Biology Research Works
Permanent URI for this collectionhttp://hdl.handle.net/1903/13
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Item DNA Barcoding Module in Undergraduate Biology Courses: A Comparative Analysis on Student Learning(2025-01-14) Kraemer, Jenna; Craig, Helen; Brucchieri, Amanda; Helbling, Yasmine; Lamp, WilliamItem Neural correlates of perceptual plasticity in the auditory midbrain and thalamus(2024-08-28) Ying, Rose; Stolzberg, Daniel J; Caras, Melissa LHearing is an active process in which listeners must detect and identify sounds, segregate and discriminate stimulus features, and extract their behavioral relevance. Adaptive changes in sound detection can emerge rapidly, during sudden shifts in acoustic or environmental context, or more slowly as a result of practice. Although we know that context- and learning-dependent changes in the spectral and temporal sensitivity of auditory cortical (ACX) neurons support many aspects of perceptual plasticity, the contribution of subcortical auditory regions to this process is less understood. Here, we recorded single- and multi-unit activity from the central nucleus of the inferior colliculus (ICC) and the ventral subdivision of the medial geniculate nucleus (MGV) of Mongolian gerbils under two different behavioral contexts: as animals performed an amplitude modulation (AM) detection task and as they were passively exposed to AM sounds. Using a signal detection framework to estimate neurometric sensitivity, we found that neural thresholds in both regions improved during task performance, and this improvement was driven by changes in firing rate rather than phase locking. We also found that ICC and MGV neurometric thresholds improved as animals learn to detect small AM depths during a multi-day perceptual training paradigm. Finally, we reveal that in the MGV, but not the ICC, context-dependent enhancements in AM sensitivity grow stronger during perceptual training, mirroring prior observations in the ACX. Together, our results suggest that the auditory midbrain and thalamus contribute to changes in sound processing and perception over rapid and slow timescales.Item Data for: Competing adaptations maintain non-adaptive variation in a wild cricket population(2024) Rayner, Jack; Eichenberger, Franca; Bainbridge, Jessica; Zhang, Shangzhe; Zhang, Xiao; Yusuf, Leeban; Balenger, Susan; Gaggiotti, Oscar; Bailey, NathanItem Null model analyses are not adequate to summarize strong associations: Rebuttal to Ulrich et al. (2022)(Wiley, 2023-10-21) Mainali, Kumar P.; Slud, EricWe recently developed a novel metric of association in pairwise co-occurrence data (Mainali et al., 2022) to address fundamental flaws in traditional indices, as elaborately discussed and conclusively shown in our published paper. Our new metric, the maximum likelihood estimator (MLE) alpha-hat of a statistical parameter alpha, quantifies the degree of association between species occupancy at ecological sites, and it is insensitive to the species prevalences and number of sites. In contrast, we showed that classic indices of co-occurrence (Jaccard, Simpson, Sørensen–Dice) can be highly sensitive to fixed margins of contingency tables, estimating wildly variable degrees of association and even reversing the direction of association for tables with different margins but the same degree-of-association alpha.Item Genetic tools for the study of the mangrove killifish, Kryptolebias marmoratus, an emerging vertebrate model for phenotypic plasticity(Wiley, 2023-08-08) Li, Cheng-Yu; Boldt, Helena; Parent, Emily; Ficklin, Jax; James, Althea; Anlage, Troy J.; Boyer, Lena M.; Pierce, Brianna R.; Siegfried, Kellee R.; Harris, Matthew P.; Haag, Eric S.Kryptolebias marmoratus (Kmar), a teleost fish of the order Cyprinodontiformes, has a suite of unique phenotypes and behaviors not observed in other fishes. Many of these phenotypes are discrete and highly plastic—varying over time within an individual, and in some cases reversible. Kmar and its interfertile sister species, K. hermaphroditus, are the only known self-fertile vertebrates. This unusual sexual mode has the potential to provide unique insights into the regulation of vertebrate sexual development, and also lends itself to genetics. Kmar is easily adapted to the lab and requires little maintenance. However, its internal fertilization and small clutch size limits its experimental use. To support Kmar as a genetic model, we compared alternative