Biology subjects

Xiao, S.

Publications and source records attributed to Xiao, S..

At least 91 records · Page 5Linked to original sources

bioRxiv2022

Haploid-resolved and chromosome-scale genome assembly in hexa-autoploid sweetpotato (Ipomoea batatas (L.) Lam)

Sweetpotato (Ipomoea batatas (L.) Lam) is the worlds seventh most important food crop by production quantity. Cultivated sweetpotato is a hexaploid (2n = 6x = 90), and its genome (B1B1B2B2B2B2) is quite complex due to polyploidy, self-incompatibility, and high heterozygosity. Here we established a haploid-resolved and chromosome-scale de novo assembly of autohexaploid sweetpotato genome sequences. Before constructing the genome, we created chromosome-scale genome sequences in I. trifida using a highly homozygous accession, Mx23Hm, with PacBio RSII and Hi-C reads. Haploid-resolved genome assembly was performed for a sweetpotato cultivar, Xushu18 by hybrid assembly with Illumina paired-end (PE) and mate-pair (MP) reads, 10X genomics reads, and PacBio RSII reads. Then, 90 chromosome-scale pseudomolecules were generated by aligning the scaffolds onto a sweetpotato linkage map. De novo assemblies were also performed for chloroplast and mitochondrial genomes in I. trifida and sweetpotato. In total, 34,386 and 175,633 genes were identified on the assembled nucleic genomes of I. trifida and sweetpotato, respectively. Functional gene annotation and RNA-Seq analysis revealed locations of starch, anthocyanin, and carotenoid pathway genes on the sweetpotato genome. This is the first report of chromosome-scale de novo assembly of the sweetpotato genome. The results are expected to contribute to genomic and genetic analyses of sweetpotato.

genomics↗

bioRxiv2022

Nested circuits mediate the decision to vocalize

Vocalizations facilitate mating and social affiliation, but may also inadvertently alert predators and rivals. Consequently, the decision to vocalize depends on brain circuits that can weigh and compare these potential benefits and risks. Male mice produce ultrasonic vocalizations (USVs) during courtship to facilitate mating and female mice produce USVs to promote social affiliation with each other. Previously we showed that a specialized set of neurons in the midbrain periaqueductal gray (PAG) are an obligatory gate for USV production in both male and female mice, and that both PAG-USV neurons and USVs can be switched on by their inputs from the preoptic area (POA) of the hypothalamus and switched off by their inputs from neurons on the border between the central and medial amygdala (AmgC/M-PAG neurons) (Michael et al., 2020). Here we show that the USV-suppressing AmgC/M-PAG neurons are strongly activated by predator cues or during social contexts that suppress USV production in male and female mice. Furthermore, a subset of USV-promoting POA neurons that provide input to the PAG-USV region also extend axon collaterals to the amygdala, where they directly inhibit AmgC/M-PAG neurons. Accordingly, AmgC/M-PAG neurons, along with POAPAG and PAG-USV neurons, form a nested hierarchical circuit in which environmental and social information converges to influence the decision to vocalize.

neuroscience↗

bioRxiv2022

High-throughput deep tissue two-photon microscopy at kilohertz frame rates

Strategies to image biological phenomena at millisecond time scales are generally technically challenging and suffer from compromises between imaging field-of-view, depth penetration and excitation efficiency in thick tissue. We present a simple and cost-effective solution that enables a conventional video-rate two-photon microscope (2PM) to perform 2D scanning at kilohertz frame rates, while preserving all the benefits of standard 2PM, which we demonstrate by imaging neurovascular dynamics in mouse brains.

bioengineering↗

bioRxiv2022

Probing Action Potential Generation and Timing under Multiplexed Basal Dendritic Computations Using Two-photon 3D Holographic Uncaging

