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Many species of animals exhibit caregiving or aggression toward conspecific offspring. The neural mechanisms underlying the infanticide and pup care remain poorly understood. Here, using monogamous mandarin voles (Microtus mandarinus), we found that more oxytocin (OT) neurons in the paraventricular nucleus (PVN) were activated during pup caring than infanticide. Optogenetic activation of OT neurons in the PVN facilitated pup caring in male and female mandarin voles. In infanticide voles, optogenetic activation of PVN OT cells or PVN-medial prefrontal cortex (mPFC) OT projection fibers prolonged latency to approach and attack pups, whereas inhibition of these OT neurons or projections facilitated approach and infanticide. Optogenetic activation of PVN OT neuron projections to the mPFC in males shortened the latency to approach and retrieve pups and facilitated the initiation of pup care, but produced no effects on pup-care females. In addition, OT release in the mPFC increased upon approaching and retrieving pups, and decreased upon attacking pups. Intraperitoneal injection of OT promoted pup care and inhibited infanticide behavior. It is suggested that the OT system, especially PVN OT neurons projecting to mPFC, modulates pup-directed behaviors and OT can be used to treat abnormal behavioral responses associated with some psychological diseases such as depression and psychosis.
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Arvicolinae , Ocitocina , Núcleo Hipotalâmico Paraventricular , Córtex Pré-Frontal , Animais , Arvicolinae/fisiologia , Ocitocina/metabolismo , Feminino , Masculino , Córtex Pré-Frontal/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Neurônios/fisiologia , Neurônios/metabolismo , Optogenética , Agressão/fisiologia , Comportamento Animal , Comportamento Paterno/fisiologiaRESUMO
This study investigates the effects of heat and ultrasonic treatments on the physicochemical parameters and rennet-induced coagulation properties of milk from a variety of species, including cow, goat, buffalo, and donkey. Milk samples were subjected to heat treatments at different temperatures (65 °C, 80 °C, 90 °C, 100 °C) and ultrasonic treatment at varying power levels (200 W, 400 W, 600 W, 800 W, 1000 W). The results revealed that changes in turbidity, particle size, zeta potential, secondary structure, and surface hydrophobicity were altered by both ultrasonic and heat treatments, as well as the kind of milk. Ultrasonic treatment of cow milk decreased α-helix content while increasing ß-turn content. Under similar ultrasonic treatment, goat milk showed a considerable increase in ß-sheet content, whereas ß-turn and random coil contents decreased compared to control samples. Notably, the water-holding capacity of gels formed from all four types of milk increased significantly with the intensity of ultrasonic and heat treatments. The hardness of buffalo milk gels increased significantly after ultrasonic and thermal treatments, ranging from 63 °C for 30 min to 90 °C for 15 min, but the hardness of cow and goat milk gels increased in varying degrees compared to their control samples. Furthermore, gels from cow and goat milk had higher storage modulus (G') and loss modulus (G'') than those from buffalo and donkey milk, and changes in G' and G'' from the examined milk were altered by ultrasonic and heat treatments. These findings offer important insights into refining milk processing procedures to improve dairy product quality and usefulness.
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The individuals often show consolation to distressed companions or show aggression to the intruders. The circuit mechanisms underlying switching between consolation and aggression remain unclear. In the present study, using male mandarin voles, we identified that two distinct subtypes of oxytocin receptor (OXTR) neurons in the medial amygdala (MeA) projecting to the anterior insula (AI) and ventrolateral aspect of ventromedial hypothalamus (VMHvl) response differently to stressed siblings or unfamiliar intruders using c-Fos or calcium recording. Oxytocin release and activities of PVN neurons projecting to MeA increased upon consoling and attacking. OXTR antagonist injection to the MeA reduced consoling and attacking. Apoptosis, optogenetic or pharmacogenetic manipulation of these two populations of neurons altered behavioral responses to these two social stimuli respectively. Here, we show that two subtypes of OXTR neurons in the MeA projecting to the AI or VMHvl causally control consolation or aggression that may underlie switch between consolation and aggression.
