Biology subjects

Wei, N.

Publications and source records attributed to Wei, N..

28 records · Page 2Linked to original sources

bioRxiv2020

Circadian rhythms of early afterdepolarizations and ventricular arrhythmias in a cardiomyocyte model

AO_SCPLOWBSTRACTC_SCPLOWSudden cardiac arrest is a malfunction of the hearts electrical system, typically caused by ventricular arrhythmias, that can lead to sudden cardiac death (SCD) within minutes. Epidemiological studies have shown that SCD and ventricular arrhythmias are more likely to occur in the morning than in the evening, and laboratory studies indicate that these daily rhythms in adverse cardiovascular events are at least partially under the control of the endogenous circadian timekeeping system. However, the biophysical mechanisms linking molecular circadian clocks to cardiac arrhythmogenesis are not fully understood. Recent experiments have shown that L-type calcium channels exhibit circadian rhythms in both expression and function in guinea pig ventricular cardiomyocytes. We developed an electrophysiological model of these cells to simulate the effect of circadian variation in L-type calcium conductance. We found that there is a circadian pattern in the occurrence of early afterdepolarizations (EADs), which are abnormal depolarizations during the repolarization phase of a cardiac action potential that can trigger fatal ventricular arrhythmias. Specifically, the model produces EADs in the morning but not at other times of day. We show that the model exhibits a codimension-2 Takens-Bogdanov bifurcation that serves as an organizing center for different types of EAD dynamics. We also simulated a 2-D spatial version of this model across a circadian cycle. We found that there is a circadian pattern in the breakup of spiral waves, which represents ventricular fibrillation in cardiac tissue. Specifically, the model produces spiral wave breakup in the morning but not in the evening. Our study is the first to propose a link between circadian rhythms and EAD formation and suggests that the efficacy of drugs targeting EAD-mediated arrhythmias may depend on the time of day that they are administered. Significance StatementWhy are life-threatening cardiac arrhythmias more likely to occur in the morning than in the evening? The electrical properties of the heart exhibit daily rhythms due to molecular circadian clocks within cardiomyocytes. Our computational model of ventricular myocytes shows that clock-controlled expression of a voltage-gated calcium ion channel leads to early afterdepolarizations (EADs) at certain times of the day. EADs, in which the membrane potential of a cardiomyocyte depolarizes a second time before fully repolarizing, can trigger arrhythmias. To our knowledge, this is the first study linking the circadian clock to EAD formation. Our results suggest that the efficacy of anti-arrhythmic medications targeting this calcium ion channel may depend on the time of day the drug is taken.

biophysics↗

bioRxiv2020

Nucleus translocation of tRNA synthetase mediates late integrated stress response

Various stress conditions are signaled through phosphorylation of translation initiation factor eIF2 to inhibit global translation while selectively activating transcription factor ATF4 to aid cell survival and recovery. However, this integrated stress response is acute and cannot resolve lasting stress. Here we report that TyrRS, a member of the aminoacyl-tRNA synthetase family capable of responding to diverse stress factors through cytosol-nucleus translocation and activating stress-response genes, also inhibits global translation, however at a later stage than eIF2/ATF4 and mTOR responses. Excluding TyrRS from the nucleus over-activates protein synthesis and increases apoptosis in cells under prolonged oxidative stress. Nuclear TyrRS transcriptionally represses translation genes by recruiting TRIM28 and/or NuRD complex. We propose TyrRS, possibly along with other family members, can sense a variety of stress signals through intrinsic properties of this enzyme and its strategically located nuclear localization signal and integrate them by nucleus-translocation to effect protective responses against prolonged stress.

molecular biology↗

bioRxiv2020

Pollinator niche partitioning and asymmetric facilitation contribute to the maintenance of diversity

AbstractMechanisms that favor rare species are key to the maintenance of diversity. One of the most critical tasks for biodiversity conservation is understanding how plant-pollinator mutualisms contribute to the persistence of rare species, yet this remains poorly understood. Using a process-based model that integrates plant-pollinator and interspecific pollen transfer networks with floral functional traits, we show that niche partitioning in pollinator use and asymmetric facilitation confer fitness advantage of rare species in a biodiversity hotspot. While co-flowering species filtered pollinators via floral traits, rare species showed greater pollinator specialization leading to higher pollination-mediated male and female fitness than abundant species. When plants shared pollinator resources, asymmetric facilitation via pollen transport dynamics benefited the rare species at the cost of the abundant ones, serving as an alternative diversity-promoting mechanism. Our results emphasize the importance of community-wide plant-pollinator interactions that affect reproduction for biodiversity maintenance.

