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1.
Fish Shellfish Immunol ; 148: 109505, 2024 May.
Article in English | MEDLINE | ID: mdl-38521144

ABSTRACT

The E11 cell line, derived from striped snakehead fish (Channa striata), possesses a distinctive feature: it is persistently infected with a C-type retrovirus. Notably, it exhibits high permissiveness to piscine nodavirus and the emerging tilapia lake virus (TiLV). Despite its popularity in TiLV research, the absence of genome assembly for the E11 cell line and Channa striata has constrained research on host-virus interactions. This study aimed to fill this gap by sequencing, assembling, and annotating the E11 cell line genome. Our efforts yielded a 600.5 Mb genome including 24 chromosomes with a BUSCO score of 98.8%. In addition, the complete proviral DNA sequence of snakehead retrovirus (SnRV) was identified in the E11 cell genome. Comparative genomic analysis between the E11 cell line and another snakehead species Channa argus revealed the loss of many immune-related gene families in the E11 cell genome, indicating a compromised immune response. We also conducted transcriptome analysis of mock- and TiLV-infected E11 cells, unveiling new perspectives on virus-virus and host-virus interactions. The TiLV infection suppressed the high expression of SnRV in E11 cells, and activated some other endogenous retroviruses. The protein-coding gene comparison revealed a pronounced up-regulation of genes involved in immune response, alongside a down-regulation of genes associated with specific metabolic processes. In summary, the genome assembly and annotation of the E11 cell line provide valuable resources to understand the SnRV and facilitate further studies on nodavirus and TiLV. The RNA-seq profiles shed light on the cellular mechanisms employed by fish cells in response to viral challenges, potentially guiding the development of therapeutic strategies against TiLV in aquaculture. This study also provides the first insights into the viral transcriptome profiles of endogenous SnRV and evading TiLV, enhancing our understanding of host-virus interactions in fish.


Subject(s)
Fish Diseases , Tilapia , Viruses , Animals , Retroviridae , Chromosomes , Gene Expression Profiling/veterinary
2.
Fish Shellfish Immunol ; 149: 109606, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705547

ABSTRACT

Moritella viscosa (M. viscosa) and sea lice (Lepeophtheirus salmonis) are severe pathogens that primarily infect the skin of Atlantic salmon (Salmo salar), which cause significant economic losses in the farming industry. However, the pathogenesis and molecular mechanisms underlying the host's immune defence at the post-transcriptional level remain unclear. Alternative splicing (AS) is an evolutionarily conserved post-transcriptional mechanism that can greatly increase the richness of the transcriptome and proteome. In this study, transcriptomic data derived from skin tissues of Atlantic salmon after M. viscosa and sea lice infections were used to examine the AS profiles and their differential expression patterns. In total, we identified 33,044 AS events (involving 13,718 genes) in the control (CON) group, 35,147 AS events (involving 14,340 genes) in the M. viscosa infection (MV) group, and 30,364 AS events (involving 13,142 genes) in the sea lice infection (LC) group, respectively. Among the five types of AS identified in our study (i.e., SE, A5SS, A3SS, MXE, and RI), SE was the most prevalent type in all three groups (i.e., CON, MV, and LC groups). Decreased percent-spliced-in (PSI) levels were observed in SE events under both MV- and LC-infected conditions, suggesting that MV or LC infection elevated exon-skipping isoforms and promoted the selection of shorter transcripts in numerous DAS genes. In addition, most of the differential AS genes were found to be associated with pathways related to mRNA regulation, epithelial or muscle development, and immune response. These findings provide novel insights into the role of AS in host-pathogen interactions and represent the first comparative analysis of AS in response to bacterial and parasitic infections in fish.


