WashU weekly Neuroscience publications | Office of Neuroscience Research

“Author Correction: TGF-β1-induced miR-503 controls cell growth and apoptosis by targeting PDCD4 in glioblastoma cells (Scientific Reports, (2017), 7, 1, (11569), 10.1038/s41598-017-11885-8)” (2019) Scientific Reports

Author Correction: TGF-β1-induced miR-503 controls cell growth and apoptosis by targeting PDCD4 in glioblastoma cells (Scientific Reports, (2017), 7, 1, (11569), 10.1038/s41598-017-11885-8)
(2019) Scientific Reports, 9 (1), art. no. 6400, .

Guo, P.^a , Yu, Y.^b , Li, H.^a , Zhang, D.^c , Gong, A.^a , Li, S.^a , Liu, W.^a , Cheng, L.^a , Qiu, Y.^d , Yao, W.^a , Li, L.^e , Feng, Y.^a

^a Department of Neurosurgery, the Affiliated Hospital of Qingdao University, Qingdao, China
^b Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, China
^c Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO 63110, United States
^d Department of Neurosurgery, South Campus, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
^e Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China

Abstract
In the original version of this Article, all instances of “TGF-ß1” were incorrectly written as “TGF-â1”. These errors have now been corrected in the HTML and PDF versions of the Article. © 2019, The Author(s).

Document Type: Erratum
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory” (2019) Nature Communications

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
(2019) Nature Communications, 10 (1), art. no. 1766, .

Franzmeier, N.^a , Rubinski, A.^a , Neitzel, J.^a , Ewers, M.^a , Weiner, M.W.^b , Aisen, P.^c , Petersen, R.^d , Jack, C.R.^d , Jagust, W.^e , Trojanowski, J.Q.^f , Toga, A.W.^g , Beckett, L.^h , Green, R.C.ⁱ , Saykin, A.J.^j , Morris, J.^k , Shaw, L.M.^f , Khachaturian, Z.^h ^l , Sorensen, G.^m , Kuller, L.ⁿ , Raichle, M.^k , Paul, S.^o , Davies, P.^p , Fillit, H.^q , Hefti, F.^r , Holtzman, D.^k , Mesulam, M.M.^s , Potter, W.^t , Snyder, P.^u , Schwartz, A.^v , Montine, T.^w , Thomas, R.G.^w , Donohue, M.^w , Walter, S.^w , Gessert, D.^w , Sather, T.^w , Jiminez, G.^w , Harvey, D.^h , Bernstein, M.^d , Thompson, P.^x , Schuff, N.^b ^h , Borowski, B.^d , Gunter, J.^d , Senjem, M.^d , Vemuri, P.^d , Jones, D.^d , Kantarci, K.^d , Ward, C.^d , Koeppe, R.A.^y , Foster, N.^z , Reiman, E.M.^aa , Chen, K.^aa , Mathis, C.ⁿ , Landau, S.^e , Cairns, N.J.^k , Householder, E.^k , Taylor-Reinwald, L.^k , Lee, V.^f , Korecka, M.^f , Figurski, M.^f , Crawford, K.^g , Neu, S.^g , Foroud, T.M.^j , Potkin, S.G.^ab , Shen, L.^j , Faber, K.^j , Kim, S.^j , Nho, K.^j , Thal, L.^c , Buckholtz, N.^ac , Albert, M.^ad , Frank, R.^ae , Hsiao, J.^ac , Kaye, J.^af , Quinn, J.^af , Lind, B.^af , Carter, R.^af , Dolen, S.^af , Schneider, L.S.^g , Pawluczyk, S.^g , Beccera, M.^g , Teodoro, L.^g , Spann, B.M.^g , Brewer, J.^c , Vanderswag, H.^c , Fleisher, A.^c ^aa , Heidebrink, J.L.^y , Lord, J.L.^y , Mason, S.S.^d , Albers, C.S.^d , Knopman, D.^d , Johnson, K.^d , Doody, R.S.^ag , Villanueva-Meyer, J.^ag , Chowdhury, M.^ag , Rountree, S.^ag , Dang, M.^ag , Stern, Y.^ag , Honig, L.S.^ag , Bell, K.L.^ag , Ances, B.^k , Carroll, M.^k , Leon, S.^k , Mintun, M.A.^k , Schneider, S.^k , Oliver, A.^k , Marson, D.^ah , Griffith, R.^ah , Clark, D.^ah , Geldmacher, D.^ah , Brockington, J.^ah , Roberson, E.^ah , Grossman, H.^ai , Mitsis, E.^ai , de Toledo-Morrell, L.^aj , Shah, R.C.^aj , Duara, R.^ak , Varon, D.^ak , Greig, M.T.^ak , Roberts, P.^ak , Onyike, C.^ad , D’Agostino, D.^ad , Kielb, S.^ad , Galvin, J.E.^al , Cerbone, B.^al , Michel, C.A.^al , Rusinek, H.^al , de Leon, M.J.^al , Glodzik, L.^al , De Santi, S.^al , Doraiswamy, P.M.^am , Petrella, J.R.^am , Wong, T.Z.^am , Arnold, S.E.^f , Karlawish, J.H.^f , Wolk, D.^f , Smith, C.D.^an , Jicha, G.^an , Hardy, P.^an , Sinha, P.^an , Oates, E.^an , Conrad, G.^an , Lopez, O.L.ⁿ , Oakley, M.A.ⁿ , Simpson, D.M.^ad , Porsteinsson, A.P.^ao , Goldstein, B.S.^ao , Martin, K.^ao , Makino, K.M.^ao , Ismail, M.S.^ao , Brand, C.^ao , Mulnard, R.A.^ab , Thai, G.^ab , McAdams-Ortiz, C.^ab , Womack, K.^ap , Mathews, D.^ap , Quiceno, M.^ap , Diaz-Arrastia, R.^ap , King, R.^ap , Weiner, M.^ap , Martin-Cook, K.^ap , DeVous, M.^ap , Levey, A.I.^aq , Lah, J.J.^aq , Cellar, J.S.^aq , Burns, J.M.^ar , Anderson, H.S.^ar , Swerdlow, R.H.^ar , Apostolova, L.^x , Tingus, K.^x , Woo, E.^x , Silverman, D.H.S.^x , Lu, P.H.^x , Bartzokis, G.^x , Graff-Radford, N.R.^as , Parfitt, F.^as , Kendall, T.^as , Johnson, H.^as , Farlow, M.R.^j , Hake, A.M.^j , Matthews, B.R.^j , Herring, S.^j , Hunt, C.^j , van Dyck, C.H.^at , Carson, R.E.^at , MacAvoy, M.G.^at , Chertkow, H.^au , Bergman, H.^au , Hosein, C.^au , Hsiung, G.-Y.R.^av , Feldman, H.^av , Mudge, B.^av , Assaly, M.^av , Bernick, C.^aw , Munic, D.^aw , Kertesz, A.^ax , Rogers, J.^ax , Trost, D.^ax , Kerwin, D.^s , Lipowski, K.^s , Wu, C.-K.^s , Johnson, N.^s , Sadowsky, C.^ay , Martinez, W.^ay , Villena, T.^ay , Turner, R.S.^az , Johnson, K.^az , Reynolds, B.^az , Sperling, R.A.ⁱ , Johnson, K.A.ⁱ , Marshall, G.ⁱ , Frey, M.ⁱ , Lane, B.ⁱ , Rosen, A.ⁱ , Tinklenberg, J.ⁱ , Sabbagh, M.N.^ba , Belden, C.M.^ba , Jacobson, S.A.^ba , Sirrel, S.A.^ba , Kowall, N.^ba , Killiany, R.^bb , Budson, A.E.^bb , Norbash, A.^bb , Johnson, P.L.^bb , Allard, J.^bc , Lerner, A.^bd , Ogrocki, P.^bd , Hudson, L.^bd , Fletcher, E.^h , Carmichael, O.^h , Olichney, J.^h , DeCarli, C.^h , Kittur, S.^be , Borrie, M.^bf , Lee, T.-Y.^bf , Bartha, R.^bf , Johnson, S.^bg , Asthana, S.^bg , Carlsson, C.M.^bg , Preda, A.^x , Nguyen, D.^x , Tariot, P.^z , Reeder, S.^z , Bates, V.^bh , Capote, H.^bh , Rainka, M.^bh , Scharre, D.W.^bi , Kataki, M.^bi , Adeli, A.^bi , Zimmerman, E.A.^bj , Celmins, D.^bj , Brown, A.D.^bj , Pearlson, G.D.^bk , Blank, K.^bk , Anderson, K.^bk , Santulli, R.B.^bl , Kitzmiller, T.J.^bl , Schwartz, E.S.^bl , Sink, K.M.^bm , Williamson, J.D.^bm , Garg, P.^bm , Watkins, F.^bm , Ott, B.R.^bn , Querfurth, H.^bn , Tremont, G.^bn , Salloway, S.^bo , Malloy, P.^bo , Correia, S.^bo , Rosen, H.J.^b , Miller, B.L.^b , Mintzer, J.^bp , Spicer, K.^bp , Bachman, D.^bp , Pasternak, S.^ax , Rachinsky, I.^ax , Drost, D.^ax , Pomara, N.^bq , Hernando, R.^bq , Sarrael, A.^bq , Schultz, S.K.^br , Boles Ponto, L.L.^br , Shim, H.^br , Smith, K.E.^br , Relkin, N.^o , Chaing, G.^o , Raudin, L.^l ^o , Smith, A.^bs , Fargher, K.^bs , Raj, B.A.^bs , Neylan, T.^b , Grafman, J.^s , Davis, M.^c , Morrison, R.^c , Hayes, J.^b , Finley, S.^b , Friedl, K.^bt , Fleischman, D.^aj , Arfanakis, K.^aj , James, O.^am , Massoglia, D.^bp , Fruehling, J.J.^bg , Harding, S.^bg , Peskind, E.R.^w , Petrie, E.C.^bi , Li, G.^bi , Yesavage, J.A.^bu , Taylor, J.L.^bu , Furst, A.J.^bu , The Alzheimer’s Disease Neuroimaging Initiative (ADNI)^bv

