Biology subjects

Lin, J.-Y.

Publications and source records attributed to Lin, J.-Y..

16 recordsLinked to original sources

bioRxiv2026

Stimulus-Specific and Generalized Taste Aversion Behaviors and Their Relationship to Cortical Dynamics

Aversive taste behaviors, such as gaping, are commonly viewed as fixed, hard-wired responses important for ejecting potentially toxic tastes from the mouth. Yet, taste responses are highly susceptible to modulation by experience and context; for instance, conditioned taste aversion (CTA), a form of learning in which rats are made to respond aversively to a sweet taste after it has been paired with gastric malaise, can cause gaping to previously acceptable tastes. Here, we compare aversive responses to saccharin sodium (sacc CS) caused by repeated aversive experience (in the form of CTA training) to those caused by naturally aversive quinine HCl, and how these responses are aligned with gustatory cortical (GC) activity. Using simultaneous single-neuron ensemble recordings in GC and electromyography (EMG) recordings in the jaw-opener muscle in awake, freely-moving rats and a machine-learning based behavioral classifier, we not only identified two classes of gaping, but characterized how these classes reflect different mechanisms driving aversive behavioral outputs. The first gape class is taste-specific and emerges following GC ensemble dynamics associated with taste identity and palatability coding, leading to canonical gaping responses to naturally or learned-aversive stimuli. The second is rapid-onset (<200 ms following taste delivery), internal state-dependent gaping the animal exhibits to all tastes in a state of heightened vigilance. This generalized aversion is subsequently suppressed once palatability-related responses emerge in GC, such that only gapes to truly aversive tastes remain. Together, these findings demonstrate that gaping is not a unitary reflex but is instead driven by multiple aversion judgment systems active in different contexts.

neuroscience↗

bioRxiv2025

Multi-Omics analyses reveal dynamic interactions between DNA methylation and transcriptional regulation during black raspberry ripening

We profiled developmental-series transcriptome, methylome, and metabolome profiling to reveal extensive epigenetic reprogramming during black raspberry (Rubus occidentalis) fruit ripening. Fruit tissues exhibit globally higher DNA methylation than leaves, particularly in CHG and CHH contexts. Local methylation in all cytosine contexts progressively decreases in promoter regions during ripening, whereas CHG and CHH methylation increase in transposon-rich regions. Two primary methylation transitions--promoter hypomethylation and CHH hypermethylation--govern transcriptional shifts in genes involved in ripening processes. Methyl-binding transcription factors with activation potential likely promote CHH hypermethylation-linked transcriptional activation. Multi-omics integration revealed coordinated anthocyanin accumulation parallels expression of biosynthetic and regulatory genes within coherent networks. Elevated non-CG methylation in heterochromatin coincides with increased transcription of histone variants mediating chromatin compaction, suggesting chromatin remodelers fine-tune accessibility for methyltransferases. Our study highlights both genome-wide and locus-specific epigenetic reprogramming and demonstrates a coordinated interplay between DNA methylation and transcriptional regulation during black raspberry fruit ripening.

genomics↗

bioRxiv2024

Changes in taste palatability across the estrous cycle are modulated by hypothalamic estradiol signaling

