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Work 1-9 of 9

Sorted by relevance

Article

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

by Marc Remke; Vijay Ramaswamy; John Peacock; David J. H. Shih; Christian Koelsche; Paul A. Northcott; Nadia Hill; Florence M. G. Cavalli; Marcel Kool; Xin Wang; Stephen C. Mack; Mark Barszczyk; A. Sorana Morrissy; Xiaochong Wu; Sameer Agnihotri; Betty Luu ; David T.W. Jones; Livia Garzia; Adrian M. Dubuc; Nataliya Zhukova; Robert Vanner; Johan M. Kros; Pim J. French; Erwin Van Meir; Rajeev Vibhakar; Karel Zitterbart; Jennifer A. Chan; Laszlo Bognar; Almos Klekner; Boleslaw Lach ; Shin Jung; Ali G. Saad; Linda M. Liau; Steffen Albrecht; Massimo Zollo; Michael Cooper; Reid C. Thompson; Oliver O. Delattre; Franck Bourdeaut; Francois F. Doz; Miklos Garami; Peter Hauser; Carlos G. Carlotti; Timothy E. Van Meter; Luca Massimi; Daniel Fults; Scott L. Pomeroy; Toshiro Kumabe ; Young Shin Ra; Jeffrey R. Leonard; Samer K. Elbabaa; Jaume Mora; Joshua B. Rubin; Yoon-Jae Cho; Roger E. McLendon; Darrell D. Bigner; Charles G. Eberhart; Maryam Fouladi; Robert J. Wechsler-Reya; Claudia C. Faria; Sidney E. Croul; Annie Huang ; Eric Bouffet; Cynthia E. Hawkins ; Peter B. Dirks; William A. Weiss ; Ulrich Schuller; Ian F. Pollack; Stefan Rutkowski; David Meyronet; Anne Jouvet; Michelle Fevre-Montange; Nada Jabado; Marta Perek-Polnik; Wieslawa A. Grajkowska; Seung-Ki Kim; James T. Rutka ; David Malkin; Uri Tabori; Stefan M. Pfister; Andrey Korshunov; Andreas von Deimling

2013

Subjects
  • Biology, Neuroscience
  • Health Sciences, Pathology
  • File Download
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Abstract:Close

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in < 5 % of cases and showed no association with increased patient age. The prognostic implications of these mutations were highly subgroup-specific. TERT mutations identified a subset with good and poor prognosis in SHH and Group 4 tumors, respectively. Monosomy 6 was mostly restricted to WNT tumors without TERT mutations. Hallmark SHH focal copy number aberrations and chromosome 10q deletion were mutually exclusive with TERT mutations within SHH tumors. TERT promoter mutations are the most common recurrent somatic point mutation in medulloblastoma, and are very highly enriched in adult SHH and WNT tumors. TERT mutations define a subset of SHH medulloblastoma with distinct demographics, cytogenetics, and outcomes.

Article

Intranasal oxytocin, but not vasopressin, augments neural responses to toddlers in human fathers

by Ting Li; Xu Chen; Jennifer Streiffer Mascaro; Ebrahim Haroon; James K Rilling

2017

Subjects
  • Anthropology, Medical and Forensic
  • Biology, Neuroscience
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Abstract:Close

This study investigates paternal brain function with the hope of better understanding the neural basis for variation in caregiving involvement among men. The neuropeptides oxytocin (OT) and vasopressin (AVP) are implicated in paternal caregiving in humans and other species. In a double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1–2 year old children to receive either 24 IU intranasal OT before one scan and placebo before the other scan (n = 15) or 20 IU intranasal AVP before one scan and placebo before the other scan (n = 15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listened to unknown infant cry stimuli. Intranasal OT, but not AVP, significantly increased the BOLD fMRI response to viewing pictures of own children within the caudate nucleus, a target of midbrain dopamine projections, as well as the dorsal anterior cingulate (dACC) and visual cortex, suggesting that intranasal oxytocin augments activation in brain regions involved in reward, empathy and attention in human fathers. OT effects also varied as a function of order of administration such that when OT was given before placebo, it increased activation within several reward-related structures (substantia nigra, ventral tegmental area, putamen) more than when it was given after placebo. Neither OT nor AVP had significant main effects on the neural response to cries. Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children, and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation, as might be found among men suffering from post-partum depression.

Article

High rates of violence, crime, academic problems, and behavioral problems in males with both early neuromotor deficits and unstable family environments

by Adrian Raine; Patricia Brennan; Birgitte Mednick; Sarnoff A. Mednick

1996

Subjects
  • Sociology, Criminology and Penology
  • Psychology, Behavioral
  • Biology, Neuroscience
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Abstract:Close

