Biology subjects

Sang, Y.

Publications and source records attributed to Sang, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Repurposing the TIGR-Tas system for programmable transcription activation

Programmable transcription activators are central to functional genomics, gene therapy, and synthetic biology. However, application of the most versatile CRISPR activators (CRISPRa) is hampered by the bulky size and compact CRISPR systems are constrained by the requirement of long protospacer adjacent motifs (PAMs). To address these limitations, we repurposed the TIGR-Tas RNA-guided DNA-targeting system as a versatile platform for gene activation. By systematically optimizing the fusion architecture of a nuclease-inactivated TasR with gene activation domains, we achieved robust, specific, and multiplexable transcriptional activation of endogenous human genes. This TIGR activation (TIGRa) system could be a superior alternative to CRISPRa systems due to its extreme compactness and potentially PAM-independent targeting capability.

genetics↗

bioRxiv2026

Multiplex genome engineering in yeast using the TIGR-Tas system

Tandem Interspaced Guide RNA (TIGR)-TIGR-associated (Tas) systems are a newly discovered family of ultracompact, modular RNA-guided DNA-targeting proteins that function without a protospacer adjacent motif (PAM) requirement. Their utility as genome engineering tools in microbes remains unexplored. Here, we report the first functional implementation of TIGR-Tas in Saccharomyces cerevisiae for genome engineering. We show that TasR from Parcubacteria (ParTasR) can be programmed by user-defined tigRNAs to generate targeted DNA double-strand breaks at yeast endogenous loci. By co-delivering ParTasR with customized tigRNAs and donor templates, we achieved precise gene fragment deletion and targeted codon substitutions at multiple genomic loci. The multiplex genome engineering capability of this TIGR-Tas system was demonstrated through high-efficiency multiplex gene disruption and chromosomal assembly of a lycopene biosynthesis pathway while inactivating an endogenous gene. This work establishes TIGR-Tas as a valuable addition to the yeast genome engineering toolbox, particularly for applications requiring PAM-independent targeting or compact delivery.

synthetic biology↗

bioRxiv2026

Intestinal lipid metabolism controls immune response through NHR-68 and gut-brain signaling in C. elegans

Animals must allocate limited energetic resources across competing defense programs in response to infection. Here, we show that the conserved nuclear hormone receptor NHR-68 integrates fatty acid metabolism with the neural control of molecular and behavioral immunity in Caenorhabditis elegans. Acting in parallel with NHR-10, NHR-68 controls genes involved in polyunsaturated fatty acid (PUFA) metabolism. Loss of NHR-68 disrupts linoleic acid (LA) homeostasis, impairing pathogen avoidance behavior. Supplementation with LA restores avoidance, and fat-3 inhibition, which elevates LA, enhances pathogen avoidance, whereas loss of LA synthesis by fat-2 inhibition diminishes this behavior, indicating that LA promotes behavioral immunity. We further show that NHR-68 acts in the intestine to regulate linoleic acid homeostasis, and that changes in intestinal lipid metabolism influence an AWC-dependent pathogen-avoidance circuit through intestine-to-neuron communication. NHR-68 suppresses activation of the PMK-1/p38 MAPK and DAF-16/FOXO pathways, which mediate molecular immune responses. These findings identify a gut-brain transcriptional circuit that connects intestinal lipid metabolism to neural and immune outputs, revealing a mechanism by which the metabolic state coordinates behavioral and molecular defenses to optimize host protection.

genetics↗

bioRxiv2025

Prolonged non-suppressible viremia sustained by a clonally expanded, genomically defective provirus with an immune-evasive HIV protein expression profile

