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1.
Nat Immunol ; 18(2): 214-224, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27992402

RESUMO

The signaling adaptor MAVS forms prion-like aggregates to activate an innate antiviral immune response after viral infection. However, the molecular mechanisms that regulate MAVS aggregation are poorly understood. Here we identified TRIM31, an E3 ubiquitin ligase of the TRIM family of proteins, as a regulator of MAVS aggregation. TRIM31 was recruited to mitochondria after viral infection and specifically regulated antiviral signaling mediated by RLR pattern-recognition receptors. TRIM31-deficient mice were more susceptible to infection with RNA virus than were wild-type mice. TRIM31 interacted with MAVS and catalyzed the Lys63 (K63)-linked polyubiquitination of Lys10, Lys311 and Lys461 on MAVS. This modification promoted the formation of prion-like aggregates of MAVS after viral infection. Our findings reveal new insights in the molecular regulation of MAVS aggregation and the cellular antiviral response through TRIM31-mediated K63-linked polyubiquitination of MAVS.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Transporte/metabolismo , Macrófagos/fisiologia , Proteínas Nucleares/metabolismo , Príons/imunologia , Viroses/imunologia , Animais , Proteínas de Transporte/genética , Células Cultivadas , Imunidade Inata/genética , Lisina/genética , Lisina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Nucleares/genética , Agregação de Receptores/genética , Transdução de Sinais/genética , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Ubiquitinação/genética
2.
J Org Chem ; 89(11): 8262-8266, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38741072

RESUMO

A convenient method for the synthesis of perdeuterated alkyl amides/amines is disclosed. Perdeuterated acetyl amides can be achieved by a hydrogen-deuterium (H/D) exchange protocol with Pt/C as a catalyst and D2O as a deuterium source under mild conditions. After removal or reduction of the acetyl group, this protocol can provide perdeuterated primary, secondary, and tertiary amines, which are difficult to achieve via other methods.

3.
Environ Sci Technol ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38344765

RESUMO

Volatile sulfur compounds, such as dimethyl sulfide (DMS), carbonyl sulfide (OCS), and carbon disulfide (CS2), have significant implications for both atmospheric chemistry and climate change. Despite the crucial role of oceans in regulating their atmospheric budgets, our comprehension of their cycles in seawater remains insufficient. To address this gap, a field investigation was conducted in the western North Pacific to clarify the sources, sinks, and biogeochemical controls of these gases in two different marine environments, including relatively eutrophic Kuroshio-Oyashio extension (KOE) and oligotrophic North Pacific subtropical gyre. Our findings revealed higher concentrations of these gases in both seawater and the atmosphere in the KOE compared to the subtropical gyre. In the KOE, nutrient-rich upwelling stimulated rapid DMS biological production, while reduced seawater temperatures hindered the removal of OCS and CS2, leading to their accumulation. Furthermore, we have quantitatively evaluated the relative contribution of each pathway to the source and sink of DMS, OCS, and CS2 within the mixed layer and identified vertical exchange as a potential sink in most cases, transporting substantial amounts of these gases from the mixed layer to deeper waters. This research advances our understanding of sulfur gas source-sink dynamics in seawater, contributing to the assessment of their marine emissions and atmospheric budgets.

