10 results on '"Caroline Lew"'
Search Results
2. Patterns of neuronal Rhes as a novel hallmark of tauopathies
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Caroline Lew, Salvatore Spina, Lea T. Grinberg, Alexander J. Ehrenberg, William W. Seeley, Helmut Heinsen, Kenneth S. Kosik, Israel Hernandez, Martin Kampmann, Bruce L. Miller, Kun Leng, and Kaitlyn N. Letourneau
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Male ,0301 basic medicine ,Neuropathology ,Biology ,Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Prenylation ,GTP-Binding Proteins ,mental disorders ,medicine ,Humans ,Lonafarnib ,Aged ,Aged, 80 and over ,Neurons ,Neocortex ,Autophagy ,Farnesyltransferase inhibitor ,Allocortex ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Tauopathies ,chemistry ,Frontotemporal Dementia ,Female ,Neurology (clinical) ,Tauopathy ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The farnesyltransferase inhibitor, Lonafarnib, reduces tau inclusions and associated atrophy in familial tauopathy models through activation of autophagy, mediated by the inhibition of farnesylation of the Ras GTPase, Rhes. While hinting at a role of Rhes in tau aggregation, it is unclear how translatable these results are for sporadic forms of tauopathy. We examined histological slides of allocortex and neocortex from multiple postmortem cases in five different tauopathies, FTLD-TDP, and healthy controls using immunofluorescence for Rhes, several tau post-translational modifications, and phospho-TDP-43. Single nucleus RNA data suggest that Rhes is found in all cortical neuron subpopulations but not in glia. Histologic investigation showed that nearly all neurons in control brains display a pattern of diffuse cytoplasmic Rhes positivity. However, in the presence of abnormal tau, but not abnormal TDP-43, the patterns of neuronal cytoplasmic Rhes tend to present as either punctiform or entirely absent. This observation reinforces the relevance of findings that link Rhes changes and tau pathology from the in vivo and in vitro models of tauopathy. The results here support a potential clinical application of Lonafarnib to tauopathies.
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- 2021
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3. The Lonafarnib target, Rhes, is uniquely dysregulated in tauopathies: A human postmortem study
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Alexander J. Ehrenberg, Kun Leng, Kaitlin Letourneau, Israel Hernandez, Caroline Lew, William W. Seeley, Salvatore Spina, Bruce L. Miller, Helmut Heinsen, Martin Kampmann, Kenneth S. Kosik, and Lea T. Grinberg
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Aging ,Epidemiology ,Health Policy ,Clinical Sciences ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurodegenerative ,Alzheimer's Disease ,Brain Disorders ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Frontotemporal Dementia (FTD) ,Developmental Neuroscience ,Geriatrics ,Neurological ,Acquired Cognitive Impairment ,2.1 Biological and endogenous factors ,Dementia ,Neurology (clinical) ,Geriatrics and Gerontology ,Aetiology ,Alzheimer's Disease Related Dementias (ADRD) - Published
- 2021
4. Neuronal correlates of sleep in neurodegenerative diseases
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Jun Yeop Oh, Christine M Walsh, Mihovil Mladinov, Cathrine Petersen, Felipe Pereira, Rakin Nasar, Tia LaMore, Caroline Lew, William W. Seeley, Bruce L. Miller, Thomas Neylan, and Lea T. Grinberg
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2021
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5. Subcortical Neuronal Correlates of Sleep in Neurodegenerative Diseases
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Jun Y. Oh, Christine M. Walsh, Kamalini Ranasinghe, Mihovil Mladinov, Felipe L. Pereira, Cathrine Petersen, Neus Falgàs, Leslie Yack, Tia Lamore, Rakin Nasar, Caroline Lew, Song Li, Thomas Metzler, Quentin Coppola, Natalie Pandher, Michael Le, Hilary W. Heuer, Helmut Heinsen, Salvatore Spina, William W. Seeley, Joel Kramer, Gil D. Rabinovici, Adam L. Boxer, Bruce L. Miller, Keith Vossel, Thomas C. Neylan, and Lea T. Grinberg
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Cohort Studies ,Male ,Neurons ,Sleep Wake Disorders ,Alzheimer Disease ,Humans ,Female ,Neurodegenerative Diseases ,Longitudinal Studies ,Neurology (clinical) ,Wakefulness ,Sleep ,Original Investigation - Abstract
