12 results on '"Schwartz, Sarah E."'
Search Results
2. Regulatory Elements Inserted into AAVs Confer Preferential Activity in Cortical Interneurons.
- Author
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Rubin, Anna N, Malik, Ruchi, Cho, Kathleen KA, Lim, Kenneth J, Lindtner, Susan, Robinson Schwartz, Sarah E, Vogt, Daniel, Sohal, Vikaas S, and Rubenstein, John LR
- Subjects
AAV ,cortical interneurons ,enhancers ,fast spiking ,regular spiking ,Neurosciences - Abstract
Cortical interneuron (CIN) dysfunction is thought to play a major role in neuropsychiatric conditions like epilepsy, schizophrenia and autism. It is therefore essential to understand how the development, physiology, and functions of CINs influence cortical circuit activity and behavior in model organisms such as mice and primates. While transgenic driver lines are powerful tools for studying CINs in mice, this technology is limited in other species. An alternative approach is to use viral vectors such as AAV, which can be used in multiple species including primates and also have potential for therapeutic use in humans. Thus, we sought to discover gene regulatory enhancer elements (REs) that can be used in viral vectors to drive expression in specific cell types. The present study describes the systematic genome-wide identification of putative REs (pREs) that are preferentially active in immature CINs by histone modification chromatin immunoprecipitation and sequencing (ChIP-seq). We evaluated two novel pREs in AAV vectors, alongside the well-established Dlx I12b enhancer, and found that they drove CIN-specific reporter expression in adult mice. We also showed that the identified Arl4d pRE could drive sufficient expression of channelrhodopsin for optogenetic rescue of behavioral deficits in the Dlx5/6 +/- mouse model of fast-spiking CIN dysfunction.
- Published
- 2020
3. Enhancing WNT Signaling Restores Cortical Neuronal Spine Maturation and Synaptogenesis in Tbr1 Mutants.
- Author
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Fazel Darbandi, Siavash, Robinson Schwartz, Sarah E, Pai, Emily Ling-Lin, Everitt, Amanda, Turner, Marc L, Cheyette, Benjamin NR, Willsey, A Jeremy, State, Matthew W, Sohal, Vikaas S, and Rubenstein, John LR
- Subjects
Thalamus ,Neurons ,Dendritic Spines ,Synapses ,Animals ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Humans ,Mice ,DNA-Binding Proteins ,T-Box Domain Proteins ,Female ,Male ,Neurogenesis ,HEK293 Cells ,Wnt Signaling Pathway ,Autism Spectrum Disorder ,ASD ,LiCl treatment ,Tbr1 ,WNT-signaling ,cortex ,excitatory neuron ,social deficit ,spine maturation ,synaptogenesis ,Intellectual and Developmental Disabilities (IDD) ,Biotechnology ,Neurosciences ,Autism ,Mental Health ,Brain Disorders ,Genetics ,Pediatric ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Biochemistry and Cell Biology ,Medical Physiology - Abstract
Tbr1 is a high-confidence autism spectrum disorder (ASD) gene encoding a transcription factor with distinct pre- and postnatal functions. Postnatally, Tbr1 conditional knockout (CKO) mutants and constitutive heterozygotes have immature dendritic spines and reduced synaptic density. Tbr1 regulates expression of several genes that underlie synaptic defects, including a kinesin (Kif1a) and a WNT-signaling ligand (Wnt7b). Furthermore, Tbr1 mutant corticothalamic neurons have reduced thalamic axonal arborization. LiCl and a GSK3β inhibitor, two WNT-signaling agonists, robustly rescue the dendritic spines and the synaptic and axonal defects, suggesting that this could have relevance for therapeutic approaches in some forms of ASD.
