Biology subjects

Dhungana, S.

Publications and source records attributed to Dhungana, S..

6 recordsLinked to original sources

bioRxiv2026

Planning in Nonhuman Primates Emerges from Structure Knowledge and is Distinct from Attention, Working Memory, Effort Control, and Learning

Forward planning involves mentally simulating future choices. Such mental simulation may constitute an independent cognitive operation, or it may be intricately linked to canonical cognitive operations supporting working memory of choice options, covert attentional information sampling, forming memory models of problem structure and effort control for pursuing future goals. Here, we test the relative independence of planning in non-human primates with an object-sequence planning task assessed together with an assay of simpler cognitive tasks. The sequence task unexpectedly masked objects at future serial positions probing NHPs to plan ahead serial future choices. We found that five of six subjects planned ahead 2-3 ordinal positions. Planning depth was predicted by knowledge of the serial structure but constituted a unique cognitive factor that was distinct from sequence memory, object memory, and learning efficacy. Similarly, planning was segregated from working memory capacity, attention, inhibitory control and effort control. These findings suggest that planning ahead constitutes a separate construct not reducible to other domain-general cognitive operations, and emerges in NHPs that successfully form an internal model of the problem structure.

animal behavior and cognition↗

bioRxiv2024

Flexible Learning and Re-ordering of Context-dependent Object Sequences in Nonhuman Primates

Intelligent behavior involves mentally arranging learned information in novel ways and is particularly well developed in humans. While nonhuman primates (NHP) will learn to arrange new items in complex serial order and re-arrange neighboring items within that order, it has remained contentious whether they are capable to re-assign items more flexibly to non-adjacent positions. Such mental re-indexing is facilitated by inferring the latent temporal structure of experiences as opposed to learning serial chains of item-item associations. Here, we tested the ability for flexible mental re-indexing in rhesus macaques. Subjects learned to serially order five objects. A change of the background context indicated when the object order changed, probing the subjects to mentally re-arrange objects to non-adjacent positions of the learned serial structure. Subjects successfully used the context cue to pro-actively re-index items to new, non-adjacent positions. Mental re-indexing was more likely when the initial order had been learned at a higher level, improved with more experience of the re-indexing rule and correlated with working memory performance in a delayed match-to-sample task. These findings suggest that NHPs inferred the latent serial structure of experiences beyond a chaining of item-item associations and mentally re-arrange items within that structure. The pattern of results indicates that NHPs form non-spatial cognitive maps of their experiences, which is a hallmark for flexible mental operations in many serially ordered behaviors including communication, counting or foraging.

animal behavior and cognition↗

bioRxiv2023

A Multi-task Platform for Profiling Cognitive and Motivational Constructs in Humans and Nonhuman Primates

BackgroundUnderstanding the neurobiological substrates of psychiatric disorders requires comprehensive evaluations of cognitive and motivational functions in preclinical research settings. The translational validity of such evaluations will be supported by (1) tasks with high construct validity that are engaging and easy to teach to human and nonhuman participants, (2) software that enables efficient switching between multiple tasks in single sessions, (3) software that supports tasks across a broad range of physical experimental setups, and (4) by platform architectures that are easily extendable and customizable to encourage future optimization and development. New MethodWe describe the Multi-task Universal Suite for Experiments (M-USE), a software platform designed to meet these requirements. It leverages the Unity video game engine and C# programming language to (1) support immersive and engaging tasks for humans and nonhuman primates, (2) allow experimenters or participants to switch between multiple tasks within-session, (3) generate builds that function across computers, tablets, and websites, and (4) is freely available online with documentation and tutorials for users and developers. M-USE includes a task library with seven pre-existing tasks assessing cognitive and motivational constructs of perception, attention, working memory, cognitive flexibility, motivational and affective self-control, relational long-term memory, and visuo-spatial problem solving. ResultsM-USE was used to test NHPs on up to six tasks per session, all available as part of the Task Library, and to extract performance metrics for all major cognitive and motivational constructs spanning the Research Domain Criteria (RDoC) of the National Institutes of Mental Health. Comparison with Existing MethodsOther experiment design and control systems exist, but do not provide the full range of features available in M-USE, including a pre-existing task library for cross-species assessments; the ability to switch seamlessly between tasks in individual sessions; cross-platform build capabilities; license-free availability; and its leveraging of video-engine capabilities used to gamify tasks. ConclusionsThe new multi-task platform facilitates cross-species translational research for understanding the neurobiological substrates of higher cognitive and motivational functions.

animal behavior and cognition↗

bioRxiv2020

Transcriptome and interactome analyses identify the TP53 interacting gene RCCD1 as a candidate susceptibility gene at the 15p26.1 breast and ovarian cancer risk locus