IMPORTANCE: Sleep disturbance is common among patients with neurodegenerative diseases. Examining the subcortical neuronal correlates of sleep disturbances is important to understanding the early-stage sleep neurodegenerative phenomena. OBJECTIVES: To examine the correlation between the number of important subcortical wake-promoting neurons and clinical sleep phenotypes in patients with Alzheimer disease (AD) or progressive supranuclear palsy (PSP). DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study enrolled 33 patients with AD, 20 patients with PSP, and 32 healthy individuals from the Memory and Aging Center of the University of California, San Francisco, between August 22, 2008, and December 31, 2020. Participants received electroencephalographic and polysomnographic sleep assessments. Postmortem neuronal analyses of brainstem hypothalamic wake-promoting neurons were performed and were included in the clinicopathological correlation analysis. No eligible participants were excluded from the study. EXPOSURES: Electroencephalographic and polysomnographic assessment of sleep and postmortem immunohistological stereological analysis of 3 wake-promoting nuclei (noradrenergic locus coeruleus [LC], orexinergic lateral hypothalamic area [LHA], and histaminergic tuberomammillary nucleus [TMN]). MAIN OUTCOMES AND MEASURES: Nocturnal sleep variables, including total sleep time, sleep maintenance, rapid eye movement (REM) latency, and time spent in REM sleep and stages 1, 2, and 3 of non-REM (NREM1, NREM2, and NREM3, respectively) sleep, and wake after sleep onset. Neurotransmitter, tau, and total neuronal counts of LC, LHA, and TMN. RESULTS: Among 19 patients included in the clinicopathological correlation analysis, the mean (SD) age at death was 70.53 (7.75) years; 10 patients (52.6%) were female; and all patients were White. After adjusting for primary diagnosis, age, sex, and time between sleep analyses and death, greater numbers of LHA and TMN neurons were correlated with decreased homeostatic sleep drive, as observed by less total sleep time (LHA: r = −0.63; P = .009; TMN: r = −0.62; P = .008), lower sleep maintenance (LHA: r = −0.85; P
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- 2022
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6. Pattern of degeneration of sleep‐wake nuclei correlates with objective sleep measurements in progressive supranuclear palsy: A quantitative clinicopathological study
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Caroline Lew, William W. Seeley, Jun Yeop Oh, Catherine Petersen, Mihovil Mladinov, Song Li, Lea T. Grinberg, Rana Eser, Leslie Ruoff, Hilary W. Heuer, Christine M. Walsh, Bruce L. Miller, Thomas C. Neylan, Claire M. Robbins, Adam L. Boxer, and Jonathan Varbel
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medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Sleep wake ,Degeneration (medical) ,medicine.disease ,Sleep in non-human animals ,Progressive supranuclear palsy ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Physical medicine and rehabilitation ,Developmental Neuroscience ,Medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business - Published
- 2020
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7. A nationwide serological survey for Dirofilaria immitis in companion cats in the United States of America: 3.5% antibody and 0.3% antigen positivity
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Daniel Felipe Barrantes Murillo, Lindsay Starkey, Theresa Wood, Rachel Smith, Byron Blagburn, Joy Bowles, Hill Allen, Caroline Lewis, Yue Shu, and Chengming Wang
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Dirofilaria immitis ,Companion cats ,USA ,Antigen testing ,Antibody detection ,Acid treatment ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Feline heartworm disease (HWD) is a complex and often misdiagnosed disease in cats, caused by the filarial nematode Dirofilaria immitis. Despite its significant impact, studies reporting the prevalence of D. immitis in apparently healthy pet cats in the USA are lacking. Methods To investigate feline heartworm seroprevalence in apparently healthy pet cats in the USA, serum samples (n = 2165) collected from cats across 47 states and Washington District of Columbia were analyzed for D. immitis antibody (Heska Corp.) and antigen (DiroCHEK®; Zoetis Inc.) with and without acid treatment of the samples. Results Antibodies to D. immitis antibodies were identified in 3.5% (76/2165) of cats from 26 states, with a significantly higher prevalence in cats from the westernmost US states (West region; 5.4%, 23/429) compared to those from the South (3.8%, 32/847), Midwest (2.7%, 9/338) and Northeast regions (2.2%, 12/551) (P
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- 2023
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8. m6A modification of a 3′ UTR site reduces RME1 mRNA levels to promote meiosis
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G. Guy Bushkin, David Pincus, Jeffrey T. Morgan, Kris Richardson, Caroline Lewis, Sze Ham Chan, David P. Bartel, and Gerald R. Fink
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Science - Abstract
Ime4p is a yeast N6-methyladenosine (m6A) methyltransferase with an unknown role in meiosis. Rme1p is a repressor of meiosis. Here the authors show that Ime4p methylates RME1 3′ UTR to reduce its expression and enable meiosis, thus providing an example of an m6A site with a physiological role.
