Biology subjects

Tian, J.

Publications and source records attributed to Tian, J..

At least 91 records · Page 5Linked to original sources

bioRxiv2020

Neonicotinoids stimulate H2-limited methane emission in Periplaneta americana through the regulation of gut bacterium community

Methane emitted by insects is considered to be an important source of atmospheric methane. Here we report the stimulation of methane emission in Periplaneta americana, an insect species with abundant methanogens, by neonicotinoids, insecticides widely used to control insect pests. The application of cycloxaprid (CYC) and imidacloprid (IMI) caused foregut expansion in P. americana, and increased the methane production and emission. Antibiotics could mostly eliminate the stimulatory effects. In P. americana gut, hydrogen levels increased and pH values decreased, which could be significantly explained by the gut bacterium community change. The proportion of several bacterium genera increased in guts following CYC treatment, and four genera from five with increased proportions could generate hydrogen at anaerobic conditions. Hydrogen is a central intermediate in methanogenesis. Gut methanogens could use the increased hydrogen to produce more methane, especially at acidic conditions. Following neonicotinoid applications, all increased methanogens in both foregut and hindgut used hydrogen as electron donor to produce methane. Besides, the up-regulation of mcrA, encoding the enzyme that catalyzes the final step of methanogenesis, suggested an enhanced methane production ability in present methanogens. In the termite Coptotermes chaohuensis, another methanogen-abundant insect species, hydrogen levels in gut and methane emission significantly increased after neonicotinoid treatment, which was similar to the results in P. americana. In summary, neonicotinoids changed bacterium community in P. americana gut to generate more hydrogen, which then stimulate gut methanogens to produce and emit more methane. The finding raised a new concern over neonicotinoid applications, and might be a potential environmental risk associated with global warming.

ecology↗

bioRxiv2020

Type I Interferon Limits Viral Dissemination-Driven Clinical Heterogeneity in a Native Murine Betacoronavirus Model of COVID-19

Emerging clinical data demonstrates that COVID-19, the disease caused by SARS-CoV2, is a syndrome that variably affects nearly every organ system. Indeed, the clinical heterogeneity of COVID-19 ranges from relatively asymptomatic to severe disease with death resultant from multiple constellations of organ failures. In addition to genetics and host characteristics, it is likely that viral dissemination is a key determinant of disease manifestation. Given the complexity of disease expression, one major limitation in current animal models is the ability to capture this clinical heterogeneity due to technical limitations related to murinizing SARS-CoV2 or humanizing mice to render susceptible to infection. Here we describe a murine model of COVID-19 using respiratory infection with the native mouse betacoronavirus MHV-A59. We find that whereas high viral inoculums uniformly led to hypoxemic respiratory failure and death, lethal dose 50% (LD50) inoculums led to a recapitulation of most hallmark clinical features of COVID-19, including lymphocytopenias, heart and liver damage, and autonomic dysfunction. We find that extrapulmonary manifestations are due to viral metastasis and identify a critical role for type-I but not type-III interferons in preventing systemic viral dissemination. Early, but not late treatment with intrapulmonary type-I interferon, as well as convalescent serum, provided significant protection from lethality by limiting viral dissemination. We thus establish a Biosafety Level II model that may be a useful addition to the current pre-clinical animal models of COVID-19 for understanding disease pathogenesis and facilitating therapeutic development for human translation.

immunology↗

bioRxiv2020

Eurycomanone regulates lipid metabolism by activating the cAMP/PKA pathway

Eurycoma longifolia Jack (ELJ) contains mainly alkaloids, and quassinoids, which are the main active ingredients. Eurycomanone (EN), one of the most common quassinoids, is said to have beneficial effects on lipid and glucose metabolism. In this study, we investigated the effects of EN on lipolysis by establishing a high-fat animal model in vivo and evaluated its efficacy as a lipolytic and anti-fatty liver agent. Oil red O staining showed morphological changes of 3T3-L1 preadipocytes after EN treatment and confirmed the inhibitory effects of EN on adipocyte differentiation. The mechanism of EN promotes lipolysis in 3T3-L1 cells was analyzed by immunofluorescence, Western blotting, quantitative real-time PCR and siRNA transfection. In C57BL/6J mice fed a high-fat diet, intragastric administration of EN (5 mg/kg and 10 mg/kg) for two weeks, decreased fat droplet mass and size, and reduced fat accumulation in the liver. Furthermore, EN activated PKA and promoted the PKA/hormone sensitive lipase lipolysis signaling pathway, thereby increasing the release of glycerol and free fatty acids from adipocytes. Our findings indicate the potential of EN as a promising alternative pharmacologic agent for the prevention of obesity.

