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Articles 1351 - 1380 of 8115
Full-Text Articles in Entire DC Network
Tmem135 Links Peroxisomes To The Regulation Of Brown Fat Mitochondrial Fission And Energy Homeostasis, Donghua Hu, Min Tan, Dongliang Lu, Brian Kleiboeker, Xuejing Liu, Hongsuk Park, Alexxai V Kravitz, Kooresh I Shoghi, Yu-Hua Tseng, Babak Razani, Akihiro Ikeda, Irfan J Lodhi
Tmem135 Links Peroxisomes To The Regulation Of Brown Fat Mitochondrial Fission And Energy Homeostasis, Donghua Hu, Min Tan, Dongliang Lu, Brian Kleiboeker, Xuejing Liu, Hongsuk Park, Alexxai V Kravitz, Kooresh I Shoghi, Yu-Hua Tseng, Babak Razani, Akihiro Ikeda, Irfan J Lodhi
2020-Current year OA Pubs
Mitochondrial morphology, which is controlled by mitochondrial fission and fusion, is an important regulator of the thermogenic capacity of brown adipocytes. Adipose-specific peroxisome deficiency impairs thermogenesis by inhibiting cold-induced mitochondrial fission due to decreased mitochondrial membrane content of the peroxisome-derived lipids called plasmalogens. Here, we identify TMEM135 as a critical mediator of the peroxisomal regulation of mitochondrial fission and thermogenesis. Adipose-specific TMEM135 knockout in mice blocks mitochondrial fission, impairs thermogenesis, and increases diet-induced obesity and insulin resistance. Conversely, TMEM135 overexpression promotes mitochondrial division, counteracts obesity and insulin resistance, and rescues thermogenesis in peroxisome-deficient mice. Mechanistically, thermogenic stimuli promote association between …
Associations Between Plasma, Imaging, And Cerebrospinal Fluid Biomarkers With Driving Behavior And Cognitive Tests: Implications For Biomarker Usefulness, Catherine M Roe, Sayeh Bayat, Ganesh M Babulal
Associations Between Plasma, Imaging, And Cerebrospinal Fluid Biomarkers With Driving Behavior And Cognitive Tests: Implications For Biomarker Usefulness, Catherine M Roe, Sayeh Bayat, Ganesh M Babulal
2020-Current year OA Pubs
BACKGROUND: Declines in instrumental activities of daily living like driving are hallmarks sequelae of Alzheimer's disease (AD). Although driving has been shown to be associated with traditional imaging and cerebrospinal fluid (CSF) biomarkers, it is possible that some biomarkers have stronger associations with specific aspects of driving behavior. Furthermore, associations between newer plasma biomarkers and driving behaviors are unknown.
OBJECTIVE: This study assessed the extent to which individual plasma, imaging, and CSF biomarkers are related to specific driving behaviors and cognitive functions among cognitively normal older adults.
METHODS: We analyzed naturalistic driving behavior from cognitively healthy older drivers (N = …
Methamphetamine-Induced Region-Specific Transcriptomic And Epigenetic Changes In The Brain Of Male Rats, Benpeng Miao, Xiaoyun Xing, Viktoriia Bazylianska, Pamela Madden, Anna Moszczynska, Bo Zhang
Methamphetamine-Induced Region-Specific Transcriptomic And Epigenetic Changes In The Brain Of Male Rats, Benpeng Miao, Xiaoyun Xing, Viktoriia Bazylianska, Pamela Madden, Anna Moszczynska, Bo Zhang
2020-Current year OA Pubs