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Agressão , Arvicolinae , Complexo Nuclear Corticomedial , Neurônios , Ocitocina , Receptores de Ocitocina , Animais , Receptores de Ocitocina/metabolismo , Receptores de Ocitocina/genética , Masculino , Agressão/fisiologia , Arvicolinae/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Ocitocina/metabolismo , Complexo Nuclear Corticomedial/metabolismo , Complexo Nuclear Corticomedial/fisiologia , Comportamento Animal/fisiologia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiologia , Comportamento Social , Proteínas Proto-Oncogênicas c-fos/metabolismo , Vias Neurais/fisiologia , OptogenéticaRESUMO
INTRODUCTION: Empathy is the ability of an individual to present and respond to the emotions of others and is thought to originate from parental behavior. Testosterone could promote aggression and inhibit biparental behavior and vasopressin (AVP) could promote aggression. Given levels of aggression and parental care are closely associated with levels of empathy, we hypothesized that testosterone may influence empathetic behavior via the AVP system. METHODS: We examined testosterone levels and tested social, empathic, and anxiety-like behaviors after castration surgery to pubertal mice, and subsequently examined the molecular levels of AVP, V1aR in different brain regions. Finally, pharmacological experiments were used to test the effects on empathic behavior by injecting testosterone in combination with V1aR antagonist. RESULTS: Here, we show that pubertal castration reduced serum testosterone levels, increased empathetic behavior and sociality, and reduced anxiety-like behaviors in male C57 mice. The pubertal castration also reduced AVP and vasopressin receptor (V1aR) protein levels, and AVP mRNA levels in the PVN. It also reduced the number of AVP-positive neurons in the PVN. In addition, pubertal subcutaneous injection of testosterone reduced emotional contagion and consolation of castrated mice, while concomitant injection of V1aR antagonists into the anterior cingulate cortex (ACC) reversed the downregulation of emotional contagion and consolation induced by testosterone. CONCLUSION: It is suggested that testosterone in puberty regulates empathetic behavior in C57 mice possibly via the AVP system in the ACC. These findings help us to understand the neuroendocrine mechanisms underlying empathetic behavior and provide potential targets for the treatment of psychiatric disorders associated with low empathy.
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Blechnopsis orientalis (Linnaeus) C. Presl (1753) is a fern used both as food and medicine. It is found primarily in southern China and Southeast Asia, thriving in warm, humid shrublands or sparse forest. The total length of the chloroplast genome is 155,211 bp, including a large single-copy region (LSC, 81,877 bp), a small single-copy region (SSC, 21,500 bp), and two inverted repeat regions (IRs, 25,917 bp). The GC content is 41.3%. A total of 131 genes were annotated, including 88 protein-coding genes, eight rRNA genes, and 35 tRNA genes. The phylogenetic analysis using the maximum-likelihood method showed that B. orientalis and Oceaniopteris gibba were closely related. This study provides genomic resources for phylogenetic genetics and resource exploitation of B. orientalis.
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Leonurus sibiricus Linnaeus 1753, an annual or biennial herb found in northern China, Mongolia, and Russia, typically grows in stony, sandy grasslands, and pine forests. This study sequenced and reported the complete chloroplast genome of L. sibiricus for the first time. The entire circular genome measures 151,689 bp in length, with a GC content of 38.4%. A total of 133 genes were annotated, including 88 protein-coding genes, 37 tRNAs, and eight rRNAs. The genome exhibits a typical quadripartite structure, comprising a large single-copy (LSC 82,820 bp) region, a small single-copy (SSC 17,619 bp) region, and a pair of inverted repeat (IR 25,625 bp each) regions. Phylogenetic analysis using the maximum-likelihood method indicates that L. sibiricus is most closely related to L. japonicus Houttuyn. This study provides valuable genomic resources for further research on the phylogenetics and biodiversity of the genus Leonurus.