^a Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, Munich, 81377, Germany
^b UC San Francisco, San Francisco, CA 94143, United States
^c UC San Diego, San Diego, CA 92093, United States
^d Mayo Clinic, Rochester, NY 14603, United States
^e UC Berkeley, Berkeley, CA 94720, United States
^f UPenn, Philadelphia, PA 9104, United States
^g USC, Los Angeles, CA 90089, United States
^h UC Davis, Davis, CA 95616, United States
ⁱ Brigham and Women’s Hospital/Harvard Medical School, Boston, MA 02115, United States
^j Indiana University, Bloomington, IN 47405, United States
^k Washington University in St Louis, St Louis, MI 63130, United States
^l Prevent Alzheimer’s Disease 2020, Rockville, MD 20850, United States
^m Siemens, Munich, 80333, Germany
ⁿ University of Pittsburgh, Pittsburgh, PA 15260, United States
^o Weill Cornell Medical College, Cornell University, New York City, NY 10065, United States
^p Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, United States
^q AD Drug Discovery Foundation, New York City, NY 10019, United States
^r Acumen Pharmaceuticals, Livermore, CA 94551, United States
^s Northwestern University, Evanston and Chicago, IL 60208, United States
^t National Institute of Mental Health, Rockville, MD 20852, United States
^u Brown University, Providence, RI 02912, United States
^v Eli Lilly, Indianapolis, IN 46225, United States
^w University of Washington, Seattle, WA 98195, United States
^x UCLA, Los Angeles, CA 90095, United States
^y University of Michigan, Ann Arbor, MI 48109, United States
^z University of Utah, Salt Lake City, UT 84112, United States
^aa Banner Alzheimer’s Institute, Phoenix, AZ 85006, United States
^ab UC Irvine, Irvine, CA 92697, United States
^ac National Institute on Aging, Bethesda, MD 20892, United States
^ad Johns Hopkins University, Baltimore, MD 21218, United States
^ae Richard Frank Consulting, Washington, DC 20001, United States
^af Oregon Health and Science University, Portland, OR 97239, United States
^ag Baylor College of Medicine, Houston, TX 77030, United States
^ah University of Alabama, Birmingham, AL 35233, United States
^ai Mount Sinai School of Medicine, New York City, NY 10029, United States
^aj Rush University Medical Center, Chicago, IL 60612, United States
^ak Wien Center, Miami, FL 33140, United States
^al New York University, New York City, NY 10003, United States
^am Duke University Medical Center, Durham, NC 27710, United States
^an University of Kentucky, Lexington, KY 0506, United States
^ao University of Rochester Medical Center, Rochester, NY 14642, United States
^ap University of Texas Southwestern Medical School, Dallas, TX 75390, United States
^aq Emory University, Atlanta, GA 30322, United States
^ar Medical Center, University of Kansas, Kansas City, KS 66103, United States
^as Mayo Clinic, Jacksonville, FL 32224, United States
^at Yale University School of Medicine, New Haven, CT 06510, United States
^au McGill University/Montreal-Jewish General Hospital, Montreal, QC H3T 1E2, Canada
^av University of British Columbia Clinic for AD & Related Disorders, Vancouver, BC V6T 1Z3, Canada
^aw Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV 89106, United States
^ax St Joseph’s Health Care, London, ON N6A 4V2, Canada
^ay Premiere Research Institute, Palm Beach Neurology, Miami, FL 33407, United States
^az Georgetown University Medical Center, Washington, DC 20007, United States
^ba Banner Sun Health Research Institute, Sun City, AZ 85351, United States
^bb Boston University, Boston, MA 02215, United States
^bc Howard University, Washington, DC 20059, United States
^bd Case Western Reserve University, Cleveland, OH 20002, United States
^be Neurological Care of CNY, Liverpool, NY 13088, United States
^bf Parkwood Hospital, London, ON N6C 0A7, Canada
^bg University of Wisconsin, Madison, WI 53706, United States
^bh Dent Neurologic Institute, Amherst, NY 14226, United States
^bi Ohio State University, Columbus, OH 43210, United States
^bj Albany Medical College, Albany, NY 12208, United States
^bk Hartford Hospital, Olin Neuropsychiatry Research Center, Hartford, CT 06114, United States
^bl Dartmouth- Hitchcock Medical Center, Lebanon, NH 03766, United States
^bm Wake Forest University Health Sciences, Winston-Salem, NC 27157, United States
^bn Rhode Island Hospital, Providence, RI 02903, United States
^bo Butler Hospital, Providence, RI 02906, United States
^bp Medical University South Carolina, Charleston, SC 29425, United States
^bq Nathan Kline Institute, Orangeburg, NY 10962, United States
^br University of Iowa College of Medicine, Iowa City, IA 52242, United States
^bs University of South Florida: USF Health Byrd Alzheimer’s Institute, Tampa, FL 33613, United States
^bt Department of Defense, Arlington, VA 22350, United States
^bu Stanford University, Stanford, CA 94305, United States