Antiretroviral therapy (ART) potently inhibits HIV replication but does not eliminate HIV proviruses integrated within the genomes of infected cells. Though ART normally suppresses HIV to clinically undetectable levels in blood, some individuals experience non-suppressible viremia (NSV) that is not attributable to suboptimal drug exposure (e.g. due to incomplete medication adherence or pharmacological issues) nor emerging HIV drug resistance, and that does not resolve following regimen modification. We now understand that NSV can originate from expanded cell clones harboring genetically identical proviruses that reactivate en masse to produce clinically detectable viremia. NSV can even originate from proviruses with genomic defects, particularly in HIVs major splice donor (MSD) site, that render the viremia non-infectious. But, because only a limited number of such cases have been described, all in HIV subtype B, the mechanisms that allow cells harboring such proviruses to produce prolonged viremia without being eliminated remain incompletely understood. We characterized a case of MSD-defective, replication-impaired NSV that lasted >4 years in an individual with non-B HIV. Our results reveal that proviruses with MSD deletions can persist by integrating into minimally differentiated CD4+ T-cell subsets that then give rise to the full spectrum of memory and effector subpopulations, and by exhibiting an HIV protein expression profile that would allow these cells to evade cellular and humoral immunity. Our results highlight the need to better understand the biological implications of persistent HIV protein and virion production by genomically defective, clonally expanded proviruses, and for clinical guidelines to acknowledge this type of viremia. ImportanceHIV cure efforts focus on eliminating the viral reservoir, strictly defined as cells harboring proviruses that can produce infectious HIV. But this definition excludes proviruses with defects in HIVs major splice donor site (MSD), which persist readily. Our results confirm that clonally expanded, MSD-defective proviruses can produce HIV transcripts, proteins and clinically-detectable viremia over long periods, underscoring the need to investigate the potential long-term biological consequences of these activities. Our findings also have clinical implications. Most HIV treatment guidelines dont acknowledge that persistent viremia during ART can originate from clonally-expanded proviruses, and all recommend that viremia >200 HIV RNA copies/mL be managed as virologic failure. Clear clinical frameworks should be developed to discriminate persistent viremia that is due to drug adherence, pharmacokinetics or emerging drug resistance (that is clinically actionable), from NSV (that is not). Genotyping of HIVs MSD could also help assess potential transmission risk during NSV.

microbiology↗

bioRxiv2024

Effects of Drought and Salinity, etc. on Root Pressure of Dracaena sanderiana

AimRoot pressure plays a crucial role in maintaining tissue hydration and ensuring the functionality of the plants hydraulic system while facilitating cellular and tissue growth. The study focuses on investigating the impact of drought, salinity, etc. on root pressure of Dracaena sanderiana. MethodsPressure sensors (PX26-100GV) were used to measure the diurnal variations in root pressure of soil-cultured and hydroponic D. sanderiana with heights ranging from 60 to 80 cm. The study also examined various influencing factors such as drought stress, salinity stress, temperatures, mineral concentration, change in leaves and roots that affect root pressure. This approach provides valuable insights into the role of root pressure in mediating water upward movement in xylem. Essential findingsThe research showed: (1) Both soil-cultured and hydroponic D. sanderiana exhibited positive root pressure throughout the day, demonstrating apparent diurnal pattern of high pressures at the day and low pressures at night. The maximum root pressure measured in the experiments was 96 kPa; (2) For soil-cultured D. sanderiana, root pressure decreased under drought and salinization (NaCl), while the diurnal rhythm remained unchanged; (3) For hydroponic D. sanderiana, under simulated drought (PEG 6000) and salt stress (NaCl), the rate of decrease in root pressure accelerated with increasing concentrations of PEG 6000 and NaCl, displaying diurnal rhythm at low concentrations but losing this pattern at high concentrations; (4) Under room temperature, root pressure of hydroponic D. sanderiana decreased with lower water temperature and increased with higher temperatures, but did not increase at 40; low concentrations of nitrate (KNO3) generally increased root pressure, however, root pressure decreased when con-centration reached 4 g{middle dot}L-1, and the diurnal rhythm remained unaffected; (5) For hydroponic D. sanderiana, the presence of leaves on the stem below the root pressure measurement point resulted in significantly lower root pressure compared to plants without leaves on the stem, while still maintaining a regular diurnal rhythm. Removal of all root hairs and the entire root system led to a rapid decline in root pressure to negative values, followed by a slow recovery to around 0 kPa. In conclusion, relative to its height, the root pressure of D. sanderiana is sufficient to transport water required for transpiration to the top of the plant, effectively countering the impact and function of transpirational pull. Moreover, root pressure shows a stable diurnal rhythm of higher values during the day and lower at night. Environmental factors such as drought, salinity stress, temperatures, mineral con-centration, and changes in leaves and roots significantly affect root pressure.

ecology↗

bioRxiv2024

A bacterial type III effector hijacks plant ubiquitin proteases to evade degradation

