Biology subjects

Truong, D.

Publications and source records attributed to Truong, D..

8 recordsLinked to original sources

bioRxiv2024

HBN-EEG: The FAIR implementation of the Healthy Brain Network (HBN) electroencephalography dataset

The Child Mind Institute (CMI) Healthy Brain Network (HBN) project has recorded phenotypic, behavioral, and neuroimaging data from [~]5,000 children and young adults between the ages of 5 and 21. Here, we present HBN-EEG, the "analysis-ready" data from its high-density (128-channel) electroencephalographic (EEG) recording sessions formatted as Brain Imaging Data Structure (BIDS) datasets. HBN-EEG also includes behavioral and task-condition events annotated using Hierarchical Event Descriptors (HED), making the datasets analysis-ready for many purposes without forensic search for unreported details. We also ensured data consistency and event integrity and marked inconsistencies. HBN-EEG sessions include six tasks, three with no participant behavioral input (passive tasks) and three including button press responses following task instructions (active tasks). Openly available participant information includes age, gender, and four psychopathology dimensions (internalizing, externalizing, attention, and p-factor) derived from a bifactor model of questionnaire data. Currently, HBN-EEG data from more than 2,600 participants is freely available on NEMAR (nemar.org) and OpenNeuro in the form of nine dataset releases, with further dataset releases to follow.

neuroscience↗

bioRxiv2021

New auranofin analogs with antibacterial properties against Burkholderia clinical isolates

Bacteria of the genus Burkholderia include pathogenic Burkholderia mallei, Burkholderia pseudomallei and the Burkholderia cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment of infections difficult. Bcc affects individuals with cystic fibrosis (CF) and the species B. cenocepacia is associated with one of the worst clinical outcomes. Following the repurposing of auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized auranofin analogs with activity against Gram-negatives. In this work, we show that two auranofin analogs, MS-40S and MS-40, have antibiotic activity against Burkholderia clinical isolates. The compounds are bactericidal against B. cenocepacia and kill stationary-phase cells and persisters without selecting for multistep resistance. Caenorhabditis elegans and Galleria mellonella tolerated high concentrations of MS-40S and MS-40, demonstrating that these compounds have low toxicity in these model organisms. In summary, we show that MS-40 and MS-40S have the potential to be effective therapeutic options to treat Burkholderia infections.

microbiology↗

bioRxiv2021

Distinct Hippocampal Neuronal Reactions Reveal Different Neuronal Codes for Memory Generalization

To survive in an ever-changing world we need to learn and memorize associations of environmental stimuli and generalize them to new situations. Both memory and generalization critically rely on the hippocampus, but it is unclear how hippocampal neuronal activities represent memory and generalization, and if a conserved hippocampal mechanism serves these functions. Here we compared neuronal activities in hippocampal CA1 region of two sub-strains of the widely used C57BL/6 mice, C57BL/6J (B6J) and C57BL/6NCrl (B6NCrl), in contextual fear conditioning. Both sub-strains learnt well but differed in freezing and generalization. They displayed distinct early-late bi-phasic reactions to the unconditioned stimulus. While in both sub-strains the neurons showing late-phase reactions were preferentially engaged in memory representation, the neuronal activity feature that correlated with generalization level differed in the two sub-strains: in B6NCrl, these neurons activity level during learning negatively correlated with the generalization level; in B6J, functional coupling of these late-phase neurons with other neurons positively correlated with the generalization level. We further found that the distinct neuronal reactions were accompanied by distinct GABAb receptor-mediated inhibition but not by differences in the major synaptic inputs or neuronal excitability of the CA1. Therefore, this comparative study reveals two signature neuronal activity features in learning that can predict generalization levels. The results also demonstrate that differences in hippocampal network properties lead to diverse hippocampal mechanisms in memory encoding and generalization.

neuroscience↗

bioRxiv2021

Capturing the nature of events and event context using Hierarchical Event Descriptors (HED)