pharmacology and toxicology↗

bioRxiv2020

JQ-1 ameliorates schistosomiasis liver fibrosis by suppressing JAK2 and STAT3 activation

Schistosomiasis is a serious parasitic infection caused by Schistosoma. The parasite deposits eggs in the host liver, causing inflammation that activates hepatic stellate cells (HSCs), which leads to liver fibrosis. Currently, there is no effective therapy for liver fibrosis; thus, treatments are urgently needed. Therefore, in the present study, mice infected with Schistosoma japonicum were treated with JQ-1, a small-molecule bromodomain inhibitor with reliable anti-tumor and anti-inflammatory activities. The fibrotic area of the liver measured by computer-assisted morphometric analysis and the expression levels of the cytoskeletal protein alpha smooth muscle actin (-SMA) and of collagen assessed by quantitative PCR and immunohistochemistry were significantly decreased in the liver following JQ-1 treatment compared with vehicle-treated controls. Total RNA was extracted from the liver of JQ-1-treated Schistosoma-infected mice for RNA-sequencing analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that JQ-1 affected biological processes and the expression of cellular components known to play key roles in HSC transdifferentiation into myofibroblasts. In vitro treatment with JQ-1 of JS-1 cells, a mouse HSC line, indicated that JQ-1 significantly inhibited JS-1 proliferation but had no effect on JS-1 activity, senescence, or apoptosis. Western blot results showed that JQ-1 inhibited the expression of phosphorylated JAK2 and phosphorylated STAT3 without altering expression levels of these non-phosphorylated proteins. Taken together, these findings suggested that JQ-1 treatment ameliorated S. japonicum egg-induced liver fibrosis, at least in part, by suppressing HSC activation and proliferation through the inhibition of JAK2/STAT3 signaling. These results lay a foundation for the development of novel approaches to treat and control liver fibrosis caused by S. japonicum. Author summaryWhen a host is infected with Schistosoma, a common parasite that affects more than a million people and hundreds of thousands of livestock, the parasite deposits eggs in the liver of the host. The eggs lead to liver inflammation, which activates stellate cells in the liver. These stellate cells generate most of the excessive extracellular matrix that replaces healthy liver parenchyma with fibrous tissue, causing liver fibrosis. Schistosoma japonicum causes the most severe liver damage of all the schistosome parasites. Therefore, inhibiting the activation of the liver stellate cells and removing the activated stellate cells are key strategies for treating liver fibrosis caused by this parasite. JQ-1 is a potent inhibitor of the BET family of bromodomain proteins and is structurally similar to inhibitors being tested in clinical trials for various types of cancers. Here we found that administering JQ-1 to mice infected with S. japonicum decreased the degree of liver fibrosis. JQ-1 inhibited the activation and proliferation of liver stellate cells by blocking the phosphorylation and thus the activation of JAK2 and STAT3 to achieve its therapeutic effects. Thus, this study provides insights into the development of new therapeutic strategies for Schistosoma-induced liver fibrosis.

pharmacology and toxicology↗

bioRxiv2020

Ten Genetic Loci Identified for Milk Yield, Fat, and Protein in Holstein Cattle

High-yield and high-quality of milk are the primary goals of dairy production. Understanding the genetic architecture underlying these milk production traits is beneficial so that genetic variants can be targeted toward the genetic improvement. In this study, we measured five milk production traits in Holstein cattle population from China. These traits included milk yield, protein yield, fat yields; fat percentage and protein percentages. We used the estimated breeding values as dependent variables to conduct the genome-wide association studies (GWAS). Breeding values were estimated through pedigree relationships by using a mixed linear model for individuals with and without phenotypic data. Genotyping was carried out on the individuals with phenotypes by using the Illumina BovineSNP150 BeadChip. The association analyses were conducted by using the Fixed and random model Circulating Probability Unification (FarmCPU) method. A total of ten SNPs was detected above the genome-wide significant threshold, including six located in previously reported QTL regions. We found eight candidate genes within distances of 120 kb upstream or downstream to the associated SNPs. The most significant SNP is on DGAT1 gene affecting milk fat and protein percentage. These genetic variants and candidate genes would be valuable resources to enhance dairy cattle breeding.