Basal dendrites of layer 5 cortical pyramidal neurons exhibit Na+ and NMDAR spikes, and are uniquely poised to influence somatic output. Nevertheless, due to technical limitations, how multibranch basal dendritic integration shapes action-potential output remains poorly mapped. Here, we combine 3D two-photon holographic transmitter-uncaging, whole-cell dynamic-clamp, and biophysical modeling, to reveal how synchronously activated synapses (distributed and clustered) across multiple basal dendritic branches impacts action-potential generation - under quiescent and in vivo like conditions. While dendritic Na+ spikes promote milli-second precision, distributed inputs and NMDAR spikes modulate firing rates via axo-somatic persistent sodium channel amplification. Action-potential precision, noise-enhanced responsiveness, and improved temporal resolution, were observed under high conductance states, revealing multiplexed dendritic control of somatic output amidst noisy membrane-voltage fluctuations and backpropagating spikes. Our results unveil a critical multibranch integration framework in which a delicate interplay between distributed synapses, clustered synapses, and axo-somatic subthreshold conductances, dictates somatic spike precision and gain.

neuroscience↗

bioRxiv2022

Pathogen effector-associated nuclear-localization of RPW8.2 amplifies its expression to boost immunity in Arabidopsis

RESISTANCE TO POWDERY MILDEW 8 (RPW8) defines a unique N-terminal coiled-coil domain of nucleotide-binding and leucine-rich repeat immune receptors required for immune signaling in plants. Arabidopsis RPW8.2 is specifically induced by the powdery mildew (PM) fungus (Golovinomyces cichoracearum) in the infected epidermal cells to activate immunity. The mechanism of RPW8.2-induction is not well understood. Here, we identify a G. cichoracearum factor delivered to the nucleus of the host cell, named Gc-RPW8.2 interacting protein 1 (GcR8IP1). Ectopic expression of GcR8IP1 in Arabidopsis or Nicotiana benthamiana suppressed host immune responses and enhanced susceptibility to PM. Host-induced gene silencing of GcR8IP1 compromised PM infectivity in susceptible Arabidopsis plants. Co-expression of GcR8IP1 with RPW8.2 increased nuclear localization of RPW8.2, which in turn, promoted transcriptional amplification of RPW8.2. Thus, RPW8.2-dependent defense strengthening is due to altered partitioning of RPW8.2 by an effector of a PM fungus, which exemplifies an atypical form of effector-triggered immunity.

plant biology↗

bioRxiv2022

SiPLATZ12 transcript factor regulates multiple yield traits and salt tolerance in foxtail millet (Setaria italica)

Grain yield and salt tolerance are critical for crop production. However, the genetic and biochemical basis underlying the trade-off of these characters remain poorly described in crops. We show here that SiPLATZ12 transcription factor positively regulates multiple elite yield traits at the expense of salt tolerance in foxtail millet. SiPLATZ12 overexpression increases seed size, panicle length, and stem diameter, while reduces plant height and salt tolerance of foxtail millet. A 9-bp insertion in the SiPLATZ12 promoter has significant effects on the different expression of SiPLATZ12, multiple yield traits, and salt tolerance between foxtail millet and its wild ancestor, green foxtail. Moreover, SiPLATZ12 upregulates the expression of genes involved in seed development, but repressing the transcription of most NHX, SOS, and CBL genes to regulate Na+, K+ and pH homeostasis. Therefore, our results uncover a domesticated site that could be used to improve grain yield and salt tolerance in foxtail millet.

molecular biology↗

bioRxiv2022

Foxn1 overexpression promotes thymic epithelial progenitor cell proliferation and mTEC maintenance, but does not prevent thymic involution

The transcription factor FOXN1 is essential for fetal thymic epithelial cell (TEC) differentiation and proliferation. In the postnatal thymus, Foxn1 levels vary widely between different TEC subsets, from low or undetectable in putative TEC progenitors to highest in the most differentiated TEC subsets. Correct Foxn1 expression is also required to maintain the postnatal microenvironment, as premature down-regulation of Foxn1 causes a rapid involution-like phenotype, while transgenic over-expression can cause thymic hyperplasia and/or delayed involution. In the current study, we investigated a K5.Foxn1 transgene that drives Foxn1 over-expression in TECs, but does not cause hyperplasia, nor does it delay or prevent aging-related involution. Similarly, this transgene cannot rescue thymus size in Foxn1lacZ/lacZ mice that undergo premature involution due to reduced Foxn1 levels. However, K5.Foxn1 transgenics do maintain TEC differentiation and cortico-medullary organization with aging both alone and in hypomorphic Foxn1lacZ/lacZ mice. Analysis of candidate TEC markers showed co-expression of progenitor and differentiation markers as well as increased proliferation in Plet-1+ TECs associated with Foxn1 expression. These results demonstrate that the functions of FOXN1 in promoting TEC proliferation and differentiation are separable and context-dependent, and suggest that modulating Foxn1 levels can regulate the balance of proliferation and differentiation in TEC progenitors.