Event-related data analysis plays a central role in EEG and MEG (MEEG) and other neuroimaging modalities such as fMRI. Choices about which events to report and how to annotate their full natures significantly influence the value, reliability, and reproducibility of neuroimaging datasets for further analysis and meta- or mega-analysis. A powerful annotation strategy using the new third-generation formulation of the Hierarchical Event Descriptors (HED) framework and tools (hedtags.org) combines robust event description with details of experiment design and metadata in a human-readable as well as machine-actionable form, making event annotation relevant to the full range of neuroimaging and other time series data. This paper considers the event design and annotation process using as a case study the well-known multi-subject, multimodal dataset of Wakeman and Henson made available by its authors as a Brain Imaging Data Structure (BIDS) dataset (bids.neuroimaging.io). We propose a set of best practices and guidelines for event annotation integrated in a natural way into the BIDS metadata file architecture, examine the impact of event design decisions, and provide a working example of organizing events in MEEG and other neuroimaging data. We demonstrate how annotations using HED can document events occurring during neuroimaging experiments as well as their interrelationships, providing machine-actionable annotation enabling automated within- and across-experiment analysis and comparisons. We discuss the evolution of HED software tools and have made an accompanying HED-annotated BIDS-formatted edition of the MEEG data of the Wakeman and Henson dataset (openneuro.org, ds003645).

neuroscience↗

bioRxiv2020

A non-canonical Hippo pathway regulates spindle disassembly and cytokinesis during meiosis in Saccharomyces cerevisiae

Meiosis in the budding yeast Saccharomyces cerevisiae is used to create haploid yeast spores from a diploid mother cell. During meiosis II, cytokinesis occurs by closure of the prospore membrane, a membrane that initiates at the spindle pole body and grows to surround each of the haploid meiotic products. Timely prospore membrane closure requires SPS1, which encodes a STE20-family GCKIII kinase. To identify genes that may activate SPS1, we utilized a histone phosphorylation defect of sps1 mutants to screen for genes with a similar phenotype and found that cdc15 shared this phenotype. CDC15 encodes a Hippo-like kinase that is part of the mitotic exit network. We find that Sps1 complexes with Cdc15, that Sps1 phosphorylation requires Cdc15, and that CDC15 is also required for timely prospore membrane closure. We also find that SPS1, like CDC15, is required for meiosis II spindle disassembly and sustained anaphase II release of Cdc14 in meiosis. However, the NDR-kinase complex encoded by DBF2/DBF20 MOB1 which functions downstream of CDC15 in mitotic cells, does not appear to play a role in spindle disassembly, timely prospore membrane closure, or sustained anaphase II Cdc14 release. Taken together, our results suggest that the mitotic exit network is rewired for exit from meiosis II, such that SPS1 replaces the NDR-kinase complex downstream of CDC15.

cell biology↗

bioRxiv2019

Effect of READ1 on latent profiles of reading disability and comorbid attention and language learning disability subtypes

Recent studies of co-occurring reading disability (RD) and attention deficit/hyperactivity disorder (ADHD), and co-occurring RD and language learning disability (LLD), support a core disability plus co-occurrence model focused on language and attention. Genetic factors have been associated with poor reading performance. However, little is known about whether different genetic variants independently contribute to RD co-occurrence subtypes. We aimed to identify subgroups of struggling readers using a latent profile analysis (LPA) in a sample of 1,432 Hispanic American and African American youth. RD classes were then tested for association with variants of READ1, a regulatory element within the candidate RD risk gene, DCDC2. Six groups were identified in the LPA using RD designation as a known-class variable. The three RD classes identified groups of subjects with neurocognitive profiles representing RD+ADHD, specific phonological deficit RD, and RD+LLD. Genetic associations across RD subtypes were investigated against functional groupings of READ1. The RU1-1 group of READ1 alleles was associated with RD cases that were marked by deficits in both processing speed and attention (RD + ADHD). The DCDC2 microdeletion that encompasses READ1 was associated with RD cases showing a phonological deficit RD profile. These findings provide evidence for differential genetic contribution to RD subtypes, and that previously implicated genetic variants for RD may share an underlying genetic architecture across population groups for reading disability.

genetics↗

bioRxiv2017

Multivariate genome-wide association study of rapid automatized naming and rapid alternating stimulus in Hispanic and African American youth.

