Scopus list of publications for November 12, 2023
13C and 15N resonance assignments of alpha synuclein fibrils amplified from Lewy Body Dementia tissue
(2023) Biomolecular NMR Assignments, 17 (2), pp. 281-286.
Barclay, A.M.a , Dhavale, D.D.b , Borcik, C.G.c d , Milchberg, M.H.c e , Kotzbauer, P.T.b , Rienstra, C.M.c d e f
a Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, United States
d National Magnetic Resonance Facility at Madison, University of Wisconsin-Madison, Madison, WI 53706, United States
e Graduate Program in Biophysics, University of Wisconsin-Madison, Madison, WI 53706, United States
f Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States
Abstract
Fibrils of the protein α-synuclein (Asyn) are implicated in the pathogenesis of Parkinson Disease, Lewy Body Dementia, and Multiple System Atrophy. Numerous forms of Asyn fibrils have been studied by solid-state NMR and resonance assignments have been reported. Here, we report a new set of 13C, 15N assignments that are unique to fibrils obtained by amplification from postmortem brain tissue of a patient diagnosed with Lewy Body Dementia. © 2023, The Author(s), under exclusive licence to Springer Nature B.V.
Author Keywords
Fibrils; Lewy Body Dementia; Parkinson Disease; Polymorphism; αSynuclein
Funding details
National Institutes of HealthNIHNS075321, NS097799, NS110436
National Institute on AgingNIAF32GM149118, P41GM136463, R01GM123455
National Institute of General Medical SciencesNIGMS
National Institute of Neurological Disorders and StrokeNINDS
Michael J. Fox Foundation for Parkinson’s ResearchMJFF
Document Type: Article
Publication Stage: Final
Source: Scopus
Ethno-racial variation in psychotic experiences in the United States: Findings from the National Latino and Asian American Survey and the National Survey of American Life
(2023) Schizophrenia Research, 262, pp. 55-59.
Oh, H.a , Verdugo, J.L.b , Karcher, N.R.c , van der Ven, E.d , Koyanagi, A.e , Smith, L.f , DeVylder, J.E.g
a Suzanne Dworak Peck School of Social Work, University of Southern California, United States
b School of Social Work, University of Michigan, United States
c Washington University in St. Louis School of Medicine, Department of Psychiatry, United States
d Dept of Clinical, Neuro- & Developmental Psychology, Vrije Universiteit Amsterdam, Netherlands
e Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, ISCIII, Spain
f Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, United Kingdom
g Silver School of Social Work, New York University, New York, United States
Abstract
Background: Ethno-racial differences in psychosis risk are documented; however, there is less research on whether these differences extend to sub-threshold psychotic experiences, and whether there is significant variation within ethno-racial categories. Methods: We analyzed data from the National Latino and Asian American Survey (NLAAS) and the National Survey of American Life (NSAL). Using multivariable logistic regression, we examined the association between race/ethnicity and lifetime psychotic experiences among Latino, Asian, and Black adults in the general population, adjusting for gender, age, nativity, education level, income level, employment status, and everyday discrimination. Results: Puerto Ricans, Cubans, and other Hispanics had greater odds of lifetime psychotic experiences when compared with Mexicans, though differences diminished when adjusting for covariates. Filipino and other Asians had greater odds of lifetime psychotic experiences when compared with Chinese, though again, differences diminished when adjusting for covariates. Among Black Americans, there were no significant ethnic subgroup differences. Conclusion: Ethno-racial differences extend across the psychosis continuum. There are nuanced health profiles across and within ethno-racial categories. Differences may be attributable to differences in experiences living in the US, underscoring the need for community-specific interventions. © 2023 Elsevier B.V.
Author Keywords
College; Disparity; Ethnicity; Psychosis; Psychotic; Race
Funding details
National Institute of Mental HealthNIMHK23MH121792
Document Type: Article
Publication Stage: Final
Source: Scopus
Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy
(2023) Proceedings of the National Academy of Sciences of the United States of America, 120 (45), pp. e2308214120.