Subject(s)
Alternative Splicing , Copepoda , Fish Diseases , Moritella , Salmo salar , Animals , Salmo salar/immunology , Salmo salar/genetics , Copepoda/physiology , Fish Diseases/immunology , Moritella/immunology , Moritella/genetics , Transcriptome , Ectoparasitic Infestations/veterinary , Ectoparasitic Infestations/immunology , Ectoparasitic Infestations/genetics
3.
Biochemistry ; 62(3): 824-834, 2023 02 07.
Article in English | MEDLINE | ID: mdl-36638317

ABSTRACT

Isonitrile lipopeptides (INLPs) are known to be related to the virulence of pathogenic mycobacteria by mediating metal transport, but their biosynthesis remains obscure. In this work, we use in vitro biochemical assays, site-directed mutagenesis, chemical synthesis, and spectroscopy techniques to scrutinize the activity of core enzymes required for INLP biosynthesis in mycobacteria. Compared to environmental Streptomyces, pathogenic Mycobacterium employ a similar chemical logic and enzymatic machinery in INLP biosynthesis, differing mainly in the fatty-acyl chain length, which is controlled by multiple enzymes in the pathway. Our in-depth study on the non-heme iron(II) and α-ketoglutarate-dependent dioxygenase for isonitrile generation, including Rv0097 from Mycobacterium tuberculosis (Mtb), demonstrates that it recognizes a free-standing small molecule substrate, different from the recent hypothesis that a carrier protein is required for Rv0097 in Mtb. A key residue in Rv0097 is further identified to dictate the varied fatty-acyl chain length specificity between Streptomyces and Mycobacterium.


Subject(s)
Lipopeptides , Mycobacterium tuberculosis , Mycobacterium tuberculosis/genetics , Metals , Mutagenesis, Site-Directed
4.
Plant Cell ; 32(4): 923-934, 2020 04.
Article in English | MEDLINE | ID: mdl-32060175

ABSTRACT

Six subspecies of hexaploid wheat (Triticum aestivum) have been identified, but the origin of Indian dwarf wheat (Triticum sphaerococcum), the only subspecies with round grains, is currently unknown. Here, we isolated the grain-shape gene Tasg-D1 in T sphaerococcum via positional cloning. Tasg-D1 encodes a Ser/Thr protein kinase glycogen synthase kinase3 (STKc_GSK3) that negatively regulates brassinosteroid signaling. Expression of TaSG-D1 and the mutant form Tasg-D1 in Arabidopsis (Arabidopsis thaliana) suggested that a single amino acid substitution in the Thr-283-Arg-284-Glu-285-Glu-286 domain of TaSG-D1 enhances protein stability in response to brassinosteroids, likely leading to formation of round grains in wheat. This gain-of-function mutation has pleiotropic effects on plant architecture and exhibits incomplete dominance. Haplotype analysis of 898 wheat accessions indicated that the origin of T sphaerococcum in ancient India involved at least two independent mutations of TaSG-D1 Our results demonstrate that modest genetic changes in a single gene can induce dramatic phenotypic changes.


Subject(s)
Amino Acid Substitution/genetics , Glycogen Synthase Kinase 3/genetics , Seeds/anatomy & histology , Triticum/anatomy & histology , Triticum/genetics , Base Sequence , Brassinosteroids/metabolism , Cloning, Molecular , Haplotypes/genetics , Phenotype , Point Mutation/genetics , Signal Transduction , Triticum/growth & development
5.
Nat Chem Biol ; 17(12): 1305-1313, 2021 12.
Article in English | MEDLINE | ID: mdl-34725510

ABSTRACT

Triacsins are an intriguing class of specialized metabolites possessing a conserved N-hydroxytriazene moiety not found in any other known natural products. Triacsins are notable as potent acyl-CoA synthetase inhibitors in lipid metabolism, yet their biosynthesis has remained elusive. Through extensive mutagenesis and biochemical studies, we here report all enzymes required to construct and install the N-hydroxytriazene pharmacophore of triacsins. Two distinct ATP-dependent enzymes were revealed to catalyze the two consecutive N-N bond formation reactions, including a glycine-utilizing, hydrazine-forming enzyme (Tri28) and a nitrite-utilizing, N-nitrosating enzyme (Tri17). This study paves the way for future mechanistic interrogation and biocatalytic application of enzymes for N-N bond formation.