Abstract
The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology. © 2019, The Author(s).

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Polygenic risk for circulating reproductive hormone levels and their influence on hippocampal volume and depression susceptibility” (2019) Psychoneuroendocrinology

Polygenic risk for circulating reproductive hormone levels and their influence on hippocampal volume and depression susceptibility
(2019) Psychoneuroendocrinology, 106, pp. 284-292.

Smeeth, D.M.^a , Dima, D.^b ^c , Jones, L.^d , Jones, I.^e , Craddock, N.^e , Owen, M.J.^e , Rietschel, M.^f ^g , Maier, W.^f , Korszun, A.^h , Rice, J.P.ⁱ , Mors, O.^j , Preisig, M.^k , Uher, R.^l , Lewis, C.M.^m , Thuret, S.^a , Powell, T.R.^m

^a Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
^b Department of Psychology, School of Arts and Social Sciences, City, University of London, London, United Kingdom
^c Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
^d Institute of Health & Society, University of Worcester, Worcester, United Kingdom
^e MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom
^f Department of Psychiatry, University of Bonn, Bonn, Germany
^g Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany
^h Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
ⁱ Department of Psychiatry, Washington University, St. Louis, MO, United States
^j Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
^k University Hospital Center and University of Lausanne, Lausanne, Switzerland
^l Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
^m Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom

Abstract
Altered reproductive hormone levels have been associated with the pathophysiology of depressive disorders and this risk may be imparted by their modulatory effect upon hippocampal structure and function. Currently it is unclear whether altered levels of reproductive hormones are causally associated with hippocampal volume reductions and the risk of depressive disorders. Here, we utilize genome-wide association study (GWAS)summary statistics from a GWAS focusing on reproductive hormones, consisting of 2913 individuals. Using this data, we generated polygenic risk scores (PRS)for estradiol, progesterone, prolactin and testosterone in the European RADIANT cohort consisting of 176 postpartum depression (PPD)cases (100% female, mean age: 41.6 years old), 2772 major depressive disorder (MDD)cases (68.6% female, mean age: 46.9 years old)and 1588 control participants (62.5% female, mean age: 42.4 years old), for which there was also a neuroimaging subset of 111 individuals (60.4% female, mean age: 50.0 years old). Only the best-fit PRS for estradiol showed a significant negative association with hippocampal volume, as well as many of its individual subfields; including the molecular layer and granule cell layer of the dentate gyrus, subiculum, CA1, CA2/3 and CA4 regions. Interestingly, several of these subfields are implicated in adult hippocampal neurogenesis. When we tested the same estradiol PRS for association with case-control status for PPD or MDD there was no significant relationship observed. Here, we provide evidence that genetic risk for higher plasma estradiol is negatively associated with hippocampal volume, but this does not translate into an increased risk of MDD or PPD. This work suggests that the relationship between reproductive hormones, the hippocampus, and depression is complex, and that there may not be a clear-cut pathway for etiology or risk moderation. © 2019 The Authors

Author Keywords
Estradiol; Hippocampal volume; Major depression; Polygenic risk scores; Postpartum depression; Reproductive hormones

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“The association between racial and socioeconomic discrimination and two stages of alcohol use in blacks” (2019) Drug and Alcohol Dependence

The association between racial and socioeconomic discrimination and two stages of alcohol use in blacks
(2019) Drug and Alcohol Dependence, 199, pp. 129-135.