Background: It is commonly assumed that individuals with both biological and psychosocial deficits are more likely to become criminal, but there is surprisingly little empirical support for this assumption. We test the hypothesis that a group with biosocial risk factors are more likely to develop behavioral and academic problems in adolescence and violent criminal offending in adulthood compared with groups with only biological or only social risk factors. Methods: Hypotheses were tested on a sample of 397 male subjects, using obstetric and early neuromotor measures collected in the first year of life; family, social, demographic, and behavioral measures at age 17 to 19 years; and criminal data at 20 to 22 years of age. Results: Cluster analysis of the risk factors indicated a group with obstetric risk factors only, a group with poverty risk factors only, and a biosocial group with both early neuromotor deficits and unstable family environments. The biosocial group had more than double the adult violence, theft, and total crime rates of the other 2 groups and bad significantly more behavioral and academic problems in adolescence. Conclusions: When early neuromotor deficits and negative family factors cluster together, individuals are particularly likely to become criminal and violent compared with those with only poverty or only obstetric risk factors. Because this biosocial group accounted for 70.2% of all crimes committed in the entire sample, early interventions that tackle these deficits might significantly reduce violence.

Article

Impaired Autonomic Nervous System Habituation in Those at Genetic Risk for Schizophrenia

by J. Meggin Hollister; Sarnoff A. Mednick; Patricia Brennan; Tyrone D. Cannon

1994

Subjects
  • Biology, Neuroscience
  • Psychology, Cognitive
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Abstract:Close

BACKGROUND: Schizophrenia has been associated with habituation of skin conductance activity. Skin conductance data from the Copenhagen High Risk Project were analyzed. We hypothesized that genetic risk for schizophrenia and development of schizophrenia later in life are related to impaired habituation of autonomic nervous system activity. METHODS: Data were collected in 1962, when subjects averaged 15 years of age and had not yet qualified for a psychiatric diagnosis. Nonspecific fluctuations in electrodermal activity were monitored during a rest period free of sensory stimulation. RESULTS: We found that an increasing level of genetic risk for schizophrenia was related to impaired habituation of autonomic nervous system activity over time. Individuals with two schizophrenia-spectrum parent evidenced no habituation, those with one spectrum parent evidence some habituation, and those with normal parents evidenced rapid habituation. Subjects who developed schizophrenia in adulthood evidenced significant deficits in habitation in adolescence. CONCLUSIONS: These results suggest that impaired habituation of spontaneous autonomic nervous system activity may represent a behavioral marker of the genetic predisposition to schizophrenia.

Article

Inhibition of cystathionine beta-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation

by Jun Yan; Shufen Hu; Kang Zou; Min Xu; Qianliang Wang; Xiuhua Miao; Shan Yu; G-Y Xu

2016

Subjects
  • Biology, Neuroscience
  • Health Sciences, Pharmacology
  • File Download
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Abstract:Close

The pathogenesis of pain in lumbar disc herniation (LDH) remains poorly understood. We have recently demonstrated that voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons were sensitized in a rat model of LDH. However, the detailed molecular mechanism for sensitization of VGSCs remains largely unknown. This study was designed to examine roles of the endogenous hydrogen sulfide synthesizing enzyme cystathionine β-synthetase (CBS) in sensitization of VGSCs in a previously validated rat model of LDH. Here we showed that inhibition of CBS activity by O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA) significantly attenuated pain hypersensitivity in LDH rats. Administration of AOAA also reduced neuronal hyperexcitability, suppressed the sodium current density, and right-shifted the V1/2 of the inactivation curve, of hindpaw innervating DRG neurons, which is retrogradely labeled by DiI. In vitro incubation of AOAA did not alter the excitability of acutely isolated DRG neurons. Furthermore, CBS was colocalized with NaV1.7 and NaV1.8 in hindpaw-innervating DRG neurons. Treatment of AOAA markedly suppressed expression of NaV1.7 and NaV1.8 in DRGs of LDH rats. These data suggest that targeting the CBS-H2S signaling at the DRG level might represent a novel therapeutic strategy for chronic pain relief in patients with LDH.

Article

Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits

by Joshua W. Buckholtz; Michael T. Treadway; Ronald L. Cowan; Neil D. Woodward; Stephen D. Benning; Rui Li; M. Sib Ansari; Ronald M. Baldwin; Ashley N. Schwartzman; Evans S. Shelby; Clarence E. Smith; David Cole; Robert M. Kessler; David H. Zald

2010

Subjects
  • Health Sciences, Mental Health
  • Biology, Neuroscience
  • Psychology, Personality
  • File Download
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Abstract:Close

Psychopathy is a personality disorder that is strongly linked to criminal behavior. Using [18 F]fallypride positron emission tomography and blood oxygen level-dependent functional magnetic resonance imaging, we found that impulsive-antisocial psychopathic traits selectively predicted nucleus accumbens dopamine release and reward anticipation-related neural activity in response to pharmacological and monetary reinforcers, respectively. These findings suggest that neurochemical and neurophysiological hyper-reactivity of the dopaminergic reward system may comprise a neural substrate for impulsive-antisocial behavior and substance abuse in psychopathy.