Subject(s)
Coenzyme A Ligases/metabolism , Streptomyces aureofaciens/enzymology , Streptomyces aureofaciens/genetics , Triazenes/metabolism , Biocatalysis , Escherichia coli/genetics , Glycine/chemistry , Hydrazines/chemistry , Lipid Metabolism , Lipids/chemistry , Nitrites/chemistry , Triazenes/chemistry
6.
Fish Shellfish Immunol ; 143: 109210, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37951318

ABSTRACT

Sea lice (Lepeophtheirus salmonis) and infectious salmon anemia virus (ISAv) are two of the most important pathogens in Atlantic salmon (Salmo salar) farming and typically cause substantial economic losses to the industry. However, the immune interactions between hosts and these pathogens are still unclear, especially in the scenario of co-infection. In this study, we artificially infected Atlantic salmon with sea lice and ISAv, and investigated the gene expression patterns of Atlantic salmon head kidneys in response to both lice only and co-infection with lice and ISAv by transcriptomic analysis. The challenge experiment indicated that co-infection resulted in a cumulative mortality rate of 47.8 %, while no mortality was observed in the lice alone infection. We identified 240 differentially expressed genes (DEGs) under the lice alone infection, of which 185 were down-regulated and 55 were up-regulated, while a total of 994 DEGs were identified in the co-infection, of which 206 were down-regulated and 788 were significantly up-regulated. The pathway enrichment analysis revealed that single-infection significantly suppressed the innate immune system (e.g., the complement system), whereas co-infection induced a strong immune response, leading to the activation of immune-related signaling pathways such as Toll-like receptors and NOD-like receptors pathways, as well as significant upregulation of genes related to the activation of interferon and MH class I protein complex. Our results provide the first global transcriptomic study of gene expression in the Atlantic salmon head kidney in response to co-infection with sea lice and ISAv, and provided the baseline knowledge for understanding the immune responses during co-infection.


Subject(s)
Coinfection , Copepoda , Fish Diseases , Isavirus , Salmo salar , Animals , Salmo salar/genetics , Copepoda/physiology , Isavirus/genetics , Coinfection/veterinary , Gene Expression Profiling/veterinary , Transcriptome , Immunity , Kidney
7.
Addict Biol ; 28(4): e13272, 2023.
Article in English | MEDLINE | ID: mdl-37016753

ABSTRACT

Great progress has been made in understanding the neural mechanisms associated with alcohol-dependent (AD) patients. However, the interactions within the reward circuits of the patients need further exploration. Glutamatergic projections from the prefrontal cortex to some brain regions are present in the reward circuit. However, little is known about the potential implications of glutamate levels in the prefrontal cortex on abnormal interactions within reward circuits in AD patients. To determine the potential roles of reward circuits in drinking, we investigated differences in resting-state functional connectivity (RSFC) and multivariate Granger causality analysis between 20 AD patients and 20 healthy controls (HC). The neuroimaging findings were then correlated with clinical variables (alcohol use disorder identification test). The ventromedial prefrontal cortex (VmPFC) is believed to play a critical role in addiction disorders, and glutamatergic projections from the prefrontal cortex to several regions of the brain are present in reward circuits. Proton magnetic resonance spectroscopy was also performed to assess the difference in glutamate levels in VmPFC between AD patients and HC. The results showed that the strength of functional connectivity in the reward circuit was generally attenuated in AD patients, and the reciprocal enhancement of activity between the right insula, left thalamus and VmPFC was found to be significantly greater in AD patients. It is worth noting that although glutamate levels in the VmPFC did not show significant differences between the two groups, the level of glutamate in the VmPFC was significantly correlated with RSFC. We hope that the current findings will help us to develop new intervention models based on the important role of the VmPFC in AD.