Pfeifer, C.W.a b , Walsh, J.T.a c , Santeford, A.a , Lin, J.B.a b , Beatty, W.L.d , Terao, R.a e , Liu, Y.A.a , Hase, K.a , Ruzycki, P.A.a f , Apte, R.S.a g h
a John F. Hardesty, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
b Neurosciences Graduate Program, Roy and Diana Vagelos Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Ophthalmology, Graduate School of Medicine, University of TokyoTokyo 1138665, Japan
f Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
g Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States
h Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R signaling between amacrine cells and microglia is dysregulated during early DR and that targeting CD200R can attenuate high glucose-induced inflammation and phagocytosis in cultured microglia. Last, we demonstrate that targeting CD200R in vivo can prevent visual dysfunction, microglia activation, and retinal inflammation in the diabetic mouse. These studies provide a molecular framework for the pivotal role that microglia play in early DR pathogenesis and identify a potential immunotherapeutic target for treating DR in patients.
Author Keywords
diabetes; inflammation; microglia; retina; retinopathy
Document Type: Article
Publication Stage: Final
Source: Scopus
UNC-49 is a redox-sensitive GABAA receptor that regulates the mitochondrial unfolded protein response cell nonautonomously
(2023) Science Advances, 9 (44), p. eadh2584.
Pohl, F.a b , Germann, A.L.c , Mao, J.a , Hou, S.b , Bakare, B.d , Kong Thoo Lin, P.d , Yates, K.d , Nonet, M.L.e , Akk, G.c f , Kornfeld, K.b , Held, J.M.a c g
a Department of Medicine, Washington University School of MedicineMO, United States
b Department of Developmental Biology, Washington University School of MedicineMO, United States
c Department of Anesthesiology, Washington University School of MedicineMO, United States
d School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, United Kingdom
e Department of Neuroscience, Washington University School of MedicineMO, United States
f Taylor Family Institute for Innovative Psychiatric Research, Washington University School of MedicineMO, United States
g Siteman Cancer Center, Washington University School of MedicineMO, United States
Abstract
The γ-aminobutyric acid-mediated (GABAergic) system participates in many aspects of organismal physiology and disease, including proteostasis, neuronal dysfunction, and life-span extension. Many of these phenotypes are also regulated by reactive oxygen species (ROS), but the redox mechanisms linking the GABAergic system to these phenotypes are not well defined. Here, we report that GABAergic redox signaling cell nonautonomously activates many stress response pathways in Caenorhabditis elegans and enhances vulnerability to proteostasis disease in the absence of oxidative stress. Cell nonautonomous redox activation of the mitochondrial unfolded protein response (mitoUPR) proteostasis network requires UNC-49, a GABAA receptor that we show is activated by hydrogen peroxide. MitoUPR induction by a spinocerebellar ataxia type 3 (SCA3) C. elegans neurodegenerative disease model was similarly dependent on UNC-49 in C. elegans. These results demonstrate a multi-tissue paradigm for redox signaling in the GABAergic system that is transduced via a GABAA receptor to function in cell nonautonomous regulation of health, proteostasis, and disease.
Document Type: Article
Publication Stage: Final
Source: Scopus
Experimentally induced active and quiet sleep engage non-overlapping transcriptional programs in Drosophila
(2023) eLife, 12, .
Anthoney, N.a , Tainton-Heap, L.a , Luong, H.b , Notaras, E.a , Kewin, A.B.a , Zhao, Q.a , Perry, T.b , Batterham, P.b , Shaw, P.J.c , van Swinderen, B.a
a Queensland Brain Institute, University of Queensland, Brisbane, Australia
b School of BioSciences, University of Melbourne, Melbourne, Australia
c Department of Neuroscience, School of Medicine, Washington University in St. Louis, St Louis, United States
Abstract
Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow-wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit fly Drosophila melanogaster is increasingly being used as a model to understand sleep functions, although it remains unclear if the fly brain also engages in different kinds of sleep as well. Here, we compare two commonly used approaches for studying sleep experimentally in Drosophila: optogenetic activation of sleep-promoting neurons and provision of a sleep-promoting drug, gaboxadol. We find that these different sleep-induction methods have similar effects on increasing sleep duration, but divergent effects on brain activity. Transcriptomic analysis reveals that drug-induced deep sleep (‘quiet’ sleep) mostly downregulates metabolism genes, whereas optogenetic ‘active’ sleep upregulates a wide range of genes relevant to normal waking functions. This suggests that optogenetics and pharmacological induction of sleep in Drosophila promote different features of sleep, which engage different sets of genes to achieve their respective functions. © 2023, Anthoney et al.