Food intake varies across the stages of a rats estrous cycle. It is reasonable to hypothesize that this cyclic fluctuation in consumption reflects an impact of hormones on taste palatability/preference, but evidence for this hypothesis has been mixed, and critical within-subject experiments in which rats sample multiple tastes during each of the four main estrous phases (metestrus, diestrus, proestrus, and estrus) have been scarce. Here, we assayed licking for pleasant (sucrose, NaCl, saccharin) and aversive (quinine-HCl, citric acid) tastes each day for 5-10 days while tracking rats estrous cycles through vaginal cytology. Initial analyses confirmed the previously-described increased consumption of pleasant stimuli 24-48 hours following the time of high estradiol. A closer look, however, revealed this effect to reflect a general magnification of palatability--higher than normal preferences for pleasant tastes and lower than normal preferences for aversive tastes--during metestrus. We hypothesized that this phenomenon might be related to estradiol processing in the lateral hypothalamus (LH), and tested this hypothesis by inhibiting LH estrogen receptor activity with ICI182,780 during tasting. Control infusions replicated the metestrus magnification of palatability pattern; ICI infusions blocked this effect as predicted, but failed to render preferences "cycle free," instead delaying the palatability magnification until diestrus. Clearly, estrous phase mediates details of taste palatability in a manner involving hypothalamic actions of estradiol; further work will be needed to explain the lack of a flat response across the cycle with hypothalamic estradiol binding inhibited, a result which perhaps suggests dynamic interplay between brain regions or hormones. Significance StatementConsummatory behaviors are impacted by many variables, including naturally circulating hormones. While it is clear that consumption is particularly high during the stages following the high-estradiol stage of the rodents estrous (and human menstrual) cycle, it is as of yet unclear whether this phenomenon reflects cycle stage-specific palatability (i.e., whether pleasant tastes are particularly delicious, and aversive tastes particularly disgusting, at particular phases). Here we show that palatability is indeed modulated by estrous phase, and that this effect is governed, at least in part, by the action of estradiol within the lateral hypothalamus. These findings shed light on the mechanisms underlying the adverse impact on human welfare due to irregularities observed across the otherwise cyclic menstrual process.

neuroscience↗

bioRxiv2023

Temporal Transcriptome Analysis Uncovers Regulatory Modules Programming Embryo Development from Embryonic Morphogenesis to Post-Germination

We profiled the soybean seed embryo transcriptome across embryonic development to post-germinative development to understand gene activities and regulatory networks promoting these processes. Transcriptomic landscapes feature highly prevalent transcripts which are categorized into early and late groups with major functions of reserve accumulation and energy generation, respectively, and both functions are dominant during late reserve accumulation as the transitioning stage. During the mid-reserve accumulation, regulatory events simultaneously dominate at the transcriptional and chromatin levels, followed by the emergence of distinct mRNA populations during late reserve accumulation throughout germination. We identified diverse functions conducted by sequentially activated genes across developmental stages. Gene coexpression network analysis reveals modules associated with developmental stages, some of which are enriched in genes with functions involved in specific developmental processes. We identified an early-desiccation-associated gene module, containing most transcription factors responsive to abiotic stress, within which one transcription factor is functionally validated to demonstrate increased drought tolerance in Arabidopsis overexpression lines. Finally, we found that a subset of genes is under purifying selection, surpasses the number of their Arabidopsis germination-specific homologs and most are active before germination from embryonic morphogenesis through dormancy, suggesting a potential role in governing physical dormancy in soybean compared to physiological dormancy in Arabidopsis. Our data represent a step toward identifying genes and regulatory networks in the soybean genome facilitating developmental programs across transition phases to bridge embryonic and germinative development.

plant biology↗

bioRxiv2023

Taste Experience Enhances Cortical Response Reliability during Latent Enhancement of Taste Aversion Learning

Learning depends on more than the association of paired stimuli in a vacuum. For example, benign experience with a taste stimulus weakens future conditioned taste aversions (CTA) to that taste--a phenomenon known as latent inhibition (Lubow and Moore, 1959). Our work has revealed a similar phenomenon in rodents whereby benign experience with tastes significantly enhances later CTA to a novel taste (Flores et al., 2016; Flores et al., 2018). This phenomenon suggests that taste experience broadly alters future taste processing in gustatory cortex (GC). To delve into this possibility, we previously have used in-vivo electrophysiology in female Long-Evans rats, recording GC activity during benign taste experience. These recordings revealed an increase in the discriminability of GC responses to both familiar and novel tastes following taste experience (Flores et al., 2022). Here, we build upon these earlier results to present a potential mechanism for this increased discriminability and salience--a reduction of cortical response variability of single-neuron responses, and enhanced coherence of ensemble responses, to the novel taste. We go on to demonstrate that the differences between pre- and post-CTA responses are greater following benign taste experience. These results suggest that benign taste experience impacts GC responses towards a novel taste pre-and post-CTA conditioning by increasing taste coding reliability at both the single-neuron and ensemble levels. Significance StatementAnimals and humans readily learn the consequences of consuming a specific taste and react by changing their behaviors. However, those changes often vary and can be influenced by previous experience. For example, our previous work has shown that inconsequential taste experiences increase the probability of a strong taste aversion. The work presented here evaluates how benign taste experience can impact cortical processing dynamics using in-vivo electrophysiology in freely behaving rats. We report that seemingly inconsequential taste experience impacts cortical plasticity. This unravels a new area of chemosensory research and may shed light on what differentiates the neural dynamics of strong and weak taste aversion learning.