Subject(s)
Alcoholism , Glutamic Acid , Humans , Alcoholism/diagnostic imaging , Prefrontal Cortex/diagnostic imaging , Brain , Ethanol , Reward , Magnetic Resonance Imaging/methods
8.
Proc Natl Acad Sci U S A ; 117(27): 16009-16018, 2020 07 07.
Article in English | MEDLINE | ID: mdl-32571913

ABSTRACT

Food and drug products contain diverse and abundant small-molecule additives (excipients) with unclear impacts on human physiology, drug safety, and response. Here, we evaluate their potential impact on intestinal drug absorption. By screening 136 unique compounds for inhibition of the key intestinal transporter OATP2B1 we identified and validated 24 potent OATP2B1 inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or noninhibitors. OATP2B1 inhibitors were also enriched for dyes, including 8 azo (R-N=N-R') dyes. Pharmacokinetic studies in mice confirmed that FD&C Red No. 40, a common azo dye excipient and a potent inhibitor of OATP2B1, decreased the plasma level of the OATP2B1 substrate fexofenadine, suggesting that FD&C Red No. 40 has the potential to block drug absorption through OATP2B1 inhibition in vivo. However, the gut microbiomes of multiple unrelated healthy individuals as well as diverse human gut bacterial isolates were capable of inactivating the identified azo dye excipients, producing metabolites that no longer inhibit OATP2B1 transport. These results support a beneficial role for the microbiome in limiting the unintended effects of food and drug additives in the intestine and provide a framework for the data-driven selection of excipients. Furthermore, the ubiquity and genetic diversity of gut bacterial azoreductases coupled to experiments in conventionally raised and gnotobiotic mice suggest that variations in gut microbial community structure may be less important to consider relative to the high concentrations of azo dyes in food products, which have the potential to saturate gut bacterial enzymatic activity.


Subject(s)
Bacteria/metabolism , Excipients/metabolism , Food Additives/metabolism , Food , Gastrointestinal Microbiome/physiology , Intestinal Absorption/physiology , Organic Anion Transporters/metabolism , ATP Binding Cassette Transporter, Subfamily B/genetics , Animals , Anti-Allergic Agents/metabolism , Anti-Allergic Agents/pharmacokinetics , Azo Compounds , Bacteria/isolation & purification , Excipients/pharmacokinetics , Female , Food Additives/pharmacokinetics , Histamine H1 Antagonists, Non-Sedating/metabolism , Histamine H1 Antagonists, Non-Sedating/pharmacokinetics , Humans , Intestinal Absorption/drug effects , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Terfenadine/analogs & derivatives , ATP-Binding Cassette Sub-Family B Member 4
9.
J Aquat Anim Health ; 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38060422

ABSTRACT

OBJECTIVE: Florfenicol (FFC) is a broad-spectrum antibiotic approved by the U.S. Food and Drug Administration to treat both systemic and external bacterial infections in food fish. The objective of this study was to evaluate the effect of FFC-medicated feed on the gut microbiota of Zebrafish Danio danio to determine (1) if the therapeutic dose of FFC-medicated feed induces dysbiosis and (2) if fish with altered gut microbiota were more susceptible to subsequent infection by the common opportunistic fish pathogen Aeromonas hydrophila. METHODS: Zebrafish that were treated with regular and FFC-medicated feeds were artificially challenged with A. hydrophila at the end of the recommended 15-day antibiotic withdrawal period. The gut microbiota of the Zebrafish at different stages was analyzed using 16S ribosomal RNA gene sequencing. RESULT: Our results found that FFC-medicated feed induced disruption of the gut microbiota. Dysbiosis was observed in all treated groups, with a significant increase in bacterial diversity, and was characterized by a remarkable bloom of Proteobacteria and a drastic decline of Mycoplasma and Cetobacterium in treated animals but without noticeable clinical signs or mortalities. In addition, the increase of Proteobacteria was not significantly reduced after the recommended 15-day withdrawal period, and the Zebrafish treated with FFC-medicated feed exhibited a significantly higher mortality rate when they were subsequently challenged with A. hydrophila compared to the control (regular feed) groups. Interestingly, the most dramatic changes in the gut microbiome composition occurred at the transition time between the late stage of the medicated treatment and the beginning of the withdrawal period instead of the time during the Aeromonas infection. CONCLUSION: The administration of FFC-medicated feed at the recommended dose induced gut dysbiosis in Zebrafish, and fish did not recover to the baseline after the recommended withdrawal period. Our findings suggest that the use of antibiotics in fish elicits a response similar to those previously described in mammals and possibly makes the host more susceptible to subsequent infections of opportunistic pathogens. This study using a controlled model system suggests that antibiotics in aquaculture may have long-term effects on the general well-being of the fish.