developmental biology↗

bioRxiv2022

Bi-Phasic Quasistatic Brain Communication for Fully Untethered Connected Brain Implants

Wireless communication using electro-magnetic (EM) fields acts as the backbone for information exchange among wearable devices around the human body. However, for Implanted devices, EM fields incur high amount of absorption in the tissue, while alternative modes of transmission including ultrasound, optical and magnetoelectric methods result in large amount of transduction losses due to conversion of one form of energy to another, thereby increasing the overall end-to-end energy loss. To solve the challenge of wireless powering and communication in a brain implant with low end-end channel loss, we present Bi-Phasic Quasistatic Brain Communication (BP-QBC), achieving < 60dB worst-case end-to-end channel loss at a channel length of ~55mm, by using Electro-quasistatic (EQS) Signaling that avoids transduction losses due to no field-modality conversion. BP-QBC utilizes dipole coupling based signal transmission within the brain tissue using differential excitation in the transmitter (TX) and differential signal pick-up at the receiver (RX), while offering ~41X lower power w.r.t. traditional Galvanic Human Body Communication (G-HBC) at a carrier frequency of 1MHz, by blocking any DC current paths through the brain tissue. Since the electrical signal transfer through the human tissue is electro-quasistatic up to several 10s of MHz range, BP-QBC allows a scalable (bps-10Mbps) duty-cycled uplink (UL) from the implant to an external wearable. The power consumption in the BP-QBC TX is only 0.52 W at 1Mbps (with 1% duty cycling), which is within the range of harvested power in the downlink (DL) from a wearable hub to an implant through the EQS brain channel, with externally applied electric currents < 1/5th of ICNIRP safety limits. Furthermore, BP-QBC eliminates the need for sub-cranial interrogators/repeaters, as it offers better signal strength due to no field transduction. Such low end-to-end channel loss with high data rates enabled by a completely new modality of brain communication and powering has deep societal and scientific impact in the fields of neurobiological research, brain-machine interfaces, electroceuticals and connected healthcare.

biophysics↗

bioRxiv2022

Genome-wide identification of SINA gene family in sugarcane and functional analysis of SsSINA1a in drought response

Sugarcane (Saccharum spp. hybrid) is a crucial sugar and energy crop that provides majority of the raw material for sugar and ethanol production globally. Drought represents one of the most critical constraints of sugarcane production in the subtropical parts of China. SEVEN IN ABSENTIA (SINA) act as an important E3 ubiquitin ligase and play a significant role in plant stress responses. However, the characteristics of the sugarcane SINA gene family have not been previously studied currently. Here, we identified 15 SsSINA in Saccharum spontaneum, 5 ShSINA in Saccharum spp. hybrid and 6 SbSINA in Sorghum bicolor based on their conserved N{square}terminal RING and C-terminal SINA domains, and these genes were distributed into three phylogenetic groups (I, {square} and {square}). Collinearity analysis showed a close genetic relationship between the SINA genes of S. spontaneum and S. bicolor. The cis-regulatory elements in the promoter regions of the SINA genes were involved in a variety of plant physiological responses. Further, we identified a SINA gene SsSINA1a that significantly induced by drought stress. Overexpression of SsSINA1a enhanced drought tolerance in Arabidopsis through reducing leaf water loss rate. These finding indicate that SsSINA1a mediates plant drought tolerance and this study provides a new potential candidate gene for sugarcane drought-resistant breeding.

molecular biology↗

bioRxiv2022

Single and complex spikes relay distinct frequency-dependent circuit information in the hippocampus

Hippocampal neurons generate either single spikes or stereotyped bursts of spikes known as complex spikes. Although single and complex spikes co-occur in the same neuron, their contribution to information processing remains unclear. We analyzed hippocampal CA1 neurons in awake mice and in behaving rats, combining cellular membrane voltage imaging with optogenetics and extracellular recordings. We found that network-driven subthreshold membrane rhythms in the theta versus gamma frequencies preferably entrained complex versus single spikes in individual neurons. Optogenetic membrane perturbation revealed a causal link between subthreshold theta and gamma power and the initiation of complex versus single spikes. Further, single and complex spikes exhibited different place field properties and frequency-dependent coding during spatial navigation. Thus, individual hippocampal neurons do not integrate theta and gamma rhythms into a combined spike timing code, but instead, transmit frequency-specific information as distinct output modes of single versus complex spikes during spatial cognition.

