symptoms. There currently exists a difference of opinion among clinicians and patients concerning the diagnosis and treatment of patients self-reporting BII.

OBJECTIVES: The first aim of this study was to determine if there is a valid indication for "en bloc" capsulectomy in patients self-reporting BII and if the type of capsulectomy performed alters long-term symptom improvement. The second goal was to identify any clinical laboratory differences between …


Rapid Detection Of An Ebola Biomarker With Optical Microring Resonators, Abraham J Qavi, Krista Meserve, M Javad Aman, Hong Vu, Larry Zeitlin, John M Dye, Jeffrey W Froude, Daisy W Leung, Lan Yang, Frederick W Holtsberg, Ryan C Bailey, Gaya K Amarasinghe Jun 2022

Rapid Detection Of An Ebola Biomarker With Optical Microring Resonators, Abraham J Qavi, Krista Meserve, M Javad Aman, Hong Vu, Larry Zeitlin, John M Dye, Jeffrey W Froude, Daisy W Leung, Lan Yang, Frederick W Holtsberg, Ryan C Bailey, Gaya K Amarasinghe

2020-Current year OA Pubs

Ebola virus (EBOV) is a highly infectious pathogen, with a case mortality rate as high as 89%. Rapid therapeutic treatments and supportive measures can drastically improve patient outcome; however, the symptoms of EBOV disease (EVD) lack specificity from other endemic diseases. Given the high mortality and significant symptom overlap, there is a critical need for sensitive, rapid diagnostics for EVD. Facile diagnosis of EVD remains a challenge. Here, we describe a rapid and sensitive diagnostic for EVD through microring resonator sensors in conjunction with a unique biomarker of EBOV infection, soluble glycoprotein (sGP). Microring resonator sensors detected sGP in under …


Perceptions Of Covid-19 Self-Testing And Recommendations For Implementation And Scale-Up Among Black/African Americans: Implications For The Covid-19 Step Project, Ucheoma Nwaozuru, Thembekile Shato, Et Al. Jun 2022

Perceptions Of Covid-19 Self-Testing And Recommendations For Implementation And Scale-Up Among Black/African Americans: Implications For The Covid-19 Step Project, Ucheoma Nwaozuru, Thembekile Shato, Et Al.

2020-Current year OA Pubs

BACKGROUND: COVID-19 self-testing (ST) is an innovative strategy with the potential to increase the access and uptake of testing and ultimately to limit the spread of the virus. To maximize the uptake and reach of this promising strategy and inform intervention development and scale up, research is needed to understand the acceptability of and willingness to use this tool. This is vital to ensure that Black/African Americans are reached by the Biden-Harris Administration's free national COVID-19 ST program. This study aimed to explore the acceptability and recommendations to promote and scale-up the uptake of COVID-19 ST among Black/African Americans.

METHODS: …


Face Identity Coding In The Deep Neural Network And Primate Brain, Jinge Wang, Runnan Cao, Nicholas J Brandmeir, Xin Li, Shuo Wang Jun 2022

Face Identity Coding In The Deep Neural Network And Primate Brain, Jinge Wang, Runnan Cao, Nicholas J Brandmeir, Xin Li, Shuo Wang

2020-Current year OA Pubs

A central challenge in face perception research is to understand how neurons encode face identities. This challenge has not been met largely due to the lack of simultaneous access to the entire face processing neural network and the lack of a comprehensive multifaceted model capable of characterizing a large number of facial features. Here, we addressed this challenge by conducting in silico experiments using a pre-trained face recognition deep neural network (DNN) with a diverse array of stimuli. We identified a subset of DNN units selective to face identities, and these identity-selective units demonstrated generalized discriminability to novel faces. Visualization …


Homotopic Contralesional Excitation Suppresses Spontaneous Circuit Repair And Global Network Reconnections Following Ischemic Stroke, Annie R Bice, Qingli Xiao, Justin Kong, Ping Yan, Zachary Pollack Rosenthal, Andrew W Kraft, Karen P Smith, Tadeusz Wieloch, Jin-Moo Lee, Joseph P Culver, Adam Q Bauer Jun 2022