10.
Angew Chem Int Ed Engl ; 62(4): e202214828, 2023 Jan 23.
Article in English | MEDLINE | ID: mdl-36383099

ABSTRACT

Extreme fast charging (XFC) of high-energy Li-ion batteries is a key enabler of electrified transportation. While previous studies mainly focused on improving Li ion mass transport in electrodes and electrolytes, the limitations of charge transfer across electrode-electrolyte interfaces remain underexplored. Herein we unravel how charge transfer kinetics dictates the fast rechargeability of Li-ion cells. Li ion transfer across the cathode-electrolyte interface is found to be rate-limiting during XFC, but the charge transfer energy barrier at both the cathode and anode have to be reduced simultaneously to prevent Li plating, which is achieved through electrolyte engineering. By unlocking charge transfer limitations, 184 Wh kg-1 pouch cells demonstrate stable XFC (10-min charge to 80 %) which is otherwise unachievable, and the lifetime of 245 Wh kg-1 21700 cells is quintupled during fast charging (25-min charge to 80 %).

11.
J Biol Chem ; 296: 100231, 2021.
Article in English | MEDLINE | ID: mdl-33361191

ABSTRACT

The isonitrile moiety is found in marine sponges and some microbes, where it plays a role in processes such as virulence and metal acquisition. Until recently only one route was known for isonitrile biosynthesis, a condensation reaction that brings together a nitrogen atom of l-Trp/l-Tyr with a carbon atom from ribulose-5-phosphate. With the discovery of ScoE, a mononuclear Fe(II) α-ketoglutarate-dependent dioxygenase from Streptomyces coeruleorubidus, a second route was identified. ScoE forms isonitrile from a glycine adduct, with both the nitrogen and carbon atoms coming from the same glycyl moiety. This reaction is part of the nonribosomal biosynthetic pathway of isonitrile lipopeptides. Here, we present structural, biochemical, and computational investigations of the mechanism of isonitrile formation by ScoE, an unprecedented reaction in the mononuclear Fe(II) α-ketoglutarate-dependent dioxygenase superfamily. The stoichiometry of this enzymatic reaction is measured, and multiple high-resolution (1.45-1.96 Å resolution) crystal structures of Fe(II)-bound ScoE are presented, providing insight into the binding of substrate, (R)-3-((carboxylmethyl)amino)butanoic acid (CABA), cosubstrate α-ketoglutarate, and an Fe(IV)=O mimic oxovanadium. Comparison to a previously published crystal structure of ScoE suggests that ScoE has an "inducible" α-ketoglutarate binding site, in which two residues arginine-157 and histidine-299 move by approximately 10 Å from the surface of the protein into the active site to create a transient α-ketoglutarate binding pocket. Together, data from structural analyses, site-directed mutagenesis, and computation provide insight into the mode of α-ketoglutarate binding, the mechanism of isonitrile formation, and how the structure of ScoE has been adapted to perform this unusual chemical reaction.