Psychostimulant methamphetamine (METH) is neurotoxic to the brain and, therefore, its misuse leads to neurological and psychiatric disorders. The gene regulatory network (GRN) response to neurotoxic METH binge remains unclear in most brain regions. Here we examined the effects of binge METH on the GRN in the nucleus accumbens, dentate gyrus, Ammon's horn, and subventricular zone in male rats. At 24 h after METH, ~16% of genes displayed altered expression and over a quarter of previously open chromatin regions - parts of the genome where genes are typically active - showed shifts in their accessibility. Intriguingly, most changes were unique …
Propofol Affords No Protection Against Delayed Cerebral Ischemia In A Mouse Model Of Subarachnoid Hemorrhage, Meizi Liu, Keshav Jayaraman, James W Nelson, Jogender Mehla, Deepti Diwan, Ananth K Vellimana, Gregory J Zipfel, Umeshkumar Athiraman
Propofol Affords No Protection Against Delayed Cerebral Ischemia In A Mouse Model Of Subarachnoid Hemorrhage, Meizi Liu, Keshav Jayaraman, James W Nelson, Jogender Mehla, Deepti Diwan, Ananth K Vellimana, Gregory J Zipfel, Umeshkumar Athiraman
2020-Current year OA Pubs
Delayed cerebral ischemia (DCI) is an important contributor to poor outcomes in aneurysmal subarachnoid hemorrhage (SAH) patients. We previously showed that volatile anesthetics such as isoflurane, sevoflurane and desflurane provided robust protection against SAH-induced DCI, but the impact of a more commonly used intravenous anesthetic agent, propofol, is not known. The goal of our current study is to examine the neurovascular protective effects of propofol on SAH-induced DCI. Twelve-week-old male wild-type mice were utilized for the study. Mice underwent endovascular perforation SAH or sham surgery followed one hour later by propofol infusion through the internal jugular vein (2 mg/kg/min continuous …
Intrinsic Tumor Resistance To Car T Cells Is A Dynamic Transcriptional State That Is Exploitable With Low-Dose Radiation, Alexander B Kim, Ssu-Yu Chou, Solomon Kang, Eric Kwon, Matthew Inkman, Jeff Szymanski, Neal Andruska, Cian Colgan, Jin Zhang, Joanna C Yang, Nathan Singh, Carl J Deselm
Intrinsic Tumor Resistance To Car T Cells Is A Dynamic Transcriptional State That Is Exploitable With Low-Dose Radiation, Alexander B Kim, Ssu-Yu Chou, Solomon Kang, Eric Kwon, Matthew Inkman, Jeff Szymanski, Neal Andruska, Cian Colgan, Jin Zhang, Joanna C Yang, Nathan Singh, Carl J Deselm
2020-Current year OA Pubs
Chimeric antigen receptor (CAR) T-cell therapy represents a major advancement for hematologic malignancies, with some patients achieving long-term remission. However, the majority of treated patients still die of their disease. A consistent predictor of response is tumor quantity, wherein a higher disease burden before CAR T-cell therapy portends a worse prognosis. Focal radiation to bulky sites of the disease can decrease tumor quantity before CAR T-cell therapy, but whether this strategy improves survival is unknown. We find that substantially reducing systemic tumor quantity using high-dose radiation to areas of bulky disease, which is commonly done clinically, is less impactful on …
Inducible Crispr-Targeted "Knockdown" Of Human Gut Bacteroides In Gnotobiotic Mice Discloses Glycan Utilization Strategies, Zachary W Beller, Darryl A Wesener, Timothy R Seebeck, Janaki L Guruge, Alexandra E Byrne, Suzanne Henrissat, Jeffrey I Gordon, Et Al.
Inducible Crispr-Targeted "Knockdown" Of Human Gut Bacteroides In Gnotobiotic Mice Discloses Glycan Utilization Strategies, Zachary W Beller, Darryl A Wesener, Timothy R Seebeck, Janaki L Guruge, Alexandra E Byrne, Suzanne Henrissat, Jeffrey I Gordon, Et Al.