neuroscience↗

bioRxiv2022

LiCl-induced sickness modulates spontaneous activity and response dynamics in rat gustatory cortex.

Gustatory Cortex (GC), a structure deeply involved in the making of consumption decisions, presumably performs this function by integrating information about taste, experiences, and internal states related to the animals health, such as illness. Here, we investigated this assertion, examining whether illness is represented in GC activity, and how this representation impacts taste responses and behavior. We recorded GC single-neuron activity and local field potentials (LFP) from healthy rats and (the same) rats made ill (via LiCl injection). We show (consistent with the extant literature) that the onset of illness-related behaviors arises contemporaneously with alterations in spontaneous 7-12Hz LFP power at [~]11 min following injection. This process was accompanied by reductions in single-neuron taste response magnitudes and discriminability, and with enhancements in palatability-relatedness - a result reflecting the collapse of responses toward a simple "good-bad" code arising in a specific subset of GC neurons. Overall, our data show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, in a manner that can easily explain illness impact on consumption. Significance StatementNeural responses in primary sensory cortex are often thought to faithfully represent physical stimuli, and while recent studies (including ours) have challenged this view by documenting enhancements and decrements in stimulus-induced firing related to animals internal states, there has been little work setting these changes in any sort of functional, mechanistic context. Here we show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, and then go beyond this to precisely characterize this response plasticity, connecting it to the specific perceptual changes that drive illness impact on consumption.

neuroscience↗

bioRxiv2020

Autonomous sensing the insulin peptide by an olfactory G protein coupled receptor modulates glucose metabolism

Along with functionally intact insulin, diabetes-associated insulin peptides are secreted by {beta} cells(1-3). By screening the expression and functional characterization of olfactory receptors in pancreatic islets, we identified Olfr109 as the receptor to detect insulin peptides. Engagement of one insulin peptide, insB:9-23, with Olfr109 diminished insulin secretion through Gi-cAMP signalling and promoted macrophage proliferation. Remarkably, Olfr109 deficiency alleviated intra-islet inflammatory responses and improved glucose homeostasis in Akita- and HFD-fed mice. We further determined the binding mode between the insB:9-23 and Olfr109. A pepducin-based Olfr109 antagonist improved glucose homeostasis in diabetic and obese mouse models. Collectively, we found that pancreatic {beta} cells use Olfr109 to autonomously detect self-secreted insulin peptides and this detection arrests insulin secretion and crosstalk with macrophages to increase intra-islet inflammation.

physiology↗

bioRxiv2020

Perturbation of amygdala-cortical projections reduces ensemble coherence of palatability coding in gustatory cortex

Taste palatability is centrally involved in consumption decisions--we ingest foods that taste good and reject those that dont. Gustatory cortex (GC) and basolateral amygdala (BLA) almost certainly work together to mediate palatability-driven behavior, but the precise nature of their interplay during taste decision-making is still unknown. To probe this issue, we discretely perturbed (with optogenetics) activity in BLA[->]GC axons during taste deliveries. This perturbation strongly altered GC taste responses, but while the perturbation itself was tonic (2s), the alterations were not--changes preferentially aligned with the onset times of previously-described taste response epochs, and reduced evidence of palatability-related activity in the "late-epoch" of the responses without reducing the amount of taste identity information available in the "middle epoch." Finally, BLA[->]GC perturbations changed behavior-linked taste response dynamics themselves, distinctively diminishing the abruptness of ensemble transitions into the late epoch. These results suggest that BLA "organizes" behavior-related GC taste dynamics.

