Biology subjects

Poudel, R.

Publications and source records attributed to Poudel, R..

10 recordsLinked to original sources

bioRxiv2023

Meta-analytic decoding of the cortical gradient of functional connectivity

Macroscale gradients have emerged as a central principle for understanding functional brain organization. Previous studies have demonstrated that a principal gradient of connectivity in the human brain exists, with unimodal primary sensorimotor regions situated at one end and transmodal regions associated with the default mode network and representative of abstract functioning at the other. The functional significance and interpretation of macroscale gradients remains a central topic of discussion in the neuroimaging community, with some studies demonstrating that gradients may be described using meta-analytic functional decoding techniques. However, additional methodological development is necessary to fully leverage available meta-analytic methods and resources and quantitatively evaluate their relative performance. Here, we conducted a comprehensive series of analyses to investigate and improve the framework of data-driven, meta-analytic methods, thereby establishing a principled approach for gradient segmentation and functional decoding. We found that a two-segment solution determined by a k-means segmentation approach and an LDA-based meta-analysis combined with the NeuroQuery database was the optimal combination of methods for decoding functional connectivity gradients. Finally, we proposed a method for decoding additional components of the gradient decomposition. The current work aims to provide recommendations on best practices and flexible methods for gradient-based functional decoding of fMRI data.

neuroscience↗

bioRxiv2022

An Arrayed Transposon Library of Ruegeria pomeroyi DSS-3

The ability to construct defined genetic mutations in many bacteria is difficult and limited. Transposon mutagenesis is often highly efficient, but is not site specific, thus selections are often needed to identify mutants of interest. The construction of arrayed mutant libraries would help to fill this need, though these libraries are costly and time consuming. To enable easier construction of arrayed libraries we developed a workflow and methodology using a hierarchical barcoding scheme to identify mutants within a multiwell plate. We applied this method to the marine Alphaproteobacterium Ruegeria pomeroyi DSS-3 and created a library with over 2,800 disrupted genes.

microbiology↗

bioRxiv2021

GuideMaker: Software to design CRISPR-Cas guide RNA pools in non-model genomes

BackgroundCRISPR-Cas systems have expanded the possibilities for gene editing in bacteria and eukaryotes. There are many excellent tools for designing the CRISPR-Cas guide RNAs for model organisms with standard Cas enzymes. GuideMaker is intended as a fast and easy-to-use design tool for atypical projects with 1) non-standard Cas enzymes, 2) non-model organisms, or 3) projects that need to design a panel of guide RNAs (gRNA) for genome-wide screens. FindingsGuideMaker can rapidly design gRNAs for gene targets across the genome from a degenerate protospacer adjacent motif (PAM) and a GenBank file. The tool applies Hierarchical Navigable Small World (HNSW) graphs to speed up the comparison of guide RNAs. This allows the user to design gRNAs targeting all genes in a typical bacterial genome in about 1-2 minutes. ConclusionsGuidemaker enables the rapid design of genome-wide gRNA for any CRISPR-Cas enzyme in non-model organisms. While GuideMaker is designed with prokaryotic genomes in mind, it can efficiently process smaller eukaryotic genomes as well. GuideMaker is available as command-line software, a stand-alone web application, and a tool in the CyCverse Discovery Environment. All versions are available under a Creative Commons CC0 1.0 Universal Public Domain Dedication.

bioinformatics↗

bioRxiv2020

Exposure to Airborne Bacteria Depends upon Vertical Stratification and Vegetation Complexity

Exposure to biodiverse aerobiomes may support human health, but it is unclear which ecological factors influence exposure. Few studies have investigated near-surface green space aerobiome dynamics, and no studies have investigated aerobiome vertical stratification in different green spaces. We used columnar sampling and next generation sequencing of the bacterial 16S rRNA gene, combined with geospatial and network analyses to investigate aerobiome spatio-compositional dynamics. We show a strong effect of habitat on bacterial diversity and network complexity. We observed aerobiome vertical stratification and network complexity that was contingent on habitat type. Tree density, closer proximity, and canopy coverage associated with greater aerobiome alpha diversity. Grassland aerobiomes exhibited greater proportions of putative pathogens compared to scrub, and also stratified vertically. We provide new insights into the urban ecosystem with potential importance for public health, whereby the possibility of differential aerobiome exposures appears to depend on habitat type and height in the airspace.