Homotopic Contralesional Excitation Suppresses Spontaneous Circuit Repair And Global Network Reconnections Following Ischemic Stroke, Annie R Bice, Qingli Xiao, Justin Kong, Ping Yan, Zachary Pollack Rosenthal, Andrew W Kraft, Karen P Smith, Tadeusz Wieloch, Jin-Moo Lee, Joseph P Culver, Adam Q Bauer

2020-Current year OA Pubs

Understanding circuit-level manipulations that affect the brain's capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems- and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received …


Stroke Recovery Phenotyping Through Network Trajectory Approaches And Graph Neural Networks, Sanjukta Krishnagopal, Keith Lohse, Robynne Braun Jun 2022

Stroke Recovery Phenotyping Through Network Trajectory Approaches And Graph Neural Networks, Sanjukta Krishnagopal, Keith Lohse, Robynne Braun

2020-Current year OA Pubs

Stroke is a leading cause of neurological injury characterized by impairments in multiple neurological domains including cognition, language, sensory and motor functions. Clinical recovery in these domains is tracked using a wide range of measures that may be continuous, ordinal, interval or categorical in nature, which can present challenges for multivariate regression approaches. This has hindered stroke researchers' ability to achieve an integrated picture of the complex time-evolving interactions among symptoms. Here, we use tools from network science and machine learning that are particularly well-suited to extracting underlying patterns in such data, and may assist in prediction of recovery patterns. …


Aspartyl Protease Inhibitors As Anti-Filarial Drugs, Liana Beld, Hyeim Jung, Christina A Bulman, Bruce A Rosa, Peter U Fischer, James W Janetka, Sara Lustigman, Judy A Sakanari, Makedonka Mitreva Jun 2022

Aspartyl Protease Inhibitors As Anti-Filarial Drugs, Liana Beld, Hyeim Jung, Christina A Bulman, Bruce A Rosa, Peter U Fischer, James W Janetka, Sara Lustigman, Judy A Sakanari, Makedonka Mitreva

2020-Current year OA Pubs

The current treatments for lymphatic filariasis and onchocerciasis do not effectively kill the adult parasitic nematodes, allowing these chronic and debilitating diseases to persist in millions of people. Thus, the discovery of new drugs with macrofilaricidal potential to treat these filarial diseases is critical. To facilitate this need, we first investigated the effects of three aspartyl protease inhibitors (APIs) that are FDA-approved as HIV antiretroviral drugs on the adult filarial nematode,


Imaging Peripheral Nerve Micro-Anatomy With Muse, 2d And 3d Approaches, Chaitanya Kolluru, Austin Todd, Aniruddha R Upadhye, Yehe Liu, Mikhail Y Berezin, Farzad Fereidouni, Richard M Levenson, Yanming Wang, Andrew J Shoffstall, Michael W Jenkins, David L Wilson Jun 2022

Imaging Peripheral Nerve Micro-Anatomy With Muse, 2d And 3d Approaches, Chaitanya Kolluru, Austin Todd, Aniruddha R Upadhye, Yehe Liu, Mikhail Y Berezin, Farzad Fereidouni, Richard M Levenson, Yanming Wang, Andrew J Shoffstall, Michael W Jenkins, David L Wilson

2020-Current year OA Pubs

Understanding peripheral nerve micro-anatomy can assist in the development of safe and effective neuromodulation devices. However, current approaches for imaging nerve morphology at the fiber level are either cumbersome, require substantial instrumentation, have a limited volume of view, or are limited in resolution/contrast. We present alternative methods based on MUSE (Microscopy with Ultraviolet Surface Excitation) imaging to investigate peripheral nerve morphology, both in 2D and 3D. For 2D imaging, fixed samples are imaged on a conventional MUSE system either label free (via auto-fluorescence) or after staining with fluorescent dyes. This method provides a simple and rapid technique to visualize myelinated …


Protocol To Analyze And Quantify Protein-Methylated Rna Interactions In Mammalian Cells With A Combination Of Rna Immunoprecipitation And Nucleoside Mass Spectrometry, Ning Tsao, Jennifer M Soll, Nima Mosammaparast Jun 2022

Protocol To Analyze And Quantify Protein-Methylated Rna Interactions In Mammalian Cells With A Combination Of Rna Immunoprecipitation And Nucleoside Mass Spectrometry, Ning Tsao, Jennifer M Soll, Nima Mosammaparast

