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Altered hippocampal transcriptome dynamics following sleep deprivation [article]

Marie E. Gaine, Ethan Bahl, Snehajyoti Chatterjee, Jacob. J. Michaelson, Ted Abel, Lisa C. Lyons
2021 bioRxiv   pre-print
AbstractWidespread sleep deprivation is a continuing public health problem in the United States and worldwide affecting adolescents and adults. Acute sleep deprivation results in decrements in spatial memory and cognitive impairments. The hippocampus is vulnerable to acute sleep deprivation with changes in gene expression, cell signaling, and protein synthesis. Sleep deprivation also has long lasting effects on memory and performance that persist after recovery sleep, as seen in behavioral
more » ... es from invertebrates to humans. Although previous research has shown that acute sleep deprivation impacts gene expression, the extent to which sleep deprivation affects gene regulation remains unknown. Using an unbiased deep RNA sequencing approach, we investigated the effects of acute sleep deprivation on gene expression in the hippocampus. We identified 1,146 genes that were significantly dysregulated following sleep deprivation with 507 genes upregulated and 639 genes downregulated, including protein coding genes and long non-coding RNAs not previously identified as impacted by sleep deprivation. Notably, genes significantly upregulated after sleep deprivation were associated with RNA splicing and the nucleus. In contrast, downregulated genes were associated with cell adhesion, dendritic localization, the synapse, and postsynaptic membrane. These results clearly demonstrate that sleep deprivation differentially regulates gene expression on multiple transcriptomic levels to impact hippocampal function.Graphical Abstract
doi:10.1101/2021.05.20.445021 fatcat:5xxfr3omlvgefnfhtgmqw5amlu

cerebroViz: An R package for anatomical visu-alization of spatiotemporal brain data

Ethan Bahl, Tanner Koomar, Jacob J. Michaelson
2016 Bioinformatics  
As communication networks increase in performance and complexity, and more dependence is placed upon them, it becomes ever more important that their behaviour is understood in an efficient and timely manner. Visualisation is an established technique for the presentation of the vast volume of data yielded in monitoring such networks. It is apparent, however, that much of the work in this area has been performed in isolation, and it is timely that a review of this research is conducted. This
more » ... surveys the techniques for the visualisation of communication networks and related measurements. The research is classified by the type of visualisation used, and is separated into three classes: geographic visualisations, where the data is presented with respect to the physical location of nodes in the network; abstract topological visualisations, where the relationships between nodes are presented independently of * The spelling 'visualisation' is used throughout this document, however, as most of the work on this subject uses the 'ize' spelling, the title has been left in this form 1 This paper is a postprint of a paper submitted to and accepted for publication in IET Communications and is subject to Institution of Engineering and Technology Copyright. The copy of record is available at IET Digital Library. physical location; and plot-based visualisation, where the focus is a single point in the network, often presented with respect to time. The research in this area is reviewed and the techniques proposed are discussed in terms of the three classes.
doi:10.1093/bioinformatics/btw726 pmid:28011779 pmcid:PMC5870797 fatcat:c4lsiuw7ufdynck4rcjcfqpr54

Altered hippocampal transcriptome dynamics following sleep deprivation

Marie E. Gaine, Ethan Bahl, Snehajyoti Chatterjee, Jacob J. Michaelson, Ted Abel, Lisa C. Lyons
2021 Molecular Brain  
The code for analyses and figures related to RNA-Seq data can be accessed through GitHub at https:// github. com/ ethan bahl/ gaine 2021_ sleep depri vation.  ... 
doi:10.1186/s13041-021-00835-1 pmid:34384474 pmcid:PMC8361790 fatcat:mdad32aixreilimmexa75uicyy

NEUROeSTIMator: Using Deep Learning to Quantify Neuronal Activation from Single-Cell and Spatial Transcriptomic Data [article]