Subject(s)
Bacterial Proteins/chemistry , Dioxygenases/chemistry , Glycine/chemistry , Iron/chemistry , Ketoglutaric Acids/chemistry , Nitriles/metabolism , Streptomyces/enzymology , Aminobutyrates/chemistry , Aminobutyrates/metabolism , Arginine/chemistry , Arginine/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Binding Sites , Cloning, Molecular , Crystallography, X-Ray , Dioxygenases/genetics , Dioxygenases/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Gene Expression , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Glycine/metabolism , Histidine/chemistry , Histidine/metabolism , Iron/metabolism , Ketoglutaric Acids/metabolism , Models, Molecular , Nitriles/chemistry , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Stereoisomerism , Streptomyces/chemistry , Streptomyces/genetics , Substrate Specificity , Vanadates/chemistry , Vanadates/metabolism
12.
J Am Chem Soc ; 144(13): 5893-5901, 2022 04 06.
Article in English | MEDLINE | ID: mdl-35254829

ABSTRACT

The isonitrile moiety is an electron-rich functionality that decorates various bioactive natural products isolated from diverse kingdoms of life. Isonitrile biosynthesis was restricted for over a decade to isonitrile synthases, a family of enzymes catalyzing a condensation reaction between l-Trp/l-Tyr and ribulose-5-phosphate. The discovery of ScoE, a non-heme iron(II) and α-ketoglutarate-dependent dioxygenase, demonstrated an alternative pathway employed by nature for isonitrile installation. Biochemical, crystallographic, and computational investigations of ScoE have previously been reported, yet the isonitrile formation mechanism remains obscure. In the present work, we employed in vitro biochemistry, chemical synthesis, spectroscopy techniques, and computational simulations that enabled us to propose a plausible molecular mechanism for isonitrile formation. Our findings demonstrate that the ScoE reaction initiates with C5 hydroxylation of (R)-3-((carboxymethyl)amino)butanoic acid to generate 1, which undergoes dehydration, presumably mediated by Tyr96 to synthesize 2 in a trans configuration. (R)-3-isocyanobutanoic acid is finally generated through radical-based decarboxylation of 2, instead of the common hydroxylation pathway employed by this enzyme superfamily.


Subject(s)
Carboxy-Lyases , Oxidoreductases , Carboxy-Lyases/chemistry , Ferrous Compounds/chemistry , Iron/chemistry , Ketoglutaric Acids/metabolism
13.
Inorg Chem ; 61(21): 8366-8378, 2022 May 30.
Article in English | MEDLINE | ID: mdl-35588477

ABSTRACT

Manganese-based compounds are expected to become promising candidates for lithium-ion battery anodes by virtue of their high theoretical specific capacity and low conversion potential. However, their application is hindered by their inferior electrical conductivity and drastic volume variations. In this work, a unique heterostructure composed of MnO and MnS spatially confined in pyrolytic carbon microspheres (MnO@MnS/C) was synthesized through an integrated solvothermal method, calcination, and low-temperature vulcanization technology. In this architecture, heterostructured MnO@MnS nanoparticles (∼10 nm) are uniformly embedded into the carbonaceous microsphere matrix to maintain the structural stability of the composite. Benefiting from the combination of structural and compositional features, the MnO@MnS/C enables abundance in electrochemically active sites, alleviated volumetric variation, a rich conductive network, and enhanced lithium-ion diffusion kinetics, thus yielding remarkable rate capability (1235 mAh·g-1 at 0.2 A·g-1 and 608 mAh·g-1 at 3.2 A·g-1) and exceptional cycling stability (522 mAh·g-1 after 2000 cycles at 3.0 A·g-1) as a competitive anode material for lithium-ion batteries. Density functional theory calculations unveil that the heterostructure promotes the transfer of electrons with improved conductivity and also accelerates the migration of lithium ions with reduced polarization resistance. This combined with the enhancement brought by spatial confinement endows the MnO@MnS/C with remarkable lithium storage performance.

14.
Angew Chem Int Ed Engl ; 61(39): e202210365, 2022 Sep 26.
Article in English | MEDLINE | ID: mdl-35938731

ABSTRACT

The access to full performance of state-of-the-art Li-ion batteries (LIBs) is hindered by the mysterious lithium plating behavior. A rapid quantified lithium plating determination method compatible with actual working conditions is an urgent necessity for safe working LIBs. In this contribution, the relationship between electrical double layer (EDL) capacitance and electrochemical active surface area (ECSA) of graphite anodes during the Li-ion intercalation and Li plating processes is unveiled. We propose an operando lithium plating determination method based on the dynamic capacitance measurement (DCM) test. Reasonable selection of alternating current (AC) frequency protects the anodic responses from the interference of cathodic responses, which allows DCM to be applied in practical LIBs. The onset of lithium plating can be quantitatively traced, demonstrating the promise for real-time operando determination for lithium plating in a working battery.