genomics↗

bioRxiv2020

Deletion of the mitochondrial matrix protein cyclophilin-D prevents parvalbumin interneuron dysfunction and cognitive deficits in a mouse model of NMDA hypofunction

Redox dysregulation and oxidative stress are final common pathways in the pathophysiology of a variety of psychiatric disorders, including schizophrenia. Oxidative stress causes dysfunction of GABAergic parvalbumin-positive interneurons (PVI), which are crucial for the coordination of neuronal synchrony during sensory- and cognitive-processing. Mitochondria are the main source of reactive oxygen species (ROS) in neurons and they control synaptic activity through their roles in energy production and intracellular calcium homeostasis. We have previously shown that in male mice transient blockade of NMDA receptors during development (subcutaneous injections of 30 mg/kg ketamine (KET) on postnatal days 7, 9, and 11) results in long-lasting alterations in synaptic transmission and reduced parvalbumin expression in the adult prefrontal cortex (PFC), contributing to a behavioral phenotype that mimics multiple symptoms associated with schizophrenia. These changes correlate with oxidative stress and impaired mitochondrial function in both PVI and pyramidal cells. Here, we show that genetic deletion (Ppif-/-) of the mitochondrial matrix protein cyclophilin D (CypD) prevents perinatal KET-induced increases in ROS and the resulting deficits in PVI function, and changes in excitatory and inhibitory synaptic transmission in the PFC. Deletion of CypD also prevented KET-induced behavioral deficits in cognitive flexibility, social interaction, and novel object recognition. Taken together, these data highlight how mitochondrial activity may play an integral role in modulating PVI-mediated cognitive processes. Significance StatementMitochondria are important modulators of oxidative stress and cell function, yet how mitochondrial dysfunction affects cell activity and synaptic transmission in psychiatric illnesses is not well understood. NMDA receptor blockade with ketamine during development causes oxidative stress, dysfunction of parvalbumin-positive interneurons (PVI), and long-lasting physiological and behavioral changes. Here we show that mice deficient for the mitochondrial matrix protein cyclophilin D show robust protection from PVI dysfunction following perinatal NMDAR-blockade. Mitochondria serve as an essential node for a number of stress-induced signaling pathways and our experiments suggest that failure of mitochondrial redox regulation can contribute to PVI dysfunction.

neuroscience↗

bioRxiv2020

Vegetation and Microbes Interact to Preserve Organic Matter in Wooded Peatlands

Peatlands have persisted as massive carbon sinks over millennia, even during past periods of climate change. The commonly accepted theory of abiotic controls (mainly anoxia and low temperature) over carbon decomposition cannot explain how vast low-latitude wooded peatlands consistently accrete peat under warm and seasonally unsaturated conditions. Similarly, that theory cannot accurately project the decomposition rate in boreal peatlands where warming and drought have decreased Sphagnum and increased shrub expansion. Here, by comparing composition and ecological traits of microbes between Sphagnum- and shrub-dominated peatlands, we present a previously unrecognized natural course that curbs carbon loss against climate change. Slow-growing microbes decisively dominate the studied wooded peatlands, concomitant with plant-induced, high recalcitrant carbon and phenolics. The slow-growing microbes inherently metabolize organic matter slowly. However, the fast-growing microbes that dominate our Sphagnum site (most boreal peatlands as well) decomposed labile carbon >30 times faster than the slow-growing microbes. We show that the high-phenolic shrub/tree induced shifts in microbial composition may compensate for positive effects of temperature and/or drought on metabolism over time in peatlands. This biotic self-sustaining process that modulates abiotic controls on carbon cycling may help better project long-term climate-carbon feedbacks in peatlands.

ecology↗

bioRxiv2020

Metabolomic markers of colorectal tumor with different clinicopathological features