Gram-negative bacterial pathogens inject effector proteins inside plant cells using a type III secretion system. These effectors manipulate plant cellular functions and suppress the plant immune system in order to promote bacterial proliferation. Despite the fact that bacterial effectors are exogenous threatening proteins potentially exposed to the protein degradation systems inside plant cells, effectors are relative stable and able to perform their virulence functions. In this work, we found that RipE1, an effector protein secreted by the bacterial wilt pathogen, Ralstonia solanacearum, undergoes phosphorylation of specific residues inside plant cells, and this promotes its stability. Moreover, RipE1 associates with plant ubiquitin proteases, which contribute to RipE1 deubiquitination and stabilization. The absence of those specific phosphorylation sites or specific host ubiquitin proteases leads to a substantial decrease in RipE1 protein accumulation, indicating that RipE1 hijacks plant post-translational modification regulators in order to promote its own stability. These results suggest that effector stability or degradation in plant cells constitute another molecular event subject to co-evolution between plants and pathogens.

plant biology↗

bioRxiv2023

Combined Partial-Nitrification and Phosphorus Removal with the co-existence of Nitrite-resistant phosphorous accumulating organisms (PAOs) and nitrifiers in the treatment of high-strength manure digestate

Concurrent biological phosphorus (P) recovery and nitrogen (N) removal in treating high-strength wastewater (such as anaerobic digestate) has been considered incompatible due to presumed conflicts in the conflicting optimum conditions required by phosphorous accumulating organisms (PAO) and nitrifiers. However, this study achieved a stable nitrite accumulation while still maintained PAO activities in one sequencing batch reactor for treating the manure digestate under two aeration schemes (continuous versus intermittent aeration). Nitrite accumulated up to 80.5 {+/-} 21.1 mg-N/L under continuous aeration (6 h) mode. Switching to intermittent aeration (equivalent to 3 h) halved nitrite accumulation but increased total nitrogen removal efficiency from 53.5 {+/-} 12.2% to 84.7 {+/-} 9.4%. Mass balance analysis indicates that nearly all ammonia was removed as N2O. Both Enhanced Biological Phosphorus Removal (EBPR) activity assessment and phenotypic trait detection via single cell Raman spectrum (SCRS) confirmed the existence of yet to be identified PAOs that are resistant to high nitrite inhibition in our system. Visual Minteq calculation indicates that high concentrations of Ca in manure digestate may form precipitates and influence the bioavailability of P forms. Therefore, both biotic and abiotic pathways lead to a total P removal rate around 61.0 {+/-} 6.8%. This study highlights new opportunities to combine short-cut nitrogen removal via partial nitrification, nitrous oxide (N2O) collection, and EBPR in commercial farm-collected digested manure wastewater. Higher N and P removal efficiency could potentially be achieved by tuning aeration schemes in combination with down-stream anammox process. SynopsisConcurrent partial nitrification, N2O accumulation, and EBPR activity were found, leading to the exploration of novel nitrite-resistant PAOs, simultaneously N/P recovery, and waste-energy conversion in treating high strength wastewater.

microbiology↗

bioRxiv2023

Chromosome-scale genome assembly of Tinospora sagittata (Oliv.) Gagnep. enhances identifying genes involved in the biosynthesis of jatrorrhizine

Tinospora sagittata (Oliv.) Gagnep. is an important medicinal tetraploid plant in the Menispermaceae family. Its tuber, namely "Radix Tinosporae" used in Traditional Chinese Medicine, is rich in medicinal terpenoids and benzylisoquinoline alkaloids (BIAs), To enhance understanding the biosynthesis of medicinal compounds, we, herein, report the assembly of a high quality chromosome-scale genome with both PacBio HiFi and Illumina sequencing technologies. The size of assembled genome was 2.33 Gb consisting of 4070 scaffolds (N50=42.06Mb), of which 92.05% were assigned to 26 pseudochromosomes in A and B sub-genomes. A phylogenetic analysis with the T. sagittata and other 16 plant genomes estimated the evolutionary placement of T. sagittata and its divergence time in Ranunculales. Further genome evolution analysis characterized one round tandem duplication about 1.5 million years ago (MYA) and one whole-genome duplication (WGD) about 86.9 MYA. WGD contributed to the duplication of clade-specific cytochrome P450 gene family in Ranunculales. Moreover, sequencing mining obtained genome-wide genes involved in the biosynthesis of alkaloids and terpenoids. TsA02G014550, one candidate, was functionally characterized to catalyze the formation of (S)-canadine in the jatrorrhizine biosynthetic pathway. Taken together, the assembled genome of T. sagittata provides useful sequences to understand the biosynthesis of jatrorrhizine and other BIAs in plants.