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Introduction: Symbiotic microbial have a significant impact on the growth and metabolism of medicinal plants. Schisandra chinensis is a very functionally rich medicinal herb; however, its microbial composition and diversity have been poorly studied. Methods: In the present study, the core microbiomes associated with the rhizospheric soil, roots, stems, leaves, and fruits of S. chinensis from six geographic locations were analyzed by a macro-genomics approach. Results: Alpha and beta diversity analyses showed that the diversity of microbial composition of S. chinensis fruits did not differ significantly among the geographic locations as compared to that in different plant compartments. Principal coordinate analysis showed that the microbial communities of S. chinensis fruits from the different ecological locations were both similar and independent. In all S. chinensis samples, Proteobacteria was the most dominant bacterial phylum, and Ascomycota and Basidiomycota were the most dominant fungal phyla. Nitrospira, Bradyrhizobium, Sphingomonas, and Pseudomonas were the marker bacterial populations in rhizospheric soils, roots, stems and leaves, and fruits, respectively, and Penicillium, Golubevia, and Cladosporium were the marker fungal populations in the rhizospheric soil and roots, stems and leaves, and fruits, respectively. Functional analyses showed a high abundance of the microbiota mainly in biosynthesis. Discussion: The present study determined the fungal structure of the symbiotic microbiome of S. chinensis, which is crucial for improving the yield and quality of S. chinensis.
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Lagochilus ilicifolius Bunge ex Bentham, Labiat. Gen is a perennial herb with much-branched stems native to Nei Mongol, Ningxia, Gansu, N Shaanxi. It can be used clinically as a hemostatic agent. The chloroplast genome length is 151,466 bp. It contained two inverted repeat regions of 25,660 bp each, a large single-copy region of length 82,504 bp, and a small single-copy region of length 17,642 bp. Also, the GC content is 38.6%. There were 133 genes annotated, including 88 known protein-coding genes, 37 tRNAs, and eight rRNAs. The phylogenetic tree was constructed using Bayesian method for plastome data of 29 species. The entire chloroplast genome of L. ilicifolius within the Lamiaceae is the first to reveal genetic taxonomy at the molecular level, and the new phylogenetic tree data can be used for future evolutionary studies.
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BACKGROUND: Pulsatilla saxatilis, a new species of the genus Pulsatilla has been discovered. The morphological information of this species has been well described, but its chloroplast genome characteristics and comparison with species of the same genus remain to be reported. RESULTS: Our results showed that the total length of chloroplast (cp.) genome of P. saxatilis is 162,659 bp, with a GC content of 37.5%. The cp. genome contains 134 genes, including 90 known protein-coding genes, 36 tRNA genes, and 8 rRNA genes. P. saxatilis demonstrated similar characteristics to other species of genus Pulsatilla. Herein, we compared cp. genomes of 10 species, including P. saxatilis, and found that the cp. genomes of the genus Pulsatilla are extremely similar, with a length of 162,322-163,851 bp. Furthermore, The SSRs of Pulsatilla ranged from 10 to 22 bp in length. Among the four structural regions of the cp. genome, most long repeats and SSRs were detected in the LSC region, followed by that in the SSC region, and least in IRA/ IRB regions. The most common types of long repeats were forward and palindromic repeats, followed by reverse repeats, and only a few complementary repeats were found in 10 cp. genomes. We also analyzed nucleotide diversity and identified ccsA_ndhD, rps16_trnK-UUU, ccsA, and rbcL, which could be used as potential molecular markers for identification of Pulsatilla species. The results of the phylogenetic tree constructed by connecting the sequences of high variation regions were consistent with those of the cp. gene phylogenetic tree, and the species more closely related to P. saxatilis was identified as the P. campanella. CONCLUSION: It was determined that the closest species to P. saxatilis is P. campanella, which is the same as the conclusion based on pollen grain characteristics, but different from the P. chinensis determined based on morphological characteristics. By revealing information on the chloroplast characteristics, development, and evolution of the cp. genome and the potential molecular markers, this study provides effective molecular data regarding the evolution, genetic diversity, and species identification of the genus Pulsatilla.