BackgroundColorectal cancer (CRC) is the result of complex interactions between the tumors molecular profile and metabolites produced by its microenvironment. Despite recent studies identifying CRC molecular subtypes, a metabolic classification system is still lacking. We aimed to explore the distinct phenotypes and subtypes of CRC at the metabolic level. MethodsWe conducted an untargeted metabolomics analysis of 51 paired tumor tissues and adjacent mucosa using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Multivariate analysis including principal component analysis, orthogonal partial least squares discriminant analysis and heat maps, univariate analysis, and pathway analysis were used to identify potential metabolic phenotypes of CRC. Unsupervised consensus clustering were used to identify robust metabolic subtypes, and evaluated their clinical relevance. ResultsA total of 173 metabolites (including nucleotides, carbohydrates, free fatty acids, and choline) were identified between CRC tumor tissue and adjacent mucosa. We found that lipid metabolism was closely related to the occurrence and progression of CRC and CRC tissues could be divided into three subtypes, and statistically significant correlations between different subtypes and clinical prognosis were observed. ConclusionsCRC tumor tissue exhibits distinct metabolic phenotypes. Metabolic differences between subtypes may provide a basis and direction for further clinical individualized treatment planning.

cancer biology↗

bioRxiv2020

Nrf2 represses ER stress-related ferroptosis in renal carcinoma cells via HO-1

Selective-induction of regulated cell death is considered as a useful strategy for developing effective therapies against renal cell carcinoma (RCC). In this study, the role of nuclear factor-E2-related factor 2 (Nrf2) and its downstream genes in erastin-induced ferroptosis of renal carcinoma cells was investigated. Erastin induced endoplasmic reticulum (ER) stress and ferroptosis in renal carcinoma cells (786-0 and Caki-1), which was confirmed by morphological changes, increased lipid oxidation and ferroptosis inhibition. Data obtained from TCGA dataset showed that Nrf2 and heme oxygenase-1 (HO-1) were not only significantly differentially expressed between RCC and normal samples, but also associated with better survival in RCC patients. Moreover, the process of ferroptosis induced by erastin in renal carcinoma cells was accompanied by increased expression of Nrf2 and HO-1. Inhibition of Nrf2 or HO-1 expression enhanced lipid ROS accumulation and ferroptosis. Furthermore, pharmacological activation of HO-1 reversed ferroptosis-sensitizing effect of Nrf2 silencing, thereby clarifying the key role of Nrf2/HO-1 pathway in erastin-induced ferroptosis in renal carcinoma cells. In summary, we identified the role of Nrf2/HO-1 signaling pathway in the protection of renal carcinoma cells from ER stress-related ferroptosis, which indicated that targeting of Nrf2/HO-1 pathway as a viable treatment strategy for RCC. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/977769v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@1068dacorg.highwire.dtl.DTLVardef@13f388eorg.highwire.dtl.DTLVardef@199fd87org.highwire.dtl.DTLVardef@d3e03a_HPS_FORMAT_FIGEXP M_FIG Graphical abstract (supplementary figure): Nrf2 protects against ER stress-related ferroptosis via HO-1 in renal cancer cells. Cystine/glutamate antiporter (SLC7A11) abbreviated as xCT. Mitochondria abbreviated as Mito. C_FIG

cancer biology↗

bioRxiv2020

Effects of rhein on bile acid homeostasis in rats

Rhein, the active ingredient of rhubarb, a medicinal and edible plant, is widely used in clinical practice. In this work, we investigated the alterations of 14 bile acids and hepatic transporters after rats were administered rhein for 5 consecutive weeks. There was no obvious injury to the liver and kidney, and there were no significant changes in biochemical indicators. However, 1,000 mg/kg rhein increased the liver total bile acid (TBA) levels, especially taurine-conjugated bile acids (t-CBAs), inhibited the expression of Farnesoid X receptor (FXR) and (bile salt export pump) BSEP mRNA, and upregulated the expression of (cholesterol 7-hydroxylase) CYP7A1 mRNA. Rhein close to the clinical dose reduced the amounts of TBAs, especially unconjugated bile acids (UCBAs), and elevated the expression of FXR and multidrug resistance-associated protein 3 (Mrp3) mRNA. These results denote that rhein is not toxic and is safe to use at a reasonable dose and timing.

pharmacology and toxicology↗

bioRxiv2020

Developing an endogenous quorum-sensing based CRISPRi circuit for autonomous and tunable dynamic regulation of multiple targets in industrial Streptomyces