4.
Phys Chem Chem Phys ; 26(16): 12681-12697, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38600841

RESUMO

The intrinsic ferromagnetism of two-dimensional transition metal carbide Co2C is remarkable. However, its practical application in spintronic devices is encumbered by a low Curie temperature (TC). To surmount this constraint, double transition-metal carbide CoMC (M = Ti, V, Cr, Mn, Fe, Ni) monolayers are constructed with the aim of improving the magnetic properties and Curie temperature of Co2C. The magnetic properties of CoMC monolayers are comprehensively investigated by first-principles calculations and the effects of hole doping and biaxial strain on the magnetic properties of CoMC (M = V, Cr, Mn) monolayers are also studied. The ground states of CoTiC, CoMnC and CoNiC monolayers all favor ferromagnetic ordering, whereas the CoVC and CoCrC monolayers favor antiferromagnetic ordering and the CoFeC monolayer is non-magnetic. Excitedly, the CoMnC monolayer displays a high total magnetic moment of 4.024µB and a TC of 1366 K. Moreover, the control of hole doping can effectively improve the TC of CoVC, CoCrC, and CoMnC monolayers to 680, 1317, 3044 K, respectively. Finally, applying the in-plain biaxial strain, the CoVC monolayer can be transformed into a ferromagnetic semiconductor under a tensile strain of 6%. The TC values of CoVC, CoCrC, and CoMnC monolayers are tuned by biaxial strain to 440, 1334 and 2390 K, respectively. Their TC above room temperature demonstrates that these monolayers have potential applications in spintronic devices. These theoretical investigations provide valuable insights into guiding experimental synthesis endeavors.

5.
PLoS Genet ; 17(8): e1009770, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34460822

RESUMO

The eye color of birds, generally referring to the color of the iris, results from both pigmentation and structural coloration. Avian iris colors exhibit striking interspecific and intraspecific variations that correspond to unique evolutionary and ecological histories. Here, we identified the genetic basis of pearl (white) iris color in domestic pigeons (Columba livia) to explore the largely unknown genetic mechanism underlying the evolution of avian iris coloration. Using a genome-wide association study (GWAS) approach in 92 pigeons, we mapped the pearl iris trait to a 9 kb region containing the facilitative glucose transporter gene SLC2A11B. A nonsense mutation (W49X) leading to a premature stop codon in SLC2A11B was identified as the causal variant. Transcriptome analysis suggested that SLC2A11B loss of function may downregulate the xanthophore-differentiation gene CSF1R and the key pteridine biosynthesis gene GCH1, thus resulting in the pearl iris phenotype. Coalescence and phylogenetic analyses indicated that the mutation originated approximately 5,400 years ago, coinciding with the onset of pigeon domestication, while positive selection was likely associated with artificial breeding. Within Aves, potentially impaired SLC2A11B was found in six species from six distinct lineages, four of which associated with their signature brown or blue eyes and lack of pteridine. Analysis of vertebrate SLC2A11B orthologs revealed relaxed selection in the avian clade, consistent with the scenario that during and after avian divergence from the reptilian ancestor, the SLC2A11B-involved development of dermal chromatophores likely degenerated in the presence of feather coverage. Our findings provide new insight into the mechanism of avian iris color variations and the evolution of pigmentation in vertebrates.


Assuntos
Columbidae/genética , Cor de Olho/genética , Cor de Olho/fisiologia , Animais , Evolução Biológica , Evolução Molecular , Olho/metabolismo , Perfilação da Expressão Gênica/métodos , Estudo de Associação Genômica Ampla , Genótipo , Proteínas Facilitadoras de Transporte de Glucose/genética , Iris/metabolismo , Mutação , Fenótipo , Filogenia , Pigmentação/genética
6.
Angew Chem Int Ed Engl ; : e202405944, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837324

RESUMO

Recently, the introduction of fluorosulfonyl (-SO2F) groups have attracted considerable research interests, as this moiety could often afford enhanced activities and new functions in the context of chemical biology and drug discovery. Herein, we report the design and synthesis of 1-fluorosulfamoyl-pyridinium (FSAP) salts, which could serve as an effective photoredox-active precursor to fluorosulfamoyl radicals and enable the direct radical C-H fluorosulfonamidation of a variety of (hetero)arenes. This method features mild conditions, visible light, broad substrate scope, good group tolerance, etc., and a metal-free protocol is also viable by using organic photocatalysts. Further, FSAP can also be applied to the radical functionalization of alkenes via 1,2-difunctionalization, radical distal migration, tandem radical-polar crossover reactions, etc. In addition, a formal C-H methylamination of (hetero)arenes by combining this radical C-H fluorosulfonamidation with subsequent hydrolysis as well as product derivatization are also demonstrated.