- Published
- 2020
4. Neonatal Tbr1 Dosage Controls Cortical Layer 6 Connectivity
- Author
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Darbandi, Siavash Fazel, Schwartz, Sarah E Robinson, Qi, Qihao, Catta-Preta, Rinaldo, Pai, Emily Ling-Lin, Mandell, Jeffrey D, Everitt, Amanda, Rubin, Anna, Krasnoff, Rebecca A, Katzman, Sol, Tastad, David, Nord, Alex S, Willsey, A Jeremy, Chen, Bin, State, Matthew W, Sohal, Vikaas S, and Rubenstein, John LR
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Human Genome ,Autism ,Behavioral and Social Science ,Mental Health ,Genetics ,Brain Disorders ,Pediatric ,Intellectual and Developmental Disabilities (IDD) ,1.1 Normal biological development and functioning ,Underpinning research ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Neurological ,Good Health and Well Being ,Animals ,Animals ,Newborn ,Cells ,Cultured ,DNA-Binding Proteins ,Gene Dosage ,Maze Learning ,Mice ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Neocortex ,Nerve Net ,T-Box Domain Proteins ,ASD ,Tbr1 ,aggression ,anxiety-like behavior ,cortical development ,development ,layer 6 ,synapses ,Psychology ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
An understanding of how heterozygous loss-of-function mutations in autism spectrum disorder (ASD) risk genes, such as TBR1, contribute to ASD remains elusive. Conditional Tbr1 deletion during late mouse gestation in cortical layer 6 neurons (Tbr1layer6 mutants) provides novel insights into its function, including dendritic patterning, synaptogenesis, and cell-intrinsic physiology. These phenotypes occur in heterozygotes, providing insights into mechanisms that may underlie ASD pathophysiology. Restoring expression of Wnt7b largely rescues the synaptic deficit in Tbr1layer6 mutant neurons. Furthermore, Tbr1layer6 heterozygotes have increased anxiety-like behavior, a phenotype seen ASD. Integrating TBR1 chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data from layer 6 neurons and activity of TBR1-bound candidate enhancers provides evidence for how TBR1 regulates layer 6 properties. Moreover, several putative TBR1 targets are ASD risk genes, placing TBR1 in a central position both for ASD risk and for regulating transcriptional circuits that control multiple steps in layer 6 development essential for the assembly of neural circuits.
- Published
- 2018
5. A Measure of Attitudes toward Interdisciplinary Healthcare Teams Around Pediatric Autism Care
- Author
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McClain, Maryellen Brunson, primary, Schwartz, Sarah E., additional, Kieffer, Kaelah E., additional, Azad, Gazi, additional, and Shahidullah, Jeffrey D., additional
- Published
- 2024
- Full Text
- View/download PDF
6. Passive Surveillance of SARS-CoV-2 in Adult Blacklegged Ticks (Ixodes Scapularis) From Northeast Pennsylvania
- Author
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Hunt, Erin A., Schwartz, Sarah E., and Chinnici, Nicole
- Subjects
Passive Surveillance ,Northeast Pennsylvania ,PCR ,White-Tailed Deer ,SARS-CoV-2 ,Ixodes scapularis ,Deer Tick ,COVID-19 ,Blacklegged Tick ,Odocoileus virginianus - Abstract
This supplemental file lists the primer sequences and synthetic positives used in this study. The purpose of this study was to test Blacklegged Ticks in Northeast Pennsylvania for SARS-CoV-2., This study was directly funded by the Dr. Jane Huffman Wildlife Genetics Institute of East Stroudsburg University, without a grant.