2020-Current year OA Pubs
Understanding how members of the human gut microbiota prioritize nutrient resources is one component of a larger effort to decipher the mechanisms defining microbial community robustness and resiliency in health and disease. This knowledge is foundational for development of microbiota-directed therapeutics. To model how bacteria prioritize glycans in the gut, germfree mice were colonized with 13 human gut bacterial strains, including seven saccharolytic
Tissue Factor Activates The Coagulation Cascade In Mouse Models Of Acute Promyelocytic Leukemia, Yohei Hisada, Tomohiro Kawano, Sierra J Archibald, John S Welch, Brandi N Reeves, Nigel Mackman
Tissue Factor Activates The Coagulation Cascade In Mouse Models Of Acute Promyelocytic Leukemia, Yohei Hisada, Tomohiro Kawano, Sierra J Archibald, John S Welch, Brandi N Reeves, Nigel Mackman
2020-Current year OA Pubs
Acute promyelocytic leukemia (APL) is associated with a high risk of bleeding and thrombosis. APL patients have an activated coagulation system, hyperfibrinolysis, and thrombocytopenia. APL cells express tissue factor (TF), a receptor and cofactor for factor VII/VIIa. This study had 2 goals. Firstly, we measured biomarkers of coagulation and fibrinolysis activation as well as platelet counts and bleeding in both mouse xenograft and allograft models of APL. Secondly, we determined the effect of inhibiting TF on the activation of coagulation in these models. We observed increased levels of plasma thrombin-antithrombin complexes (TAT), D-dimer, and plasmin-antiplasmin complexes, reduced platelet counts, and …
Blockade Of Interferon Signaling Decreases Gut Barrier Integrity And Promotes Severe West Nile Virus Disease, Shih-Ching Lin, Fang R Zhao, Hana Janova, Adrian Gervais, Summer Rucknagel, Kristy O Murray, Jean-Laurent Casanova, Michael S Diamond
Blockade Of Interferon Signaling Decreases Gut Barrier Integrity And Promotes Severe West Nile Virus Disease, Shih-Ching Lin, Fang R Zhao, Hana Janova, Adrian Gervais, Summer Rucknagel, Kristy O Murray, Jean-Laurent Casanova, Michael S Diamond
2020-Current year OA Pubs
The determinants of severe disease caused by West Nile virus (WNV) and why only ~1% of individuals progress to encephalitis remain poorly understood. Here, we use human and mouse enteroids, and a mouse model of pathogenesis, to explore the capacity of WNV to directly infect gastrointestinal (GI) tract cells and contribute to disease severity. At baseline, WNV poorly infects human and mouse enteroid cultures and enterocytes in mice. However, when STAT1 or type I interferon (IFN) responses are absent, GI tract cells become infected, and this is associated with augmented GI tract and blood-brain barrier (BBB) permeability, accumulation of gut-derived …
Non-Uniform Temporal Scaling Of Developmental Processes In The Mammalian Cortex, Annalisa Paolino, Elizabeth H Haines, Evan J Bailey, Dylan A Black, Ching Moey, Fernando García-Moreno, Linda J Richards, Rodrigo Suárez, Laura R Fenlon
Non-Uniform Temporal Scaling Of Developmental Processes In The Mammalian Cortex, Annalisa Paolino, Elizabeth H Haines, Evan J Bailey, Dylan A Black, Ching Moey, Fernando García-Moreno, Linda J Richards, Rodrigo Suárez, Laura R Fenlon
2020-Current year OA Pubs
The time that it takes the brain to develop is highly variable across animals. Although staging systems equate major developmental milestones between mammalian species, it remains unclear how distinct processes of cortical development scale within these timeframes. Here, we compare the timing of cortical development in two mammals of similar size but different developmental pace: eutherian mice and marsupial fat-tailed dunnarts. Our results reveal that the temporal relationship between cell birth and laminar specification aligns to equivalent stages between these species, but that migration and axon extension do not scale uniformly according to the developmental stages, and are relatively more …
Molecular Imaging Of Ace2 Expression In Infectious Disease And Cancer, Zhiyao Li, Abbie Hasson, Lasya Daggumati, Hanwen Zhang, Daniel L J Thorek
Molecular Imaging Of Ace2 Expression In Infectious Disease And Cancer, Zhiyao Li, Abbie Hasson, Lasya Daggumati, Hanwen Zhang, Daniel L J Thorek
2020-Current year OA Pubs
Angiotensin-converting enzyme 2 (ACE2) is a cell-surface receptor that plays a critical role in the pathogenesis of SARS-CoV-2 infection. Through the use of ligands engineered for the receptor, ACE2 imaging has emerged as a valuable tool for preclinical and clinical research. These can be used to visualize the expression and distribution of ACE2 in tissues and cells. A variety of techniques including optical, magnetic resonance, and nuclear medicine contrast agents have been developed and employed in the preclinical setting. Positron-emitting radiotracers for highly sensitive and quantitative tomography have also been translated in the context of SARS-CoV-2-infected and control patients. Together …
Bap1 Promotes Osteoclast Function By Metabolic Reprogramming, Nidhi Rohatgi, Wei Zou, Yongjia Li, Kevin Cho, Patrick L Collins, Eric Tycksen, Gaurav Pandey, Carl J Deselm, Gary J Patti, Anwesha Dey, Steven L Teitelbaum
Bap1 Promotes Osteoclast Function By Metabolic Reprogramming, Nidhi Rohatgi, Wei Zou, Yongjia Li, Kevin Cho, Patrick L Collins, Eric Tycksen, Gaurav Pandey, Carl J Deselm, Gary J Patti, Anwesha Dey, Steven L Teitelbaum
2020-Current year OA Pubs
Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1
18s Rrna Methyltransferases Dimt1 And Bud23 Drive Intergenerational Hormesis, Noa Liberman, Eric Lieberman Greer, Et Al.