7.
BMC Genomics ; 24(1): 507, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37648967

RESUMO

BACKGROUND: The Mongolian gazelle (Procapra gutturosa) population has shown a considerable range of contractions and local extinctions over the last century, owing to habitat fragmentation and poaching. A thorough understanding of the genetic diversity and structure of Mongolian gazelle populations in fragmented habitats is critical for planning effective conservation strategies. RESULT: In this study, we used eight microsatellite loci and mitochondrial cytochrome b (Cytb) to compare the levels of genetic diversity and genetic structure of Mongolian gazelle populations in the Hulun Lake National Nature Reserve (HLH) with those in the China-Mongolia border area (BJ). The results showed that the nucleotide diversity and observed heterozygosity of the HLH population were lower than those of the BJ population. Moreover, the HLH and BJ populations showed genetic differentiation. We concluded that the HLH population had lower genetic diversity and a distinct genetic structure compared with the BJ population. CONCLUSION: The genetic diversity of fragmented Mongolian gazelle populations, can be improved by protecting these populations while reinforcing their gene exchange with other populations. For example, attempts can be made to introduce new individuals with higher genetic diversity from other populations to reduce inbreeding.


Assuntos
Antílopes , Humanos , Animais , Antílopes/genética , China , Citocromos b/genética , Deriva Genética , Variação Genética
8.
Cell Mol Neurobiol ; 43(8): 4279-4293, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37864627

RESUMO

To investigate the molecular mechanism of communication network factor 1 (CCN1) regulating pentylenetetrazol (PTZ)-induced epileptogenesis, deepen the understanding of epilepsy seizure pathogenesis, and provide new drug action targets for its clinical prevention and treatment. Differentially expressed genes (DEGs) on microarrays GSE47516 and GSE88992 were analyzed online using GEO2R. Pathway enrichment and protein-protein interaction network (PPI) analysis of DEGs were carried out using Metascape. Brain tissue samples of severe traumatic brain injury patients (named Healthy group) and refractory epilepsy patients (named Epilepsy group) were obtained and analyzed by qRT-PCR and immunohistochemistry (IHC) staining. A PTZ-induced epilepsy mouse model was established and verified. Morphological changes of neurons in mouse brain tissue were detected using hematoxylin and eosin (HE) staining. qRT-PCR was conducted to detect the mRNA expressions of apoptosis-associated proteins Bax, Caspase-3 and bcl2. TUNEL staining was performed to detect brain neuron apoptosis. The levels of myocardial enzymology, GSH, MDA and ROS in blood of mouse were detected by biochemical assay. CCN1 expression was increased in epilepsy brain tissue samples. CCN1 decreasing effectively prolongs seizure incubation period and decreases seizure duration. Silencing of CCN1 also reduces neuronal damage and apoptosis, decreases mRNA and protein expression of proapoptotic proteins Bax and Caspase-3, increases mRNA expression of antiapoptotic protein Bcl2. Moreover, decrease of CCN1 decreases myocardial enzymatic indexes CK and CK-MB levels, reduces myocardial tissue hemorrhage, and relieves oxidative stress response in hippocampal and myocardial tissue. CCN1 expression is increased in epileptic samples. CCN1 decreasing protects brain tissue by attenuating oxidative stress and inhibiting neuronal apoptosis triggered by PTZ injection, which probably by regulating Nrf2/HO-1 pathway.


Assuntos
Epilepsia , Pentilenotetrazol , Humanos , Camundongos , Animais , Pentilenotetrazol/efeitos adversos , Caspase 3/metabolismo , Proteína X Associada a bcl-2/metabolismo , Epilepsia/induzido quimicamente , Epilepsia/genética , Epilepsia/tratamento farmacológico , Convulsões/induzido quimicamente , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo
9.
Environ Sci Technol ; 57(28): 10284-10294, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37357464