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Genoma de Cloroplastos , Pulsatilla , Animais , Filogenia , Espécies em Perigo de Extinção , Pulsatilla/genética , Cloroplastos/genéticaRESUMO
Paternal deprivation (PD) impairs social cognition and sociality and increases levels of anxiety-like behavior. However, whether PD affects the levels of empathy in offspring and its underlying mechanisms remain unknown. The present study found that PD increased anxiety-like behavior in mandarin voles (Microtus mandarinus), impaired sociality, reduced the ability of emotional contagion, and the level of consolation behavior. Meanwhile, PD reduced OT neurons in the paraventricular nucleus (PVN) in both male and female mandarin voles. PD decreased the level of OT receptor (OTR) mRNA in the anterior cingulate cortex (ACC) of male and female mandarin voles. Besides, OTR overexpression in the ACC reversed the PD-induced changes in anxiety-like behavior, social preference, emotional contagion, and consolation behavior. Interference of OTR expression in the ACC increased levels of anxiety-like behaviors, while it reduced levels of sociality, emotional contagion, and consolation. These results revealed that the OTR in the ACC is involved in the effects of PD on empathetic behaviors, and provide mechanistic insight into how social experiences affect empathetic behaviors.
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Arvicolinae , Comportamento Animal , Giro do Cíngulo , Privação Paterna , Animais , Feminino , Masculino , Ansiedade/metabolismo , Arvicolinae/fisiologia , Giro do Cíngulo/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Receptores de Ocitocina/metabolismo , Receptores de Ocitocina/genética , Comportamento SocialRESUMO
Pulsatilla chinensis f. alba D. K. Zang 1993 is a forma of Pulsatilla chinensis (Bge.) Regel, the root of P. chinensis is traditional Chinese medicine called Pulsatillae radix. The biggest difference between P. chinensis f. alba and P. chinensis is that P. chinensis f. alba sepals is white. The complete chloroplast genome of P. chinensis f. alba was sequenced using the Illumina NovaSeq platform for the first time. The lengths of the genome, large single-copy (LSC), small single-copy (SSC), two inverted repeats (IRs), and GC content were 163,654 bp, 82,355 bp, 19,069 bp, 31,115 bp, and 37.2%, respectively. It had 134 genes, including 90 protein-coding genes, 36 tRNA genes, and eight rRNA genes. The maximum-likelihood tree indicated that P. chinensis f. alba had a closer relationship with P. chinensis. This study would provide a theoretical basis for the further study of Pulsatilla plants genetics phylogenetic research.
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Grewia biloba var. parviflora (Bunge) Hand.-Mazz. (1933), a shrub or small tree, is native to northern and southern China. It is an excellent relief and medicinal plant. The complete chloroplast genome is 158,043 bp in length, with a large single-copy region of 86,957 bp, a small single-copy region of 20,138 bp, two inverted repeat regions of 25,474 bp each, and a GC content of 37.4%. There were 129 genes annotated, including 84 known protein-coding genes, 37 tRNAs, and eight rRNAs. The phylogenetic trees are constructed using plastome data from 38 species and the maximum-likelihood method. The results of the chloroplast genome-wide analysis and the phylogenetic tree show the taxonomic phylogeny of the G. biloba var. parviflora in relation to other species, increasing the accuracy of the phylogenetic classification of the plant.