ecology↗

bioRxiv2019

PhyB induces intron retention and uORF-mediated translational inhibition of PIF3

The phytochrome B (phyB) photoreceptor stimulates light responses in plants in part by inactivating repressors of light responses such as phytochrome-interacting factor 3 (PIF3). It has been established that activated phyB inhibits PIF3 by rapid protein degradation and decreased transcription. PIF3 protein degradation has been shown to be mediated by EIN3-BINDING F-BOX PROTEIN (EBF) and LIGHT-RESPONSE BTB (LRB) E3 ligases, the latter simultaneously targeting phyB for degradation. In this study, we show that PIF3 level is additionally regulated by alternative splicing and protein translation. Overaccumulation of photo-activated phyB, which occur in the mutant defective for LRB genes under continuous red light (Rc), induces a specific alternative splicing of PIF3 that results in retention of an intron in the 5UTR of PIF3 mRNA. In turn, the upstream opening reading frames (uORF) contained within this intron inhibit PIF3 protein synthesis. The phyB-dependent alternative splicing of PIF3 is diurnally regulated under the short-day light cycle. We hypothesize that this reversible regulatory mechanism may be utilized to fine-tune the level of PIF3 protein in light-grown plants, and may contribute to the oscillation of PIF3 protein abundance under the short-day environment.\n\nOne Sentence SummaryLight down-regulates PIF3 by multiple mechanisms. We show that phyB induces an alternative splicing event that inhibits PIF3 protein translation, and that is regulated by short-day diurnal cycle.

plant biology↗

bioRxiv2019

Empathic contagious pain and consolation in laboratory rodents: species and sex differences

Laboratory rodents are gregarious in nature and have a feeling of empathy when witnessing a familiar conspecific in pain. The rodent observers express two levels of empathic responses: observational contagious pain (OCP) and consolation. Here we examined the sex and species difference of OCP and consolation in male and female mice and rats. We observed no species difference in both OCP and consolation, but significant species difference in general social (allo-mouth and/or allo-tail sniffing) and non-social (self-grooming) behaviors. For sex difference, male mouse observers showed more allolicking and allogrooming behaviors toward a familiar conspecific in pain during and longer time increase in pain sensitivity after the PDSI than female mouse observers. However, no sex difference was observed in rats. Our results highlighted an evolutionary view of empathy that social animals including rodents also have the ability to feel, recognize, understand and share the others distressing states.

animal behavior and cognition↗

bioRxiv2019

Revisiting the Origin of the Octoploid Strawberry

The cultivated strawberry, Fragaria xananassa, originated in France approximately 270 years ago via hybridization between two wild species introduced from North and South America. Both the cultivated strawberry and its parental species are octoploids with 2n=8x=56 chromosomes. In the recent publication of the genome of the cultivated strawberry, the authors present a novel phylogenetic hypothesis, proposing that each of the four subgenomes originated from a different 2n=2x=14 diploid progenitor. They further suggest that the hexaploid species Fragaria moschata was a direct ancestor of the strawberries. We reanalyzed the four octoploid subgenomes in a phylogenomic context, and found that only two extant diploids were progenitors, a result that is consistent with several previous studies. We also conducted a phylogenetic analysis of genetic linkage-mapped loci in the hexaploid F. moschata, and resolved its origin as independent of the octoploids. We identified assumptions in their tree-searching algorithm that prevented it from accepting extinct or unsampled progenitors, and we argue that this is a critical weakness of their approach. Correctly identifying their diploid progenitors is important for understanding and predicting the responses of polyploid plants to climate change and associated environmental stress.

plant biology↗

bioRxiv2018

Both functional trait divergence and trait plasticity confer polyploid advantage in changing environments

Polyploidy, or whole genome duplication, exists in all eukaryotes and is thought to drive ecological and evolutionary success especially in plants. The mechanisms of polyploid success in ecologically relevant contexts, however, remain largely unknown. Here we conducted an extensive test of functional trait divergence and trait plasticity in conferring polyploid fitness advantage in changing environments by growing clonal replicates of a worldwide genotype collection of six polyploid and five diploid wild strawberry (Fragaria) species in three climatically different common gardens. Among leaf functional traits, we detected divergence in means but not plasticities between polyploids and diploids, suggesting that increased genomic redundancy does not necessarily translate into broader phenotypic amplitude in polyploids. Across the heterogeneous garden environments, however, polyploids exhibited fitness advantage, which was conferred by both trait means and adaptive trait plasticities, supporting a jack-and-master hypothesis for polyploids. Our findings provide unparalleled insight into the prevalence and persistence of polyploidization.

ecology↗

bioRxiv2018

Inhibition of Hsp70 suppresses neuronal hyperexcitability and attenuates seizures by enhancing A-type potassium currents