ecology↗

bioRxiv2020

The cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug-related and natural-reward stimuli

BackgroundThe cue-reactivity paradigm is a widely adopted neuroimaging probe engendering brain activity linked with attentional, affective, and reward processes following presentation of appetitive stimuli. Given the multiple mental operations invoked, we sought to decompose cue-related brain activity into constituent components employing emergent meta-analytic techniques when considering drug and natural reward-related cues. MethodsWe conducted multiple coordinate-based meta-analyses delineating common and distinct brain activity convergence across cue-reactivity studies (N=196 articles) involving drug (n=133) or natural reward-related (n=63) visual stimuli. Subsequently, we characterized the connectivity profiles of identified brain regions by using them as seeds in task-independent and task-dependent functional connectivity analyses. Using hierarchical clustering on these connectivity profiles, we grouped cue-related brain regions into subnetworks. Functional decoding was then employed to characterize mental operations linked with each subnetwork. ResultsAcross all studies, pooled activity convergence was observed in the striatum, amygdala, thalamus, cingulate, insula, and multiple frontal, parietal, and occipital regions. Drug-distinct convergence (drug>natural) was observed notably in the posterior cingulate cortex (PCC), dorsolateral prefrontal cortex (dlPFC), and temporal and parietal regions, whereas distinct natural reward convergence (natural>drug) was observed in thalamic, insular, orbitofrontal, and occipital regions. Hierarchical clustering using each regions connectivity profiles identified six subnetworks, involving: 1) occipital and thalamic (lateral geniculate nucleus) regions functionally linked with early visual processing, 2) occipital-temporal regions associated with higher level visual association, 3) parietal-frontal regions linked with cognitive control mechanisms, 4) posterior and ventral insula as well as anterior cingulate cortex (ACC) functionally linked with salient event detection, 5) nucleus accumbens, PCC, precuneus, ACC, and thalamus (mediodorsal) associated with subjective valuation, and 6) bilateral amygdalae, orbitofrontal, and dorsal insula regions linked with affective processes. ConclusionsThese outcomes suggest multifaceted brain activity during the cue-reactivity paradigm can be decomposed into more elemental processes and indicate that while drugs of abuse usurp the brains natural reward processing system, some regions appear distinctly related to drug cue-reactivity (e.g., PCC, dlPFC).

neuroscience↗

bioRxiv2020

Common and distinct brain activity associated with risky and ambiguous decision-making

Two often-studied forms of uncertain decision-making (DM) are risky-DM (outcome probabilities known) and ambiguous-DM (outcome probabilities unknown). While DM in general is associated with activation of several brain regions, previous neuroimaging efforts suggest a dissociation between activity linked with risky and ambiguous choices. However, the common and distinct neurobiological correlates associated with risky- and ambiguous-DM, as well as their specificity when compared to perceptual-DM (as a control condition), remains to be clarified. We conducted multiple meta-analyses on neuroimaging results from 151 studies to characterize common and domain-specific brain activity during risky-, ambiguous-, and perceptual-DM. When considering all DM tasks, convergent activity was observed in brain regions considered to be consituents of the canonical salience, valuation, and executive control networks. When considering subgroups of studies, risky-DM (vs. perceptual-DM) was linked with convergent activity in the striatum and anterior cingulate cortex (ACC), regions associated with reward-related processes (determined by objective functional decoding). When considering ambiguous-DM (vs. perceptual-DM), activity convergence was observed in the lateral prefrontal cortex and insula, regions implicated in affectively-neutral mental processes (e.g., cognitive control and behavioral responding; determined by functional decoding). An exploratory meta-analysis comparing brain activity between substance users and non-users during risky-DM identified reduced convergent activity among users in the striatum, cingulate, and thalamus. Taken together, these findings suggest a dissociation of brain regions linked with risky- and ambiguous-DM reflecting possible differential functionality and highlight brain alterations potentially contributing to poor decision-making in the context of substance use disorders.

