Biology subjects

Carlson, J. M.

Publications and source records attributed to Carlson, J. M..

9 recordsLinked to original sources

bioRxiv2024

Large-scale statistical mapping of T-cell receptor β sequences to Human Leukocyte Antigens

T-cell receptors (TCRs) interacting with peptides presented by human leukocyte antigens (HLAs) are the foundation of the adaptive immune system but population-level analysis of TCR-HLA interactions is lacking. Here we statistically associate[~] 106 public TCRs to specific HLAs using the TCR{beta} repertoires sampled from 4,144 HLA-genotyped subjects. The TCRs we associate are specific to unique HLA allotypes, not allelic groups, and to the paired -{beta} heterodimer of class II HLAs though exceptions are observed. This specificity permits highly accurate imputation of 248 class I and II HLAs from the TCR{beta} repertoire. Notably, 45 HLA-DP and -DQ heterodimers lack associated TCRs because they likely arise from non-functional trans-complementation. The public class I and II HLA-associated TCRs we identify are primarily expressed on CD8+ and CD4+ memory T cells, respectively, which are responding to various common antigens. Our results recapitulate fundamental biology, provide insights into the functionality of HLAs and demonstrate the power and potential of population-level TCR repertoire sequencing.

immunology↗

bioRxiv2023

Evaluating the efficiency and accuracy of a commercial test for estimating genetic risk of bovine congestive heart failure

BackgroundBovine congestive heart failure (BCHF) is a significant cause of death in feedlot cattle in the Western Great Plains of North America. Single nucleotide polymorphisms (SNPs) in the ARRDC3 and NFIA genes have been previously associated with BCHF and genetic tests can classify animals by their risk for disease. Here, our aims were to evaluate the efficiency (genotypes obtained / samples tested) of a rapid DNA extraction kit and the accuracy of a 2-SNP assay for BCHF risk. MethodsSkin biopsies from 100 cattle were randomized and extracted with a proprietary rapid DNA extraction kit. A custom duplex, combined sequence amplification and nucleotide detection (C-SAND) assay was developed and run once on a commercial thermocycling machine to determine the genotypes. Both the rapidly extracted DNA and highly purified reference DNA from the same individuals were genotyped with the 2-SNP assay by operators blinded to the sample identity. The C-SAND genotypes were compared to known genotypes derived from a bead array assay. A priori standards for missing and incorrect genotypes were set at less than 3% and 1%, respectively. ResultsWhen using reference DNA samples, there were no missing and no incorrect C-SAND-derived genotypes, meeting the a priori standards. When DNA samples from the rapid extraction kit were used, genotypes were not determined for 5% of the samples. Of the 95 samples successfully extracted, there were 0% and 3% incorrect genotypes for the respective ARRDC3 and NFIA SNPs. ConclusionsThis duplex C-SAND assay and thermocycling machine combination were efficient and accurate when reference DNA was used, meeting a priori standards. Although the reduced efficiency of the rapid extraction kit can be overcome by repeated testing, increased genotype errors present an important issue. Despite these challenges, this rapid extraction kit and assay can be a reasonable tool for producers to select animals with reduced BCHF risk.

genetics↗

bioRxiv2021

A gut commensal niche regulates stable association of a multispecies microbiota

The intestines of animals are typically colonized by a complex, relatively stable microbiota that influences health and fitness, but the underlying mechanisms of colonization remain poorly understood. As a typical animal, the fruit fly, Drosophila melanogaster, is associated with a consistent set of commensal bacterial species, yet the reason for this consistency is unknown. Here, we use gnotobiotic flies, microscopy, and microbial pulse-chase protocols to show that a commensal niche exists within the proventriculus region of the Drosophila foregut that selectively binds bacteria with exquisite strain-level specificity. Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus physically remodels the niche to favor secondary colonization by Acetobacter. Our results provide a mechanistic framework for understanding the establishment and stability of an intestinal microbiome. One-Sentence SummaryA strain-specific set of bacteria inhabits a defined spatial region of the Drosophila gut that forms a commensal niche.