Dynamic regulation has emerged as an effective strategy to improve product titers by balancing metabolic networks, which can be implemented by coupling gene expression to pathway-independent regulatory elements, such as quorum-sensing (QS) systems. However, these QS-based circuits are often created on heterologous systems and must be carefully tuned through tedious testing and optimization process to make them work well, which hampers their application in industrial microbes including streptomycetes. In this study, we design a pathway-independent QS circuit by directly integrating an endogenous QS system with CRISPRi (named EQCi) in the industrial rapamycin-producing strain Streptomyces rapamycinicus. EQCi has the advantages of both the QS system and CRISPRi, which enables tunable, fully autonomous and dynamic regulation of multiple targets simultaneously. To demonstrate its effectiveness, we downregulate three key nodes in essential pathways separately to divert metabolic flux toward rapamycin biosynthesis. In each case, significant increases in rapamycin titers are achieved. We further apply EQCi to simultaneously control these three key nodes with proper repression strength by changing sgRNA targeting positions. The final rapamycin titer reaches to 1836{+/-}191 mg/L, which is the highest reported titer. Notably, compared to traditional static engineering strategy, which result in growth arrest and suboptimal rapamycin titers, EQCi regulation substantially promote rapamycin titers without affecting cell growth, which indicates that it can achieve the trade-off between essential pathways and product synthesis. Collectively, this study provides a simple and effective strategy for optimizing product titers and may have the potential to apply to other industrial microorganisms.

bioengineering↗

bioRxiv2020

Post-transcriptional Regulation is the Major Driver of microRNA Expression Variation

MicroRNA (miRNA) expression patterns are highly variable across human tissues and across cancer specimens. The intuitive assumption is that transcription is the main contributor to mature miRNA expression patterns, with post-transcriptional processes further modifying miRNA expression levels. Here we report the surprising model that, on the global level, post-transcriptional regulation dominates over transcriptional regulation in determining mature miRNA expression patterns in both normal tissues and cancer. Taking advantage of large genomic datasets in which the expression of both mature miRNAs and their host genes have been quantified, we establish and validate transcriptional and post-transcriptional metrics, with miRNA host gene expression estimating transcriptional regulation and mature miRNA to host gene ratio estimating post-transcriptional regulation. On average, the post-transcriptional metric contributes 2.8-fold more than the transcriptional metric to the variance of mature miRNA expression. The variation of the balance between the two mature miRNAs (5p and 3p miRNAs) produced from the same precursor hairpin is a non-negligible contributor to miRNA expression, explaining [~]27% of the variance of miRNAs post-transcriptional metric. Data of normal tissues yield similar results as cancer specimens. Additionally, the post-transcriptional metric is superior to the transcriptional metric in classifying cancer types. We further demonstrate that the post-transcriptional metric separates miRNAs into distinct groups, suggesting that there are groups of miRNAs that are co-regulated on the post-transcriptional level. Our data support a model in which the post-transcriptional regulation is the major driver of miRNA expression variation, and paves a way toward better mechanistic understanding of post-transcriptional regulation of mature miRNA expression.

bioinformatics↗

bioRxiv2019

microRNA seedless sites attenuate strong-seed-site-mediated target repression

MicroRNAs (miRNAs) regulate protein-coding gene expression primarily through cognitive binding sites in the 3 untranslated regions (3' UTRs). Seed sites are sequences in messenger RNAs (mRNAs) that form perfect Watson-Crick base-paring with a miRNAs seed region, which can effectively reduce mRNA abundance and/or repress protein translation. Some seedless sites, which do no form perfect seed-pairing with a miRNA, can also lead to target repression, often with lower efficacy. Here we report the surprising finding that when seedless sites and seed sites are co-present in the same 3UTR, seedless sites attenuate strong-seed-site-mediated target suppression, independent of 3' UTR length. This attenuation effect is detectable in >70% of transcriptomic datasets examined, in which specific miRNAs are experimentally increased or decreased. The attenuation effect is confirmed by 3UTR reporter assays and mediated through base-pairing between miRNA and seedless sites. Furthermore, this seedless-site-based attenuation effect could affect seed sites of the same miRNA or another miRNA, thus partially explaining the variability in target suppression and miRNA-mediated gene upregulation. Our findings reveal an unexpected principle of miRNA-mediated gene regulation, and could impact the understanding of many miRNA-regulated biological processes.