Haeny, A.M.^a , Sartor, C.E.^a ^b , Arshanapally, S.^c , Ahuja, M.^d , Werner, K.B.^e , Bucholz, K.K.^b

^a Department of Psychiatry, Yale School of Medicine, 389 Whitney Avenue New HavenCT 06511, United States
^b Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, United States
^c Yale School of Public Health, 60 College St., New Haven, CT 06510, United States
^d Brown School of Social Work, Washington University, 1 Brookings Dr, St. Louis, MO 63130, United States
^e Missouri Institute of Mental Health, University of Missouri-St. Louis, 4633 World Pkwy Cir, St. Louis, MO 63134, United States

Abstract
Background: This study aimed to characterize the associations of racial and socioeconomic discrimination with timing of alcohol initiation and progression from initiation to problem drinking in Black youth. Methods: Data were drawn from a high-risk family study of alcohol use disorder. Mothers and their offspring (N = 806; M age = 17.87, SD age = 3.91; 50% female)were assessed via telephone interview. Cox proportional hazards regression analyses were used to examine associations between discrimination and timing of first drink and progression from first drink to problem drinking in two separate models. Predictor variables were considered in a step-wise fashion, starting with offspring racial and socioeconomic discrimination, then adding (2)maternal racial and/or socioeconomic discrimination experiences; (3)religious service attendance and social support as potential moderators; and (4)psychiatric and psychosocial risk factors and other substance use. Results: Offspring racial discrimination (HR: 2.01, CI: 1.17–3.46 ≤ age 13)and maternal experiences of discrimination (HR: 0.79, CI: 0.67−0.93)were associated with timing of initiation in the unadjusted model only; offspring socioeconomic discrimination predicted timing of initiation among female offspring, even after adjusting for all covariates (HR: 1.49, CI: 1.14–1.93). Socioeconomic discrimination predicted a quicker transition from first use to problem drinking exclusively in the unadjusted model (HR: 1.70, CI: 1.12–2.58 ≤ age 18). No moderating effects of religious service attendance or social support were observed for either alcohol outcome. Conclusions: Findings suggest socioeconomic discrimination is a robust risk factor for initiating alcohol use in young Black female youth and should be considered in the development of targeted prevention programs. © 2019 Elsevier B.V.

Author Keywords
African American; Alcohol; Discrimination; Socioeconomic Status

Document Type: Article
Publication Stage: Final
Source: Scopus

“Involvement in Sports, Hippocampal Volume, and Depressive Symptoms in Children” (2019) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Involvement in Sports, Hippocampal Volume, and Depressive Symptoms in Children
(2019) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 4 (5), pp. 484-492. Cited 1 time.

Gorham, L.S.^a , Jernigan, T.^d ^e , Hudziak, J.^f ^g , Barch, D.M.^a ^b ^c

^a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
^b Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
^c Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
^d Department of Cognitive Science, University of California–San Diego, San Diego, CA, United States
^e Center for Human Development, University of California–San Diego, San Diego, CA, United States
^f Department of Psychiatry, University of Vermont, Burlington, VT, United States
^g Vermont Center for Children, Youth, and Families, Burlington, VT, United States

Abstract
Background: Recent studies have found that higher levels of exercise are associated with fewer symptoms of depression among young people. In addition, research suggests that exercise may modify hippocampal volume, a brain region that has been found to show reduced volume in depression. However, it is not clear whether this relationship emerges as early as preadolescence. Methods: We examined data from a nationwide sample of 4191 children 9 to 11 years of age from the Adolescent Brain and Cognitive Development Study. The parents of the children completed the Child Behavior Checklist, providing data about the child’s depressive symptoms, and the Sports and Activities Questionnaire, which provided data about the child’s participation in 23 sports. Children also took part in a structural magnetic resonance imaging scan, providing us with measures of bilateral hippocampal volume. Results: Sports involvement interacted with sex to predict depressive symptoms, with a negative relationship found in boys only (t = −5.257, β = −.115, p <.001). Sports involvement was positively correlated with hippocampal volume in both boys and girls (t = 2.810, β =.035, p =.007). Hippocampal volume also interacted with sex to predict depressive symptoms, with a negative relationship in boys (t = −2.562, β = −.070, p =.010), and served as a partial mediator for the relationship between involvement in sports and depressive symptoms in boys. Conclusions: These findings help illuminate a potential neural mechanism for the impact of exercise on the developing brain, and the differential effects in boys versus girls mirror findings in the animal literature. More research is needed to understand the causal relationships between these constructs. © 2019 Society of Biological Psychiatry

Author Keywords
Children; Depression; Exercise; Hippocampus; Neuroimaging; Structural

Document Type: Article
Publication Stage: Final
Source: Scopus

“ACR Appropriateness Criteria ® Suspected Spine Trauma” (2019) Journal of the American College of Radiology

ACR Appropriateness Criteria ® Suspected Spine Trauma
(2019) Journal of the American College of Radiology, 16 (5), pp. S264-S285.

Beckmann, N.M.^a , West, O.C.^b , Nunez, D., Jr.^c , Kirsch, C.F.E.^d , Aulino, J.M.^e , Broder, J.S.^f , Cassidy, R.C.^g , Czuczman, G.J.^h , Demertzis, J.L.ⁱ , Johnson, M.M.^j , Motamedi, K.^k , Reitman, C.^l , Shah, L.M.^m , Than, K.ⁿ , Ying-Kou Yung, E.^o , Beaman, F.D.^p , Kransdorf, M.J.^q , Bykowski, J.^r , Expert Panel on Neurological Imaging and Musculoskeletal Imaging:^s

^a Research Author, UTHealth-McGovern Medical School, Houston, TX, United States
^b UTHealth-McGovern Medical School, Houston, TX, United States
^c Brigham & Women’s Hospital & Harvard Medical School, Boston, MA, United States
^d Panel Chair (Neurological), Northwell Health, Zucker Hofstra School of Medicine at Northwell, Manhasset, NY, United States
^e Vanderbilt University Medical Center, Nashville, TN, United States
^f Duke University School of Medicine, Durham, North Carolina; American College of Emergency Physicians, United States
^g UK Healthcare Spine and Total Joint Service, Lexington, Kentucky; American Academy of Orthopaedic Surgeons, United States
^h Radiology Imaging Associates, Denver, CO, United States
ⁱ Washington University School of Medicine, Saint Louis, MO, United States
^j UTHealth-McGovern Medical School, Houston, Texas; neurosurgical consultant, United States
^k David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
^l Medical University of South Carolina, Charleston, South Carolina; North American Spine Society, United States
^m University of Utah, Salt Lake City, UT, United States
ⁿ Oregon Health & Science University, Portland, Oregon; neurosurgical consultant, United States
^o Nuclear Radiologist, Weston, CT, United States
^p Panel Chair (Musculoskeletal), University of Kentucky, Lexington, KY, United States
^q Specialty Chair (Musculoskeletal), Mayo Clinic, Phoenix, AZ, United States
^r Specialty Chair (Neurological), UC San Diego Health Center, San Diego, CA, United States