microbiology↗

bioRxiv2021

Stochastic microbiome assembly depends on context

Observational studies reveal substantial variability in microbiome composition across individuals. While some of this variability can be explained by external factors like environmental, dietary, and genetic differences between individuals, in this paper we show that for the model organism Drosophila melanogaster the process of microbiome assembly is inherently stochastic and contributes a baseline level of microbiome variability even among organisms that are identically reared, housed, and fed. In germ-free flies fed known combinations of bacterial species, we find that some species colonize more frequently than others even when fed at the same high concentration. We develop a new ecological technique that infers the presence of interactions between bacterial species based on their colonization odds in different contexts, requiring only presence/absence data from two-species experiments. We use a progressive sequence of probabilistic models, in which the colonization of each bacterial species is treated as an independent stochastic process, to reproduce the empirical distributions of colonization outcomes across experiments. We find that incorporating context-dependent interactions substantially improves the performance of the models. Stochastic, context-dependent microbiome assembly underlies clinical therapies like fecal microbiota transplantation and probiotic administration, and should inform the design of synthetic fecal transplants and dosing regimes. Significance StatementIndividuals are constantly exposed to microbial organisms that may or may not colonize their gut microbiome, and newborn individuals assemble their microbiomes through a number of these acquisition events. Since microbiome composition has been shown to influence host physiology, a mechanistic understanding of community assembly has potentially therapeutic applications. In this paper we study microbiome acquisition in a highly-controlled setting using germ-free fruit flies inoculated with specific bacterial species at known abundances. Our approach revealed that acquisition events are stochastic, and the colonization odds of different species in different contexts encode ecological information about interactions. These findings have consequences for microbiome-based therapies like fecal microbiota transplantation that attempt to modify a persons gut microbiome by deliberately introducing foreign microbes.

microbiology↗

bioRxiv2020

Dorsal anterior cingulate cortex intrinsic functional connectivity linked to electrocortical measures of error-monitoring

The error-related negativity (ERN) is a response-locked event-related potential, occurring approximately 50 ms following an erroneous response at frontocentral electrode sites. Source localization and functional magnetic resonance imaging (fMRI) research indicate that the ERN is likely generated by activity in the dorsal anterior cingulate cortex (dACC). The dACC is thought to be a part of a broader network of brain regions that collectively comprise an error-monitoring network. However, little is known about how intrinsic connectivity within the dACC-based error-monitoring network contributes to variability in ERN amplitude. The purpose of this study was to assess the relationship between dACC functional connectivity and ERN amplitude. In a sample of 53 highly trait-anxious individuals, the ERN was elicited in a flanker task and functional connectivity was assessed in a 10-minute resting-state fMRI scan. Results suggest that the strength of dACC seeded functional connectivity with the supplementary motor area is correlated with the {Delta}ERN (i.e., incorrect - correct responses) amplitude such that greater {Delta}ERN amplitude was accompanied by greater functional coupling between these regions. In addition to the dACC, exploratory analyses found that functional connectivity in the caudate, cerebellum, and a number of regions in the error-monitoring network were linked to variability in {Delta}ERN amplitude. In sum, ERN amplitude appears to be related to the strength of functional connectivity between error-monitoring and motor control regions of the brain.

neuroscience↗

bioRxiv2020

Attentional bias to threat and gray mater volume morphology in high anxious individuals

In a sample of highly anxious individuals, the relationship between gray matter volume brain morphology and attentional bias to threat was assessed. Participants performed a dot-probe task of attentional bias to threat and gray matter volume was acquired from whole brain structural T1-weighted MRI scans. The results replicate previous findings in unselected samples that elevated attentional bias to threat is linked to greater gray matter volume in the anterior cingulate cortex, middle frontal gyrus, and striatum. In addition, we provide novel evidence that elevated attentional bias to threat is associated with greater gray matter volume in the right posterior parietal cortex, cerebellum, and other distributed regions. Lastly, exploratory analyses provide initial evidence that distinct sub-regions of the right posterior parietal cortex may contribute to attentional bias in a sex-specific manner. Our results illuminate how differences in gray matter volume morphology relate to attentional bias to threat in anxious individuals. This knowledge could inform neurocognitive models of anxiety-related attentional bias to threat and targets of neuroplasticity in anxiety interventions such as attention bias modification.

neuroscience↗

bioRxiv2020

Variation and variability in Drosophila grooming behavior

Behavioral differences can be observed between species or populations (variation) or between individuals in a genetically similar population (variability). Here, we investigate genetic differences as a possible source of variation and variability in Drosophila grooming. Grooming confers survival and social benefits. Grooming features of five Drosophila species exposed to a dust irritant were analyzed. Aspects of grooming behavior, such as anterior to posterior progression, were conserved between and within species. However, significant differences in activity levels, proportion of time spent in different cleaning movements, and grooming syntax were identified between species. All species tested showed individual variability in the order and duration of action sequences. Genetic diversity was not found to correlate with grooming variability within a species: melanogaster flies bred to increase or decrease genetic heterogeneity exhibited similar variability in grooming syntax. Individual flies observed on consecutive days also showed grooming sequence variability. Standardization of sensory input using optogenetics reduced but did not eliminate this variability. In aggregate, these data suggest that sequence variability may be a conserved feature of grooming behavior itself. These results also demonstrate that large genetic differences result in distinguishable grooming phenotypes (variation), but that genetic heterogeneity within a population does not necessarily correspond to an increase in the range of grooming behavior (variability).