Author Keywords
calcium imaging; D. melanogaster; gaboxadol; neuroscience; optogenetics; RNA seq; sleep
Document Type: Article
Publication Stage: Final
Source: Scopus
Revealing object-based cognitive control in a moving object paradigm
(2023) Journal of Experimental Psychology. Human perception and Performance, 49 (11), pp. 1467-1484.
Colvett, J.S.a , Weidler, B.J.b , Bugg, J.M.a
a Department of Psychological and Brain Sciences, Washington University in St Louis
b Department of Psychology, Towson University
Abstract
Object-based attention and flexible adjustments of cognitive control based on contextual cues signaling the likelihood of distraction are well documented. However, no prior research has conclusively demonstrated that people flexibly adjust cognitive control to minimize distraction based on learned associations between task-irrelevant objects and distraction likelihood (i.e., object-based cognitive control). To fill this gap, we developed a novel paradigm during which participants responded to flanker stimuli appearing in one of multiple locations on two simultaneously presented objects. One object predicted a low likelihood of encountering an incongruent flanker stimulus and the other a high likelihood. After each response, the objects rotated clockwise such that all locations on average were 50% congruent, thereby eliminating confounds between location and likelihood of incongruence. Object-based cognitive control was evidenced by reduced flanker compatibility effects in the high compared to low conflict object. Across four experiments, we demonstrated that object-based cognitive control was dependent on a strong manipulation of the likelihood of conflict between objects and movement of the objects between trials. The novel evidence for object-based cognitive control is important in showing that people exploit not only location as a cue to guide control, but additionally objects, mirroring evidence on object and location-based attention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Document Type: Article
Publication Stage: Final
Source: Scopus
Being Present for the Future: Exploring Mindfulness and Prospective Memory
(2023) Journal of Cognitive Enhancement, .
Nuño, C.O.a b , Shelton, J.T.a
a Department of Psychology, University of Tennessee at Chattanooga, Chattanooga, United States
b Present address: Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
Abstract
While mindfulness research has become a trending topic in cognitive science, there is a gap in the literature that fails to address the possible relationship between mindfulness and prospective memory. To explore this relationship, students randomly assigned to either an app-based meditation condition or active control condition were asked to remember and complete 10 self-concordant academic tasks (both time-based and non-time-based) over the course of 5 days. Academic task completion (i.e., prospective remembering) was indexed by successful submission of pictures indicative of the intended-to-be-completed task at the appropriate, aforementioned time and/or day. Results from Bayesian models showed a high probability that time-based tasks were more difficult to complete than non-time-based tasks. Very brief app-based mindfulness meditation was more likely to increase completion of time-based tasks compared to non-time-based tasks; however, the increase in performance was likely to be very modest. Trait mindfulness measures illustrated a high likelihood that some features of mindfulness were positively associated with task completion, while other aspects were likely to be negatively related to performance. Importantly, the variance accounted for by any of the mindfulness traits was very likely to be small. Hence, it appears that brief app-based mindfulness training only modestly increases prospective remembering, with a higher likelihood for the more attentionally demanding tasks. Considering these findings, being present, in the moment, may not produce robust effects on remembering in the future, but students may reap the potential mental health benefits of meditation without compromising their ability to complete future tasks. © 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Author Keywords
Academic performance; Attention; Bayesian modeling; Mindfulness; Prospective memory
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Impact of Eating a Carbohydrate-Restricted Diet on Cortical Atrophy in a Cross-Section of Amyloid Positive Patients with Alzheimer’s Disease: A Small Sample Study
(2023) Journal of Alzheimer’s Disease: JAD, 96 (1), pp. 329-342.
