Biology subjects

Yang, Y.-Y.

Publications and source records attributed to Yang, Y.-Y..

4 recordsLinked to original sources

bioRxiv2021

Geraniol Enhances Inhibitory Inputs to Paraventricular Thalamic Nucleus and Induces Sedation in Mice

Geraniol (GE), a plant-derived acyclic monoterpene, shows a wide variety of beneficial effects. Notably, recent studies have reported the potential sedative effects of GE in fish and rats. However, the mechanisms of GE in sedation remain elusive. Here, we found that GE reduced locomotion, relieved pentylenetetrazol (PTZ)-induced seizures, altered the electroencephalogram (EEG), and facilitated general anesthesia in mice. Meanwhile, GE decreased c-Fos expression and suppressed the calcium activity in the paraventricular thalamic nucleus (PVT). Microinjection of GE into the PVT reduced locomotion and facilitated propofol-induced anesthesia. Furthermore, the electrophysiology results showed that GE-induced dramatic membrane hyperpolarization and suppressed the neuronal activity of PVT neurons, mainly by prolonging spontaneous inhibitory postsynaptic currents and inducing tonic inhibitory currents via GABAA receptors. Our study revealed that GE enhances inhibitory inputs to PVT neurons and induces sedation in mice. These findings provide a potential candidate for further development of sedatives and anesthetics. Graphic Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/441289v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@fd8424org.highwire.dtl.DTLVardef@1ee77caorg.highwire.dtl.DTLVardef@faab42org.highwire.dtl.DTLVardef@101b921_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Gene duplications and genomic conflict underlie major pulses of phenotypic evolution in gymnosperms

Inferring the intrinsic and extrinsic drivers of species diversification and phenotypic disparity across the Tree of Life is a major challenge in evolutionary biology. In green plants, polyploidy (or whole-genome duplication, WGD) is known to play a major role in microevolution and speciation1, but the extent to which WGD has shaped macroevolutionary patterns of diversification and phenotypic innovation across plant phylogeny remains an open question. Here we examine the relationship of various facets of genomic evolution--including gene and genome duplication, genome size, and chromosome number--with macroevolutionary patterns of phenotypic innovation, species diversification, and climatic occupancy in gymnosperms. We show that genomic changes, such as WGD and genome-size shifts, underlie the origins of most major extant gymnosperm clades, and notably our results support an ancestral WGD in the gymnosperm lineage. Spikes of gene duplication typically coincide with major spikes of phenotypic innovation, while increased rates of phenotypic evolution are typically found at nodes with high gene-tree conflict, representing historic population-level dynamics during speciation. Most shifts in gymnosperm diversification since the rise of angiosperms are decoupled from putative WGDs and instead are associated with increased rates of climatic occupancy evolution, particularly in cooler and/or more arid climatic conditions, suggesting that ecological opportunity, especially in the later Cenozoic, and environmental heterogeneity have driven a resurgence of gymnosperm diversification. Our study provides critical insight on the processes underlying diversification and phenotypic evolution in gymnosperms, with important broader implications for the major drivers of both micro- and macroevolution in plants.

evolutionary biology↗

bioRxiv2021

The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation

Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 severity, including the TRIM4 interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein. Viral NSP1 protein adjacency to the EIF3 complex was associated with inhibited host protein translation whereas ORF6 localization with MAVS was associated with inhibited RIG-I 2CARD-mediated IFNB1 promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 protease, with specific functional cleavage sequences in host proteins CWC22 and FANCD2. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2. Author SummarySARS-CoV-2 is the latest pathogenic coronavirus to emerge as a public health threat. We create a database of proximal host proteins to 17 SARS-CoV-2 viral proteins. We validate that NSP1 is proximal to the EIF3 translation initiation complex and is a potent inhibitor of translation. We also identify ORF6 antagonism of RNA-mediate innate immune signaling. We produce a database of potential host targets of the viral protease NSP5, and create a fluorescence-based assay to screen cleavage of peptide sequences. We believe that this data will be useful for identifying roles for many of the uncharacterized SARS-CoV-2 proteins and provide insights into the pathogenicity of new or emerging coronaviruses.

microbiology↗

bioRxiv2019

Base-rate neglect and neural computations for subjective weight in probabilistic inference

AO_SCPLOWBSTRACTC_SCPLOWHumans show systematic biases when estimating probability of uncertain events. Base-rate neglect is a well-known bias that describes the tendency to underweight information from the past relative to the present. In this study, we characterized base-rate neglect at the computational and neural implementation levels. At the computational level, we established that base-rate neglect arises from insufficient adjustment to weighting prior information in response to changes in prior variability. At the neural implementation level, we found that orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) represent subjective weighting of information that reflects base-rate neglect. Critically, both subjective-weight and subjective-value signals that guide choice were found in mPFC. However, subjective-weight signals preceded subjective-value signals. These results indicate that when facing multiple sources of information, estimation bias such as base-rate neglect arises from information weighting computed in OFC and mPFC, which directly contributes to subjective-value computations that guide decisions under uncertainty.\n\nSO_SCPLOWIGNIFICANCEC_SCPLOW SO_SCPLOWTATEMENTC_SCPLOWFacing uncertainty, estimating the probability of different potential outcomes carries significant weight in affecting how we act and decide. Decades of research show that humans are prone to giving biased estimation but it remains elusive how these biases arise in the brain. We focus on base-rate neglect, a well-known bias in probability estimation and find that it is tightly associated with activity in the medial prefrontal cortex and orbitofrontal cortex. These regions represent the degree to which human participants weigh different sources of information, suggesting that base-rate neglect arises from information-weighting computations in the brain. As technology provides us the opportunity to seek and gather information at an ever-increasing pace, understanding information-weighting and its biases also carry important policy implications.

neuroscience↗