genomics↗

bioRxiv2023

Chromosomal-level genome assembly of Populus lasiocarpa

Despite widespread biodiversity loss, our understanding of how species and populations will respond to accelerated climate change remains limited. In this study, we predict the evolutionary responses of Populus lasiocarpa, a key alpine forest tree species primarily found in the mountainous regions of a global biodiversity hotspot, to climate change. We accomplish this by generating and integrating a new reference genome for P. lasiocarpa, re-sequencing data for 200 samples, and gene expression profiles for leaf and root tissue following exposure to heat and waterlogging. Analyses of the re-sequencing data indicate that demographic dynamics, divergent selection, and long-term balancing selection have shaped and maintained genetic variation within and between populations over historical timescales. In examining genomic signatures of contemporary climate adaptation, we found that haplotype blocks, characterized by inversion polymorphisms that suppress recombination, play a crucial role in clustering environmentally adaptive variations. Comparison of evolved and plastic gene expression show that genes with expression plasticity generally align with evolved responses, highlighting the adaptive role of plasticity. Lastly, we incorporated local adaptation, migration, genetic load, and plasticity responses into our predictions of population-level climate change risks. Our findings reveal that western populations, primarily distributed in the Hengduan Mountains--a region known for its environmental heterogeneity and significant biodiversity--are the most vulnerable to climate change and should be prioritized for conservation and management. Overall, our study advances understanding of the relative roles of long-term natural selection, local environmental adaptation, and immediate plasticity responses in driving evolutionary adaptation to climate change in keystone species.

genomics↗

bioRxiv2023

Chromosomal-level genome assembly of Populus davidiana

Despite the population structure and genetic differentiation of P. davidiana has been reported, little is known about the P. davidiana genome characterization with the genomes assembled at the chromosome level. As one of the most widely distributed and ecologically important tree species in China, P. davidiana is an excellent resource to understand population adaption to climate and environment change. Here we present a high-quality assembly based on long-read sequences and Hi-C data. This assembly is assembled into 19 contiguous chromosomes which provides a powerful tool for future association studies.

genomics↗

bioRxiv2023

How Do Deer Respiratory Epithelial Cells Weather The Initial Storm of SARS-CoV-2?

The potential infectivity of SARS-CoV-2 in animals raises a public health and economic concern, particularly the high susceptibility of white-tailed deer (WTD) to SARS-CoV-2. The disparity in the disease outcome between humans and WTD is very intriguing, as the latter are often asymptomatic, subclinical carriers of SARS-CoV-2. To date, no studies have evaluated the innate immune factors responsible for the contrasting SARS-CoV-2-associated disease outcomes in these mammalian species. A comparative transcriptomic analysis in primary respiratory epithelial cells of human (HRECs) and WTD (Deer-RECs) infected with SARS-CoV-2 was assessed throughout 48 hours post inoculation (hpi). Both HRECs and Deer-RECs were susceptible to SARS-COV-2, with significantly (P < 0.001) lower virus replication in Deer-RECs. The number of differentially expressed genes (DEG) gradually increased in Deer-RECs but decreased in HRECs throughout the infection. The ingenuity pathway analysis of DEGs further identified that genes commonly altered during SARS-CoV-2 infection mainly belong to cytokine and chemokine response pathways mediated via IL-17 and NF-{kappa}B signaling pathways. Inhibition of the NF-{kappa}B signaling in the Deer-RECs pathway was predicted as early as 6 hpi. The findings from this study could explain the lack of clinical signs reported in WTD in response to SARS-CoV-2 infection as opposed to the severe clinical outcomes reported in humans. HIGHLIGHTSO_LIWhite-tailed deer primary respiratory epithelial cells are susceptible to SARS- CoV-2 without causing hyper cytokine gene expression. C_LIO_LIDownregulation of IL-17 and NF-{kappa}B signaling pathways after SARS-CoV-2 infection could be key to the regulated cytokine response in deer cells. C_LIO_LIDeer innate immune system could play a critical role in early antiviral and tissue repair response following SARS-CoV-2 infection. C_LI

genomics↗

bioRxiv2023

The cation channel mechanisms of subthreshold inward depolarizing currents in the VTA dopaminergic neurons and their roles in the depression-like behavior

The slow-intrinsic-pacemaker dopaminergic (DA) neurons originating in the ventral tegmental area (VTA) are implicated in various mood- and emotion-related disorders, such as anxiety, fear, stress and depression. Abnormal activity of projection-specific VTA DA neurons is the key factor in the development of these disorders. Here, we describe the crucial role for the NALCN and TRPC6, non-selective cation channels in mediating the subthreshold inward depolarizing current and driving the firing of action potentials of VTA DA neurons in physiological condition. Furthermore, we demonstrate that down-regulation of TRPC6 protein expression in the VTA DA neurons likely contributes to the reduced activity of projection-specific VTA DA neuron in chronic mild unpredictable stress (CMUS) depressive mice. In consistent with these, selective knockdown of TRPC6 channels in the VTA DA neurons conferred mice with depression-like behavior. This current study suggests down-regulation of TRPC6 expression/function is involved in reduced VTA DA neuron firing and chronic stress-induced depression-like behavior of mice.