Bramen, J.E.a b c , Siddarth, P.a d , Popa, E.S.a , Kress, G.T.a e , Rapozo, M.K.a , Hodes, J.F.a f , Ganapathi, A.S.a , Slyapich, C.B.a , Glatt, R.M.a , Pierce, K.a , Porter, V.R.a b c , Wong, C.a c , Kim, M.a c , Dye, R.V.a g , Panos, S.a , Bookheimer, T.a , Togashi, T.a g , Loong, S.a g , Raji, C.A.a h , Bookheimer, S.Y.a d , Roach, J.C.g , Merrill, D.A.a b c d
a Pacific Brain Health Center, Pacific Neuroscience Institute and Foundation, Santa Monica, CA, United States
b Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, CA, United States
c Providence Saint John’s Health Center, Santa Monica, CA, United States
d David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
e Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
f Drexel University College of Medicine, Philadelphia, PA, United States
g Institute for Systems Biology, Seattle, WA, United States
h Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States
Abstract
BACKGROUND: A carbohydrate-restricted diet aimed at lowering insulin levels has the potential to slow Alzheimer’s disease (AD). Restricting carbohydrate consumption reduces insulin resistance, which could improve glucose uptake and neural health. A hallmark feature of AD is widespread cortical thinning; however, no study has demonstrated that lower net carbohydrate (nCHO) intake is linked to attenuated cortical atrophy in patients with AD and confirmed amyloidosis. OBJECTIVE: We tested the hypothesis that individuals with AD and confirmed amyloid burden eating a carbohydrate-restricted diet have thicker cortex than those eating a moderate-to-high carbohydrate diet. METHODS: A total of 31 patients (mean age 71.4±7.0 years) with AD and confirmed amyloid burden were divided into two groups based on a 130 g/day nCHO cutoff. Cortical thickness was estimated from T1-weighted MRI using FreeSurfer. Cortical surface analyses were corrected for multiple comparisons using cluster-wise probability. We assessed group differences using a two-tailed two-independent sample t-test. Linear regression analyses using nCHO as a continuous variable, accounting for confounders, were also conducted. RESULTS: The lower nCHO group had significantly thicker cortex within somatomotor and visual networks. Linear regression analysis revealed that lower nCHO intake levels had a significant association with cortical thickness within the frontoparietal, cingulo-opercular, and visual networks. CONCLUSIONS: Restricting carbohydrates may be associated with reduced atrophy in patients with AD. Lowering nCHO to under 130 g/day would allow patients to follow the well-validated MIND diet while benefiting from lower insulin levels.
Author Keywords
Alzheimer’s disease; amyloid; atrophy; carbohydrate-restricted; carbohydrates; cerebral cortical thinning; cognitive dysfunction; diet; magnetic resonance imaging
Document Type: Article
Publication Stage: Final
Source: Scopus
Data-driven MRI analysis reveals fitness-related functional change in default mode network and cognition following an exercise intervention
(2023) Psychophysiology, .