neuroscience↗

bioRxiv2022

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model

Spinal cord injury (SCI) can cause severe motor impairment. Post-SCI treatment has focused primarily on secondary injury, with neuroinflammation and neuronal apoptosis as the primary therapeutic targets. Aucubin (Au), a Chinese herbal medicine, exerts anti-inflammatory and neuroprotective effects. The therapeutic effects of Au in SCI have not been reported. We showed that Au can promote functional recovery after SCI. Recovery may occur through the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-{kappa}B) pathway to promote M2/M1 polarization in microglia and inhibit mitochondrial dysfunction to reduce neuronal apoptosis. These biochemical changes result in reduced secondary injury and facilitate axon regeneration. Therefore, Au may be a promising post-SCI therapeutic medication.

cell biology↗

bioRxiv2022

Ccdc38 is required for sperm flagellum biogenesis and male fertility in mouse

Sperm flagellum is essential for male fertility, defects in flagellum biogenesis are associated with male infertility. Deficiency of CCDC42 is associated with malformation of the mouse sperm flagella. Here, we find that the testis-specific expressed protein CCDC38 (coiled-coil domain containing 38) interacts with CCDC42 and localizes on manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in distorted manchette, multiple morphological abnormalities of the flagella (MMAF) of spermatozoa, and eventually male sterility. Furthermore, we find that CCDC38 interacts with intra-flagellar transport protein 88 (IFT88) as well as the outer dense fibrous 2 (ODF2), and its depletion reduces the transportation of ODF2 to flagellum. Altogether, our results uncover the essential role of CCDC38 during sperm flagellum biogenesis, and suggesting the defects of these genes might be associated with male infertility in human being. Summary statementWe demonstrated that CCDC38, localizes on manchette and sperm tail, is crucial for male fertility.

developmental biology↗

bioRxiv2022

Three amphioxus reference genomes reveal gene and chromosome evolution of chordates

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding into the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention or rearrangements between descendants of whole genome duplications (WGDs), which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its 3D chromatin architecture at the onset of zygotic activation, and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes, and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

evolutionary biology↗

bioRxiv2022

GJA1-20k, an internally translated isoform of Connexin 43, is an actin capping protein

Previously, we identified that GJA1-20k, an internally translated isoform of Connexin 43, mediates an actin-dependent protective form of mitochondrial fission (Shimura, Nuebel et al. 2021). We found that when GJA1-20k is present, bands of actin surround mitochondria at locations enriched with GJA1-20k, inducing mitochondrial fission which generates less oxygen free radicals, protecting hearts subjected to ischemia-reperfusion injury. Here, we report that GJA1-20k is a direct actin binding protein and thereby identify the mechanism by which GJA1-20k is able to recruit and stabilize actin filaments around the mitochondria. Surprisingly, GJA1-20k functions as a canonical actin capping protein, producing both truncated actin puncta and stabilized actin filaments. GJA1-20k contains an RPEL-like actin binding motif, and we confirm with both computational modeling and biochemistry, that this domain is crucial for actin capping. The actin capping functionality of GJA1-20k adds GJA1-20k to the family of proteins that regulate actin dynamics. As a stress responsive protein, GJA1-20k can help explain cytoskeletal dependent responses to cellular stress, from delivery of channels to affecting mitochondrial size and function.

cell biology↗

bioRxiv2022

Adjunctive inhibition of the integrated stress response pathway accelerates bacterial clearance in a mouse model of tuberculosis