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The plant-associated microbiome has an effect on plant growth. Pulsatilla chinensis (Bge.) Regel is an important Chinese medicinal plant. Currently, there is little understanding of the P. chinensis-associated microbiome and its diversity and composition. Here, the core microbiome associated with the root, leaf, and rhizospheric soil compartments of P. chinensis from five geographical locations was analyzed by the metagenomics approach. The alpha and beta diversity analysis showed that the microbiome associated with P. chinensis was shaped by the compartment, especially in the bacterial community. The geographical location had little influence on microbial community diversity associated with root and leaf. Hierarchical clustering distinguished the microbial communities of rhizospheric soil based on their geographical location and among the soil properties, pH was showed the more stronger effect on the diversity of rhizospheric soil microbial communities. Proteobacteria was the most dominant bacterial phylum in the root, leaf, and rhizospheric soil. Ascomycota and Basidiomycota were the most dominant fungal phyla in different compartments. Rhizobacter, Anoxybacillus, and IMCC26256 were the most important marker bacterial species for root, leaf, and rhizospheric soil screened by random forest, respectively. The fungal marker species for root, leaf, and rhizospheric soil were not only different across the compartments but also the geographical locations. Functional analysis showed that P. chinensis-associated microbiome had the similar function which had no obvious relationship with geographical location and compartment. The associated microbiome indicated in this study can be used for identifying microorganisms related to the quality and growth of P. chinensis. KEY POINTS: ⢠Microbiome associated with P. chinensis was shaped by the compartment ⢠Microbiome composition and abundance associated with rhizospheric soil were affected by the geographical location ⢠Compared with fungi, bacterial associated with P. chinensis composition and diversity were more stable in different geographical locations and compartments.
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Microbiota , Plantas Medicinais , Pulsatilla , Rizosfera , Microbiologia do Solo , Raízes de Plantas/microbiologia , Bactérias/genética , Solo/químicaRESUMO
Male mammals display different paternal responses to pups, either attacking or killing the young offspring, or contrastingly, caring for them. The neural circuit mechanism underlying the between-individual variation in the pup-directed responsiveness of male mammals remains unclear. Monogamous mandarin voles were used to complete the present study. The male individuals were identified as paternal and infanticidal voles, according their behavioral responses to pups. It was found that the serotonin release in the medial preoptic area (MPOA), as well as the serotonergic neuron activity, significantly increased upon licking the pups, but showed no changes after attacking the pups, as revealed by the in vivo fiber photometry of the fluorescence signal from the 5-HT 1.0 sensor and the calcium imaging indicator, respectively. It was verified that the 5-HTergic neural projections to the MPOA originated mainly from the ventral part of the dorsal raphe (vDR). Furthermore, the chemogenetic inhibition of serotonergic projections from the vDR to the MPOA decreased the paternal behaviors and shortened the latency to attack the pups. In contrast, the activation of serotonergic neurons via optogenetics extended the licking duration and inhibited infanticide. Collectively, these results elucidate that the serotonergic projections from the vDR to the MPOA, a previously unrecognized pathway, regulate the paternal responses of virgin male mandarin voles to pups.
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Núcleo Dorsal da Rafe , Área Pré-Óptica , Humanos , Animais , Masculino , Área Pré-Óptica/metabolismo , Pai , Comportamento Animal/fisiologia , ArvicolinaeRESUMO
Chronic social stress can cause psychological disease. Although oxytocin (OT) has been showed to modulate effects of chronic social defeat stress (CSDS) on emotional and social behaviors, however, how OT circuits mediate effects of CSDS on emotional and social abnormalities remains unclear. Here, we found that repeated intraperitoneal OT administration in the process of CSDS buffered adverse effects of CSDS on emotional and social behaviors in mandarin voles (Microtus mandarinus) of both sexes except no effect on depression-like behavior of males. Repeated OT treatments during CSDS prevented decrease of oxytocin receptors in nucleus accumbens (NAc) in females, but produced no effects on males. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools, we determined that the activation of the paraventricular nucleus (PVN)-the shell of NAc (NAcs) projections before social defeat during CSDS process significantly prevented the increase of the anxiety-like behaviors and social avoidance induced by CSDS in both sexes, and reversed the depressive-like behaviors induced by CSDS only in females. Besides, optogenetic activation of PVN-NAcs projections after CSDS reduced anxiety-like behaviors and increased levels of sociality. Collectively, we suggest that PVN-NAcs projections modulate emotional and social behaviors during or after the process of CSDS sex-specifically, although AAV viruses did not specifically infect OT neurons. These findings offer potential targets for preventing or treating emotional and social disorders induced by chronic stress.