bioinformatics↗

bioRxiv2019

Self-assembly of multi-component mitochondrial nucleoids via phase separation

Mitochondria contain an autonomous and spatially segregated genome. The organizational unit of their genome is the nucleoid, which consists of mitochondrial DNA (mtDNA) and associated architectural proteins. Here, we show that phase separation is the primary physical mechanism for assembly and size-control of the mitochondrial nucleoid. The major mtDNA-binding protein TFAM spontaneously phase separates in vitro via weak, multivalent interactions into viscoelastic droplets with slow internal dynamics. In combination, TFAM and mtDNA form multiphase, gel-like structures in vitro, which recapitulate the in vivo dynamic behavior of mt-nucleoids. Enlarged, phase-separated, yet transcriptionally active, nucleoids are present in mitochondria from patients with the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS) and are associated with mitochondrial dysfunction. These results point to phase separation as an evolutionarily conserved mechanism of genome organization. HighlightsO_LIMitochondrial genomes are organized by phase separation. C_LIO_LIThe main packaging protein TFAM and mtDNA combine to form viscoelastic, multiphase droplets in vitro. C_LIO_LIMitochondrial nucleoids exhibit phase behavior in vivo, including dynamic rearrangements and heterogenous organization. C_LIO_LICoalescence and enlargement of mt-nucleoids occur upon loss of mitochondrial homeostasis as well as in prematurely aged cells and are associated with mitochondrial dysfunction. C_LI

cell biology↗

bioRxiv2019

Both Determinants of Allosteric and Active Sites Responsible for Catalytic Activity of Delta 12 Fatty Acid Desaturase by Domain Swapping

Cheese lacks essential fatty acids (EFAs). Delta 12 fatty acid desaturase (FADS12) is a critical enzyme required for EFA biosynthesis in fermentation of the predominant strains of cheese. Previously, we identified the FADS12 gene and characterized its function for the first time in Geotrichum candidum, a dominant strain used to manufacture soft cheese with white rind. In this study, we analyzed the molecular mechanism of FADS12 function by swapping domains from Mortierella alpina and G. candidum that had, respectively, high and low oleic acid conversion rates. The results revealed three regions that are essential to this process, including regions from the end of the second transmembrane domain to the beginning of the third transmembrane domain, from the end of the third transmembrane domain to the beginning of the fourth transmembrane domain, and from the 30-amino acid from the end of the sixth transmembrane domain to the C-terminal end region. Based on our domain swapping analyses, nine pairs of amino acids including H112, S118, H156, Q161, K301, R306, E307, A309 and S323 in MaFADS12 (K123, A129, N167, M172, T302, D307, I308, E310 and D324 in GcFADS12) were identified as having a significantly effect on FADS12 catalytic efficiency, and linoleic acid and its analogues (12,13-cyclopropenoid fatty acid) were found to inhibit the catalytic activity of FADS12 and related recombinant enzymes. Furthermore, the molecular mechanism of FADS12 inhibition was analyzed. The results revealed two allosteric domains, including one domain from the N-terminal region to the beginning of the first transmembrane domain and another from the 31st amino acid from the end of the sixth transmembrane domain to the C terminus. Y4 and F398 amino acid residues from MaFADS12 and eight pairs of amino acids including G56, L60, L344, G10, Q13, S24, K326 and L344 in MaFADS12 (while Y66, F70, F345, F20, Y23, Y34, F327 and F345 in GcFADS12) played a pivotal role in FADS12 inhibition. Finally, we found that both allosteric and active sites were responsible for the catalytic activity of FADS12 at various temperatures, pH, and times. This study offers a solid theoretical basis to develop preconditioning methods to increase the rate at which GcFADS12 converts oleic and linoleic acids to produce higher levels of EFAs in cheese.

molecular biology↗

bioRxiv2019

Recent origin of an XX/XY sex-determination system in the ancient plant lineage Ginkgo biloba