Abstract
Injuries to the cervical and thoracolumbar spine are commonly encountered in trauma patients presenting for treatment. Cervical spine injuries occur in 3% to 4% and thoracolumbar fractures in 4% to 7% of blunt trauma patients presenting to the emergency department. Clear, validated criteria exist for screening the cervical spine in blunt trauma. Screening criteria for cervical vascular injury and thoracolumbar spine injury have less validation and widespread acceptance compared with cervical spine screening. No validated criteria exist for screening of neurologic injuries in the setting of spine trauma. CT is preferred to radiographs for initial assessment of spine trauma. CT angiography and MR angiography are both acceptable in assessment for cervical vascular injury. MRI is preferred to CT myelography for assessing neurologic injury in the setting of spine trauma. MRI is usually appropriate when there is concern for ligament injury or in screening obtunded patients for cervical spine instability. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. © 2019 American College of Radiology

Author Keywords
Appropriate Use Criteria; Appropriateness Criteria; AUC; Cervical; Neurologic injury; Spine; Thoracolumbar; Trauma; Vascular injury

Document Type: Article
Publication Stage: Final
Source: Scopus

“Immune myopathy with large histiocyte-related myofiber necrosis” (2019) Neurology

Immune myopathy with large histiocyte-related myofiber necrosis
(2019) Neurology, 92 (15), pp. e1763-e1772.

Pestronk, A., Sinha, N., Alhumayyd, Z., Ly, C., Schmidt, R., Bucelli, R.

From the Departments of Neurology (A.P., C.L., R.B.) and Pathology and Immunology (A.P., N.S., R.S.), Washington University School of Medicine, Saint Louis, MO; and Department of Neurology (Z.A.), King Saud University, Riyadh, Saudi Arabia

Abstract
OBJECTIVE: To describe the features of a new, pathologically distinctive, acquired myopathy with an unusual pattern of scattered necrotic muscle fibers that are neighbored, surrounded, or invaded, by large, often multinucleated, histiocytic cells. METHODS: Retrospective review of records and muscle pathology of 4 patients. RESULTS: Clinical features common to our patients included muscle pain and proximal, symmetric, moderate to severe, weakness in the arms and legs progressing over 1-4 weeks. Patients had other associated systemic disorders, including anemia in all, and hemophagocytic lymphohistiocytosis, hepatic disease, Raynaud phenomenon, metastatic cancer, and cardiomyopathy, in 1 patient each. Serum creatine kinase (CK) levels at presentation were very high, ranging from 10,000 to 102,000 U/L. Three patients improved within 3 months after treatment. Muscle pathology included scattered necrotic muscle fibers with cytoplasm that stained for C5b-9 complement, especially around fiber peripheries, pale on nicotinamide adenine dinucleotide and often dark on hematoxylin & eosin. Large, often multinucleated, cells with features of histiocytes, including anatomical features on electron microscopy and immunostaining for major histocompatibility complex Class I and histiocyte markers (HAM56, CD68, CD163, and S100), were usually closely apposed to the surface of, or invaded, necrotic myofibers. CONCLUSIONS: Patients with large-histiocyte-associated myopathy (LHIM) had a subacute onset of proximal predominant weakness, associated systemic disorders, very high serum CK, and a pathologically distinctive pattern of large histiocyte-associated muscle fiber necrosis. LHIM may be caused by an autoimmune, histiocyte-mediated attack directed against muscle fibers. © 2019 American Academy of Neurology.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Technology-Based Alcohol Interventions in Primary Care: Systematic Review” (2019) Journal of medical Internet research

Technology-Based Alcohol Interventions in Primary Care: Systematic Review
(2019) Journal of medical Internet research, 21 (4), p. e10859.

Ramsey, A.T.^a , Satterfield, J.M.^b , Gerke, D.R.^c , Proctor, E.K.^d

^a Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
^b Department of Medicine, University of California San Francisco, San Francisco, CA, United States
^c Graduate School of Social Work, University of Denver, Denver, CO, United States
^d Brown School of Social Work, Washington University in St Louis, St Louis, MO, United States

Abstract
BACKGROUND: Primary care settings are uniquely positioned to reach individuals at risk of alcohol use disorder through technology-delivered behavioral health interventions. Despite emerging effectiveness data, few efforts have been made to summarize the collective findings from these delivery approaches. OBJECTIVE: The aim of this study was to review recent literature on the use of technology to deliver, enhance, or support the implementation of alcohol-related interventions in primary care. We focused on addressing questions related to (1) categorization or target of the intervention, (2) descriptive characteristics and context of delivery, (3) reported efficacy, and (4) factors influencing efficacy. METHODS: We conducted a comprehensive search and systematic review of completed studies at the intersection of primary care, technology, and alcohol-related problems published from January 2000 to December 2018 within EBSCO databases, ProQuest Dissertations, and Cochrane Reviews. Of 2307 initial records, 42 were included and coded independently by 2 investigators. RESULTS: Compared with the years of 2000 to 2009, published studies on technology-based alcohol interventions in primary care nearly tripled during the years of 2010 to 2018. Of the 42 included studies, 28 (64%) were randomized controlled trials. Furthermore, studies were rated on risk of bias and found to be predominantly low risk (n=18), followed by moderate risk (n=16), and high risk (n=8). Of the 24 studies with primary or secondary efficacy outcomes related to drinking and drinking-related harms, 17 (71%) reported reduced drinking or harm in all primary and secondary efficacy outcomes. Furthermore, of the 31 studies with direct comparisons with treatment as usual (TAU), 13 (42%) reported that at least half of the primary and secondary efficacy outcomes of the technology-based interventions were superior to TAU. High efficacy was associated with provider involvement and the reported use of an implementation strategy to deliver the technology-based intervention. CONCLUSIONS: Our systematic review has highlighted a pattern of growth in the number of studies evaluating technology-based alcohol interventions in primary care. Although these interventions appear to be largely beneficial in primary care, outcomes may be enhanced by provider involvement and implementation strategy use. This review enables better understanding of the typologies and efficacy of these interventions and informs recommendations for those developing and implementing technology-based alcohol interventions in primary care settings. ©Alex T Ramsey, Jason M Satterfield, Donald R Gerke, Enola K Proctor. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.04.2019.