animal behavior and cognition↗

bioRxiv2020

Dynamic community detection reveals transient reorganization of functional brain networks across a female menstrual cycle

Sex steroid hormones have been shown to alter regional brain activity, but the extent to which they modulate connectivity within and between large-scale functional brain networks over time has yet to be characterized. Here, we applied dynamic community detection techniques to data from a highly sampled female with 30 consecutive days of brain imaging and venipuncture measurements to characterize changes in resting-state community structure across the menstrual cycle. Four stable functional communities were identified consisting of nodes from visual, default mode, frontal control, and somatomotor networks. Limbic, subcortical, and attention networks exhibited higher than expected levels of nodal flexibility, a hallmark of between-network integration and transient functional reorganization. The most striking reorganization occurred in a default mode subnetwork localized to regions of the prefrontal cortex, coincident with peaks in serum levels of estradiol, luteinizing hormone, and follicle stimulating hormone. Nodes from these regions exhibited strong intra-network increases in functional connectivity, leading to a split in the stable default mode core community and the transient formation of a new functional community. Probing the spatiotemporal basis of human brain-hormone interactions with dynamic community detection suggests that ovulation results in a temporary, localized patterns of brain network reorganization. Author SummarySex steroid hormones influence the central nervous system across multiple spatiotemporal scales. Estrogen and progesterone concentrations rise and fall throughout the menstrual cycle, but it remains poorly understood how day-to-day fluctuations in hormones shape human brain dynamics. Here, we assessed the structure and stability of resting-state brain network activity in concordance with serum hormone levels from a female who underwent fMRI and venipuncture for 30 consecutive days. Our results reveal that while network structure is largely stable over the menstrual cycle, there is temporary reorganization of several largescale functional brain networks during the ovulatory window. In particular, a default mode subnetwork exhibits increased connectivity with itself and with regions from temporoparietal and limbic networks, providing novel perspective into brain-hormone interactions.

neuroscience↗

bioRxiv2017

High-dimensional microbiome interactions shape host fitness

Gut bacteria can affect key aspects of host fitness, such as development, fecundity, and lifespan, while the host in turn shapes the gut microbiome. Microbiomes co-evolve with their hosts and have been implicated in host speciation. However, it is unclear to what extent individual species versus community interactions within the microbiome are linked to host fitness. Here we combinatorially dissect the natural microbiome of Drosophila melanogaster and reveal that interactions between bacteria shape host fitness through life history tradeoffs. We find that the same microbial interactions that shape host fitness also shape microbiome abundances, suggesting a potential evolutionary mechanism by which microbiome communities (rather than just individual species) may be intertwined in co-selection with their hosts. Empirically, we made germ-free flies colonized with each possible combination of the five core species of fly gut bacteria. We measured the resulting bacterial community abundances and fly fitness traits including development, reproduction, and lifespan. The fly gut promoted bacterial diversity, which in turn accelerated development, reproduction, and aging: flies that reproduced more died sooner. From these measurements we calculated the impact of bacterial interactions on fly fitness by adapting the mathematics of genetic epistasis to the microbiome. Host physiology phenotypes were highly dependent on interactions between bacterial species. Higher-order interactions (involving 3, 4, and 5 species) were widely prevalent and impacted both host physiology and the maintenance of gut diversity. The parallel impacts of bacterial interactions on the microbiome and on host fitness suggest that microbiome interactions may be key drivers of evolution.\n\nSignificanceAll animals have associated microbial communities called microbiomes that can influence the physiology and fitness of their host. It is unclear to what extent individual microbial species versus ecology of the microbiome influences fitness of the host. Here we mapped all the possible interactions between individual species of bacteria with each other and with the hosts physiology. Our approach revealed that the same bacterial interactions that shape microbiome abundances also shape host fitness traits. This relationship provides a feedback that may favor the emergence of co-evolving microbiome-host units.

microbiology↗