neuroscience↗

bioRxiv2022

A Possible Unitary Mechanism for General Anesthesia

The oxygen reduction reaction (ORR) is of high importance, among others because of its role in cellular respiration and in the operation of fuel cells. Recently, a possible relation between respiration and general anesthesia has been found. This work aims to explore whether anesthesia related gases affect the ORR. In ORR, oxygen which is in its triplet ground state is reduced to form products that are all in the singlet state. While this process is "in principle" forbidden because of spin conservation, it is known that if the electrons transferred in the ORR are spin polarized, the reaction occurs efficiently. Here we show, in electrochemical experiments, that the efficiency of the oxygen reduction is reduced by the presence of general anesthetics in solution. We suggest that a spin-orbit coupling to the anesthetics depolarizes the spins. This causes both a reduction in reaction efficiency and a change in the reaction products. The findings may point to a possible relation between ORR efficiency and anesthetic action. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/518334v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@4a5b8aorg.highwire.dtl.DTLVardef@1bfc961org.highwire.dtl.DTLVardef@3e002corg.highwire.dtl.DTLVardef@7d74f0_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus

There is an urgent need for efficient and safe vaccines against the monkeypox virus (MPXV) in response to the rapidly spreading monkeypox epidemic. In the age of COVID-19, mRNA vaccines have been highly successful and emerged as platforms enabling rapid development and large-scale preparation. Here, we have developed two MPXV quadrivalent mRNA vaccines, named mRNA-A-LNP and mRNA-B-LNP, based on two IMVs (A29L and M1R) and two EEVs (A35R and B6R). By administering mRNA-A-LNP and mRNA-B-LNP intramuscularly twice, mice have induced MPXV-specific IgG antibodies and potent Vaccinia virus (VACV)-specific neutralizing antibodies. Additionally, it elicited durable MPXV-specific killer memory T-cell immunity as well as memory B-cell immunity in mice. Furthermore, the passive transfer of sera from mRNA-A-LNP and mRNA-B-LNP-immunized mice protected nude mice against the VACV challenge. In addition, two doses of mRNA-A-LNP and mRNA-B-LNP were also protective against the VACV challenge in mice. Overall, our results demonstrated that mRNA-A-LNP and mRNA-B-LNP appear to be safe and effective vaccine candidates against monkeypox epidemics, as well as against outbreaks caused by other orthopoxviruses, including the smallpox virus.

immunology↗

bioRxiv2022

Genomic insights into present local adaptation and future climate change vulnerability of a keystone forest tree species in East Asian

Rapid global climate change is posing a huge threat to biodiversity. Assessments of the adaptive capacity for most taxa is usually performed on the species as a whole, but fails to incorporate intraspecific adaptive variation that may play a fundamental role in buffering future shifting climates. Here we generate a chromosome-scale genome assembly for Populus koreana, a pioneer and keystone tree species in East Asia temperate forests. We also obtain whole-genome sequences of 230 individuals collected from 24 natural populations. An integration of population genomics and environmental variables was performed to reveal the genomic basis of local adaptation to diverse climate variable. We identify a set of climate-associated single nucleotide polymorphisms (SNPs), insertions-deletions (Indels) and structural variations (SVs), in particular numerous adaptive non-coding variants distributed across the genome of P. koreana. We incorporate these variants into an environmental modelling scheme to predict spatiotemporal responses of P. koreana to future climate change. Our results highlight the insights that the integration of genomic and climate data can shed on the future evolutionary adaptive capacities of a species to changing environmental conditions.

evolutionary biology↗

bioRxiv2021

Virus-Targeted Transcriptomic Analyses Implicate Ranaviral Interaction with Host Interferon Response in Frog Virus 3-infected Frog Tissues