Ethan Bahl, Snehajyoti Chatterjee, Muhammad Elsadany, Yann Vanrobaeys, Li-Chun Lin, K Peter Giese, Ted Abel, Jacob Michaelson
2022 bioRxiv   pre-print
Neuronal activity-dependent transcription directs molecular processes that regulate synaptic plasticity, brain circuit development, behavioral adaptation, and long-term memory. Single cell RNA-sequencing technologies (scRNAseq) are rapidly developing and allow for the interrogation of activity-dependent transcription at cellular resolution. Here, we present NEUROeSTIMator, a deep learning model that integrates signals of activation distributed throughout the broader transcriptome to estimate
more » ... ronal activation in a way that is robust against differences in species, cell type, and brain region. We demonstrate this method's ability to accurately detect neuronal activity in previously published single cell and time course studies of activity-induced gene expression. Further, using spatial transcriptomic techniques, we demonstrate the model's ability to identify patterns of learning-induced activation. In conclusion, NEUROeSTIMator is a powerful and broadly applicable tool for measuring neuronal activation, whether as a critical covariate or a primary readout of interest.
doi:10.1101/2022.04.08.487573 fatcat:tdyoemq4tnbqdnrshvadwkwt5a

Clinical autism subscales have common genetic liability that is heritable, pleiotropic, and generalizable to the general population [article]

Taylor R Thomas, Tanner Koomar, Lucas Casten, Ashton Tener, Ethan Bahl, Jacob J Michaelson
2021 medRxiv   pre-print
The complexity of autism's phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is unclear whether clinical autism instruments such as the Social Communication Questionnaire (SCQ), Repetitive Behaviors Scale-Revised (RBS-R), and Developmental Coordination Disorder Questionnaire (DCDQ) are more genetically informative than case-control. We employed the SPARK autism cohort (N = 6,449) to illuminate the genetic etiology of these twelve
more » ... es. In comparison to the heritability of autism case-control at 0.12, the RBS-R subscales were increased, ranging from 0.18 to 0.30 (all p < 0.05). Heritability of the DCDQ subscales ranged from 0.07 to 0.09 and the SCQ subscales from 0 to 0.09 (all p > 0.05). We also found evidence for genetic correlations among the RBS-R, SCQ, and DCDQ. GWAS followed by projection of polygenic scores (PGS) into ABCD revealed significant associations with CBCL social and thought problems, while the autism case-control PGS did not significantly associate. In phenotypic correlation analyses, the autism case-control PGS did not predict the subscales in SPARK, and sex-stratified correlations showed no effect in males and a surprising negative effect in females. Notably, other PGS did predict the subscales, with the strongest being educational attainment negatively correlated, while ADHD and major depression were positively correlated. Overall, our analyses suggest that clinical subscales are more genetically powerful than case-control, and that of the three instruments investigated, the RBS-R shows the greatest evidence of common genetic signal in both autistic and general population samples.
doi:10.1101/2021.08.30.21262845 fatcat:u7uhglciczaild5rhzux25mftq

Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors

Michael Lutter, Ethan Bahl, Claire Hannah, Dabney Hofammann, Summer Acevedo, Huxing Cui, Carrie J. McAdams, Jacob J. Michaelson, Hubert Vaudry
2017 PLoS ONE  
Objective Eating disorders develop through a combination of genetic vulnerability and environmental stress, however the genetic basis of this risk is unknown. Methods To understand the genetic basis of this risk, we performed whole exome sequencing on 93 unrelated individuals with eating disorders (38 restricted-eating and 55 binge-eating) to identify novel damaging variants. Candidate genes with an excessive burden of predicted damaging variants were then prioritized based upon an unbiased,
more » ... a-driven bioinformatic analysis. One top candidate pathway was empirically tested for therapeutic potential in a mouse model of binge-like eating. Results An excessive burden of novel damaging variants was identified in 186 genes in the restricted-eating group and 245 genes in the binge-eating group. This list is significantly enriched (OR = 4.6, p<0.0001) for genes involved in neuropeptide/neurotrophic pathways implicated in appetite regulation, including neurotensin-, glucagon-like peptide 1-and BDNF-signaling. Administration of the glucagon-like peptide 1 receptor agonist exendin-4 significantly reduced food intake in a mouse model of 'binge-like' eating. Conclusions These findings implicate ultra-rare and novel damaging variants in neuropeptide/neurotropic factor signaling pathways in the development of eating disorder behaviors and identify glucagon-like peptide 1-receptor agonists as a potential treatment for binge eating.
doi:10.1371/journal.pone.0181556 pmid:28846695 pmcid:PMC5573281 fatcat:hl3ars6xevg4bbfwaxjnvbufum

The CBP KIX domain regulates long-term memory and circadian activity [article]