neuroscience↗

bioRxiv2020

Comparative Analysis of Embryo Proper and Suspensor Transcriptomes in Plant Embryos With Different Morphologies

An important question is what genes govern the differentiation of plant embryos into suspensor and embryo-proper regions following fertilization and division of the zygote. We compared embryo proper and suspensor transcriptomes of four plants that vary in embryo morphology within the suspensor region. We determined that genes encoding enzymes in several metabolic pathways leading to the formation of hormones, such as gibberellic acid, and other metabolites are up-regulated in giant Scarlet Runner Bean and Common Bean suspensors. Genes involved in transport and Golgi body organization are up-regulated within the suspensors of these plants as well - strengthening the view that giant specialized suspensors serve as a hormone factory and a conduit for transferring substances to the developing embryo proper. By contrast, genes controlling transcriptional regulation, development, and cell division are up-regulated primarily within the embryo proper. Transcriptomes from less specialized soybean and Arabidopsis suspensors demonstrated that fewer genes encoding metabolic enzymes and hormones are up-regulated. Genes active in the embryo proper, however, are functionally similar to those active in Scarlet Runner Bean and Common Bean embryo proper regions. We uncovered a set of suspensor- and embryo-proper-specific transcription factors (TFs) that are shared by all embryos irrespective of morphology, suggesting that they are involved in early differentiation processes common to all plants. ChIP-Seq experiments with Scarlet Runner Bean and soybean WOX9, an up-regulated suspensor TF, gained entry into a regulatory network important for suspensor development irrespective of morphology. SignificanceHow plant embryos are differentiated into embryo proper and suspensor regions following fertilization is a major unanswered question. The suspensor is unique because it can vary in morphology in different plant species. We hypothesized that regulatory genes controlling the specification of embryo proper and suspensor regions should be shared by all plants irrespective of embryo morphology. We compared embryo proper and suspensor transcriptomes of plants with distinct suspensor morphologies. Scarlet Runner Bean and Common Bean have highly specialized giant suspensor regions, whereas soybean and Arabidopsis suspensors are smaller and less specialized. We uncovered a small set of embryo-proper- and suspensor-specific transcription factors shared by all embryos irrespective of morphology, suggesting that they play an important role in early embryo differentiation.

plant biology↗

bioRxiv2020

Dual GRIN lens two-photon endoscopy for high-speed volumetric and deep brain imaging

Studying neural connections and activities in vivo is fundamental to understanding brain functions. Given the cm-size brain and three-dimensional neural circuit dynamics, deep-tissue, high-speed volumetric imaging is highly desirable for brain study. With sub-micrometer spatial resolution, intrinsic optical sectioning, and deep-tissue penetration capability, two-photon microscopy (2PM) has found a niche in neuroscience. However, current 2PM typically relies on slow axial scan for volumetric imaging, and the maximal penetration depth is only about 1 mm. Here, we demonstrate that by integrating two gradient-index (GRIN) lenses into 2PM, both penetration depth and volume-imaging rate can be significantly improved. Specifically, an 8-mm long GRIN lens allows imaging relay through a whole mouse brain, while a tunable acoustic gradient-index (TAG) lens provides sub-second volume rate via 100 kHz [~] 1 MHz axial scan. This technique enables the study of calcium dynamics in cm-deep brain regions with sub-cellular and sub-second spatiotemporal resolution, paving the way for interrogating deep-brain functional connectome.

bioengineering↗

bioRxiv2020

Distinct Inductions of and Responses to Type I and Type III Interferons PromoteInfections in Two SARS-CoV-2 Isolates

