Biology subjects

Pak, D.

Publications and source records attributed to Pak, D..

6 recordsLinked to original sources

bioRxiv2026

Between Behaviors: Comparison of Two Dynamical Models of Behavioral Switching for \textit{C. Elegans} Locomotion

Organisms must manage a trade-off between robustness and flexibility as they enact adaptive behaviors. One way organisms achieve this is by navigating a network of quasi-stable behavioral states. Evidence for such behavioral states has been observed in many organisms, and new methods for detecting these states have taken on a prominent research focus. Although dynamical models demonstrating behavioral switching have been developed significantly over the past few decades, theories of the similarities and differences among these models, necessary for advancing empirical modeling, have not yet been fully elaborated. Here, we consider behavioral switching in two different classes of dynamical models of the forward-reversal behavioral transition in C. elegans. We first show how fundamentally different models can give rise to similar phenomena under noisy conditions. We then analyze the deterministic aspects of these models to expand on their differences, clarifying the theoretical relationship between them. Finally, we demonstrate how sequence models can be further extended to incorporate dwell times for behavioral states. Our work contributes toward a broader theoretical understanding of behavioral switching in adaptive systems.

animal behavior and cognition↗

bioRxiv2025

CCL5/CCR5 signaling modulates depression-relevant behavior, neuronal oscillations, and long-term depression of synaptic activity.

Major depressive disorder (MDD) is a debilitating disorder, often associated with perseverative thinking and anxiety. Localized reductions in pyramidal cell activity may contribute to associated symptoms, and effective antidepressant treatments typically enhance overall neuronal excitation. CCL5 is a chemokine that has been shown to reduce excitatory-neuronal activity, and is also increased with MDD and conditions that increase MDD risk. Here, we investigate the CCL5/CCR5 axis for its ability to modulate depression-relevant endpoints that are diminished in MDD, including neuronal oscillations, as well as biochemical and behavioral correlates of the disorder. In comparison to wildtype mice, CCR5 knockouts had increased gamma and theta power, and stronger theta/high-gamma phase amplitude coupling during dark-cycle EEG recordings. Compared to strain-matched wildtype mice, CCR5 knockouts also demonstrated reduced anxiety, increased sucrose preference, and improved associative memory. Proteomic analysis of the hippocampus showed that CCR5 knockouts had reduced levels of the GABA receptor alpha-4 subunit, which mediates tonic inhibition and restricts pyramidal cell plasticity. In complementary primary neuronal culture studies, CCL5 diminished GSK-3{beta} activity and impaired NMDA-dependent long-term depression (LTD), a form of plasticity that promotes cognitive flexibility. In addition, CCL5 signaling increased parvalbumin expression in GABAergic neurons through a CCR5-dependent manner. In combination with the ability of CCR5 to restrain gamma oscillation power and LTD, our data raise the possibility that CCL5/CCR5 signaling inhibits neuronal excitation through increased PV+ interneuron activity. Moreover, data are consistent with the possibility that CCR5 antagonists might share the ability of established antidepressants to both increase PC excitation and reduce PC inhibition. Significance StatementMajor depressive disorder (MDD) is a global leading cause of disability, and is associated with increased chemokine activation and inflammation. In this study, we investigate how the CCR5/CCL5 chemokine axis regulates behavioral and cognitive endpoints associated with MDD. This study aims to provide insight to how chemokine signaling underlies mood and behavioral symptoms of neuropsychiatric disorders. We hope this research supports further investigation of CCR5 antagonists for MDD and related mood and anxiety disorders.

neuroscience↗

bioRxiv2024

The Importance of Nonsense Errors: Estimating the Rate and Implications of Drop-Off Errors during Protein Synthesis

The process of mRNA translation is both energetically costly and relatively error-prone compared to transcription and replication. Nonsense errors during mRNA translation occur when a ribosome drops off a transcript before reaching a stop codon, resulting in energetic investment in an incomplete and likely non-functional protein. Nonsense errors impose a potentially significant energy burden on the cell, making it critical to quantify their frequency and energetic cost. Here, we present a model of ribosome movement for estimating protein production, elongation, and nonsense error rates from high-throughput ribosome profiling data. Applying this model to an exemplary ribosome profiling dataset in S. cerevisiae, we find that nonsense error rates vary between codons, in conflict with the general assumption of uniform rates across sense codons. Using our parameter estimates, we find multiple lines of evidence that selection against nonsense errors is a prominent force shaping coding-sequence evolution, including that nonsense errors place an energetic burden on cells comparable to ribosome pausing. Our results indicate greater consideration should be given to the impact of nonsense errors in shaping coding-sequence evolution. Author SummaryThe process of mRNA translation is both energetically expensive and relatively error-prone. As such, natural selection is thought to shape the evolution of CDSs to reduce the cost of these errors when they occur. Nonsense errors (NSEs) occur when a ribosome stops translation prior to completing a functional protein, resulting in wasted energy on non-functional product. Despite their functional consequences, NSEs and their effects on sequence evolution are generally understudied compared to other types of translation errors. This is in part due to the challenge of quantifying these errors from omics-scale data. We present a model for quantifying codon-specific estimates of elongation and NSE rates from ribosome profiling data, which gives a snapshot of the actively translating ribosomes in a cell. Although it is well-established that sense codons vary in their elongation rates, we find evidence that codons also vary in their NSE rates. Using our parameter estimates, we find multiple lines of evidence for selection against NSEs shaping patterns of codon usage bias. Our results suggest the cost of NSEs are comparable to the cost of ribosome pausing, and thus may play a greater role in coding-sequence evolution than previously appreciated.