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- 2019
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9. Isolation and Quantification of Metabolite Levels in Murine Tumor Interstitial Fluid by LC/MS
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Mark Sullivan, Caroline Lewis, and Alexander Muir
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Biology (General) ,QH301-705.5 - Abstract
Cancer is a disease characterized by altered metabolism, and there has been renewed interest in understanding the metabolism of tumors. Even though nutrient availability is a critical determinant of tumor metabolism, there has been little systematic study of the nutrients directly available to cancer cells in the tumor microenvironment. Previous work characterizing the metabolites present in the tumor interstitial fluid has been restricted to the measurement of a small number of nutrients such as glucose and lactate in a limited number of samples. Here we adapt a centrifugation-based method of tumor interstitial fluid isolation readily applicable to a number of sample types and a mass spectrometry-based method for the absolute quantitation of many metabolites in interstitial fluid samples. In this method, tumor interstitial fluid (TIF) is analyzed by liquid chromatography-mass spectrometry (LC/MS) using both isotope dilution and external standard calibration to derive absolute concentrations of targeted metabolites present in interstitial fluid. The use of isotope dilution allows for accurate absolute quantitation of metabolites, as other methods of quantitation are inadequate for determining nutrient concentrations in biological fluids due to matrix effects that alter the apparent concentration of metabolites depending on the composition of the fluid in which they are contained. This method therefore can be applied to measure the absolute concentrations of many metabolites in interstitial fluid from diverse tumor types, as well as most other biological fluids, allowing for characterization of nutrient levels in the microenvironment of solid tumors.
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- 2019
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10. The relationship between fearfulness, GABA+, and fear-related BOLD responses in the insula.
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Ilona Lipp, C John Evans, Caroline Lewis, Kevin Murphy, Richard G Wise, and Xavier Caseras
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Medicine ,Science - Abstract
The inhibitory neurotransmitter GABA plays a crucial role in anxiety and fear, but its relationship to brain activation during fear reactions is not clear. Previous studies suggest that GABA agonists lead to an attenuation of emotion-processing related BOLD signals in the insula. The aim of this study was to investigate the relationship between GABA concentration and fear-related BOLD responses in this region. In 44 female participants with different levels of fearfulness, GABA concentration in the left insula was measured using a GABA+ MRS acquisition during rest; additionally, BOLD signals were obtained during performance of a fear provocation paradigm. Fearfulness was not associated with GABA+ in the left insula, but could predict fear-related BOLD responses in a cluster in the left anterior insula. The BOLD signal change in this cluster did not correlate with GABA+ concentration. However, we found a significant positive correlation between GABA+ concentration and fear-related BOLD responses in a different cluster that included parts of the left insula, amygdala and putamen. Our findings indicate that low insular GABA concentration is not a predisposition for fearfulness, and that several factors influence whether a correlation between GABA and BOLD can be found.
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- 2015
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