Lloyd, K.M.a , Morris, T.P.a , Anteraper, S.b , Voss, M.c , Nieto-Castanon, A.d , Whitfield-Gabrieli, S.a , Fanning, J.e , Gothe, N.f , Salerno, E.A.g , Erickson, K.I.h i j , Hillman, C.H.a k , McAuley, E.f , Kramer, A.F.a f
a Northeastern University, Boston, MA, United States
b Carle Illinois Advanced Imaging Center, Urbana, IL, United States
c University of Iowa, Iowa City, IA, United States
d Boston University, Boston, MA, United States
e Wake Forest University, Winston-Salem, NC, United States
f University of Illinois, Urbana, IL, United States
g Washington University in St. Louis, St. Louis, MO, United States
h University of Pittsburgh, Pittsburgh, PA, United States
i PROFITH “PROmoting FITness and Health Through Physical Activity” Research Group, University of Granada, Granada, Spain
j AdventHealth Research Institute, Neuroscience Institute, Orlando, FL, United States
k Department of Physical Therapy, Movement, and Rehabilitation Sciences, Northeastern University, Boston, MA, United States
Abstract
Previous research has indicated that cardiorespiratory fitness (CRF) is structurally and functionally neuroprotective in older adults. However, questions remain regarding the mechanistic role of CRF on cognitive and brain health. The purposes of this study were to investigate if higher pre-intervention CRF was associated with greater change in functional brain connectivity during an exercise intervention and to determine if the magnitude of change in connectivity was related to better post-intervention cognitive performance. The sample included low-active older adults (n = 139) who completed a 6-month exercise intervention and underwent neuropsychological testing, functional neuroimaging, and CRF testing before and after the intervention. A data-driven multi-voxel pattern analysis was performed on resting-state MRI scans to determine changes in whole-brain patterns of connectivity from pre- to post-intervention as a function of pre-intervention CRF. Results revealed a positive correlation between pre-intervention CRF and changes in functional connectivity in the precentral gyrus. Using the precentral gyrus as a seed, analyses indicated that CRF-related connectivity changes within the precentral gyrus were derived from increased correlation strength within clusters located in the Dorsal Attention Network (DAN) and increased anti-correlation strength within clusters located in the Default Mode Network (DMN). Exploratory analysis demonstrated that connectivity change between the precentral gyrus seed and DMN clusters were associated with improved post-intervention performance on perceptual speed tasks. These findings suggest that in a sample of low-active and mostly lower-fit older adults, even subtle individual differences in CRF may influence the relationship between functional connectivity and aspects of cognition following a 6-month exercise intervention. © 2023 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.
Author Keywords
cardiorespiratory fitness; cognition; default mode network; individual differences
Funding details
National Institutes of HealthNIHR37 AG025667
National Institute on AgingNIA
Abbott NutritionC4712
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Effect of musical cues on gait in individuals with Parkinson disease with comorbid dementia
(2023) Gait and Posture, .
Tueth, L.E.a , Haussler, A.M.a , Lohse, K.R.a b , Rawson, K.S.a b , Earhart, G.M.a b c , Harrison, E.C.a d
a Washington University in St. Louis School of Medicine, Program in Physical Therapy, United States
b Washington University in St. Louis School of Medicine, Department of Neurology, United States
c Washington University in St. Louis School of Medicine, Department of Neuroscience, United States
d Washington University in St. Louis, Performing Arts Department, United States
Abstract
Background: Individuals with Parkinson disease and comorbid dementia (PDD) demonstrate gait impairments, but little is known about how these individuals respond to interventions for gait dysfunction. Rhythmic auditory stimulation (RAS), which utilizes music or other auditory cues to alter gait, has been shown to be effective for improving gait in individuals with PD without dementia, but has not been explored in individuals with PDD. Research question: Can individuals with PDD modulate their gait in response to music and mental singing cues? Methods: This single center, cross-sectional, interventional study included 17 individuals with PDD. Participants received Music and Mental singing cues at tempos of 90 %, 100 %, 110 %, and 120 % of their uncued walking cadence. Participants were instructed to walk to the beat of the song. Gait variables were collected using APDM Opal sensors. Data were analyzed using mixed effect models to explore the impact of tempo and cue type (Music vs Mental) on selected gait parameters of velocity, cadence, and stride length. Results: Mixed effects models showed a significant effect of tempo but not for cue type for velocity (F=11.51, p < .001), cadence (F=11.13, p < .001), and stride length (F=5.68, p = .002). When looking at the marginal means, velocity at a cue rate of 90 % was significantly different from 100 %, indicating participants walked slower with a cue rate of 90 %. Participants did not significantly increase their velocity, cadence, or stride length with faster cue rates of 110 % and 120 % Significance: Individuals with PDD appear to be able to slow their velocity in response to slower cues, but do not appear to be able to increase their velocity, cadence, or stride length in response to faster cue tempos. This is different from what has been reported in individuals with PD without dementia. Further research is necessary to understand the underlying mechanism for these differences. © 2023 Elsevier B.V.
Author Keywords
Cueing; Dementia; Gait; Parkinson’s disease
Funding details
National Institutes of HealthNIHR61 AT010753
Document Type: Article
Publication Stage: Article in Press
Source: Scopus