evolutionary biology↗

bioRxiv2023

Proliferation in malaria parasites: how resource limitation can prevent evolution of greater virulence

For parasites, robust proliferation within hosts is crucial for establishing the infection and creating opportunities for onward transmission. While faster proliferation enhances transmission rates, it is often assumed to curtail transmission duration by killing the host (virulence), a tradeoff constraining parasite evolution. Yet in many diseases, including malaria, the preponderance of infections with mild or absent symptoms suggests that host mortality is not a sufficient constraint, raising the question of what restrains evolution towards faster proliferation. In malaria infections, the maximum rate of proliferation is determined by the burst size, the number of daughter parasites produced per infected red blood cell. Larger burst sizes should expand the pool of infected red blood cells that can be used to produce the specialized transmission forms needed to infect mosquitoes. We use a within-host model parameterized for rodent malaria parasites (Plasmodium chabaudi) to project the transmission consequences of burst size, focusing on initial acute infection where re-source limitation and risk of host mortality are greatest. We find that resource limitation restricts evolution towards higher burst sizes below the level predicted by host mortality alone. Our results suggest resource limitation could represent a more general constraint than virulence-transmission tradeoffs, preventing evolution towards faster proliferation.

ecology↗

bioRxiv2021

Multi-scale phenological niches in diverse Amazonian plant communities

Phenology has long been hypothesized as an avenue for niche partitioning or interspecific facilitation, both promoting species coexistence. Tropical plant communities exhibit striking diversity in reproductive phenology, but many are also noted for large synchronous reproductive events. Here we study whether the phenology of seed fall in such communities is non-random, what are the temporal scales of phenological patterns, and ecological factors that drive reproductive phenology. We applied multivariate wavelet analyses to test for phenological synchrony versus compensatory dynamics (i.e. anti-synchronous patterns where one species decline is compensated by the rise of another) among species and across temporal scales. We used data from long-term seed rain monitoring of hyperdiverse plant communities in the western Amazon. We found significant synchronous whole-community phenology at multiple time scales, consistent with shared environmental responses or positive interactions among species. We also observed both compensatory and synchronous phenology within groups of species likely to share traits (confamilials) and seed dispersal mechanisms. Wind-dispersed species exhibited significant synchrony at ~6 mo scales, suggesting these species share phenological niches to match seasonality of wind. Our results suggest that community phenology is shaped by shared environmental responses but that the diversity of tropical plant phenology may partly result from temporal niche partitioning. The scale-specificity and time-localized nature of community phenology patterns highlights the importance of multiple and shifting drivers of phenology. Open research statementData are provided as private-for-peer review. Code and data can be found at https://github.com/pakdamie/treephenology which is currently public. This submission does not use novel code.

ecology↗

bioRxiv2018

A 117 year retrospective analysis of Pennsylvania tick community dynamics

BackgroundTick-borne diseases have been increasing at the local, national, and global levels. Researchers studying ticks and tick-borne disease need a thorough knowledge of the pathogens, vectors, and epidemiology of disease spread. Three surveillance approaches are commonly used to provide insight into tick-borne disease risk: human disease case surveillance, active tick surveillance, and passive tick surveillance. Long-term passive surveillance can provide up-to-date data on the spatial variability and temporal dynamics of ectoparasite communities and shed light into the ecology of rarer tick species. We present a retrospective analysis on compiled data of ticks from Pennsylvania over the last 117 years.\n\nMethodsWe compiled data from ticks collected during tick surveillance research, and from citizen-based submissions to the Penn State University Department of Entomology (PSUEnt). Specimens were deposited at the PSUEnt arthropod collections that eventually became The Frost Entomological Museum. While most of the specimens were submitted by the public, a subset of the data were collected through active methods (flagging or dragging, or removal of ticks from wildlife). We analyzed all data from 1900-2017 for tick community composition, host associations, and spatio-temporal dynamics.\n\nResultsIn total there were 4,491 submission lots consisting of 7,132 tick specimens. Twenty-four different species were identified, with the large proportion of submissions represented by five tick species. We observed a shift in tick community composition in which the dominant species of tick (Ixodes cookei) was overtaken in abundance by Dermacentor variabilis in the early 1990s, and then replaced in abundance by I. scapularis. We analyzed host data and identified overlaps in host range amongst tick species, suggesting potential hubs of pathogen transfer between different tick vectors and their reservoir hosts.\n\nConclusionsWe highlight the importance of long-term passive tick surveillance in investigating the ecology of both common and rare tick species. Information on the geographic distribution, host-association, and seasonality of the tick community can help researchers and health-officials to identify high-risk areas.

ecology↗