Author Keywords
alcohol drinking; alcohol-related disorders; computers; implementation science; internet; mobile health; primary health care; review; risky health behavior

Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Staying awake to stay alive: A circuit controlling starvation-induced waking” (2019) PLoS biology

Staying awake to stay alive: A circuit controlling starvation-induced waking
(2019) PLoS biology, 17 (3), p. e3000199.

Melnattur, K., Shaw, P.

Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States

Abstract
The balance of sleep and wake is plastic and changes to meet environmental demands. Mechanisms that allow an animal to suppress sleep and maintain waking in potentially adverse situations could serve adaptive functions in evolution. The fruit fly, Drosophila melanogaster, is well poised as a system in which to explore these questions. The environment changes sleep and wake in flies, e.g., starvation induces waking in Drosophila as it does in many animals. Further, the sophisticated neurobiological toolkit available to Drosophila researchers gives the fly a great advantage as a system to investigate the precise neurobiological mechanisms underlying these adaptive changes. In a paper in this issue of PLOS Biology, Yurgel and colleagues elegantly exploit the advantages of the Drosophila model to map starvation-induced wakefulness to a single pair of peptidergic neurons and their partners.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Pathways Linking Childhood Personality to Later Life Outcomes” (2019) Child Development Perspectives

Pathways Linking Childhood Personality to Later Life Outcomes
(2019) Child Development Perspectives, .

Hill, P.L.^a , Edmonds, G.W.^b , Jackson, J.J.^a

^a Washington University in St. Louis, United States
^b Oregon Research Institute, United States

Abstract
Dispositional characteristics are associated with important life outcomes across the lifespan, often predicting those outcomes decades in advance. Evidence demonstrates that personality characteristics measured during childhood and adolescence uniquely affect later life outcomes above and beyond adult personality. Currently, it is unclear why personality produces unique effects at different life stages, given the modest consistency of personality across the lifespan. In this article, we offer possible explanations for why these unique predictive effects may occur, charting pathways that link childhood personality to later outcomes that differ from how adult personality influences the same products. We conclude by suggesting directions for longitudinal investigations into when, why, and how assessments of childhood personality can help advance our understanding of lifespan development. © 2019 Society for Research in Child Development

Author Keywords
lifespan development; personality; personality development

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Factors associated with depression and anxiety symptoms among children seeking treatment for obesity: A social-ecological approach” (2019) Pediatric Obesity

Factors associated with depression and anxiety symptoms among children seeking treatment for obesity: A social-ecological approach
(2019) Pediatric Obesity, art. no. e12518, .

Sheinbein, D.H.^a , Stein, R.I.^b , Hayes, J.F.^c , Brown, M.L.^c , Balantekin, K.N.^d , Conlon, R.P.K.^e , Saelens, B.E.^f ^g , Perri, M.G.^h , Welch, R.R.^c , Schechtman, K.B.ⁱ , Epstein, L.H.^j , Wilfley, D.E.^c

^a University of Missouri School of Medicine, Columbia, MO, United States
^b Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
^c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
^d Department of Exercise and Nutritional Sciences, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, United States
^e Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
^f Seattle Children’s Research Institute, Seattle, WA, United States
^g Department of Pediatrics, University of Washington, Seattle, WA, United States
^h College of Public Health and Health Professions, University of Florida, Gainesville, FL, United States
ⁱ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States
^j Department of Pediatrics, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, United States

Abstract
Background: Children with overweight/obesity are more likely to exhibit symptoms of depression and anxiety than are their peers without overweight/obesity; however, the rates and correlates of depression and anxiety symptoms among children seeking obesity treatment remain unclear. Objectives: Examine the prevalence and associated factors of depression and anxiety symptoms among treatment-seeking children with overweight/obesity. Methods: Children 7 to 11 years old (N = 241) and their parents completed assessments before beginning family-based behavioral weight-loss treatment. Disorder-specific self-report questionnaires assessed child depression and anxiety. The social-ecological model served as a framework for examining factors associated with depression and anxiety symptoms. Results: Among our sample, 39.8% (96/241) met clinical cutoffs for depression and/or anxiety symptomatology. Specifically, of these 96, 48 met criteria for both depression and anxiety, 24 for depression only, and 24 for anxiety only. Child eating disorder pathology, parents’ use of psychological control (ie, a parenting style characterized by emotional manipulation), and lower child subjective social status were significantly associated with greater child depression symptomatology. Child eating disorder pathology and parent psychological control were significantly associated with greater child anxiety symptomatology. Conclusion: Nearly 40% of children exhibited psychopathology symptoms, and a variety of correlates were found. Thus, pediatric weight-loss providers may consider screening for and addressing mental health concerns (and associated factors) prior to and during treatment. © 2019 World Obesity Federation

Author Keywords
Anxiety; children; depression; obesity; psychopathology

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants” (2019) Journal of Autism and Developmental Disorders

The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants
(2019) Journal of Autism and Developmental Disorders, .