2020-Current year OA Pubs

Cellular RNAs are modified by both physiological factors and exogenous agents, such as methyl methanesulfonate (MMS). However, techniques for analyzing how proteins may interact with these modified RNAs are limited. Here, we provide a protocol combining RNA immunoprecipitation (RIP) with mass spectrometry (MS) to analyze the methylation state of the RNAs bound by Flag-tagged proteins in mammalian cells. The approach is highly quantitative and can simultaneously detect several methylated nucleosides in a single experiment. For complete details on the use and execution of this protocol, please refer to Tsao et al. (2021).


Cryo-Em Structure Of The Prothrombin-Prothrombinase Complex, Eliza A Ruben, Brock Summers, Michael J Rau, James A J Fitzpatrick, Enrico Di Cera Jun 2022

Cryo-Em Structure Of The Prothrombin-Prothrombinase Complex, Eliza A Ruben, Brock Summers, Michael J Rau, James A J Fitzpatrick, Enrico Di Cera

2020-Current year OA Pubs

The intrinsic and extrinsic pathways of the coagulation cascade converge to a common step where the prothrombinase complex, comprising the enzyme factor Xa (fXa), the cofactor fVa, Ca2+ and phospholipids, activates the zymogen prothrombin to the protease thrombin. The reaction entails cleavage at 2 sites, R271 and R320, generating the intermediates prethrombin 2 and meizothrombin, respectively. The molecular basis of these interactions that are central to hemostasis remains elusive. We solved 2 cryogenic electron microscopy (cryo-EM) structures of the fVa-fXa complex, 1 free on nanodiscs at 5.3-Å resolution and the other bound to prothrombin at near atomic 4.1-Å resolution. In …


The Csf In Neurosarcoidosis Contains Consistent Clonal Expansion Of Cd8 T Cells, But Not Cd4 T Cells, Michael A Paley, Brandi J Baker, S Richard Dunham, Nicole Linskey, Claudia Cantoni, Kenneth Lee, Lynn M Hassman, Jennifer Laurent, Elisha D O Roberson, David B Clifford, Wayne M Yokoyama Jun 2022

The Csf In Neurosarcoidosis Contains Consistent Clonal Expansion Of Cd8 T Cells, But Not Cd4 T Cells, Michael A Paley, Brandi J Baker, S Richard Dunham, Nicole Linskey, Claudia Cantoni, Kenneth Lee, Lynn M Hassman, Jennifer Laurent, Elisha D O Roberson, David B Clifford, Wayne M Yokoyama

2020-Current year OA Pubs

The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders.


Piperine Derivatives Enhance Fusion And Axonal Transport Of Mitochondria By Activating Mitofusins, Lihong Zhang, Xiawei Dang, Antonietta Franco, Haiyang Zhao, Gerald W. Dorn Ii Jun 2022

Piperine Derivatives Enhance Fusion And Axonal Transport Of Mitochondria By Activating Mitofusins, Lihong Zhang, Xiawei Dang, Antonietta Franco, Haiyang Zhao, Gerald W. Dorn Ii

2020-Current year OA Pubs

No abstract provided.


The Microbiome Restrains Melanoma Bone Growth By Promoting Intestinal Nk And Th1 Cell Homing To Bone, Subhashis Pal, Daniel S. Perrien, Tetsuya Yumoto, Roberta Faccio, Andreea Stoica, Jonathan Adams, Craig M. Coopersmith, Rheinallt M. Jones, M. Neale Weitzmann, Roberto Pacifici Jun 2022

The Microbiome Restrains Melanoma Bone Growth By Promoting Intestinal Nk And Th1 Cell Homing To Bone, Subhashis Pal, Daniel S. Perrien, Tetsuya Yumoto, Roberta Faccio, Andreea Stoica, Jonathan Adams, Craig M. Coopersmith, Rheinallt M. Jones, M. Neale Weitzmann, Roberto Pacifici