Reading disability is a complex neurodevelopmental disorder that is characterized by difficulties in reading despite educational opportunity and normal intelligence. Performance on rapid automatized naming (RAN) and rapid alternating stimulus (RAS) tests gives a reliable predictor of reading outcome. These tasks involve the integration of different neural and cognitive processes required in a mature reading brain. Most studies examining the genetic factors that contribute to RAN and RAS performance have focused on pedigree-based analyses in samples of European descent, with limited representation of groups with Hispanic or African ancestry. In the present study, we conducted a multivariate genome-wide association analysis to identify shared genetic factors that contribute to performance across RAN Objects, RAN Letters, and RAS Letters/Numbers in a sample of Hispanic and African American youth (n=1,331). We then tested whether these factors also contribute to variance in reading fluency and word reading. Genome-wide significant, pleiotropic, effects across RAN Objects, RAN Letters, and RAS Letters/Numbers were observed for SNPs located on chromosome 10q23.31 (rs1555839, multivariate association, p=2.23 x 10-8), which also showed significant association with reading fluency and word reading performance (p <0.001). Bioinformatic analysis of this region using epigenetic data from the NIH Roadmap Epigenomics Mapping Consortium indicates active transcription of the gene RNLS in the brain. Neuroimaging genetic analysis of fourteen cortical regions in an independent sample of typically developing children across multiple ethnicities (n=690) showed that rs1555839 was associated with variation in volume of the right inferior parietal cortex--a region of the brain that processes numerical information and has been implicated in reading disability. This study provides support for a novel locus on chromosome 10q23.31 associated with RAN, RAS, and reading-related performance.\n\nAUTHOR SUMMARYReading disability has a strong genetic component that is explained by multiple genes and genetic factors. The complex genetic architecture along with diverse cognitive impairments associated with reading disability, poses challenges in identifying novel genes and variants that confer risk. One method to begin parsing genetic and neurobiological mechanisms that contribute to reading disability is to take advantage of the high correlation among reading-related cognitive traits like rapid automatized naming (RAN) and rapid alternating stimulus (RAS) to identify shared genetic factors that contribute to common biological mechanisms. In the present study, we used a multivariate genome-wide analysis approach that identified a region of chromosome 10q23.31 associated with variation in RAN Objects, RAN Letters, and RAS Letters/Numbers performance in a sample of 1,331 Hispanic and African American youth in the Genes, Reading, and Dyslexia (GRaD) Study. Genetic variants in this region were also associated with reading fluency in GRaD, and differences in brain structures implicated in reading disability in a separate sample of 690 children. The gene, RNLS, is located within the implicated region of chromosome 10q23.31 and plays a role in breaking down a class of chemical messengers known to affect attention, learning, and memory in the brain. These findings provide a basis to inform our understanding of the biological basis of reading disability.

genetics↗

bioRxiv2017

tDCS changes in motor excitability are specific to orientation of current flow

Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the cephalic cortex result in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS. Here we test this idea by measuring changes in cortico-spinal excitability by Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP), following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus. Current flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces none-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is through to select different afferent pathways to M1. Our results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.\n\nHighlights O_LIDirection of current flow is important for tDCS after-effects.\nC_LIO_LItDCS modulates excitability between two electrodes.\nC_LIO_LItDCS differentially modulates PA and AP inputs into M1.\nC_LI\n\nAbbreviations\n\nFundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

neuroscience↗