neuroscience↗

bioRxiv2019

Integration of system phenotypes in microbiome networks to identify candidate synthetic communities: a study of the grafted tomato rhizobiome

Understanding factors influencing microbial interactions, and designing methods to identify key taxa, are complex challenges for achieving microbiome-based agriculture. Here we study how grafting and the choice of rootstock influence root-associated fungal communities in a grafted tomato system. We studied three tomato rootstocks (BHN589, RST-04-106 and Maxifort) grafted to a BHN589 scion and profiled the fungal communities in the endosphere and rhizosphere by sequencing the Internal Transcribed Spacer (ITS2). The data provided evidence for a rootstock effect (explaining ~2% of the total captured variation, p < 0.01) on the fungal community. Moreover, the most productive rootstock, Maxifort, supported greater fungal species richness than the other rootstocks or controls. We then constructed a phenotype-OTU network analysis (PhONA) using an integrated machine learning and network analysis approach based on sequence-based fungal Operational Taxonomic Units (OTUs) and associated tomato yield data. PhONA provides a graphical framework to select a testable and manageable number of OTUs to support microbiome-enhanced agriculture. We identified differentially abundant OTUs specific to each rootstock in both endosphere and rhizosphere compartments. Subsequent analyses using PhONA identified OTUs that were directly associated with tomato fruit yield, and others that were indirectly linked to yield through their links to these OTUs. Fungal OTUs that are directly or indirectly linked with tomato yield may represent candidates for synthetic communities to be explored in agricultural systems. IMPORTANCEThe realized benefits of microbiome analyses for plant health and disease management are often limited by the lack of methods to select manageable and testable synthetic microbiomes. We evaluated the composition and diversity of root-associated fungal communities from grafted tomatoes. We then constructed a phenotype-OTU network analysis (PhONA) using these linear and network models. By incorporating yield data in the network, PhONA identified OTUs that were directly predictive of tomato yield, and others that were indirectly linked to yield through their links to these OTUs. Follow-up functional studies of taxa associated with effective rootstocks, identified using approaches like PhONA, could support the design of synthetic fungal communities for microbiome-based crop production and disease management. The PhONA framework is flexible for incorporation of other phenotypic data and the underlying models can readily be generalized to accommodate other microbiome or other omics data.

ecology↗

bioRxiv2019

Meta-analytic clustering dissociates brain activity and behavior profiles across reward processing paradigms

Reward learning is a ubiquitous cognitive mechanism guiding adaptive choices and behaviors, and when impaired, can lead to considerable mental health consequences. Reward-related functional neuroimaging studies have begun to implicate networks of brain regions essential for processing various peripheral influences (e.g., risk, subjective preference, delay, social context) involved in the multifaceted reward processing construct. To provide a more complete neurocognitive perspective on reward processing that synthesizes findings across the literature while also appreciating these peripheral influences, we utilized emerging meta-analytic techniques to elucidate brain regions, and in turn networks, consistently engaged in distinct aspects of reward processing. Using a data-driven, meta-analytic, k-means clustering approach, we dissociated seven meta-analytic groupings (MAGs) of neuroimaging results (i.e., brain activity maps) from 749 experimental contrasts across 176 reward processing studies involving 13,358 healthy participants. We then performed an exploratory functional decoding approach to gain insight into the putative functions associated with each MAG. We identified a seven-MAG clustering solution which represented dissociable patterns of convergent brain activity across reward processing tasks. Additionally, our functional decoding analyses revealed that each of these MAGs mapped onto discrete behavior profiles that suggested specialized roles in predicting value (MAG-1 & MAG-2) and processing a variety of emotional (MAG-3), external (MAG-4 & MAG-5), and internal (MAG-6 & MAG-7) influences across reward processing paradigms. These findings support and extend aspects of well-accepted reward learning theories and highlight large-scale brain network activity associated with distinct aspects of reward processing.