15.
Proteins ; 89(1): 132-137, 2021 01.
Article in English | MEDLINE | ID: mdl-32852843

ABSTRACT

Natural products and natural product-derived compounds have been widely used for pharmaceuticals for many years, and the search for new natural products that may have interesting activity is ongoing. Abyssomicins are natural product molecules that have antibiotic activity via inhibition of the folate synthesis pathway in microbiota. These compounds also appear to undergo a required [4 + 2] cycloaddition in their biosynthetic pathway. Here we report the structure of an flavin adenine dinucleotide-dependent reductase, AbsH3, from the biosynthetic gene cluster of novel abyssomicins found in Streptomyces sp. LC-6-2.


Subject(s)
Biological Products , Streptomyces , Biological Products/metabolism , Biosynthetic Pathways , Flavin-Adenine Dinucleotide/metabolism , Oxidoreductases/genetics , Oxidoreductases/metabolism , Streptomyces/genetics
16.
Reprod Fertil Dev ; 33(12): 736-745, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34602123

ABSTRACT

The long-term storage of spermatozoa in the female reproductive tract is limited by the innate immune system. Oestrogen plays a role in regulating the innate immune system. Thus, exploring the expression of genes in the Toll-like receptor (TLR) 2/4 pathway and oestrogen receptors in the oviduct of Mauremys reevesii could contribute to our understanding of the mechanism of sperm storage. In this study, three parts of the oviduct (isthmus, uterus and vagina) in three mated and unmated female turtles were used to perform immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR). Immunohistochemistry revealed that the TLR2/4 protein was mainly distributed in epithelial tissues and glandular cell membranes, and that TLR2/4 levels in the oviduct were significantly decreased in mated compared with unmated turtles. Real-time qPCR indicated that TLR2/4, myeloid differentiation factor 88 (MyD88), interleukin 1 receptor associated kinase 4 (IRAK4), TNF receptor associated factor 6 (TRAF6), interferon regulatory factor 3 (IRF3) and interleukin 6 (IL6) mRNA expression was significantly higher in the oviduct of unmated than mated turtles, whereas the opposite was true for the expression of oestrogen receptor 1 (ESR1) and progesterone receptor (PGR). These results indicate that when spermatozoa are stored in the oviduct, an increase in oestrogen suppresses the immune response induced by the TLR2/4 pathway so that spermatozoa are not removed as a foreign substance, but stored until fertilisation. The findings of this study are relevant to our understanding of the relationship between sperm storage and the innate immune system in the oviduct of reptiles.


Subject(s)
Immunity, Innate/physiology , Oviducts/metabolism , Receptors, Estrogen/physiology , Spermatozoa/physiology , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Animals , Female , Male , Turtles
17.
Dis Aquat Organ ; 143: 51-56, 2021 Jan 28.
Article in English | MEDLINE | ID: mdl-33506815