Paterson, S.J.^a , Wolff, J.J.^c , Elison, J.T.^d , Winder-Patel, B.^e , Zwaigenbaum, L.^f , Estes, A.^g , Pandey, J.^b ^l , Schultz, R.T.^b ^l , Botteron, K.^h , Dager, S.R.ⁱ , Hazlett, H.C.^j ^k , Piven, J.^j ^k , Piven, J.^m , Hazlett, H.C.^m , Chappell, C.^m , Dager, S.^m , Estes, A.^m , Shaw, D.^m , Botteron, K.N.^m , McKinstry, R.C.^m , Constantino, J.^m , Pruett, J.^m , Schultz, R.T.^m , Paterson, S.^m , Zwaigenbaum, L.^m , Elison, J.^m , Evans, A.C.^m , Collins, D.L.^m , Pike, G.B.^m , Fonov, V.^m , Kostopoulos, P.^m , Das, S.^m , Gerig, G.^m , Styner, M.^m , Gu, H.^m , the IBIS Network^m

^a Department of Psychology, Temple University, Philadelphia, PA, United States
^b Center for Autism Research, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
^c Department of Educational Psychology, University of Minnesota, Minneapolis, MN, United States
^d Institute of Child Development & Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
^e The MIND Institute, UC Davis, Sacramento, CA, United States
^f Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
^g Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, United States
^h Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
ⁱ Department of Radiology, University of Washington, Seattle, WA, United States
^j The Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
^k Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
^l Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

Abstract
The present study investigated the relationship between infant temperament characteristics and autism spectrum disorder (ASD) risk status. Temperament was examined at 6, 12, and 24 months in 282 infants at high familial risk for ASD and 114 low-risk controls using the Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire. Infants were divided into three groups at 24 months: High-Risk Positive—classified as ASD (HR Pos), High-Risk Negative (HR Neg), and Low-Risk Negative (LR Neg). At 6 and 12 months HR Pos infants exhibited lower Surgency and Regulatory Capacity than LR Neg infants. By 12 months they also demonstrated increased Negative Affect. Group differences remained, when early signs of ASD were controlled for, suggesting that temperament differences could be useful targets for understanding the development of ASD. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Author Keywords
Autism spectrum disorder; Infancy; Temperament

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Calnexin promotes the folding of mutant iduronate 2-sulfatase related to mucopolysaccharidosis type II” (2019) Biochemical and Biophysical Research Communications

Calnexin promotes the folding of mutant iduronate 2-sulfatase related to mucopolysaccharidosis type II
(2019) Biochemical and Biophysical Research Communications, .

Osaki, Y.^a ^b ^c , Matsuhisa, K.^a , Che, W.^a , Kaneko, M.^a , Asada, R.^a ^d , Masaki, T.^c , Imaizumi, K.^a , Saito, A.^b

^a Department of Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan
^b Department of Stress Protein Processing, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan
^c Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan
^d Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Mucopolysaccharidosis type II (MPS II) is one of the most common mucopolysaccharidoses, which is caused by mutation of the gene encoding iduronate 2-sulfatase (IDS). The loss of function of IDS leads to the accumulation of heparan sulfate and dermatan sulfate of glycosaminoglycans throughout the body, resulting in skeletal deformities, mental retardation, rigid joints, and thick skin. Recently, enzyme replacement therapy has become a common strategy for treating this condition. However, its effectiveness on the central nervous system (CNS) is limited because intravenously administered recombinant IDS (rIDS) cannot pass through the blood brain barrier. Therefore, several methods for delivering rIDS to the CNS, using anti-human transferrin receptor antibody and adeno-associated virus 9, have been explored. To investigate additional approaches for treatment, more cognition about the intracellular dynamics of mutant IDS is essential. We have already found that mutant IDS accumulated in the endoplasmic reticulum (ER) and was degraded by ER-associated degradation (ERAD). Although the dynamics of degradation of mutant IDS was revealed, the molecular mechanism related to the folding of mutant IDS in the ER remained unclear. In this research, we confirmed that mutant IDS retained in the ER would be folded by binding with calnexin (CNX). Thus, knockdown of CNX reduced the translocation of mutant IDS from ER to lysosome and its enzyme activity, indicating that the correct folding of this protein via interaction with CNX ensures its functional activity. These findings reveal the possibility that modifying the interaction of mutant IDS and CNX could contribute to alternative therapeutic strategies for MPS II. © 2019

Author Keywords
Calnexin cycle; ER-associated degradation; Iduronate 2-sulfatase

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Examining daily physical activity in community-dwelling adults with stroke using social cognitive theory: an exploratory, qualitative study” (2019) Disability and Rehabilitation

Examining daily physical activity in community-dwelling adults with stroke using social cognitive theory: an exploratory, qualitative study
(2019) Disability and Rehabilitation, .

Bailey, R.

Brown School, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Purpose: A better understanding of psychosocial factors underlying daily physical activity (i.e. physical activity performed throughout the day) in stroke survivors could be used to develop interventions to promote post-stroke physical activity, particularly in individuals for whom exercise is difficult. Methods: In-depth qualitative interviews were conducted with 15 ambulatory, community-dwelling stroke survivors. Interview transcripts were analyzed using directed content analysis, guided by Social Cognitive Theory, to investigate outcomes expectations, self-efficacy, self-regulation, and social-support for daily physical activity. Results: Participants reported that physical and mental health, and independence and recovery, were important outcomes expectations. Self-efficacy was enhanced through mental perceptions and mastery experiences. Planning, problem-solving, reviewing performance, and establishing routines that require physical activity were important self-regulation strategies. Social support provided praise and encouragement and physical assistance, but was also a barrier when friends and family were overprotective. Conclusions: Participants reported that the investigated Social Cognitive Theory constructs were important psychosocial factors for daily physical activity. Future research and clinical investigations should empirically test the use of strategies to modify these factors for promoting daily physical activity in community-dwelling adults with stroke.Implications for rehabilitation Interventions to increase physical activity after stroke are needed. Outcomes expectations, self-efficacy, self-regulation, and social support were reported by participants as important psychosocial factors underlying daily physical activity. These psychosocial factors should be explored with individual patients and clients to determine which are most deficient, and where amenable to change, targeted for intervention to promote daily physical activity. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Author Keywords
Outcomes expectations; physical activity; self-efficacy; self-regulation; social cognitive theory; social support; stroke

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock” (2019) EMBO Reports

CDK1 and CDK2 regulate NICD1 turnover and the periodicity of the segmentation clock
(2019) EMBO Reports, art. no. e46436, .