The recent emerging coronavirus, SARS-CoV-2, has been rapidly and widely spread and causing an ongoing viral pneumonia outbreak worldwide. It has been observed that SARS-CoV-2 patients show a rather long and asymptomatic incubation time. We characterized the abilities to induce and to response to IFN{beta}/IFN{lambda}1 of two or our clinical isolates, SARS-CoV-2/NTU01/TWN/human/2020 and SARS-CoV-2/NTU02/TWN/human/2020, which exhibit only two amino acid differences over the [~]30kb viral genome. We found that both isolates may infect Huh7, A549 and Calu-3 cells, yet the RIG-I-like receptor-dependent antiviral signaling was poorly induced in these cells in the early infections. Unexpectedly, we found that the intracellular vRNA levels of these isolates were sustained upon to type I/III IFN treatments, and this phenotype was more pronounced in the Taiwan/NTU01/2020 isolate. The type I/III IFN responses are antiviral but partially proviral in the case of SARS-CoV-2 infections. Poor induction and response to innate immunity may contribute to destitute neutralization index of the antibody produced, and indeed we found that the patient serum could not efficiently neutralize SARS-CoV-2 virions. With better understandings of the interplay between SARS-CoV-2 and the host antiviral innate immunity, our report may provide new insights for the regimen of therapies for SARS-CoV-2 infected patients.

microbiology↗

bioRxiv2019

Developing a DeSipher method for conformational change detection of membrane receptor complex at residue resolution

While one dimensional 1H nuclear magnetic resonance (1D 1H-NMR) spectroscopy is one of the most important and convenient method for measuring conformation change in biomacromolecules, characterization of protein dynamics in large membrane protein complexes by 1D 1H-NMR remains challenging, due to the difficulty of spectra assignment, low signal-to-noise ratio (S/N) and the need for large amount of protein. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion in Escherichia coli cells, and the measurement of multiple conformational states in membrane protein complex by 1D 1H-NMR. The unique up-field 1H-NMR chemical shift of TMSiPhe, highly efficient and specific incorporation of TMSiPhe enabled facile assignment of the TMSiPhe 1H-NMR signal, and characterization of multiple conformational state in a 150 kilodalton (kD) membrane protein complex, using only 5 M of protein and 20 min spectra accumulation time. This highly efficient and convenient methods should be broadly applicable for the investigation of dynamic conformation change of protein complexes.

biochemistry↗

bioRxiv2019

In vitro pancreatic islet cluster expansion facilitated by hormones and chemicals

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalized drug testing. However, such a protocol has not been realized yet. Propagation could be divided by two steps, which are: (1) expansion in vitro and (2) repeat passaging. Even the in vitro expansion of the islet has not been achieved to date. Here, we describe a method to enable the expansion of islet clusters isolated from pregnant mice or wild-type rats by employing a combination of specific regeneration factors and chemical compounds in vitro. The expanded islet clusters expressed insulin, glucagon and somatostatin, which are markers corresponding to pancreatic {beta} cells, cells and {delta} cells, respectively. These different types of cells grouped together, were spatially organized and functioned similarly to primary islets. Further mechanistic analysis revealed that forskolin in our recipe contributed to renewal and regeneration, whereas exendin4 was essential for preserving islet cell identity. Our results provide a novel method for the in vitro expansion of islet clusters, which is an important step forward in developing future protocols and medium used for islet tissue propagation in vitro. Such method is important for future regenerative diabetes therapies and personalized medicine using large amounts of pancreatic islets derived from the same person.

cell biology↗

bioRxiv2019

Deletion of Stk11 and Fos in BLA projection neurons alters their intrinsic excitability and impairs formation of long-term aversive memory

Conditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms are poorly understood, however. We used RNAseq from BLApn to identify learning-related changes in Stk11, a kinase with well-studied roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 restricted to BLApn completely blocks memory when occurring prior to training, but not following it, despite altering neither BLApn-dependent encoding of taste palatability in gustatory cortex, nor transcriptional activation of BLApn during training. Deletion of Stk11 in BLApn also increases their intrinsic excitability. Conversely, BLApn activated by CTA to express the immediate early gene Fos had reduced excitability. BLApn knockout of Fos also increased excitability and impaired learning. These data suggest that Stk11 and Fos expression play key roles in CTA long-term memory formation, perhaps by modulating the intrinsic excitability of BLApn.