18s Rrna Methyltransferases Dimt1 And Bud23 Drive Intergenerational Hormesis, Noa Liberman, Eric Lieberman Greer, Et Al.
2020-Current year OA Pubs
Heritable non-genetic information can regulate a variety of complex phenotypes. However, what specific non-genetic cues are transmitted from parents to their descendants are poorly understood. Here, we perform metabolic methyl-labeling experiments to track the heritable transmission of methylation from ancestors to their descendants in the nematode Caenorhabditis elegans (C. elegans). We find heritable methylation in DNA, RNA, proteins, and lipids. We find that parental starvation elicits reduced fertility, increased heat stress resistance, and extended longevity in fed, naïve progeny. This intergenerational hormesis is accompanied by a heritable increase in N6'-dimethyl adenosine (m
Development And Evaluation Of A Wearable Peripheral Vascular Compensation Sensor In A Swine Model Of Hemorrhage, Francesca Bonetta-Misteli, Toi Collins, Todd Pavek, Madison Carlgren, Derek Bashe, Antonina Frolova, Leonid Shmuylovich, Christine M O'Brien
Development And Evaluation Of A Wearable Peripheral Vascular Compensation Sensor In A Swine Model Of Hemorrhage, Francesca Bonetta-Misteli, Toi Collins, Todd Pavek, Madison Carlgren, Derek Bashe, Antonina Frolova, Leonid Shmuylovich, Christine M O'Brien
2020-Current year OA Pubs
Postpartum hemorrhage (PPH) is the leading and most preventable cause of maternal mortality, particularly in low-resource settings. PPH is currently diagnosed through visual estimation of blood loss or monitoring of vital signs. Visual assessment routinely underestimates blood loss beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The measured LSFI signal produced a linear response in phantom …
First-In-Human Prospective Trial Of Sonobiopsy In High-Grade Glioma Patients Using Neuronavigation-Guided Focused Ultrasound, Jinyun Yuan, Lu Xu, Chih-Yen Chien, Yaoheng Yang, Yimei Yue, Siaka Fadera, Andrew H Stark, Katherine E Schwetye, Arash Nazeri, Rupen Desai, Umeshkumar Athiraman, Aadel A Chaudhuri, Hong Chen, Eric C Leuthardt
First-In-Human Prospective Trial Of Sonobiopsy In High-Grade Glioma Patients Using Neuronavigation-Guided Focused Ultrasound, Jinyun Yuan, Lu Xu, Chih-Yen Chien, Yaoheng Yang, Yimei Yue, Siaka Fadera, Andrew H Stark, Katherine E Schwetye, Arash Nazeri, Rupen Desai, Umeshkumar Athiraman, Aadel A Chaudhuri, Hong Chen, Eric C Leuthardt
2020-Current year OA Pubs
Sonobiopsy is an emerging technology that combines focused ultrasound (FUS) with microbubbles to enrich circulating brain disease-specific biomarkers for noninvasive molecular diagnosis of brain diseases. Here, we report the first-in-human prospective trial of sonobiopsy in high-grade glioma patients to evaluate its feasibility and safety in enriching plasma circulating tumor biomarkers. A nimble FUS device integrated with a clinical neuronavigation system was used to perform sonobiopsy following an established clinical workflow for neuronavigation. Analysis of blood samples collected before and after FUS sonication showed that sonobiopsy enriched plasma circulating tumor DNA (ctDNA), including a maximum increase of 1.6-fold for the mononucleosome …
Ifn-Λ Derived From Nonsusceptible Enterocytes Acts On Tuft Cells To Limit Persistent Norovirus, Harshad Ingle, Heyde Makimaa, Somya Aggarwal, Hongju Deng, Lynne Foster, Yuhao Li, Elizabeth A Kennedy, Stefan T Peterson, Craig B Wilen, Sanghyun Lee, Mehul S Suthar, Megan T Baldridge
Ifn-Λ Derived From Nonsusceptible Enterocytes Acts On Tuft Cells To Limit Persistent Norovirus, Harshad Ingle, Heyde Makimaa, Somya Aggarwal, Hongju Deng, Lynne Foster, Yuhao Li, Elizabeth A Kennedy, Stefan T Peterson, Craig B Wilen, Sanghyun Lee, Mehul S Suthar, Megan T Baldridge