Carrieri, F.A.^a , Murray, P.J.^b , Ditsova, D.^a , Ferris, M.A.^c , Davies, P.^d , Dale, J.K.^a

^a Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom
^b Department of Mathematics, University of Dundee, Dundee, United Kingdom
^c Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, United States
^d Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom

Abstract
All vertebrates share a segmented body axis. Segments form from the rostral end of the presomitic mesoderm (PSM) with a periodicity that is regulated by the segmentation clock. The segmentation clock is a molecular oscillator that exhibits dynamic clock gene expression across the PSM with a periodicity that matches somite formation. Notch signalling is crucial to this process. Altering Notch intracellular domain (NICD) stability affects both the clock period and somite size. However, the mechanism by which NICD stability is regulated in this context is unclear. We identified a highly conserved site crucial for NICD recognition by the SCF E3 ligase, which targets NICD for degradation. We demonstrate both CDK1 and CDK2 can phosphorylate NICD in the domain where this crucial residue lies and that NICD levels vary in a cell cycle-dependent manner. Inhibiting CDK1 or CDK2 activity increases NICD levels both in vitro and in vivo, leading to a delay of clock gene oscillations and an increase in somite size. © 2019 The Authors. Published under the terms of the CC BY 4.0 license

Author Keywords
cell cycle; FBXW7; Notch; phosphorylation; somitogenesis

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Central and peripheral innervation patterns of defined axial motor units in larval zebrafish” (2019) Journal of Comparative Neurology

Central and peripheral innervation patterns of defined axial motor units in larval zebrafish
(2019) Journal of Comparative Neurology, .

Bello-Rojas, S.^a ^d , Istrate, A.E.^b ^e , Kishore, S.^c , McLean, D.L.^a ^b ^c

^a Interdepartmental Neuroscience Postbaccalaureate Research Education Program, Northwestern University, Evanston, IL, United States
^b Masters Program in Neurobiology, Northwestern University, Evanston, IL, United States
^c Department of Neurobiology, Northwestern University, Evanston, IL, United States
^d Department of Neuroscience, Washington University School of Medicine in St Louis, St Louis, MO, United States
^e School of Medicine, Case Western Reserve University, Cleveland, OH, United States

Abstract
Spinal motor neurons and the peripheral muscle fibers they innervate form discrete motor units that execute movements of varying force and speed. Subsets of spinal motor neurons also exhibit axon collaterals that influence motor output centrally. Here, we have used in vivo imaging to anatomically characterize the central and peripheral innervation patterns of axial motor units in larval zebrafish. Using early born “primary” motor neurons and their division of epaxial and hypaxial muscle into four distinct quadrants as a reference, we define three distinct types of later born “secondary” motor units. The largest is “m-type” units, which innervate deeper fast-twitch muscle fibers via medial nerves. Next in size are “ms-type” secondaries, which innervate superficial fast-twitch and slow fibers via medial and septal nerves, followed by “s-type” units, which exclusively innervate superficial slow muscle fibers via septal nerves. All types of secondaries innervate up to four axial quadrants. Central axon collaterals are found in subsets of primaries based on soma position and predominantly in secondary fast-twitch units (m, ms) with increasing likelihood based on number of quadrants innervated. Collaterals are labeled by synaptophysin-tagged fluorescent proteins, but not PSD95, consistent with their output function. Also, PSD95 dendrite labeling reveals that larger motor units receive more excitatory synaptic input. Collaterals are largely restricted to the neuropil, however, perisomatic connections are observed between motor units. These observations suggest that recurrent interactions are dominated by motor neurons recruited during stronger movements and set the stage for functional investigations of recurrent motor circuitry in larval zebrafish. © 2019 Wiley Periodicals, Inc.

Author Keywords
axial muscle; motor neurons; motor units; recurrent circuits; RRID: Addgene_74314; RRID: Addgene_74316; spinal cord; zebrafish

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Age-Related Differences in Motivational Integration and Cognitive Control” (2019) Cognitive, Affective and Behavioral Neuroscience

Age-Related Differences in Motivational Integration and Cognitive Control
(2019) Cognitive, Affective and Behavioral Neuroscience, .

Yee, D.M., Adams, S., Beck, A., Braver, T.S.

Cognitive Control and Psychopathology Laboratory, Psychological and Brain Sciences, Washington University in St. Louis, 1 Brookings Drive, Campus Box 1125, St. Louis, MO 63130, United States

Abstract
Motivational incentives play an influential role in value-based decision-making and cognitive control. A compelling hypothesis in the literature suggests that the motivational value of diverse incentives are integrated in the brain into a common currency value signal that influences decision-making and behavior. To investigate whether motivational integration processes change during healthy aging, we tested older (N = 44) and younger (N = 54) adults in an innovative incentive integration task paradigm that establishes dissociable and additive effects of liquid (e.g., juice, neutral, saltwater) and monetary incentives on cognitive task performance. The results reveal that motivational incentives improve cognitive task performance in both older and younger adults, providing novel evidence demonstrating that age-related cognitive control deficits can be ameliorated with sufficient incentive motivation. Additional analyses revealed clear age-related differences in motivational integration. Younger adult task performance was modulated by both monetary and liquid incentives, whereas monetary reward effects were more gradual in older adults and more strongly impacted by trial-by-trial performance feedback. A surprising discovery was that older adults shifted attention from liquid valence toward monetary reward throughout task performance, but younger adults shifted attention from monetary reward toward integrating both monetary reward and liquid valence by the end of the task, suggesting differential strategic utilization of incentives. These data suggest that older adults may have impairments in incentive integration and employ different motivational strategies to improve cognitive task performance. The findings suggest potential candidate neural mechanisms that may serve as the locus of age-related change, providing targets for future cognitive neuroscience investigations. © 2019, The Psychonomic Society, Inc.

Author Keywords
Aging; Cognitive control; Decision-making; Motivation; Reward

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Catastrophic drug errors involving tranexamic acid administered during spinal anaesthesia” (2019) Anaesthesia

Catastrophic drug errors involving tranexamic acid administered during spinal anaesthesia
(2019) Anaesthesia, .

Palanisamy, A.^a , Kinsella, S.M.^b

^a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
^b Department of Anaesthesia, St Michael’s Hospital, Bristol, United Kingdom

Author Keywords
anaesthesia, spinal; bupivacaine; Luer; medication error; toxicity; tranexamic acid; wrong route error

Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus

“A bright future? Optogenetics in the periphery for pain research and therapy” (2018) Pain

A bright future? Optogenetics in the periphery for pain research and therapy
(2018) Pain, 159, pp. S65-S73.

Mickle, A.D., Gereau, R.W., 4th

Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, 660 South Euclid Ave, St. Louis, MO 63110, United States

Document Type: Article
Publication Stage: Final
Source: Scopus