2020-Current year OA Pubs

Bone metastases are frequent complications of malignant melanoma leading to reduced quality of life and significant morbidity. Regulation of immune cells by the gut microbiome influences cancer progression, but the role of the microbiome in tumor growth in bone is unknown. Using intracardiac or intratibial injections of B16-F10 melanoma cells into mice, we showed that gut microbiome depletion by broad-spectrum antibiotics accelerated intraosseous tumor growth and osteolysis. Microbiome depletion blunted melanoma-induced expansion of intestinal NK cells and Th1 cells and their migration from the gut to tumor-bearing bones. Demonstrating the functional relevance of immune cell trafficking from the gut to …


Csf Tau Phosphorylation At Thr205 Is Associated With Loss Of White Matter Integrity In Autosomal Dominant Alzheimer Disease, Jeremy F. Strain, Nicolas Barthelemy, Kanta Horie, Brian A. Gordon, Collin Kilgore, Andrew Aschenbrenner, Carlos Cruchaga, Chengjie Xiong, Nelly Joseph-Mathurin, Jason Hassenstab, Anne M. Fagan, Yan Li, Celeste M. Karch, Richard J. Perrin, Sarah B. Berman, Jasmeer P. Chhatwal, Neill R. Graff-Radford, Hiroshi Mori, Johannes Levin, James M. Noble, Ricardo Allegri, Peter R. Schofield, Daniel S. Marcus, David M. Holtzman, John C. Morris, Tammie L. S. Benzinger, Eric M. Mcdade, Randall J. Bateman, Beau M. Ances Jun 2022

Csf Tau Phosphorylation At Thr205 Is Associated With Loss Of White Matter Integrity In Autosomal Dominant Alzheimer Disease, Jeremy F. Strain, Nicolas Barthelemy, Kanta Horie, Brian A. Gordon, Collin Kilgore, Andrew Aschenbrenner, Carlos Cruchaga, Chengjie Xiong, Nelly Joseph-Mathurin, Jason Hassenstab, Anne M. Fagan, Yan Li, Celeste M. Karch, Richard J. Perrin, Sarah B. Berman, Jasmeer P. Chhatwal, Neill R. Graff-Radford, Hiroshi Mori, Johannes Levin, James M. Noble, Ricardo Allegri, Peter R. Schofield, Daniel S. Marcus, David M. Holtzman, John C. Morris, Tammie L. S. Benzinger, Eric M. Mcdade, Randall J. Bateman, Beau M. Ances

2020-Current year OA Pubs

BACKGROUND: Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer's disease (AD). However, it remains unknown whether white matter (WM) decline due to AD is associated with specific Tau phosphorylation site(s).

METHODS: In autosomal dominant AD (ADAD) mutation carriers (MC) and non-carriers (NC) we compared cerebrospinal fluid (CSF) phosphorylation at tau sites (pT217, pT181, pS202, and pT205) and total tau with WM measures, as derived from diffusion tensor imaging (DTI), and cognition. A WM composite metric, derived from a principal component analysis, was used to identify spatial decline seen in ADAD.

RESULTS: The …


A Dual-Center Cohort Study On The Association Between Early Deep Sedation And Clinical Outcomes In Mechanically Ventilated Patients During The Covid-19 Pandemic: The Covid-Sed Study, Robert J Stephens, Erin M Evans, Michael J Pajor, Ryan D Pappal, Haley M Egan, Max Wei, Hunter Hayes, Jason A Morris, Nicholas Becker, Brian W Roberts, Marin H Kollef, Nicholas M Mohr, Brian M Fuller Jun 2022

A Dual-Center Cohort Study On The Association Between Early Deep Sedation And Clinical Outcomes In Mechanically Ventilated Patients During The Covid-19 Pandemic: The Covid-Sed Study, Robert J Stephens, Erin M Evans, Michael J Pajor, Ryan D Pappal, Haley M Egan, Max Wei, Hunter Hayes, Jason A Morris, Nicholas Becker, Brian W Roberts, Marin H Kollef, Nicholas M Mohr, Brian M Fuller

2020-Current year OA Pubs

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.

STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over …


Metabolic Biomarkers Assessed With Pet/Ct Predict Sex-Specific Longitudinal Outcomes In Patients With Diffuse Large B-Cell Lymphoma, Shama Jaswal, Vanessa Sanders, Priyanka Pullarkat, Stephanie Teja, Amber Salter, Marcus P Watkins, Norman Atagu, Daniel R Ludwig, Joyce Mhlanga, Vincent M Mellnick, Linda R Peterson, Nancy L Bartlett, Brad S Kahl, Todd A Fehniger, Armin Ghobadi, Amanda F Cashen, Neha Mehta-Shah, Joseph E Ippolito Jun 2022

Metabolic Biomarkers Assessed With Pet/Ct Predict Sex-Specific Longitudinal Outcomes In Patients With Diffuse Large B-Cell Lymphoma, Shama Jaswal, Vanessa Sanders, Priyanka Pullarkat, Stephanie Teja, Amber Salter, Marcus P Watkins, Norman Atagu, Daniel R Ludwig, Joyce Mhlanga, Vincent M Mellnick, Linda R Peterson, Nancy L Bartlett, Brad S Kahl, Todd A Fehniger, Armin Ghobadi, Amanda F Cashen, Neha Mehta-Shah, Joseph E Ippolito

2020-Current year OA Pubs

In many cancers, including lymphoma, males have higher incidence and mortality than females. Emerging evidence demonstrates that one mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. We wanted to determine if visceral fat and tumor glucose uptake with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could predict sex-dependent outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis of 160 patients (84 males; 76 females) with DLBCL who had imaging at initial staging and after completion of therapy. CT-based relative visceral fat area …


Exploring The Impact Of Trem2 In Tumor-Associated Macrophages, Darya Khantakova, Simone Brioschi, Martina Molgora Jun 2022

Exploring The Impact Of Trem2 In Tumor-Associated Macrophages, Darya Khantakova, Simone Brioschi, Martina Molgora

2020-Current year OA Pubs

Tumor-associated macrophages (TAMs) represent a key component of the tumor microenvironment and are generally associated with immunosuppression and poor prognosis. TREM2 is a transmembrane receptor of the immunoglobulin superfamily expressed in myeloid cells. TREM2 has been extensively studied in microglia and neurodegenerative diseases and recently emerged as a marker of pro-tumorigenic macrophages. The accumulation of TREM2-expressing TAMs was reported across numerous cancer patients and tumor models. TREM2 genetic blockade or TREM2 targeting with antibodies resulted in improved tumor control, enhanced response to anti-PD1, and significant changes in the tumor immune landscape. Preclinical studies paved the way for an ongoing clinical …


Distributed Learning For Heterogeneous Clinical Data With Application To Integrating Covid-19 Data Across 230 Sites, Jiayi Tong, Chongliang Luo, Md Nazmul Islam, Natalie E Sheils, John Buresh, Mackenzie Edmondson, Peter A Merkel, Ebbing Lautenbach, Rui Duan, Yong Chen Jun 2022

Distributed Learning For Heterogeneous Clinical Data With Application To Integrating Covid-19 Data Across 230 Sites, Jiayi Tong, Chongliang Luo, Md Nazmul Islam, Natalie E Sheils, John Buresh, Mackenzie Edmondson, Peter A Merkel, Ebbing Lautenbach, Rui Duan, Yong Chen

2020-Current year OA Pubs

Integrating real-world data (RWD) from several clinical sites offers great opportunities to improve estimation with a more general population compared to analyses based on a single clinical site. However, sharing patient-level data across sites is practically challenging due to concerns about maintaining patient privacy. We develop a distributed algorithm to integrate heterogeneous RWD from multiple clinical sites without sharing patient-level data. The proposed distributed conditional logistic regression (dCLR) algorithm can effectively account for between-site heterogeneity and requires only one round of communication. Our simulation study and data application with the data of 14,215 COVID-19 patients from 230 clinical sites in …


Indoleamine 2,3-Dioxygenase 1 Activation In Mature Cdc1 Promotes Tolerogenic Education Of Inflammatory Cdc2 Via Metabolic Communication, Marco Gargaro, Carlos G. Briseño, Prachi Bagadia, Vivek Durai, Derek J. Theisen, Sunkyung Kim, Marco Colonna, Theresa L. Murphy, Kenneth M. Murphy, Et Al. Jun 2022

Indoleamine 2,3-Dioxygenase 1 Activation In Mature Cdc1 Promotes Tolerogenic Education Of Inflammatory Cdc2 Via Metabolic Communication, Marco Gargaro, Carlos G. Briseño, Prachi Bagadia, Vivek Durai, Derek J. Theisen, Sunkyung Kim, Marco Colonna, Theresa L. Murphy, Kenneth M. Murphy, Et Al.