ABSTRACT

Myxobolus cerebralis (Hofer, 1903), the etiological agent of salmonid whirling disease, reportedly matures in only the oligochaete 'Tubifex tubifex'. The concept of 'T. tubifex' is problematic because it is renowned as a species complex (or having 'strains'), and many sequences ascribed to this taxon in GenBank are misidentified or indicate several cryptic species. These facts cast doubt on the long-held notion that M. cerebralis is strictly host-specific to the single definitive host, T. tubifex. Herein, as part of an ongoing regional whirling disease monitoring project, oligochaetes (452 specimens) were collected from 31 riverine sites in western North Carolina (August through September 2015) and screened for infection by M. cerebralis. The species-specific nested PCR for M. cerebralis was positive for 8 oligochaete specimens from the French Broad River Basin (Mill Creek and Watauga River) and New River Basin (Big Horse Creek). We individually barcoded these M. cerebralis-positive oligochaete specimens using cytochrome oxidase 1 (CO1) primers and then conducted a Bayesian inference phylogenetic analysis. We identified 2 oligochaete genotypes: one sister to a clade comprising Limnodrilus udekemianus (Haplotaxida: Naididae) and another sister to Limnodrilus hoffmeisteri. This is the first detection of M. cerebralis from an oligochaete in the SE USA and the first detection of M. cerebralis from an oligochaete other than T. tubifex. These results suggest that other non-T. tubifex definitive hosts can harbor the pathogen and should be considered in the context of fish hatchery biosecurity and monitoring wild trout streams for M. cerebralis and whirling disease in the southeastern USA.


Subject(s)
Fish Diseases , Horse Diseases , Myxobolus , Oligochaeta , Animals , Bayes Theorem , Eukaryota , Horses , Myxobolus/genetics , North Carolina , Phylogeny
18.
Chem Soc Rev ; 49(12): 3806-3833, 2020 Jun 21.
Article in English | MEDLINE | ID: mdl-32478786

ABSTRACT

With the impetus to accelerate worldwide market adoption of electrical vehicles and afford consumer electronics with better user experience, advancing fast-charging technology is an inevitable trend. However, current high-energy lithium-ion batteries are unable to support ultrafast power input without any adverse consequences, with the capacity fade and safety concerns of the mainstream graphite-based anodes being the key technological barrier. The aim of this review is to summarise the fundamentals, challenges, and solutions to enable graphite anodes that are capable of high-rate charging. First, we explore the complicated yet intriguing graphite-electrolyte interface during intercalation based on existing theories. Second, we analyse the key dilemmas facing fast-charging graphite anodes. Finally, some promising strategies proposed during the past few years are highlighted so as to outline current trends and future perspectives in this field.

19.
Angew Chem Int Ed Engl ; 60(7): 3402-3406, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33107707

ABSTRACT

Lithium-ion batteries with routine carbonate electrolytes cannot exhibit satisfactory fast-charging performance and lithium plating is widely observed at low temperatures. Herein we demonstrate that a localized high-concentration electrolyte consisting of 1.5 M lithium bis(fluorosulfonyl)imide in dimethoxyethane with bis(2,2,2-trifluoroethyl) ether as the diluent, enables fast-charging of working batteries. A uniform and robust solid electrolyte interphase (SEI) can be achieved on graphite surface through the preferential decomposition of anions. The established SEI can significantly inhibit ether solvent co-intercalation into graphite and achieve highly reversible Li+ intercalation/de-intercalation. The graphite | Li cells exhibit fast-charging potential (340 mAh g-1 at 0.2 C and 220 mAh g-1 at 4 C), excellent cycling stability (ca. 85.5 % initial capacity retention for 200 cycles at 4 C), and impressive low-temperature performance.

20.
Angew Chem Int Ed Engl ; 60(23): 13007-13012, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-33793052

ABSTRACT

Uncontrolled Li plating in graphite electrodes endangers battery life and safety, driving tremendous efforts aiming to eliminate Li plating. Herein we systematically investigate the boundary of Li plating in graphite electrode for safe lithium-ion batteries. The cell exhibits superior safety performance than that with Li dendrites by defining the endurable amount of uniform Li plating in graphite anode. The presence of "dead Li" can be eliminated owing to the uniform distribution of Li plating, and the average Coulombic efficiency for deposited Li during reversible plating/stripping process is decoupled as high as about 99.5 %. Attributing to the limited Li plating with superior Coulombic efficiency, the LiNi0.5 Mn0.3 Co0.2 O2 | graphite cell achieves a high capacity retention of 80.2 % over 500 cycles. This work sheds a different light on further improving the fast-charging capability, low-temperature performance, and energy density of practical lithium-ion batteries.

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