The heat shock protein 70 (Hsp70) is upregulated in response to stress and has been implicated as a stress marker in temporal lobe epilepsy (TLE). However, whether Hsp70 plays a pathologic or protective role in TLE remains unclear. Here we report that Hsp70 exerts an unexpected deleterious role in kainic acid (KA)-induced seizures, and inhibition of Hsp70 suppresses neuronal hyperexcitability and attenuates both acute and chronic seizures via enhancing A-type potassium currents primarily formed by Kv4 -subunits and auxiliary KChIPs. Proteosomal degradation of Kv4-KChIP4a channel complexes is enhanced by Hsp70, which can be reversed by the Hsp70 inhibitors, 2-phenylethynesulfonamide (PES) and VER-155008 (VER). In cultured hippocampal neurons, either PES or VER can increase A-type Kv4 current to suppress neuronal hyperexcitability. Mechanistically, Hsp70-CHIP complexes directly bind to the N-terminus of auxiliary KChIP4a and target Kv4-KChIP4a complexes to the proteasome. Our findings reveal a previously unrecognized role of Hsp70 in mediating degradation of Kv4-KChIP4a complexes and regulating neuronal excitability, thus highlighting a therapeutic potential for hyperexcitability-related neurological disorders through Hsp70 inhibition.

neuroscience↗

bioRxiv2017

The effects of host species and sexual dimorphism differ among root, leaf and flower microbiomes of wild strawberries in situ

Plant-associated microbiomes profoundly influence host interactions with below- and aboveground environments. Characterizing plant-associated microbiomes in experimental settings have revealed important drivers of microbiota assemblies within host species. However, it remains unclear how important these individual drivers (e.g., organ type, host species, host sexual phenotype) are in structuring the patterns of plant-microbiota association in the wild.\n\nUsing 16s rRNA sequencing, we characterized root, leaf and flower microbiomes in three closely related, sexually polymorphic Fragaria species, in the broadly sympatric portion of their native ranges in Oregon, USA. Taking into account the potential influence of broad-scale abiotic environments, we quantified the relative effects of organ type, host species and sex on the - and {beta}-diversity of bacterial communities in these wild populations. Our statistical models showed that organ type explained the largest variation of compositional and phylogenetic - and {beta}-diversity of plant microbiomes, and its overall effect exceeded that of host plant species. Yet, the influence of host species increased from root to leaf to flower microbiomes. We found strong sexual dimorphism in flower and leaf microbiomes, especially in host species with the most complete separation of sexes. Our results provide the first demonstration of enhanced effects of host species and sexual dimorphism from root to flower microbiomes. While these findings await manipulative experiments to disentangle contributions of micro-environment and the residing microbiota from host genetic effects, we anticipate that such phenotypic patterns of host species-microbiota association may be broadly applicable to other plants in the wild.

microbiology↗

bioRxiv2017

Repeated translocation of a gene cassette drives sex chromosome turnover in strawberries

Turnovers of sex-determining systems represent important diversifying forces across eukaryotes. Shifts in sex chromosomes, but conservation of the master sex-determining genes, characterize distantly-related animal lineages. Yet in plants, where separate sexes have evolved repeatedly and sex chromosomes are typically homomorphic, we do not know whether such translocations drive turnovers within closely related groups. This phenomenon can only be demonstrated by identifying sex-associated nucleotide sequences, still largely unknown in plants. The wild North American octoploid strawberries (Fragaria) exhibit separate sexes (dioecy) with homomorphic, female heterogametic (ZW) inheritance, yet sex maps to at least three different chromosomes. To characterize these turnovers, we sequenced the complete genomes of 60 plants of known sex from five Fragaria taxa. We identified 31-mers unique to females and assembled their reads into contigs. Remarkably, a short (13 kb) sequence is observed in nearly all females and never in male-fertile individuals, implicating it as the sex-determining region (SDR). This female-specific \"SDR cassette\" contains both a gene with a known role in fruit and pollen production and a novel retrogene absent on Z and autosomal chromosomes. Comparing SDR cassettes across taxa reveals a history of repeated translocation, which can be ordered temporally due to the capture of adjacent sequence with each successive move. The accumulation of these \"souvenirs\" suggests an adaptive basis for the expanding (up to at least 23 kb) hemizygous region. This is the first plant SDR known to be translocated, and it suggests a new mechanism (\"move-lock-grow\") for expansion and diversification of incipient sex chromosomes.\n\nSignificance StatementSex chromosomes frequently restructure themselves during organismal evolution, often becoming highly differentiated. This dynamic process is poorly understood for most taxa, especially during the early stages typical of many dioecious plants. In wild strawberries, a sex-determining region of DNA has repeatedly changed its genomic location, each time increasing the size of the hemizygous female-specific sequence. This observation shows for the first time that plant sex regions can \"jump\", and suggests that this phenomenon may be adaptive by gathering and locking new genes into linkage with sex. This conserved and presumed causal sequence with a variable genomic location presents a unique opportunity to understand how sex chromosomes first begin to differentiate.

evolutionary biology↗