2020-Current year OA Pubs
Norovirus is a leading cause of epidemic viral gastroenteritis, with no currently approved vaccines or antivirals. Murine norovirus (MNoV) is a well-characterized model of norovirus pathogenesis in vivo, and persistent strains exhibit lifelong intestinal infection. Interferon-λ (IFN-λ) is a potent antiviral that rapidly cures MNoV. We previously demonstrated that IFN-λ signaling in intestinal epithelial cells (IECs) controls persistent MNoV, and here demonstrate that IFN-λ acts on tuft cells, the exclusive site of MNoV persistence, to limit infection. While interrogating the source of IFN-λ to regulate MNoV, we confirmed that MDA5-MAVS signaling, required for IFN-λ induction to MNoV in vitro, controls …
Educating Perioperative Nurses On Preventing Hypothermia In Surgical Patients, Bethany Geisler
Educating Perioperative Nurses On Preventing Hypothermia In Surgical Patients, Bethany Geisler
Doctor of Nursing Practice (DNP) Student Projects
Perioperative hypothermia (PH) is a preventable complication of surgical procedures that has been linked to postoperative conditions such as coagulopathies, increased cardiac morbidity, surgical site infection, increased incidence of pressure ulcers, increased length of hospital stay, and increased financial expense. Anesthetic agents given to patients during surgery directly contribute to PH and associated complications.
Background: Perioperative is a time frame involving the three stages of surgery (preoperative, intraoperative, and postoperative). Hypothermia is defined as body core temperature below 36 degrees Celsius. The incidence of PH ranges from 11% to 90% depending on the anesthesia administered, type of surgery, length of …
Picobirnaviruses Encode Proteins That Are Functional Bacterial Lysins, Tianyu Gan, David Wang
Picobirnaviruses Encode Proteins That Are Functional Bacterial Lysins, Tianyu Gan, David Wang
2020-Current year OA Pubs
Picobirnaviruses (PBVs) are double-stranded RNA viruses frequently detected in human and animal enteric viromes. Associations of PBVs with enteric graft-versus-host disease and type I diabetes during pregnancy have been established. Since their discovery in 1988, PBVs have been generally assumed to be animal-infecting viruses despite the lack of culture system, animal model, or detection in animal cells or tissues. Recent studies have proposed that bacteria or fungi could be the hosts of PBVs based on genomic analysis. Here, we functionally demonstrate that multiple PBVs of different genome organizations encode bacterial lysins that lyse
Erg K+ Channels Mediate A Major Component Of Action Potential Repolarization In Lymphatic Muscle, Hae Jin Kim, Min Li, Emma C Erlich, Gwendalyn J Randolph, Michael J Davis
Erg K+ Channels Mediate A Major Component Of Action Potential Repolarization In Lymphatic Muscle, Hae Jin Kim, Min Li, Emma C Erlich, Gwendalyn J Randolph, Michael J Davis
2020-Current year OA Pubs
Smooth muscle cells in the walls of collecting lymphatic vessels fire spontaneous action potentials (APs), which conduct rapidly over the muscle layer to initiate contractions that propel lymph. Several ion channels have been implicated in the currents underlying the AP spike and the preceding diastolic depolarization, but the molecular identities of K
Single Genomic Enhancers Drive Experience-Dependent Gabaergic Plasticity To Maintain Sensory Processing In The Adult Cortex, Ori Roethler, Eran Zohar, Katayun Cohen-Kashi Malina, Lidor Bitan, Harrison Wren Gabel, Ivo Spiegel
Single Genomic Enhancers Drive Experience-Dependent Gabaergic Plasticity To Maintain Sensory Processing In The Adult Cortex, Ori Roethler, Eran Zohar, Katayun Cohen-Kashi Malina, Lidor Bitan, Harrison Wren Gabel, Ivo Spiegel
2020-Current year OA Pubs