husbandry techniques to maximize recovery of early cleavage-stage embryos. We find that frequent egg collection enhances yield, and that protease treatment promotes the greatest hatching success. We completed a forward mutagenesis screen and recovered several mutant lines that serve as important tools for genetics in this model. Several will serve as useful viable recessive markers for marking crosses. Importantly, the mutant kissylips lays embryos at twice the rate of wild-type. Combining frequent egg collection with the kissylips mutant background allows for a substantial enhancement of early embryo yield. These improvements were sufficient to allow experimental analysis of early development and the successful mono- and bi-allelic targeted knockout of an endogenous tyrosinase gene with CRISPR/Cas9 nucleases. Collectively, these tools will facilitate modern developmental genetics in this fascinating fish, leading to future insights into the regulation of plasticity.Item Organization of orbitofrontal-auditory pathways in the Mongolian gerbil(Wiley, 2023-07-21) Ying, Rose; Hamlette, Lashaka; Nikoobakht, Laudan; Balaji, Rakshita; Miko, Nicole; Caras, Melissa L.Sound perception is highly malleable, rapidly adjusting to the acoustic environment and behavioral demands. This flexibility is the result of ongoing changes in auditory cortical activity driven by fluctuations in attention, arousal, or prior expectations. Recent work suggests that the orbitofrontal cortex (OFC) may mediate some of these rapid changes, but the anatomical connections between the OFC and the auditory system are not well characterized. Here, we used virally mediated fluorescent tracers to map the projection from OFC to the auditory midbrain, thalamus, and cortex in a classic animal model for auditory research, the Mongolian gerbil (Meriones unguiculatus). We observed no connectivity between the OFC and the auditory midbrain, and an extremely sparse connection between the dorsolateral OFC and higher order auditory thalamic regions. In contrast, we observed a robust connection between the ventral and medial subdivisions of the OFC and the auditory cortex, with a clear bias for secondary auditory cortical regions. OFC axon terminals were found in all auditory cortical lamina but were significantly more concentrated in the infragranular layers. Tissue-clearing and lightsheet microscopy further revealed that auditory cortical-projecting OFC neurons send extensive axon collaterals throughout the brain, targeting both sensory and non-sensory regions involved in learning, decision-making, and memory. These findings provide a more detailed map of orbitofrontal-auditory connections and shed light on the possible role of the OFC in supporting auditory cognition.Item Orbitofrontal Cortex Modulates Auditory Cortical Sensitivity and Sound Perception in Mongolian gerbils(Current Biology, 2024) Macedo-Lima, Matheus; Hamlette, Lashaka Sierra; Caras, Melissa L.Sensory perception is dynamic, quickly adapting to sudden shifts in environmental or behavioral context. Though decades of work have established that these dynamics are mediated by rapid fluctuations in sensory cortical activity, we have a limited understanding of the brain regions and pathways that orchestrate these changes. Neurons in the orbitofrontal cortex (OFC) encode contextual information, and recent data suggest that some of these signals are transmitted to sensory cortices. Whether and how these signals shape sensory encoding and perceptual sensitivity remains uncertain. Here, we asked whether the OFC mediates context-dependent changes in auditory cortical sensitivity and sound perception by monitoring and manipulating OFC activity in freely moving Mongolian gerbils of both sexes under two behavioral contexts: passive sound exposure and engagement in an amplitude modulation (AM) detection task. We found that the majority of OFC neurons, including the specific subset that innervate the auditory cortex, were strongly modulated by task engagement. Pharmacological inactivation of the OFC prevented rapid context-dependent changes in auditory cortical firing, and significantly impaired behavioral AM detection. Our findings suggest that contextual information from the OFC mediates rapid plasticity in the auditory cortex and facilitates the perception of behaviorally relevant sounds.Item Impaired Focal Adhesion Kinase-Grb2 Interaction during Elevated Activity in Hippocampal Neurons(MDPI, 