RESUMO

Organosulfates (OSs) could be potentially important compounds in marine organic aerosols, while their formation in marine atmospheres is far from clear due to a lack of cruise observations. In this work, shipboard atmospheric observations were conducted over the Yellow Sea and Bohai Sea to investigate the abundance and formation of biogenic isoprene/monoterpene-OSs in marine aerosols. The quantified OSs and NOSs accounted for 0.04-6.9% of marine organic aerosols and were 0.07-2.2% of the non-sea-salt (nss) sulfate in terms of sulfur content. Isoprene-related (nitrooxy-)OSs occupied 27-87% of the total quantified OSs, following the abundance order of summer > autumn > spring or winter. This order was driven by the marine phytoplankton biomass and sea surface temperature (SST), which controlled the seawater and atmospheric isoprene concentration levels. Under the severe impacts of anthropogenic pollutants from the East Asia continent in winter, monoterpene nitrooxy-OSs, generated with NOx involved in, increased to 34.4 ± 35.5 ng/m3 and contributed 68% of the quantified (nitrooxy-)OSs. Our results highlight the notable roles of biogenic OSs in marine organic aerosols over regions with high biological activity and high SST. The formation of biogenic OSs and their roles in altering marine aerosol properties calls for elaboration through cruise observations in different marine environments.


Assuntos
Poluentes Atmosféricos , Poluentes Ambientais , Fitoplâncton , Poluentes Atmosféricos/análise , Monoterpenos , Aerossóis/análise
10.
J Immunol ; 207(6): 1652-1661, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34426543

RESUMO

The IκB kinase (IKK) complex plays a vital role in regulating the NF-κB activation. Aberrant NF-κB activation is involved in various inflammatory diseases. Thus, targeting IKK activation is an ideal therapeutic strategy to cure and prevent inflammatory diseases related to NF-κB activation. In a previous study, we demonstrated that IKK-interacting protein (IKIP) inhibits the phosphorylation of IKKα/ß and the activation of NF-κB through disruption of the formation of IKK complex. In this study, we identified a 15-aa peptide derived from mouse IKIP (46-60 aa of IKIP), which specifically suppressed IKK activation and NF-κB targeted gene expression via disrupting the association of IKKß and NEMO. Importantly, administration of the peptide reduced LPS-induced acute inflammation and attenuated Zymosan-induced acute arthritis in mice. These findings suggest that this IKIP peptide may be a promising therapeutic reagent in the prevention and treatment of inflammatory diseases.


Assuntos
Quinase I-kappa B/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , NF-kappa B/metabolismo , Peptídeos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Camundongos , Camundongos Knockout , Ligação Proteica , Transdução de Sinais/genética , Zimosan/efeitos adversos
11.
J Immunol ; 206(8): 1832-1843, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33789983

RESUMO

CARD9 is an essential adaptor protein in antifungal innate immunity mediated by C-type lectin receptors. The activity of CARD9 is critically regulated by ubiquitination; however, the deubiquitinases involved in CARD9 regulation remain incompletely understood. In this study, we identified ovarian tumor deubiquitinase 1 (OTUD1) as an essential regulator of CARD9. OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathway. OTUD1 deficiency impaired CARD9-mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation. Importantly, Otud1 -/- mice were more susceptible to fungal infection than wild-type mice in vivo. Collectively, our results identify OTUD1 as an essential regulatory component for the CARD9 signaling pathway and antifungal innate immunity through deubiquitinating CARD9.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Candida albicans/fisiologia , Candidíase/imunologia , Enzimas Desubiquitinantes/metabolismo , Neutrófilos/imunologia , Proteases Específicas de Ubiquitina/metabolismo , Animais , Células Cultivadas , Citotoxicidade Imunológica , Enzimas Desubiquitinantes/genética , Modelos Animais de Doenças , Humanos , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Células RAW 264.7 , Transdução de Sinais , Proteases Específicas de Ubiquitina/genética , Ubiquitinação
12.
Environ Res ; 220: 115211, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36603657