Experience-dependent plasticity of synapses modulates information processing in neural circuits and is essential for cognitive functions. The genome, via non-coding enhancers, was proposed to control information processing and circuit plasticity by regulating experience-induced transcription of genes that modulate specific sets of synapses. To test this idea, we analyze here the cellular and circuit functions of the genomic mechanisms that control the experience-induced transcription of Igf1 (insulin-like growth factor 1) in vasoactive intestinal peptide (VIP) interneurons (INs) in the visual cortex of adult mice. We find that two sensory-induced enhancers selectively and cooperatively drive the activity-induced transcription of Igf1 to thereby …
Acute Kidney Injury-Induced Circulating Tnfr1/2 Elevations Correlate With Persistent Kidney Injury And Progression To Fibrosis, Akshayakeerthi Arthanarisami, Yohei Komaru, Charikleia Katsouridi, Julian Schumacher, Deborah K Verges, Liang Ning, Mai M Abdelmageed, Andreas Herrlich, Eirini Kefaloyianni
Acute Kidney Injury-Induced Circulating Tnfr1/2 Elevations Correlate With Persistent Kidney Injury And Progression To Fibrosis, Akshayakeerthi Arthanarisami, Yohei Komaru, Charikleia Katsouridi, Julian Schumacher, Deborah K Verges, Liang Ning, Mai M Abdelmageed, Andreas Herrlich, Eirini Kefaloyianni
2020-Current year OA Pubs
Elevated levels of circulating tumor necrosis factor receptors 1 and 2 (cTNFR1/2) predict chronic kidney disease (CKD) progression; however, the mechanisms of their release remain unknown. Whether acute kidney injury (AKI) drives cTNFR1/2 elevations and whether they predict disease outcomes after AKI remain unknown. In this study, we used AKI patient serum and urine samples, mouse models of kidney injury (ischemic, obstructive, and toxic), and progression to fibrosis, nephrectomy, and related single-cell RNA-sequencing datasets to experimentally test the role of kidney injury on cTNFR1/2 levels. We show that TNFR1/2 serum and urine levels are highly elevated in all of the …
Lem2 Is Essential For Cardiac Development By Maintaining Nuclear Integrity, Jacob A Ross, Didier Hodzic, Et Al.
Lem2 Is Essential For Cardiac Development By Maintaining Nuclear Integrity, Jacob A Ross, Didier Hodzic, Et Al.
2020-Current year OA Pubs
AIMS: Nuclear envelope integrity is essential for the compartmentalization of the nucleus and cytoplasm. Importantly, mutations in genes encoding nuclear envelope (NE) and associated proteins are the second highest cause of familial dilated cardiomyopathy. One such NE protein that causes cardiomyopathy in humans and affects mouse heart development is Lem2. However, its role in the heart remains poorly understood.
METHODS AND RESULTS: We generated mice in which Lem2 was specifically ablated either in embryonic cardiomyocytes (Lem2 cKO) or in adult cardiomyocytes (Lem2 iCKO) and carried out detailed physiological, tissue, and cellular analyses. High-resolution episcopic microscopy was used for three-dimensional reconstructions …
Medication And Road Test Performance Among Cognitively Healthy Older Adults, David B Carr, Kebede Beyene, Jason Doherty, Samantha A Murphy, Ann M Johnson, Hailee Domash, Noah Riley, Alexis Walker, Ashwin Sabapathy, John C Morris, Ganesh M Babulal
Medication And Road Test Performance Among Cognitively Healthy Older Adults, David B Carr, Kebede Beyene, Jason Doherty, Samantha A Murphy, Ann M Johnson, Hailee Domash, Noah Riley, Alexis Walker, Ashwin Sabapathy, John C Morris, Ganesh M Babulal
2020-Current year OA Pubs
IMPORTANCE: Older adults are increasingly prescribed medications that have adverse effects. Prior studies have found a higher risk of motor vehicle crashes to be associated with certain medication use.