Article

Morbidity and Mortality Associated With Meningioma After Cranial Radiotherapy: A Report From the Childhood Cancer Survivor Study

by Daniel C. Bowers; Chaya S. Moskowitz; Joanne F. Chou; Claire M. Mazewski; Joseph P. Neglia; Gregory T. Armstrong; Wendy M. Leisenring; Leslie L. Robison; Kevin C. Oeffinger

2017

Subjects
  • Health Sciences, Oncology
  • Biology, Neuroscience
  • File Download
  • View Abstract

Abstract:Close

Purpose: Little is known about neurologic morbidity attributable to cranial radiotherapy (CRT) -associated meningiomas. Materials and Methods: From 4,221 survivors exposed to CRT in the Childhood Cancer Survivor Study, a diagnosis of meningioma and onset of neurologic sequelae were ascertained. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% CIs to evaluate the factors associated with neurologic sequelae after subsequent meningioma. Results: One hundred ninety-nine meningiomas were identified among 169 participants. The median interval from primary cancer to meningioma diagnosis was 22 years (5 to 37 years). The cumulative incidence of a subsequent meningioma by age 40 years was 5.6% (95% CI, 4.7% to 6.7%). CRT doses of 20 to 29.9 Gy (HR, 1.6; 95% CI,1.0 to 2.6) and doses ≥ 30 Gy (HR, 2.6; 95% CI, 1.6 to 4.2) were associated with an increased risk of meningioma compared with CRT doses of 1.5 to 19.9 Gy (P < .001). Within 6 months before or subsequent to a meningioma diagnosis, 20% (30 of 149) reported at least one new neurologic sequela, including seizures (8.3%), auditory-vestibular-visual deficits (6%), focal neurologic dysfunction (7.1%), and severe headaches (5.3%). Survivors reporting a meningioma had increased risks of neurologic sequelae > 5 years after primary cancer diagnosis, including seizures (HR, 10.0; 95% CI, 7.0 to 15.3); auditory-vestibular-visual sensory deficits (HR, 2.3; 95% CI, 1.3 to 4.0); focal neurologic dysfunction (HR, 4.9; 95% CI, 3.2 to 7.5); and severe headaches (HR, 3.2; 95% CI, 1.9 to 5.4). With a median follow-up of 72 months after meningioma diagnosis (range, 3.8 to 395 months), 22 participants (13%) were deceased, including six deaths attributed to a meningioma. Conclusion: Childhood cancer survivors exposed to CRT and subsequently diagnosed with a meningioma experience significant neurologic morbidity.

Article

Epigenetic mechanisms in neurogenesis

by Bing Yao; Kimberly M. Christian; Chuan He; Peng Jin; Guo-li Ming; Hongjun Song

2016

Subjects
  • Biology, Neuroscience
  • Biology, Genetics
  • Biology, Cell
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Abstract:Close

In the embryonic and adult brain, neural stem cells proliferate and give rise to neurons and glia through highly regulated processes. Epigenetic mechanisms-including DNA and histone modifications, as well as regulation by non-coding RNAs-have pivotal roles in different stages of neurogenesis. Aberrant epigenetic regulation also contributes to the pathogenesis of various brain disorders. Here, we review recent advances in our understanding of epigenetic regulation in neurogenesis and its dysregulation in brain disorders, including discussion of newly identified DNA cytosine modifications. We also briefly cover the emerging field of epitranscriptomics, which involves modifications of mRNAs and long non-coding RNAs.

Article

Balance, Body Motion, and Muscle Activity After High-Volume Short-Term Dance-Based Rehabilitation in Persons With Parkinson Disease: A Pilot Study

by Johnathan McKay; Lena Ting; Madeleine Hackney

2016

Subjects
  • Biology, Neuroscience
  • Health Sciences, Rehabilitation and Therapy
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Background and Purpose: The objectives of this pilot study were to (1) evaluate the feasibility and investigate the efficacy of a 3-week, high-volume (450 minutes per week) Adapted Tango intervention for community-dwelling individuals with mild-moderate Parkinson disease (PD) and (2) investigate the potential efficacy of Adapted Tango in modifying electromyographic (EMG) activity and center of body mass (CoM) displacement during automatic postural responses to support surface perturbations. Methods: Individuals with PD (n = 26) were recruited for highvolume Adapted Tango (15 lessons, 1.5 hour each over 3 weeks). Twenty participants were assessed with clinical balance and gait measures before and after the intervention. Nine participants were also assessed with support-surface translation perturbations. Results: Overall adherence to the intervention was 77%. At posttest, peak forward CoM displacement was reduced (4.0 ± 0.9 cm, pretest, vs 3.7 ± 1.1 cm, posttest; P = 0.03; Cohen's d = 0.30) and correlated to improvements on Berg Balance Scale (p = .0.68; P = 0.04) and Dynamic Gait Index (p =.0.75; P = 0.03). Overall antagonist onset time was delayed (27 ms; P = 0.02; d = 0.90) and duration was reduced (56 ms, .39%, P = 0.02; d = 0.45). Reductions in EMG magnitude were also observed (P < 0.05). Discussion and Conclusions: Following participation in Adapted Tango, changes in kinematic and some EMG measures of perturbation responses were observed in addition to improvements in clinical measures. We conclude that 3-week, high-volume Adapted Tango is feasible and represents a viable alternative to longer duration adapted dance programs.
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