- Published
- 2023
- Full Text
- View/download PDF
7. Relationship between Speed of Response Inhibition and Ability to Suppress a Step in Midlife and Older Adults
- Author
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England, Derek, primary, Ruddy, Kathy L., additional, Dakin, Christopher J., additional, Schwartz, Sarah E., additional, Butler, Blake, additional, and Bolton, David A. E., additional
- Published
- 2021
- Full Text
- View/download PDF
8. Early Adolescent Substance Use in a National Sample of Mexican Youths: Demographic Characteristics that Predict Use of Alcohol, Tobacco, and Others Drugs
- Author
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Vázquez, Alejandro L., Domenech Rodríguez, Melanie M., Schwartz, Sarah E., Amador Buenabad, Nancy G., Bustos Gamiño, Marycarmen N., Lourdes Gutierrez López, María de, Villatoro Velázquez, Jorge A., and American Psychological Association
- Subjects
early adolescence ,substance use ,Psychology ,intentions ,elementary ,Mexico - Abstract
The United States and Mexico have seen significant increases in the prevalence of substance use among Latinx adolescents in the last 20 years. Research is needed to address rising national rates of substances use to inform the development of policies and intervention programs targeting Latinx youth. Our primary aim was to identify demographic factors associated with substance initiation and use among elementary age Latinx youth. Data for the present study include 52,171 elementary students in 5th and 6th grades, who participated in the National Survey of Drug Use Among Students (ENCODE) in Mexico. Youths reported demographic information, rates of substance use for alcohol, tobacco, marijuana, inhalant, and other substances, or intention for first time substance use. Findings suggest that Latinx youth who were boys, of indigenous heritage, nonreligious, and overage for their grade were especially at risk for reporting lifetime alcohol, tobacco, marijuana, inhalant, and other substance use. Boys and youth with indigenous heritage were more likely to report intentions to try alcohol, tobacco, and other substances for the first time. High subjective economic status was associated with lower risk for reporting lifetime tobacco use and substance use intentions in general. Efforts are needed to disseminate accessible substance use prevention programs during early adolescence to encourage positive developmental trajectories among Latinx youths at an elevated risk for substance initiation and use. Clinical and research implications are discussed.
- Published
- 2019
9. Motor Preparation for Compensatory Reach-to-Grasp Responses When Viewing a Wall-Mounted Safety Handle
- Author
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Bolton, David A.E., Cole, David M., Zhan, Jixun, Mansour, Manhoud, Rydalch, Garrett, McDannald, Douglas W., Schwartz, Sarah E., and Elsevier
- Subjects
Corticospinal excitability ,Affordance ,Reactive balance ,Anticipatory set ,Kinesiology ,Transcranial magnetic stimulation - Abstract
The present study explored how motor cortical activity was influenced by visual perception of complex environments that either afforded or obstructed arm and leg reactions in young, healthy adults. Most importantly, we focused on compensatory balance reactions where the arms were required to regain stability following unexpected postural perturbation. Our first question was if motor cortical activity from the hand area automatically corresponds to the visual environment. Affordance-based priming of the motor system was assessed using single-pulse Transcranial Magnetic Stimulation (TMS) to determine if visual access to a wall-mounted support handle influenced corticospinal excitability. We evaluated if hand actions were automatically facilitated and/or suppressed by viewing an available handle within graspable range. Our second question was if the requirement for rapid movement to recover balance played a role in modulating any affordance effect in the hands. The goal was to disentangle motor demands related to postural threat from the impact of observation alone. For balance trials, a custom-built, lean and release apparatus was used to impose temporally unpredictable postural perturbations. In all balance trials, perturbations were of sufficient magnitude to evoke a compensatory change-in-support response; therefore, any recovery action needed to carefully take into account the affordances and constraints of the perceived environment to prevent a fall. Consistent with our first hypothesis, activity in an intrinsic hand muscle was increased when participants passively viewed a wall-mounted safety handle, in both seated and standing contexts. Contrary to our second hypothesis, this visual priming was absent when perturbations were imposed and the handle was needed to regain balance. Our results reveal that motor set is influenced by simply viewing objects that afford a grasp. We suggest that such preparation may provide an advantage when generating balance recovery actions that require quickly grasping a supportive handle. This priming effect likely competes with other task-dependent influences that regulate cortical motor output. Future studies should expand from limitations inherent with single-pulse TMS alone, to determine if vision of our surrounding world influences motor set in other contexts (e.g., intensified postural threat) and investigate if this priming corresponds to overt behavior.
- Published
- 2019
10. Exact Approaches for Bias Detection and Avoidance with Small, Sparse, or Correlated Categorical Data
- Author
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Schwartz, Sarah E.