OBJECTIVE: To determine whether specific medication classes were associated with performance decline as assessed by a standardized road test in a community sample of cognitively healthy older adults, to evaluate additional associations of poor road test performance with comorbid medical conditions and demographic characteristics, and to test the hypothesis that specific medication classes (ie, antidepressants, benzodiazepines, sedatives or hypnotics, anticholinergics, antihistamines, and nonsteroidal anti-inflammatory drugs or acetaminophen) would be associated with …
Determinants Of Ifgf13-Mediated Regulation Of Myocardial Voltage-Gated Sodium (Nav) Channels In Mouse, Adrien Lesage, Maxime Lorenzini, Sophie Burel, Marine Sarlandie, Floriane Bibault, Cecilia Lindskog, Daniel Maloney, Jonathan R Silva, R Reid Townsend, Jeanne M Nerbonne, Céline Marionneau
Determinants Of Ifgf13-Mediated Regulation Of Myocardial Voltage-Gated Sodium (Nav) Channels In Mouse, Adrien Lesage, Maxime Lorenzini, Sophie Burel, Marine Sarlandie, Floriane Bibault, Cecilia Lindskog, Daniel Maloney, Jonathan R Silva, R Reid Townsend, Jeanne M Nerbonne, Céline Marionneau
2020-Current year OA Pubs
Posttranslational regulation of cardiac NaV1.5 channels is critical in modulating channel expression and function, yet their regulation by phosphorylation of accessory proteins has gone largely unexplored. Using phosphoproteomic analysis of NaV channel complexes from adult mouse left ventricles, we identified nine phosphorylation sites on intracellular fibroblast growth factor 13 (iFGF13). To explore the potential roles of these phosphosites in regulating cardiac NaV currents, we abolished expression of iFGF13 in neonatal and adult mouse ventricular myocytes and rescued it with wild-type (WT), phosphosilent, or phosphomimetic iFGF13-VY. While the increased rate of closed-state inactivation of NaV channels induced by Fgf13 knockout in …
Autoantibodies Neutralizing Type I Ifns Underlie West Nile Virus Encephalitis In ∼40% Of Patients, Adrian Gervais, Shih-Ching Lin, Michael S Diamond, Et Al.
Autoantibodies Neutralizing Type I Ifns Underlie West Nile Virus Encephalitis In ∼40% Of Patients, Adrian Gervais, Shih-Ching Lin, Michael S Diamond, Et Al.
2020-Current year OA Pubs
Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.
Kv12-Encoded K+ Channels Drive The Day-Night Switch In The Repetitive Firing Rates Of Scn Neurons, Tracey O Hermanstyne, Nien-Du Yang, Daniel Granados-Fuentes, Xiaofan Li, Rebecca L Mellor, Timothy Jegla, Erik D Herzog, Jeanne M Nerbonne
Kv12-Encoded K+ Channels Drive The Day-Night Switch In The Repetitive Firing Rates Of Scn Neurons, Tracey O Hermanstyne, Nien-Du Yang, Daniel Granados-Fuentes, Xiaofan Li, Rebecca L Mellor, Timothy Jegla, Erik D Herzog, Jeanne M Nerbonne
2020-Current year OA Pubs
Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations in the spontaneous firing rates of neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals. The K+ conductance(s) driving these daily rhythms in the repetitive firing rates of SCN neurons, however, have not been identified. To test the hypothesis that subthreshold Kv12.1/Kv12.2-encoded K+ channels play a role, we obtained current-clamp recordings from SCN neurons in slices prepared from adult mice harboring targeted disruptions in the Kcnh8 (Kv12.1-/-) or Kcnh3 (Kv12.2-/-) locus. We found that mean nighttime repetitive firing rates …
Mitochondrial Pyruvate Metabolism And Glutaminolysis Toggle Steady-State And Emergency Myelopoiesis, Hannah A Pizzato, Yahui Wang, Michael J Wolfgang, Brian N Finck, Gary J Patti, Deepta Bhattacharya
Mitochondrial Pyruvate Metabolism And Glutaminolysis Toggle Steady-State And Emergency Myelopoiesis, Hannah A Pizzato, Yahui Wang, Michael J Wolfgang, Brian N Finck, Gary J Patti, Deepta Bhattacharya
2020-Current year OA Pubs
To define the metabolic requirements of hematopoiesis, we examined blood lineages in mice conditionally deficient in genes required for long-chain fatty acid oxidation (Cpt2), glutaminolysis (Gls), or mitochondrial pyruvate import (Mpc2). Genetic ablation of Cpt2 or Gls minimally impacted most blood lineages. In contrast, deletion of Mpc2 led to a sharp decline in mature myeloid cells and a slower reduction in T cells, whereas other hematopoietic lineages were unaffected. Yet MPC2-deficient monocytes and neutrophils rapidly recovered due to a transient and specific increase in myeloid progenitor proliferation. Competitive bone marrow chimera and stable isotope tracing experiments demonstrated that this proliferative …
Integrate-Circ And Integrate-Vis: Unbiased Detection And Visualization Of Fusion-Derived Circular Rna, Jace Webster, Hung Mai, Amy Ly, Christopher Maher
Integrate-Circ And Integrate-Vis: Unbiased Detection And Visualization Of Fusion-Derived Circular Rna, Jace Webster, Hung Mai, Amy Ly, Christopher Maher
2020-Current year OA Pubs
MOTIVATION: Backsplicing of RNA results in circularized rather than linear transcripts, known as circular RNA (circRNA). A recently discovered and poorly understood subset of circRNAs that are composed of multiple genes, termed fusion-derived circular RNAs (fcircRNAs), represent a class of potential biomarkers shown to have oncogenic potential. Detection of fcircRNAs eludes existing analytical tools, making it difficult to more comprehensively assess their prevalence and function. Improved detection methods may lead to additional biological and clinical insights related to fcircRNAs.