neuroscience↗

bioRxiv2019

Single and population coding of taste in the gustatory cortex of awake mice

Electrophysiological analysis has reveals much about the broad coding and neural ensemble dynamics that characterize gustatory cortical (GC) taste processing in awake rats, and about how these dynamics relate to behavior. With regard to mice, meanwhile, data concerning cortical taste coding have largely been restricted to imaging--a technique that reveals average levels of neural responsiveness, but that (currently) lacks the temporal sensitivity necessary for evaluation of fast response dynamics; furthermore, the few extant studies have thus far failed to provide consensus on basic features of coding. We have recorded the spiking activity of ensembles of GC neurons while presenting representatives of the basic taste modalities (sweet, salty, sour and bitter) to awake mice. Our first central result is the identification of similarities between rat and mouse taste processing: most mouse GC neurons (~66%) responded distinctly to multiple (3-4) tastes; temporal coding analyses further reveal, for the first time, that single mouse GC neurons sequentially code taste identity and palatability--the latter responses emerging ~0.5s after the former--with whole GC ensembles transitioning suddenly and coherently from coding taste identity to coding taste palatability. The second finding is that spatial location plays very little role in any aspect of taste responses--neither between- (anterior-posterior) nor within-mouse (dorsal-ventral) mapping revealed anatomical regions with narrow or temporally simple taste responses. These data confirm recent results showing that mouse cortical taste responses are not \"gustatopic,\" but also go beyond these imaging results to show that mice process tastes through time.

neuroscience↗

bioRxiv2018

Seed Genome Hypomethylated Regions Are Enriched In Transcription Factor Genes

The precise mechanisms that control gene activity during seed development remain largely unknown. Previously, we showed that several genes essential for seed development, including those encoding storage proteins, fatty acid biosynthesis enzymes, and transcriptional regulators, such as ABI3 and FUS3, are located within hypomethylated regions of the soybean genome. These hypomethylated regions are similar to the DNA methylation valleys (DMVs), or canyons, found in mammalian cells. Here, we address the question of the extent to which DMVs are present within seed genomes, and what role they might play in seed development. We scanned soybean and Arabidopsis seed genomes from post-fertilization through dormancy and germination for regions that contain < 5% or < 0.4% bulk methylation in CG-, CHG-, and CHH-contexts over all developmental stages. We found that DMVs represent extensive portions of seed genomes, range in size from 5 to 76 kb, are scattered throughout all chromosomes, and are hypomethylated throughout the plant life cycle. Significantly, DMVs are enriched greatly in transcription factor genes, and other developmental genes, that play critical roles in seed formation. Many DMV genes are regulated with respect to seed stage, region, and tissue - and contain H3K4me3, H3K27me3, or bivalent marks that fluctuate during development. Our results indicate that DMVs are a unique regulatory feature of both plant and animal genomes, and that a large number of seed genes are regulated in the absence of methylation changes during development - probably by the action of specific transcription factors and epigenetic events at the chromatin level.\n\nSignificanceWe scanned soybean and Arabidopsis seed genomes for hypomethylated regions, or DNA Methylation Valleys (DMVs), present in mammalian cells. A significant fraction of seed genomes contain DMV regions that have < 5% bulk DNA methylation, or, in many cases, no detectable DNA methylation. Methylation levels of seed DMVs do not vary detectably during seed development with respect to time, region, and tissue, and are present prior to fertilization. Seed DMVs are enriched in transcription factor genes and other genes critical for seed development, and are also decorated with histone marks that fluctuate with developmental stage, resembling in significant ways their animal counterparts. We conclude that many genes playing important roles in seed formation are regulated in the absence of detectable DNA methylation events, and suggest that selective action of transcriptional activators and repressors, as well as chromatin epigenetic events play important roles in making a seed - particularly embryo formation.

plant biology↗