Common genetic variation in a region on chromosome 15q26 confers susceptibility to breast and ovarian cancer. The P53 interacting gene RCCD1 in this region is a candidate susceptibility gene for both cancers. In this study, a colocalization analysis of breast and ovarian cancer case-control genetic association studies in over 145,000 and 146,000 controls fine mapped the shared association in this region to 17 pleiotropic credible causal risk variants (Pbreast < 1.16 x 10-14 and P ovary < 7.50 x 10-7). These variants were strongly associated with the expression of RCCD1 in normal breast and ovarian tissues. Circular chromosome conformation capture (4C) analysis of RCCD1 in breast and ovarian cancer cells identified similar patterns of cis-interaction and significant binding site enrichment for the BRCA2 interacting gene EMSY (Padjusted = 9.24 x 10-6). The 4C analysis pinpointed a single 2kB RCCD1 cis-interaction that contained two of the 17 shared risk variants. RCCD1 trans-interacting regions mapped to previously identified genome wide significant (P < 5 x 10-8) breast cancer risk loci (1p34.2 and 3p14.1) and to the pleiotropic breast-ovarian cancer risk locus at chromosome 9q34.2. Stable overexpression of RCCD1 in breast and ovarian cancer precursor cells identified 13 and 11 differentially expressed genes (DEGs) respectively associated with breast and ovarian cancer risk at genome-wide significance (PMAGMA < 2.6 x 10-6 after Bonferroni correction). Eighty-two DEGs shared between breast and ovarian cancer were strongly enriched in TP53 (P = 9.9 x 10-4), Hippo (P = 2.51 x 10-3) and TNF signaling (P = 4.7 x 10-3) pathways.

genetics↗

bioRxiv2019

Interaction between induced and natural variation at oil yellow1 delays flowering in maize

We previously demonstrated that maize (Zea mays) locus very oil yellow1 (vey1) encodes a putative cis-regulatory expression polymorphism at the magnesium chelatase subunit I gene (aka oil yellow1) that strongly modifies the chlorophyll content of the semi-dominant Oy1-N1989 mutants. The vey1 allele of Mo17 inbred line reduces chlorophyll content in the mutants leading to reduced photosynthetic output. Oy1-N1989 mutants in B73 reached reproductive maturity four days later than wild-type siblings. Enhancement of Oy1-N1989 by the Mo17 allele at the vey1 QTL delayed maturity further, resulting in detection of a flowering time QTL in two bi-parental mapping populations crossed to Oy1-N1989. The near isogenic lines of B73 harboring the vey1 allele from Mo17 delayed flowering of Oy1-N1989 mutants by twelve days. Just as previously observed for chlorophyll content, vey1 had no effect on reproductive maturity in the absence of the Oy1-N1989 allele. Loss of chlorophyll biosynthesis in Oy1-N1989 mutants and enhancement by vey1 reduced CO2 assimilation. We attempted to separate the effects of photosynthesis on the induction of flowering from a possible impact of chlorophyll metabolites and retrograde signaling by manually reducing leaf area. Removal of leaves, independent of the Oy1-N1989 mutant, delayed flowering but surprisingly reduced chlorophyll contents of emerging leaves. Thus, defoliation did not completely separate the identity of the signal(s) that regulates flowering time from changes in chlorophyll content in the foliage. These findings illustrate the necessity to explore the linkage between metabolism and the mechanisms that connect it to flowering time regulation.

plant biology↗

bioRxiv2019

Temporal Effects on Radiation Responses in Nonhuman Primates: Identification of Biofluid Small Molecule Signatures by Gas Chromatography - Mass Spectrometry Metabolomics

Whole body exposure to ionizing radiation (IR) (> 0.7 Gy) damages tissues leading to a range of physical symptoms contributing to acute radiation syndrome (ARS). Radiation biodosimetry aims to determine characteristic early biomarkers indicative of radiation exposure (generally at doses > 2 Gy) and is a necessity for effective triage in the event of an unanticipated radiological incident and emergency preparedness. Radiation metabolomics can address this aim by assessing metabolic perturbations following various emergency scenarios (e.g., elapsed time to medical care, absorbed dose, combined injury). Gas chromatography - mass spectrometry (GC-MS) is a standardized platform ideal for chromatographic separation, identification, and quantification of metabolites to discriminate molecular signatures that can be utilized in assessing radiation injury. We performed GC time-of-flight (TOF) MS for global profiling of nonhuman primate (NHP) urine and serum samples up to 60 d after a single 4 Gy {gamma}-ray total body exposure. Multivariate statistical analysis showed a higher separation of groups from urine signatures vs. serum signatures. We identified biofluid markers involved in amino acid, lipid, purine, and serotonin metabolism, some of which may indicate host microbiome dysbiosis. Sex differences were observed amino acid fold changes in serum samples. Additionally, we explored mitochondrial dysfunction by analysis of tricarboxylic acid (TCA) intermediates with a GC tandem quadrupole (TQ) MS platform in samples collected in a time course during the first week (1, 3, 5, and 7 d) after exposure. By adding this temporal component to our previous work exploring dose effects at a single time point of 7 d, we observed the highest fold changes occurring at 3 d, returning closer to basal levels by 7 d. These results emphasize the utility of both MS-based metabolomics for biodosimetry and complementary analytical platforms for increased metabolome coverage.

biochemistry↗