RESUMO

The Pacific Ocean plays an important role in regulating the budget of climatically active gases and the burden of sulfate aerosols. Here, a field investigation was conducted to clarify the key processes and factors controlling climatically active gases, including dimethyl sulfide (DMS), carbonyl sulfide (OCS), carbon disulfide (CS2), and carbon dioxide (CO2), in both surface seawater and the lower atmosphere of the western Pacific. In addition, the relative contributions of different sources to atmospheric sulfate aerosols were quantitatively estimated, and their causes were explored. The maximum concentrations of DMS, OCS and CS2 and the minimum partial pressure of CO2 (pCO2) were observed in the Kuroshio-Oyashio Extension. Kuroshio-induced mesoscale eddies brought abundant nutrients and organic matter from the subsurface layer of Oyashio into the euphotic layer, thus enhancing primary productivity and accelerating the photoreaction of organic matter. These processes led to higher concentrations of DMS, OCS and CS2 and lower pCO2. However, the oligotrophic subsurface layer in the subtropical gyre and the strong barrier layer in the equatorial waters suppressed the upward fluxes of nutrients and organic matter, resulting in lower surface concentrations of DMS, OCS, and CS2 in these areas. Being far from the continents, atmospheric concentrations of DMS, OCS and CS2 and pCO2 in the western Pacific generally were observed to depend on the local sea-to-air exchange and may be regulated by atmospheric oxidation and mixing of air masses. In general, oceanic DMS emissions played an important role in the formation of sulfate aerosols in the western Pacific (accounting for ∼19.5% of total sulfate aerosols), especially in the Kuroshio-Oyashio Extension (∼32.3%). These processes in seawater may also determine the variations and emissions of other climatically active gases from biogenic and photochemical sources.


Assuntos
Dióxido de Carbono , Gases , Sulfatos , Oceano Pacífico , Aerossóis
13.
Int J Mol Sci ; 24(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37298549

RESUMO

The Corsac fox (Vulpes corsac) is a species of fox distributed in the arid prairie regions of Central and Northern Asia, with distinct adaptations to dry environments. Here, we applied Oxford-Nanopore sequencing and a chromosome structure capture technique to assemble the first Corsac fox genome, which was then assembled into chromosome fragments. The genome assembly has a total length of 2.2 Gb with a contig N50 of 41.62 Mb and a scaffold N50 of 132.2 Mb over 18 pseudo-chromosomal scaffolds. The genome contained approximately 32.67% of repeat sequences. A total of 20,511 protein-coding genes were predicted, of which 88.9% were functionally annotated. Phylogenetic analyses indicated a close relation to the Red fox (Vulpes vulpes) with an estimated divergence time of ~3.7 million years ago (MYA). We performed separate enrichment analyses of species-unique genes, the expanded and contracted gene families, and positively selected genes. The results suggest an enrichment of pathways related to protein synthesis and response and an evolutionary mechanism by which cells respond to protein denaturation in response to heat stress. The enrichment of pathways related to lipid and glucose metabolism, potentially preventing stress from dehydration, and positive selection of genes related to vision, as well as stress responses in harsh environments, may reveal adaptive evolutionary mechanisms in the Corsac fox under harsh drought conditions. Additional detection of positive selection for genes associated with gustatory receptors may reveal a unique desert diet strategy for the species. This high-quality genome provides a valuable resource for studying mammalian drought adaptation and evolution in the genus Vulpes.


Assuntos
Cromossomos , Raposas , Animais , Raposas/genética , Filogenia , Cromossomos/genética , Genoma/genética , Sequências Repetitivas de Ácido Nucleico
14.
J Neuroradiol ; 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37652263

RESUMO

PURPOSE: To determine if machine learning (ML) or deep learning (DL) pipelines perform better in AI-based three-class classification of glioblastoma (GBM), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL). METHODOLOGY: Retrospective analysis included 502 cases for training (208 GBM, 67 PCNSL and 227 IMD), with external validation on 86 cases (27:27:32). Multiparametric MRI images (T1W, T2W, FLAIR, DWI and T1-CE) were co-registered, resampled, denoised and intensity normalized, followed by semiautomatic 3D segmentation of the enhancing tumor (ET) and peritumoral region (PTR). Model performance was assessed using several ML pipelines and 3D-convolutional neural networks (3D-CNN) using sequence specific masks, as well as combination of masks. All pipelines were trained and evaluated with 5-fold nested cross-validation on internal data followed by external validation using multi-class AUC. RESULTS: Two ML models achieved similar performance on test set, one using T2-ET and T2-PTR masks (AUC: 0.885, 95% CI: [0.816, 0.935] and another using T1-CE-ET and FLAIR-PTR mask (AUC: 0.878, CI: [0.804, 0.930]). The best performing DL models achieved an AUC of 0.854, (CI [0.774, 0.914]) on external data using T1-CE-ET and T2-PTR masks, followed by model derived from T1-CE-ET, ADC-ET and FLAIR-PTR masks (AUC: 0.851, CI [0.772, 0.909]). CONCLUSION: Both ML and DL derived pipelines achieved similar performance. T1-CE mask was used in three of the top four overall models. Additionally, all four models had some mask derived from PTR, either T2WI or FLAIR.