2020-Current year OA Pubs

Conventional dendritic cells (cDCs), cDC1 and cDC2, act both to initiate immunity and maintain self-tolerance. The tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is used by cDCs in maintaining tolerance, but its role in different subsets remains unclear. At homeostasis, only mature CCR7


Impact Of Web-Based Cognitive Behavioral Therapy For Insomnia On Stress, Health, Mood, Cognitive, Inflammatory, And Neurodegenerative Outcomes In Rural Dementia Caregivers: Protocol For The Nitecapp Cares And Nitecapp Shares Randomized Controlled Trial, Christina S Mccrae, Ashley F Curtis, Amelia Cottle, David B Beversdorf, Joel Shenker, Brian P Mooney, Mihail Popescu, Marilyn Rantz, Maureen Groer, Phyllis Stein, Mojgan Golzy, Melanie A Stearns, Angelynn Simenson, Neetu Nair, Meredeth A Rowe Jun 2022

Impact Of Web-Based Cognitive Behavioral Therapy For Insomnia On Stress, Health, Mood, Cognitive, Inflammatory, And Neurodegenerative Outcomes In Rural Dementia Caregivers: Protocol For The Nitecapp Cares And Nitecapp Shares Randomized Controlled Trial, Christina S Mccrae, Ashley F Curtis, Amelia Cottle, David B Beversdorf, Joel Shenker, Brian P Mooney, Mihail Popescu, Marilyn Rantz, Maureen Groer, Phyllis Stein, Mojgan Golzy, Melanie A Stearns, Angelynn Simenson, Neetu Nair, Meredeth A Rowe

2020-Current year OA Pubs

BACKGROUND: Chronic insomnia affects up to 63% of family dementia caregivers. Research suggests that chronic insomnia prompts changes in central stress processing that have downstream negative effects on health and mood, as well as on cognitive, inflammatory, and neurodegenerative functioning. We hypothesize that cognitive behavioral therapy for insomnia (CBT-I) will reverse those downstream effects by improving insomnia and restoring healthy central stress processing. Rural caregivers are particularly vulnerable, but they have limited access to CBT-I; therefore, we developed an accessible digital version using community input (NiteCAPP CARES).

OBJECTIVE: This trial will evaluate the acceptability, feasibility, and short-term and long-term effects …


Primary Prevention Of Stroke In Children With Sickle Cell Anemia In Nigeria: Protocol For A Mixed Methods Implementation Study In A Community Hospital, Halima Bello-Manga, Lawal Haliru, Kudrat Abdulkareem Ahmed, Abdulkadir Musa Tabari, Bilkisu Usman Farouk, Gloria Yimi Bahago, Aisha Shuaibu Kazaure, Abdulrasheed Sani Muhammad, Samira Abubakar Gwarzo, Ana A Baumann, Michael R Debaun, Allison A King Jun 2022

Primary Prevention Of Stroke In Children With Sickle Cell Anemia In Nigeria: Protocol For A Mixed Methods Implementation Study In A Community Hospital, Halima Bello-Manga, Lawal Haliru, Kudrat Abdulkareem Ahmed, Abdulkadir Musa Tabari, Bilkisu Usman Farouk, Gloria Yimi Bahago, Aisha Shuaibu Kazaure, Abdulrasheed Sani Muhammad, Samira Abubakar Gwarzo, Ana A Baumann, Michael R Debaun, Allison A King

2020-Current year OA Pubs

BACKGROUND: In Nigeria, approximately 150,000 children with sickle cell anemia (SCA) are born annually, accounting for more than half of all SCA births worldwide. Without intervention, about 11% of children with SCA will develop a stroke before their 20th birthday. Evidence-based practices for primary stroke prevention include screening for abnormal transcranial Doppler (TCD) measurements coupled with regular blood transfusion therapy for at least one year, followed by hydroxyurea (HU) therapy indefinitely. In high-resource countries, this strategy contributes to a 92% decrease in stroke incidence rates. In 2016, as part of a capacity building objective of the Stroke Prevention Trial in …