Snehajyoti Chatterjee, Christopher C Angelakos, Ethan Bahl, Joshua D Hawk, Marie E Gaine, Shane G Poplawski, Anne Schneider-Anthony, Manish Yadav, Giulia S Porcari, Jean-Christophe Cassel, K. Peter Giese, Jacob J Michaelson (+3 others)
2020 bioRxiv   pre-print
CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors. Identifying specific domain functions for multi-action proteins is essential to understand processes necessary for healthy living including cognitive function and a robust circadian clock. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with
more » ... ons that prevent phospho-CREB (Ser133) binding. We found that CBPKIX/KIX mice were impaired in long-term, but not short-term spatial memory in the Morris water maze. Using an unbiased analysis of gene expression after training for hippocampus-dependent memory, we discovered dysregulation of CREB and CLOCK target genes and downregulation of circadian genes in CBPKIX/KIX mice. With our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark, although phase resetting to light was comparable to wildtype. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.
doi:10.1101/2020.06.08.130815 fatcat:5h3njbpuazf25jb3iw3hcegn5y

Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts [article]

Brooke G. McKenna, Yongchao Huang, Kévin Vervier, Dabney Hofammann, Mary Cafferata, Seima Al-Momani, Florencia Lowenthal, Angela Zhang, Jin Young Koh, Savantha Thenuwara, Leo Brueggeman, Ethan Bahl (+6 others)
2020 medRxiv   pre-print
Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is one paradigm for investigating this male bias, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been inconsistent and the relationships between androgen exposure and behavior remains unclear. Here, we measured both digit ratio
more » ... culinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N=763) and compared these proxies of androgen exposure to clinical and parent-reported features. We found that FLM was significantly associated with diagnostic burden in males and females (Z=3.1, p=0.002), while DRM was not (Z=-1.6, p=0.11). When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior (Z=3.1, p=0.002; Z=2.1, p=0.03, respectively), also in a sex-invariant manner. Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels (t=2.0, p=0.04), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels (t=-2.3, p=0.02). Finally, using the SPARK cohort (N=9,419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning (t=-2.5, p=0.01, and t=4.5, p=6e-6 for testosterone and SHBG, respectively). Remarkably, these quantitative sex effects on social functioning were on the same order of magnitude as the effect of binary sex itself (binary male:-0.23 +/- 0.05; testosterone:-0.07 +/- 0.026 per SD of PRS; SHBG: 0.11 +/- 0.026 per SD of PRS). These findings and their replication in the large SPARK cohort lend strong support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females.
doi:10.1101/2020.08.03.20155671 fatcat:iz3g6yy4r5hgnasae5ezvpnvyi

The CBP KIX domain regulates long-term memory and circadian activity

Snehajyoti Chatterjee, Christopher C Angelakos, Ethan Bahl, Joshua D Hawk, Marie E Gaine, Shane G Poplawski, Anne Schneider-Anthony, Manish Yadav, Giulia S Porcari, Jean-Christophe Cassel, K Peter Giese, Jacob J Michaelson (+3 others)
2020 BMC Biology  
CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors potentially affecting expression of thousands of genes. Identifying specific domain functions for multi-domain proteins is essential to understand processes such as cognitive function and circadian clocks. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX
more » ... mice with mutations that prevent phospho-CREB (Ser133) binding. We found that CBPKIX/KIX mice were impaired in long-term memory, but not learning acquisition or short-term memory for the Morris water maze. Using an unbiased analysis of gene expression in the dorsal hippocampus after training in the Morris water maze or contextual fear conditioning, we discovered dysregulation of CREB, CLOCK, and BMAL1 target genes and downregulation of circadian genes in CBPKIX/KIX mice. Given our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity and phase resetting in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark. Interestingly, CBPKIX/KIX mice displayed phase delays and advances in response to photic stimulation comparable to wildtype littermates. Thus, this work delineates site-specific regulation of the circadian clock by a multi-domain protein. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.
doi:10.1186/s12915-020-00886-1 pmid:33121486 pmcid:PMC7597000 fatcat:l3avakvri5grpbrjxbmeuipbgu

Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts

Brooke G. McKenna, Yongchao Huang, Kévin Vervier, Dabney Hofammann, Mary Cafferata, Seima Al-Momani, Florencia Lowenthal, Angela Zhang, Jin-Young Koh, Savantha Thenuwara, Leo Brueggeman, Ethan Bahl (+6 others)
2021 Molecular Autism  
Background Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain
more » ... lear. Methods Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores. Results We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all $$p<0.05$$ p < 0.05 ), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ($$\rho =0.19$$ ρ = 0.19 , $$p=0.004$$ p = 0.004 ; $$\rho =0.2$$ ρ = 0.2 , $$p=0.004$$ p = 0.004 , respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ($$t=4.0$$ t = 4.0 , $$p=8.8\times 10^{-5}$$ p = 8.8 × 10 - 5 ), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ($$t=-3.3$$ t = - 3.3 , $$p=0.001$$ p = 0.001 ). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ($$t=-2.3$$ t = - 2.3 , $$p=0.02$$ p = 0.02 , and $$t=4.2$$ t = 4.2 , $$p={3.2\times 10^{-5}}$$ p = 3.2 × 10 - 5 for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: $$-0.22\pm 0.05$$ - 0.22 ± 0.05 ; testosterone: $$-0.35\pm 0.15$$ - 0.35 ± 0.15 from 0.1%-ile to 99.9%-ile; SHBG: $$0.64\pm 0.15$$ 0.64 ± 0.15 from 0.1%-ile to 99.9%-ile). Limitations In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules. Conclusions These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females.
doi:10.1186/s13229-021-00450-w pmid:34108004 pmcid:PMC8190870 fatcat:upvvlclmonczfnvaarm4ddjkji

SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness [article]

Kizzmekia S. Corbett, Darin Edwards, Sarah R. Leist, Olubukola M. Abiona, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, Sunny Himansu, Alexandra Schafer, Cynthia T. Ziwawo, Anthony T. DiPiazza, Kenneth H. Dinnon, Sayda M. Elbashir (+47 others)
2020 biorxiv/medrxiv  
A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both
more » ... tent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.
doi:10.1101/2020.06.11.145920 pmid:32577634 pmcid:PMC7301911 fatcat:hq4p3gvlrrhhzkuw4ntjqmqcrm

Page 495 of Chemistry and Chemical Industry Vol. 38, Issue 9 [page]

1985 Chemistry and Chemical Industry  
[PdCl.] dhO120K iz BITS BTeEDh (BAHL) OBRES-AE KR-RREE 2B19.  ...  @HLMIISYVA=VYRBROGKLEAHKFHER (RR ALAZEA) Ol RFE ¢ AAS > REFS AA 2B20. 7ZOL=~bUYVBRODPEFHER (RPAH) O DEBT +> SHB—-R ER 2B21. 1,2-Bis (diphenyl phosphino) ethane D#i( I ) #4 Me hE GRAM - RAM) HR BAC COR  ... 

Acknowledgments [chapter]

2019 Girls Will Be Boys  
I am particularly grateful to Jason Bahling, who formatted, equalized, and arranged the images on a short deadline.  ...  Campwala, Joel Chaidez, Maria Gould, Ethan Guillen, Luke Habberstad, Jon Lehman, Emily Teitsworth, and Nadia Sussman for pulling me back into the world outside of higher education.  ... 
doi:10.36019/9780813574851-001 fatcat:vseqxylykzgmdlidk6uyxgymlm

Page 11 of The New England Journal of Medicine Vol. 186, Issue 6 [page]

1922 The New England Journal of Medicine  
Coon, William Bahl ...<css Dept. of Health. 1912 Cooney, Margaret Blanche..Maverhill. 67 Winter St. 1909 Cooney, Michael Edward..Northampton. 16 Center St. iz Cooper, Alden Vernon.....  ...  Crandall, Walter Midkiff..Fort Ethan Allen, Vt. Crandell, Arthur Richmond.Taunton. 48 Church Green. Crandon, Le Roi Goddard..Boston. | 366 Commonwealth Av. 1906 Crane, Bayard Taylor.....Rutland.  ... 

Phytochemical screening and evaluation of Berginia ligulata root extract for antimicrobial activity

Rishi Kumar Shukla
2013 Environment conservation journal  
Chemical inve shown the presence of β-sitosterol, β glucoside, bergenin (Bahl et al., 197 haanbhed, antimicrobial activity, phytochemical scree stem of medicine lacked adequate icularly in light (WHO  ...  Quality Control rials, WHO, Geneva,. of Berginia ligulata root extract Extracts ether Diethyl ether Acetone Ethan + + + + + - + + + - + + - + + - + + - - + - - + Berginia  ... 
doi:10.36953/ecj.2013.14317 fatcat:pt6wvi46inboxp7m7usjedgnta
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