15.
Bioinformatics ; 37(18): 2920-2929, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-33730153

RESUMO

MOTIVATION: For network-assisted analysis, which has become a popular method of data mining, network construction is a crucial task. Network construction relies on the accurate quantification of direct associations among variables. The existence of multiscale associations among variables presents several quantification challenges, especially when quantifying nonlinear direct interactions. RESULTS: In this study, the multiscale part mutual information (MPMI), based on part mutual information (PMI) and nonlinear partial association (NPA), was developed for effectively quantifying nonlinear direct associations among variables in networks with multiscale associations. First, we defined the MPMI in theory and derived its five important properties. Second, an experiment in a three-node network was carried out to numerically estimate its quantification ability under two cases of strong associations. Third, experiments of the MPMI and comparisons with the PMI, NPA and conditional mutual information were performed on simulated datasets and on datasets from DREAM challenge project. Finally, the MPMI was applied to real datasets of glioblastoma and lung adenocarcinoma to validate its effectiveness. Results showed that the MPMI is an effective alternative measure for quantifying nonlinear direct associations in networks, especially those with multiscale associations. AVAILABILITY AND IMPLEMENTATION: The source code of MPMI is available online at https://github.com/CDMB-lab/MPMI. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Glioblastoma , Software , Humanos
16.
J Org Chem ; 87(23): 16084-16089, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36395460

RESUMO

Despite several synthetic approaches that have been developed for α-deuterated amino acids, the synthesis of ß-deuterated amino acids has remained a challenge. Herein, we disclose a palladium catalyzed H/D exchange protocol for a ß-deuterated N-protected amino amide, which can be converted to a ß-deuterated amino acid simply by removal of protecting groups. This protocol is highly efficient, simply manipulated, and appliable for deuterium-labeling of many amino amides. In addition, deuterium labeling of phenylalanine derivatives was also successful when pivalic acid served as an additive to promote the H/D exchange process.


Assuntos
Aminoácidos , Paládio , Deutério , Amidas , Catálise
17.
Microb Ecol ; 83(3): 753-765, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34189610

RESUMO

The gut microbiome is integral for the host's living and environmental adaptation and crucially important for understanding host adaptive mechanisms. The red fox (Vulpes vulpes) dominates a wider ecological niche and more complicated habitat than that of the corsac fox (V. corsac). However, the adaptive mechanisms (in particular, the gut microbiome responsible for this kind of difference) are still unclear. Therefore, we investigated the gut microbiome of these two species in the Hulunbuir grassland, China, and evaluated their microbiome composition, function, and adaptive mechanisms. We profiled the gut microbiome and metabolism function of red and corsac foxes via 16S rRNA gene and metagenome sequencing. The foxes harbored species-specific microbiomes and functions that were related to ecological niche and habitat. The red fox had abundant Bacteroides, which leads to significant enrichment of metabolic pathways (K12373 and K21572) and enzymes related to chitin and carbohydrate degradation that may help the red fox adapt to a wider niche. The corsac fox harbored large proportions of Blautia, Terrisporobacter, and ATP-binding cassette (ABC) transporters (K01990, K02003, and K06147) that can help maintain corsac fox health, allowing it to live in harsh habitats. These results indicate that the gut microbiome of the red and corsac foxes may have different abilities which may provide these species with differing capabilities to adapt to different ecological niches and habitats, thus providing important microbiome data for understanding the mechanisms of host adaptation to different niches and habitats.