Frog Virus 3 (FV3) is a large dsDNA virus that cause global infections in amphibians, fish and reptiles, and contribute to amphibian declines. FV3s genome contains near 100 putative open reading frames (ORFs). Previous studies have classified these coding genes into temporal classes as immediate early, delayed early and late viral transcripts based on their sequential expression during FV3 infection. To genome-wide characterize ranaviral gene expression, we performed a whole transcriptomic analysis (RNA-Seq) using total RNA samples containing both viral and cellular transcripts from FV3-infected Xenopus laevis adult tissues using two FV3 strains, a wild type (FV3-WT) and an ORF64R-deleted recombinant (FV3-{Delta}64R). In samples from the infected intestine, liver, spleen, lung and especially kidney, a FV3-targeted transcriptomic analysis mapped reads spanning the full-genome coverage at [~]10x depth on both positive and negative strands. By contrast, reads were only mapped to partial genomic regions in samples from the infected thymus, skin and muscle. Extensive analyses validated the expression of almost all annotated 98 ORFs and profiled their differential expression in a tissue-, virus-, and temporal class-dependent manners. Further studies identified several putative ORFs that encode hypothetical proteins containing viral mimicking conserved domains found in host interferon (IFN) regulatory factors (IRFs) and IFN receptors. This study provides the first comprehensive genome-wide viral transcriptome profiling during infection and across multiple amphibian host tissues that will serve as instrumental reference. It also presents evidence implying that ranaviruses like FV3 have acquired previously unknown molecular mimics interfering with host IFN signaling during evolution. ImportanceFrog Virus 3 (FV3), are large dsDNA viruses that cause devastating infections globally in amphibians, fish and reptiles, and contribute to catastrophic amphibian declines. FV3s large genome encodes near 100 coding genes, of which most have been functionally uncharacterized in the viral pathogenesis. Using a whole transcriptomic analysis (RNA-Seq) in FV3-infected amphibian samples, we determined a genome-wide virus transcriptome and profiled their differential expression in a tissue-, virus-, and temporal class-dependent manners. Further studies identified several putative ORFs that encode hypothetical proteins containing viral mimicking conserved domains found in host interferon (IFN) regulatory factors (IRFs) and IFN receptors. This study provides the first comprehensive genome-wide viral transcriptome profiling during infection and across multiple amphibian host tissues that will serve as instrumental reference. It also presents evidence implying that ranaviruses like FV3 have acquired previously unknown molecular mimics interfering with host IFN signaling during evolution.

microbiology↗

bioRxiv2020

A bacterial effector uncovers a metabolic pathway involved in resistance to bacterial wilt disease

Bacterial wilt caused by the soil-borne pathogen Ralstonia solanacearum is a devastating disease worldwide. Upon plant colonization, R. solanacearum replicates massively, causing plant wilting and death; collapsed infected tissues then serve as a source of inoculum. In this work, we show that the metabolic pathway mediated by pyruvate decarboxylases (PDCs), activated in response to low oxygen and involved in drought stress tolerance, contributes to resistance against bacterial wilt disease. Arabidopsis and tomato plants with deficient PDC activity are more susceptible to bacterial wilt, and treatment with either pyruvic acid or acetic acid (substrate and product of the PDC pathway, respectively) enhances resistance. An effector protein secreted by R. solanacearum, RipAK, interacts with PDCs and inhibits their oligomerisation and enzymatic activity. This work reveals a metabolic pathway involved in resistance to biotic and abiotic stresses, and a bacterial virulence strategy to promote disease and the completion of the pathogenic life cycle.

plant biology↗

bioRxiv2020

Epigenetic Evolution of ACE2 and IL-6 Genes as Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates

Current novel coronavirus disease (COVID-19) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. Since these host factors are subjected to epigenetic regulation, relevant analyses on some key genes underlying COVID-19 pathogenesis were performed to longitudinally decipher their epigenetic correlation to COVID-19 susceptibility. The genes of host angiotensin-converting enzyme 2 (ACE2, as the major virus receptor) and interleukin (IL)-6 (a key immune-pathological factor triggering cytokine storm) were shown to evince active epigenetic evolution via histone modification and cis/trans-factors interaction across different vertebrate species. Extensive analyses revealed that ACE2 ad IL-6 genes are among a subset of non-canonical interferon-stimulated genes (non-ISGs), which have been designated recently for their unconventional responses to interferons (IFNs) and inflammatory stimuli through an epigenetic cascade. Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of key cis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 and IL6 gene promoters across representative COVID-19-susceptible species compared to unsusceptible ones. Findings characterize ACE2 and IL-6 genes as non-ISGs that respond differently to inflammatory and IFN signaling from the canonical ISGs and their epigenetic properties may serve as biomarkers to longitudinally predict COVID-19 susceptibility in vertebrates and partially explain COVID-19 inequality in people of different subgroups.

evolutionary biology↗