neuroscience↗

bioRxiv2019

Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder

Although tobacco use disorder is linked with functional alterations in the striatum, anterior cingulate cortex (ACC), and insula, preclinical evidence also implicates the habenula as a contributor to negative reinforcement mechanisms maintaining nicotine use. The habenula is a small and understudied epithalamic nucleus involved in reward and aversive processing that is hypothesized to be hyperactive during nicotine withdrawal thereby contributing to anhedonia. In a pharmacologic fMRI study involving administration of nicotine and varenicline, two relatively efficacious cessation aids, we utilized a positive and negative performance feedback task previously shown to differentially activate the striatum and habenula. By administering these nicotinic drugs (vs. placebos) to both overnight abstinent smokers (n=24) and nonsmokers (n=20), we delineated feedback-related functional alterations both as a function of a chronic smoking history (trait: smokers vs. nonsmokers) and as a function of drug administration (state: nicotine, varenicline). We observed that smokers showed less ventral striatal responsivity to positive feedback, an alteration not mitigated by drug administration, but rather correlated with higher trait-level addiction severity among smokers and elevated self-reported negative affect across all participants. Conversely, nicotine administration reduced habenula activity following both positive and negative feedback among abstinent smokers, but not nonsmokers; greater habenula activity correlated with elevated abstinence-induced, state-level tobacco craving among smokers and elevated social anhedonia across all participants. These outcomes highlight a dissociation between neurobiological processes linked with the trait of dependence severity and with the state of acute nicotine withdrawal. Interventions simultaneously targeting both aspects may improve currently poor cessation outcomes.\n\nOne-sentence teaserIn a pharmacological fMRI study, e dissociate brain alterations in the habenula linked with nicotine withdrawal and striatal alterations linked with addiction.

neuroscience↗

bioRxiv2018

Rootstocks shape the rhizobiome: Rhizosphere and endosphere bacterial communities in the grafted tomato system

Root-associated microbes are critical to plant health and performance, although understanding of the factors that structure these microbial communities and theory to predict microbial assemblages are still limited. Here we use a grafted tomato system to study the effects of rootstock genotypes and grafting in endosphere and rhizosphere microbiomes that were evaluated by sequencing 16S rRNA. We compared the microbiomes of nongrafted tomato cultivar BHN589, selfgrafted BHN589, and BHN589 grafted to Maxifort or RST-04-106 hybrid rootstocks. OTU-based bacterial diversity was greater in Maxifort compared to nongraft controls, whereas bacterial diversity in the controls (selfgraft and nongraft) and the other rootstock (RST-04-106) was similar. Grafting itself did not affect bacterial diversity; diversity in the selfgraft was similar to the nongraft. Bacterial diversity was higher in the rhizosphere than in the endosphere for all treatments. However, despite the lower overall diversity, there was a greater number of differentially abundant OTUs (DAOTUs) in the endosphere, with the greatest number of DAOTUs associated with Maxifort. In a PERMANOVA analysis, there was evidence for an effect of rootstock genotype on bacterial communities. The endosphere-rhizosphere compartment and study site explained a high percentage of the differences among bacterial communities. Further analyses identified OTUs responsive to rootstock genotypes in both the endosphere and the rhizosphere. Our findings highlight the effects of rootstocks on bacterial diversity and composition. The influence of rootstock and plant compartment on microbial communities indicates opportunities for the development of designer communities and microbiome-based breeding to improve future crop production.\n\nImportanceUnderstanding factors that control microbial communities is essential for designing and supporting microbiome-based agriculture. In this study, we used a grafted tomato system to study the effect of rootstock genotypes and grafting on bacterial communities colonizing the endosphere and the rhizosphere. Comparing the bacterial communities in control treatments (nongraft and selfgraft plants) with the hybrid rootstocks used by farmers, we evaluated the effect of rootstocks on overall bacterial diversity and composition. These findings indicate the potential for using plant genotype to indirectly select bacterial taxa. In addition, we identify taxa responsive to each rootstock treatments, which may represent candidate taxa useful for biocontrol and in biofertilizers.

microbiology↗