Sexual dimorphism like dioecy (separate male and female individuals) have evolved in diverse multicellular eukaryotes while the molecular mechanisms underlying the development of such a key biological trait remains elusive (1). The living fossil Ginkgo biloba represents an early diverged lineage of land plants with dioecy. However, its sex-determination system and molecular basis have long been controversial or unknown. In the present research, we assembled the first and largest to date chromosome-level genome of a non-model tree species using Hi-C data. With this reference genome, we addressed both questions using genome resequencing data gathered from 97 male and 265 female trees of ginkgo, as well as transcriptome data from three developmental stages for both sexes. Our results support vertebrate-like XY chromosomes for ginkgo and five potential sex-determination genes, which may originate ~14 million years ago. This is the earliest diverged sex determination region in all reported plants as yet. The present research resolved a long-term controversy, lay a foundation for future studies on the origin and evolution of plant sexes, and provide genetic markers for sex identification of ginkgo which will be valuable for both nurseries and field ecology of ginkgo.

evolutionary biology↗

bioRxiv2018

Garcinia cambogia extract removes calcium oxalate kidney stones in both genetic and non-genetic Drosophila models of nephrolithiasis

Kidney stone formers with family history have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication available for treatment. Here, we show that Garcinia cambogia extract (GCE) efficiently removes calcium oxalate kidney stones from Malpighian tubules in both genetic and non-genetic Drosophila models of nephrolithiasis, and hydroxycitrate -a major component of GCE, directly dissolves calcium oxalate stones in Drosophila Malpighian tubules ex vivo. Our study discovers a potential novel therapeutic strategy for the clinical treatment of nephrolithiasis and suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future.

pharmacology and toxicology↗

bioRxiv2018

Differential gene expression, including Sjfs800, in Schistosoma japonicum females before, during, and after male-female pairing

Schistosomiasis is a prevalent but neglected tropical disease caused by parasitic trematodes of the genus Schistosoma, with the primary disease-causing species being S. haematobium, S. mansoni, and S. japonicum. Male-female pairing of schistosomes is necessary for sexual maturity and the production of a large number of eggs, which are primarily responsible for schistosomiasis dissemination and pathology. Here, we used microarray hybridization, bioinformatics, quantitative PCR, in situ hybridization, and gene silencing assays to identify genes that play critical roles in S. japonicum reproduction biology, particularly in vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. Microarray hybridization analyses generated a comprehensive set of genes differentially transcribed before and after male-female pairing. Although the transcript profiles of females were similar 16 and 18 days after host infection, marked gene expression changes were observed at 24 days. The 30 most abundantly transcribed genes on day 24 included those associated with vitellarium development. Among these, genes for female-specific 800 (fs800), eggshell precursor protein, and superoxide dismutase (cu-zn-SOD) were substantially upregulated. Our in situ hybridization results in female S. japonicum indicated that cu-zn-SOD mRNA was highest in the ovary and vitellarium, eggshell precursor protein mRNA was expressed in the ovary, ootype, and vitellarium, and Sjfs800 mRNA was observed only in the vitellarium, localized in mature vitelline cells. Knocking down the Sjfs800 gene in female S. japonicum by approximately 60% reduced the number of mature vitelline cells, decreased rates of pairing and oviposition, and decreased the number of eggs produced in each male-female pairing by about 50%. These results indicate that Sjfs800 is essential for vitellarium development and egg production in S. japonicum and suggest that Sjfs800 regulation may provide a novel approach for the prevention or treatment of schistosomiasis.\n\nAuthor SummarySchistosomiasis is a common but largely unstudied tropical disease caused by parasitic trematodes of the genus Schistosoma. The eggs of schistosomes are responsible for schistosomiasis transmission and pathology, and the production of these eggs is dependent on the pairing of females and males. In this study, we determined which genes in Schistosoma japonicum females were differentially expressed before and after pairing with males, identifying the 30 most abundantly expressed of these genes. Among these 30 genes, we further characterized those in female S. japonicum that were upregulated after pairing and that were related to reproduction and vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. We identified three such genes, S. japonicum female-specific 800 (Sjfs800), eggshell precursor protein, and superoxide dismutase, and confirmed that the mRNAs for these genes were primarily localized in reproductive structures. By using gene silencing techniques to reduce the amount of Sjfs800 mRNA in females by about 60%, we determined that Sjfs800 plays a key role in development of the vitellarium and egg production. This finding suggests that regulation of Sjfs800 may provide a novel approach to reduce egg counts and thus aid in the prevention or treatment of schistosomiasis.

genomics↗