- Subjects
multinomial outcome ,trend test ,Statistics and Probability ,conditioning ,exact test ,logistic regression ,Mathematics - Abstract
Every day, traditional statistical methodology are used world wide to study a variety of topics and provides insight regarding countless subjects. Each technique is based on a distinct set of assumptions to ensure valid results. Additionally, many statistical approaches rely on large sample behavior and may collapse or degenerate in the presence of small, spare, or correlated data. This dissertation details several advancements to detect these conditions, avoid their consequences, and analyze data in a different way to yield trustworthy results. One of the most commonly used modeling techniques for outcomes with only two possible categorical values (eg. live/die, pass/fail, better/worse, ect.) is logistic regression. While some potential complications with this approach are widely known, many investigators are unaware that their particular data does not meet the foundational assumptions, since they are not easy to verify. We have developed a routine for determining if a researcher should be concerned about potential bias in logistic regression results, so they can take steps to mitigate the bias or use a different procedure altogether to model the data. Correlated data may arise from common situations such as multi-site medical studies, research on family units, or investigations on student achievement within classrooms. In these circumstance the associations between cluster members must be included in any statistical analysis testing the hypothesis of a connection be-tween two variables in order for results to be valid. Previously investigators had to choose between using a method intended for small or sparse data while assuming independence between observations or a method that allowed for correlation between observations, while requiring large samples to be reliable. We present a new method that allows for small, clustered samples to be assessed for a relationship between a two-level predictor (eg. treatment/control) and a categorical outcome (eg. low/medium/high).
- Published
- 2017
11. Neonatal Tbr1 Dosage Controls Cortical Layer 6 Connectivity.
- Author
-
Fazel Darbandi, Siavash, Fazel Darbandi, Siavash, Robinson Schwartz, Sarah E, Qi, Qihao, Catta-Preta, Rinaldo, Pai, Emily Ling-Lin, Mandell, Jeffrey D, Everitt, Amanda, Rubin, Anna, Krasnoff, Rebecca A, Katzman, Sol, Tastad, David, Nord, Alex S, Willsey, A Jeremy, Chen, Bin, State, Matthew W, Sohal, Vikaas S, Rubenstein, John LR, Fazel Darbandi, Siavash, Fazel Darbandi, Siavash, Robinson Schwartz, Sarah E, Qi, Qihao, Catta-Preta, Rinaldo, Pai, Emily Ling-Lin, Mandell, Jeffrey D, Everitt, Amanda, Rubin, Anna, Krasnoff, Rebecca A, Katzman, Sol, Tastad, David, Nord, Alex S, Willsey, A Jeremy, Chen, Bin, State, Matthew W, Sohal, Vikaas S, and Rubenstein, John LR
- Abstract
An understanding of how heterozygous loss-of-function mutations in autism spectrum disorder (ASD) risk genes, such as TBR1, contribute to ASD remains elusive. Conditional Tbr1 deletion during late mouse gestation in cortical layer 6 neurons (Tbr1layer6 mutants) provides novel insights into its function, including dendritic patterning, synaptogenesis, and cell-intrinsic physiology. These phenotypes occur in heterozygotes, providing insights into mechanisms that may underlie ASD pathophysiology. Restoring expression of Wnt7b largely rescues the synaptic deficit in Tbr1layer6 mutant neurons. Furthermore, Tbr1layer6 heterozygotes have increased anxiety-like behavior, a phenotype seen ASD. Integrating TBR1 chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data from layer 6 neurons and activity of TBR1-bound candidate enhancers provides evidence for how TBR1 regulates layer 6 properties. Moreover, several putative TBR1 targets are ASD risk genes, placing TBR1 in a central position both for ASD risk and for regulating transcriptional circuits that control multiple steps in layer 6 development essential for the assembly of neural circuits.
- Published
- 2018
12. Neonatal Tbr1 Dosage Controls Cortical Layer 6 Connectivity
- Author
-
Fazel Darbandi, Siavash, primary, Robinson Schwartz, Sarah E., additional, Qi, Qihao, additional, Catta-Preta, Rinaldo, additional, Pai, Emily Ling-Lin, additional, Mandell, Jeffrey D., additional, Everitt, Amanda, additional, Rubin, Anna, additional, Krasnoff, Rebecca A., additional, Katzman, Sol, additional, Tastad, David, additional, Nord, Alex S., additional, Willsey, A. Jeremy, additional, Chen, Bin, additional, State, Matthew W., additional, Sohal, Vikaas S., additional, and Rubenstein, John L.R., additional
- Published
- 2018
- Full Text
- View/download PDF
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