Biology subjects

Dhungana, A.

Publications and source records attributed to Dhungana, A..

5 recordsLinked to original sources

bioRxiv2025

CaneCestry : A Web-based Toolbox for Efficient Pedigree Analysis and Visualization.

Genetic variability is the lifeblood of all breeding programs. This variability is acted on via selection to identify elite progeny that can be utilized agronomically or exploited as parents. Sugarcane breeders are tasked with creating optimal genetic variation through crossing. Prior knowledge of pedigree and parental performance allows breeders to discern which crosses to prioritize, since the time to make crossing decisions and the space to evaluate tens and thousands of progenies are both limited resources in sugarcane variety development programs. In this project, we have developed a user-friendly, web-based platform called CaneCestry that provides a wide range of tools utilizing pedigree information. CaneCestry can be utilized to generate family trees for parents involved in a potential cross, enabling the breeder to efficiently display and visualize the lineage of the genotypes contained within. Kinship matrices are a powerful numerical representation of relationships between individuals in a population. While the calculation of kinship can be computationally intensive, CaneCestry is built upon a framework allowing for efficient cloud-based computation. These numerical representations of kinship elucidate the relatedness of potential parents, allowing the breeder to make the most informed crosses while avoiding inbreeding depression. Kinship matrices can also be utilized to enhance prediction models by adding the relatedness of the involved genotypes as a covariate, accounting for additive genetic control of traits. CaneCestry provides a comprehensive, web-based set of tools available in the office and field, enabling sugarcane breeders to utilize pedigree information in all stages of their breeding program.

bioinformatics↗

bioRxiv2024

Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting homeostatic astrocyte function

Compulsive actions are typically thought to reflect the dominance of habits over goal-directed action. To address this, we mimicked the striatal neuroinflammation that is frequently exhibited in individuals with compulsive disorders in rats, by injecting the endotoxin lipopolysaccharide into the posterior dorsomedial striatum, and assessed the consequences for behavioural control. Surprisingly, this manipulation caused rats to acquire and maintain goal-directed actions under conditions that would otherwise produce habits. Immunohistochemical analyses indicated that these behaviours were a result of astrocytic proliferation. To probe this further, we chemogenetically activated the Gi-pathway in striatal astrocytes, which altered the firing properties of nearby medium spiny neurons and modulated goal-directed action control. Together, results show that striatal neuroinflammation is sufficient to bias action selection toward excessive goal-directed control via dysregulated astrocyte function. If translatable, our findings suggest that, contrary to conventional views, individuals with striatal neuroinflammation might be more prone to maladaptive goal-directed actions than habits, and future interventions should aim to restore appropriate action control.

animal behavior and cognition↗

bioRxiv2024

Hippocampal neuroinflammation causes sex-specific disruptions in instrumental conditioning, Pavlovian approach, and neuronal excitation

Hippocampal neuroinflammation is present in multiple diseases and disorders that impact motivated behaviour in a sex-specific manner, but whether neuroinflammation alone is sufficient to disrupt such behaviour is unknown. We investigated this question here using mice. First, the application of an endotoxin to primary cultures containing only hippocampal neurons did not affect their activation. However, when the same endotoxin was applied to mixed neuronal/glial cultures it did increase neuronal activation, providing initial indications of how it might be able to effect behavioural change. We next demonstrated neuroinflammatory effects on behaviour directly, demonstrating that intra-hippocampal administration of the same endotoxin increased locomotor activity and accelerated goal-directed learning in both male and female mice. In contrast, hippocampal neuroinflammation caused sex-specific disruptions to the acquisition of instrumental actions and to Pavlovian food-approach memories. Finally, we showed that hippocampal neuroinflammation had a sexually dimorphic effect on neuronal activation: increasing it in females and decreasing it in males.

animal behavior and cognition↗

bioRxiv2022

Goal-directed action is transiently impaired in an hAPP-J20 mouse model of Alzheimer's disease, and in aging male mice regardless of genotype

Cognitive-behavioural testing in preclinical models of Alzheimers disease has typically been limited to visuo-spatial memory tests and has failed to capture the broad scope of deficits patients also display in goal-directed action control. The current study addresses this gap by providing the first comprehensive investigation of how goal-directed actions are affected in a transgenic mouse model of Alzheimers disease. Specifically, we tested outcome devaluation performance - a popular test of goal-directed action - in male and female human amyloid precursor protein (hAPP)-J20 mice. Mice were first trained to press a left and right lever for unique pellet and sucrose outcomes respectively (counterbalanced) over four days. On test, mice were fed one of the two outcomes to reduce its value via sensory specific satiety and subsequently given a choice between levers. Goal-directed action was intact for 36-week-old wildtype mice of both sexes, because they responded more on the lever associated with the still-valued outcome than that associated with the devalued outcome (i.e. Valued > Devalued). Goal-directed action was impaired (Valued = Devalued) for J20 mice of both sexes, and for 52-week-old male mice regardless of genotype. Following an additional 4 days of lever press training (i.e., 8 days lever pressing in total), outcome devaluation was intact for all mice regardless of age or genotype. Immunohistochemical analysis revealed that increased microglial expression in the dorsal CA1 region of the hippocampus was associated with poorer outcome devaluation performance on initial tests, but not with tests performed after 8 days of lever pressing. Together, these data demonstrate that goal-directed action is transiently impaired in J20 mice of both sexes and in aging male mice regardless of genotype, and that this impairment is related to neuroinflammation in the dorsal CA1 region of the hippocampus.

animal behavior and cognition↗

bioRxiv2019

The influence of environmental setting on the community ecology of Ediacaran organisms

The broad-scale environment plays a substantial role in shaping modern marine ecosystems, but the degree to which palaeocommunities were influenced by their environment is unclear. To investigate how broad-scale environment influenced the community ecology of early animal ecosystems we employed spatial point process analyses to examine the community structure of seven bedding-plane assemblages of late Ediacaran age (558–550 Ma), drawn from a range of environmental settings and global localities. The studied palaeocommunities exhibit marked differences in the response of their component taxa to sub-metre-scale habitat heterogeneities on the seafloor. Shallow-marine palaeocommunities were heavily influenced by local habitat heterogeneities, in contrast to their deep-water counterparts. Lower species richness in deep-water Ediacaran assemblages compared to shallow-water counterparts across the studied time-interval could have been driven by this environmental patchiness, because habitat heterogeneities correspond to higher diversity in modern marine environments. The presence of grazers and detritivores within shallow-water communities may have promoted local patchiness, potentially initiating a chain of increasing heterogeneity of benthic communities from shallow to deep-marine depositional environments. Our results provide quantitative support for the “Savannah” hypothesis for early animal diversification – whereby Ediacaran diversification was driven by patchiness in the local benthic environment.Author Contributions E. Mitchell conceived this paper and wrote the first draft. N. Bobkov, A. Kolesnikov, N. Sozonov and D. Grazhdankin collected the data for DS surface. N. Bobkov and N. Sozonov performed the analyses on DS surface. N. Bykova, S. Xiao, and D. Grazhdankin collected the data for WS, KH1 and KH2 surfaces and E. Mitchell performed the analyses. A. Dhungana and A. Liu collected the data for FUN4 and FUN5 surfaces and A. Dhungana performed the analyses. T. Mustill and D. Grazhdankin collected the data for KS and T. Mustill and E. Mitchell performed the analyses. I. Hogarth developed the software for preliminary KS surface analyses. E. Mitchell, N. Bobkov, N. Bykova, A. Dhungana, A. Kolesnikov, A. Liu, S. Xiao and D. Grazhdankin discussed the results and prepared the manuscript.View Full Text

paleontology↗