RESULTS: We developed the first unbiased tool for detecting fcircRNAs (INTEGRATE-Circ) and visualizing fcircRNAs (INTEGRATE-Vis) from RNA-Seq data. We found that …
Neutralization, Effector Function And Immune Imprinting Of Omicron Variants, Amin Addetia, James Brett Case, Suzanne M Scheaffer, Bradley Whitener, Michael S Diamond, Et Al.
Neutralization, Effector Function And Immune Imprinting Of Omicron Variants, Amin Addetia, James Brett Case, Suzanne M Scheaffer, Bradley Whitener, Michael S Diamond, Et Al.
2020-Current year OA Pubs
Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain
Neuroinflammation In The Amygdala Is Associated With Recent Depressive Symptoms, Wei Zhang, Jerrel Rutlin, Sarah A Eisenstein, Yong Wang, Deanna M Barch, Tamara Hershey, Ryan Bogdan, Janine D Bijsterbosch
Neuroinflammation In The Amygdala Is Associated With Recent Depressive Symptoms, Wei Zhang, Jerrel Rutlin, Sarah A Eisenstein, Yong Wang, Deanna M Barch, Tamara Hershey, Ryan Bogdan, Janine D Bijsterbosch
2020-Current year OA Pubs
BACKGROUND: Converging evidence suggests that elevated inflammation may contribute to depression. Yet, the link between peripheral inflammation and neuroinflammation in depression is unclear. Here, using data from the UK Biobank, we estimated associations among depression, C-reactive protein (CRP) as a measure of peripheral inflammation, and neuroinflammation as indexed by diffusion basis spectral imaging-based restricted fraction (DBSI-RF).
METHODS: DBSI-RF was derived from diffusion-weighted imaging data (N = 11,512) for whole-brain gray matter (global-RF), and regions of interest in the bilateral amygdala (amygdala-RF) and hippocampus (hippocampus-RF), and CRP was estimated from blood (serum) samples. Self-reported recent depression symptoms were measured using a …
Fluorescence-Guided Surgical System Using Holographic Display: From Phantom Studies To Canine Patients, Mebin B. George, Benjamin Lew, Zuodong Liang, Steven Blair, Zhongmin Zhu, Nan Cui, Jamie Ludwig, Mohamed Zayed, Laura Selmic, Viktor Gruev
Fluorescence-Guided Surgical System Using Holographic Display: From Phantom Studies To Canine Patients, Mebin B. George, Benjamin Lew, Zuodong Liang, Steven Blair, Zhongmin Zhu, Nan Cui, Jamie Ludwig, Mohamed Zayed, Laura Selmic, Viktor Gruev
2020-Current year OA Pubs
SIGNIFICANCE: Holographic display technology is a promising area of research that can lead to significant advancements in cancer surgery. We present the benefits of combining bioinspired multispectral imaging technology with holographic goggles for fluorescence-guided cancer surgery. Through a series of experiments with 43D-printed phantoms, small animal models of cancer, and surgeries on canine patients with head and neck cancer, we showcase the advantages of this holistic approach.
AIM: The aim of our study is to demonstrate the feasibility and potential benefits of utilizing holographic display for fluorescence-guided surgery through a series of experiments involving 3D-printed phantoms and canine patients with …