Tuberculosis (TB) is a devastating infectious disease that continues to cause millions of human deaths every year. Even though most cases of TB can be cured with a 6-month antibiotic combination therapy, these long treatment durations have led to the emergence of multi-drug resistance and pose a major hurdle to global TB control. Despite numerous advances in TB drug development, a substantially shortened treatment time has yet to be achieved. Given the rise in antibiotic resistance, an alternative strategy to the direct targeting of M. tuberculosis (M.tb) is the development of host-directed therapies (HDTs) that promote bacterial clearance and/or lung health when given adjunctive to standard TB antibiotics. We recently discovered that a small molecule inhibitor of the Integrated Stress Response (ISR), which is abnormally activated in TB and associated with the formation of necrotic granulomas, reduced M.tb numbers and lung inflammation in mice. Here, we evaluated the therapeutic potential of adjunctive ISR inhibition in the context of standard TB therapy. Throughout the course of treatment, ISR inhibition robustly lowered bacterial burdens compared to standard TB therapy alone and accelerated the time-to-sterility in mice, as demonstrated by significantly reduced relapse rates after 4 months of treatment. In addition, mice receiving adjunctive ISR inhibition tended to have reduced lung necrosis and inflammation. Together, our findings identify the ISR pathway as a promising therapeutic target with the potential of shortening TB treatment durations and improving lung health.

microbiology↗

bioRxiv2021

Spatially regulated protease activity in lymph nodes renders B cell follicles a sanctuary for retention of intact antigens

The structural integrity of vaccine antigens is critical, as antigen degradation in vivo could eliminate neutralizing epitopes and create competing B cell responses against irrelevant breakdown products. Using FRET imaging and imaging zymography, we found that protease activity and antigen breakdown are spatially heterogeneous in lymph nodes. Following protein immunization, antigens are rapidly degraded in the subcapsular sinus, paracortex, and interfollicular regions of the tissue. By contrast, the follicles and follicular dendritic cell (FDC) networks exhibit low protease activity and antigen degradation rates. Immunization regimens targeting antigen rapidly to FDCs led to germinal centers (GCs) where responses to intact antigen were highly dominant, while traditional bolus immunizations led to weaker GC responses where more GC B cells bound to breakdown products than intact antigen. Thus, spatially-compartmentalized antigen proteolysis impacts humoral immunity and can be exploited to enhance vaccine-induced production of antibody responses against key pathogen structural epitopes.

immunology↗

bioRxiv2021

DEAD-box RNA helicase 18 disrupts IRF3-binding to the interferon-β promoter

The production of type I interferons (IFN-/{beta}) requires strict control to avoid excessive activation during viral infections. The binding of interferon regulatory factor 3 (IRF3) to the IFN-{beta} promoter region in the nucleus is essential for IFN-{beta} transcription; however, whether nuclear factors have important negative-regulatory roles in this process is largely unknown. By screening for IRF3-interacting partners in the nucleus, we identified DEAD-box RNA helicase 18 (DDX18) as an important negative regulator of intranuclear IRF3. Overexpression of DDX18 suppressed virus- and IRF3-induced IFN-{beta} production, whereas knockdown of DDX18 expression or knockout of the DDX18 gene had opposite effects. Mechanistically, DDX18 interacts with IRF3 and decreases the binding of IRF3 to the IFN-{beta} promoter after viral infection. DDX18 knockdown mice (Ddx18+/-) further demonstrated that DDX18 suppressed antiviral innate immunity in vivo. Thus, despite many members of the DDX family act as important positive regulators in the cytoplasm, DDX18 plays a unique "braking" role in balancing virus-induced type I IFN production.

immunology↗

bioRxiv2021

Oxalic acid binds to gustatory receptor Gr23a and inhibits feeding in the brown planthopper

Plants produce diverse secondary compounds as natural protection against microbial and insect attack. Most of these compounds, including bitters and acids, are sensed by insect gustatory receptors (Grs). Acids are potentially toxic to insects, but there are few reports on sour compounds as ligands of insect Grs. Here, using two different heterologous expression systems, the insect Sf9 cell line and the mammalian HEK293T cell line, we started from crude extracts of rice (Oryza sativa) and successfully identified oxalic acid (OA) as a ligand of NlGr23a, a Gr in the brown planthopper Nilaparvata lugens. The antifeedant effect of OA on the brown planthopper was dose dependent, and NlGr23a is essential for OAs antifeedant activity in both artificial diets and rice plants. NlGr23a is also indispensable for tarsal OA sensing. To our knowledge, OA is the first identified ligand starting from plant crude extracts and the first known strong acid for insect Grs. These findings on rice-planthopper interactions will be of broad interest for pest control in agriculture and also for better understanding of how insects select host plants. Research organismNilaparvata lugens

ecology↗