2015-07-10) Murase, SachikoExcitatory/inhibitory imbalances are implicated in many neurological disorders. Previously, we showed that chronically elevated network activity induces vulnerability in neurons due to loss of signal transducer and activator of transcription 3 (STAT3) signaling in response to the impairment of the serine/threonine kinase, extracellular-signal-regulated kinases 1/2 (Erk1/2) activation. However, how phosphorylation of Erk1/2 decreases during elevated neuronal activity was unknown. Here I show the pErk1/2 decrease induced by 4-aminopyridine (4-AP), an A-type potassium channel inhibitor can be blocked by a broad-spectrum matrix-metalloproteinase (MMP) inhibitor, FN-439. Surface expression levels of integrin β1 dramatically decrease when neurons are challenged by chronically elevated activity, which is reversed by FN-439. Treatment with 4-AP induces degradation of focal adhesion kinase (FAK), the mediator of integrin signaling. As a result, interactions between FAK and growth factor receptor-bound protein 2 (Grb2), the adaptor protein that mediates Erk1/2 activation by integrin, are severely impaired. Together, these data suggest the loss of integrin signaling during elevated activity causes vulnerability in neurons.Item Membrane Affinity of Platensimycin and Its Dialkylamine Analogs(MDPI, 2015-08-04) Rowe, Ian; Guo, Min; Yasmann, Anthony; Cember, Abigail; Sintim, Herman O.; Sukharev, SergeiMembrane permeability is a desired property in drug design, but there have been difficulties in quantifying the direct drug partitioning into native membranes. Platensimycin (PL) is a new promising antibiotic whose biosynthetic production is costly. Six dialkylamine analogs of PL were synthesized with identical pharmacophores but different side chains; five of them were found inactive. To address the possibility that their activity is limited by the permeation step, we calculated polarity, measured surface activity and the ability to insert into the phospholipid monolayers. The partitioning of PL and the analogs into the cytoplasmic membrane of E. coli was assessed by activation curve shifts of a re-engineered mechanosensitive channel, MscS, in patch-clamp experiments. Despite predicted differences in polarity, the affinities to lipid monolayers and native membranes were comparable for most of the analogs. For PL and the di-myrtenyl analog QD-11, both carrying bulky sidechains, the affinity for the native membrane was lower than for monolayers (half-membranes), signifying that intercalation must overcome the lateral pressure of the bilayer. We conclude that the biological activity among the studied PL analogs is unlikely to be limited by their membrane permeability. We also discuss the capacity of endogenous tension-activated channels to detect asymmetric partitioning of exogenous substances into the native bacterial membrane and the different contributions to the thermodynamic force which drives permeation.Item Supplementary materials for Plasmodium vivax antigen candidate prediction improves with the addition of Plasmodium falciparum data(2023) Chou, Renee Ti; Ouattara, Amed; Takala-Harrison, Shannon; Cummings, Michael P.Intensive malaria control and elimination efforts have led to substantial reductions in malaria incidence over the past two decades. However, the reduction in Plasmodium falciparum malaria cases has led to a species shift in some geographic areas, with P. vivax predominating in many areas outside of Africa. Despite its wide geographic distribution, P. vivax vaccine development has lagged far behind that for P. falciparum, in part due to the inability to cultivate P. vivax in vitro, hindering traditional approaches for antigen identification. In a prior study, we have used a positive-unlabeled random forest (PURF) machine learning approach to identify P. falciparum antigens for consideration in vaccine development efforts. Here we integrate systems data from P. falciparum (the better-studied species) to improve PURF models to predict potential P. vivax vaccine antigen candidates. We further show that inclusion of known antigens from the other species is critical for model performance, but the inclusion of unlabeled proteins the other species can result in misdirection of the model toward predictors of species classification, rather than antigen identification. Beyond malaria, incorporating antigens from a closely related species may aid in vaccine development for emerging pathogens having few or no known antigens.