Assuntos
Raposas , Microbioma Gastrointestinal , Animais , Ecossistema , RNA Ribossômico 16S/genética , Especificidade da Espécie
18.
Org Biomol Chem ; 20(6): 1176-1180, 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35044395

RESUMO

We disclose a silver catalyzed H/D exchange reaction, which can introduce the deuterium atom at the ß position of thiophene rings without the assistance of any coordinating groups. The advantages of this reaction include operation in open air, usage of D2O as the deuterium source, good tolerance to a range of functional groups and obtaining high atom% deuterium incorporation. In addition, this H/D exchange reaction is employed for direct deuteration of a thiophene based monomer, which is usually prepared by multistep synthesis from expensive deuterated starting materials.

19.
Appl Microbiol Biotechnol ; 106(7): 2445-2454, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35262786

RESUMO

Nitriles derived from glucosinolates (GSLs) in rapeseed meal (RSM) can cause lesions on animal liver and kidneys. Nitrilase converts nitriles to carboxylic acids and NH3, eliminating their toxicity. Here we describe a nitrilase, BnNIT2, from Brassica napus (optimal temperature, 45 °C; pH, 7.0) that is stable at 40 °C and has a wide substrate specificity. Recombinant BnNIT2 converted the three main nitriles from GSLs (3-hydroxy-4-pentenenitrile, 3-butenenitrile, and 4-pentenenitrile), with the highest specific activity (58.6 U/mg) for 4-pentenenitrile. We used mutagenesis to improve the thermostability of BnNIT2; the resulting mutant BnNIT2-H90M had an ~ 14.5% increase in residual activity at 50 °C for 1 h. To verify the functionality of BnNIT2, GSLs were extracted from RSM and converted into nitriles at pH 5.0 in the presence of Fe2+. Then, BnNIT2 was used to degrade the nitriles from GSLs; ultimately, ~ 80% of nitriles were removed. Thus BnNIT2 is a potential enzyme for detoxification of RSM. KEY POINTS: • Functional identification of the plant nitrilase BnNIT2. • Identified a mutant, H90M, with improved thermostability. • BnNIT2 was capable of degrading nitriles from transformed GSLs.


Assuntos
Brassica napus , Brassica rapa , Aminoidrolases , Animais , Brassica napus/metabolismo , Brassica rapa/metabolismo , Glucosinolatos/metabolismo , Nitrilas/metabolismo , Especificidade por Substrato
20.
Nucleic Acids Res ; 48(17): 9571-9588, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32813023

RESUMO

Iron is essential for all bacteria. In most bacteria, intracellular iron homeostasis is tightly regulated by the ferric uptake regulator Fur. However, how Fur activates the iron-uptake system during iron deficiency is not fully elucidated. In this study, we found that YdiV, the flagella gene inhibitor, is involved in iron homeostasis in Escherichia coli. Iron deficiency triggers overexpression of YdiV. High levels of YdiV then transforms Fur into a novel form which does not bind DNA in a peptidyl-prolyl cis-trans isomerase SlyD dependent manner. Thus, the cooperation of YdiV, SlyD and Fur activates the gene expression of iron-uptake systems under conditions of iron deficiency. Bacterial invasion assays also demonstrated that both ydiV and slyD are necessary for the survival and growth of uropathogenic E. coli in bladder epithelial cells. This reveals a mechanism where YdiV not only represses flagella expression to make E. coli invisible to the host immune system, but it also promotes iron acquisition to help E. coli overcome host nutritional immunity.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Escherichia coli/metabolismo , Ferro/metabolismo , Peptidilprolil Isomerase/metabolismo , Proteínas Repressoras/metabolismo , Escherichia coli Uropatogênica/patogenicidade , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Linhagem Celular , DNA Bacteriano/metabolismo , Células Epiteliais/microbiologia , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Homeostase , Humanos , Peptidilprolil Isomerase/genética , Conformação Proteica , Proteínas Repressoras/química , Proteínas Repressoras/genética , Bexiga Urinária/microbiologia , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/crescimento & desenvolvimento , Escherichia coli Uropatogênica/metabolismo
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