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Ocitocina , Núcleo Hipotalâmico Paraventricular , Feminino , Masculino , Animais , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Accumbens , Derrota Social , Comportamento Social , Arvicolinae , Estresse Psicológico/metabolismoRESUMO
BACKGROUND: Burdock is a biennial herb of Asteraceae found in Northern Europe, Eurasia, Siberia, and China. Its mature dry fruits, called Niu Bang Zi, are recorded in various traditional Chinese medicine books. With the development of sequencing technology, the mitochondrial, chloroplast, and nuclear genomes, transcriptome, and sequence-related amplified polymorphism (SRAP) fingerprints of burdock have all been reported. To make better use of this data for further research and analysis, a burdock database was constructed. RESULTS: This burdock multi-omics database contains two burdock genome datasets, two transcriptome datasets, eight burdock chloroplast genomes, one burdock mitochondrial genome, one A. tomentosum chloroplast genome, one A. tomentosum mitochondrial genome, 26 phenotypes of burdock varieties, burdock rhizosphere-associated microorganisms, and chemical constituents of burdock fruit, pericarp, and kernel at different growth stages (using UPLC-Q-TOF-MS). The wild and cultivation distribution of burdock in China was summarized, and the main active components and pharmacological effects of burdock currently reported were concluded. The database contains ten central functional modules: Home, Genome, Transcriptome, Jbrowse, Search, Tools, SRAP fingerprints, Associated microorganisms, Chemical, and Publications. Among these, the "Tools" module can be used to perform sequence homology alignment (Blast), multiple sequence alignment analysis (Muscle), homologous protein prediction (Genewise), primer design (Primer), large-scale genome analysis (Lastz), and GO and KEGG enrichment analyses (GO Enrichment and KEGG Enrichment). CONCLUSIONS: The database URL is http://210.22.121.250:41352/ . This burdock database integrates molecular and chemical data to provide a comprehensive information and analysis platform for interested researchers and can be of immense help to the cultivation, breeding, and molecular pharmacognosy research of burdock.
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Arctium , Plantas Medicinais , Plantas Medicinais/genética , Arctium/genética , Arctium/química , Multiômica , Melhoramento Vegetal , Medicina Tradicional Chinesa , Extratos Vegetais/químicaRESUMO
A fragile karst ecosystem presents ecosystem services affected by the environment and interactions between ecosystem services. However, the ecosystem in the karst area is characterized by low environmental capacity and low resistance to force disturbance. Current research mainly focuses on the trade-off/synergy of ecosystem services in the karst area yet it lacks inductive analysis of the multiple chain path among ecosystem services. This paper quantitatively identified dominant factors influencing spatial differentiation of surface runoff, soil moisture, sediment yield, and net primary productivity (NPP) and determined the chain path. The chain paths of surface runoff-soil moisture-NPP and NPP-surface runoff-sediment yield were analyzed. The results showed that land use and soil type were the dominant factors, and chain effects of ecosystem services were diverse under the various dominant factor gradients. The mediation effects of paddy soil (97.21 %) and mountain meadow soil (55.56 %) were high, and surface runoff had a greater impact on NPP by affecting soil moisture. Among the diverse land use types, the mediation effect of surface runoff on NPP affecting sediment yield varied greatly (from 5 to 100 %). In addition, its variation trend was consistent with that of the soil moisture as the mediation variable. The mediation effect of surface runoff on construction land was the highest (99.43 %). This study provides the scientific basis for selecting more effective water and soil conservation measures by analyzing the chain relationships of multiple ecosystem services under different environmental factor gradients.
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A facile synthesis of 1H-imidazoles by direct oxidative annulation of aryl methyl ketones and primary amines has been developed in the presence of TEMPO under weakly acidic conditions. By replacing amines with ammonium acetate, 2H-imidazole skeletons were achieved for the first time from ketones. Substrates containing various functional groups, such as alkyl, aryl, naphthyl, halogen (F, Cl, Br, I), nitro, trifluoromethyl, sulfonyl ester, furyl, thienyl, and pyridyl groups, were readily transformed into the desired products. The application potential of this method was verified by the scale-up synthesis and Sonogashira coupling functionalization of imidazoles. Mechanistically, the α-TEMPO-enamine adduct may serve as the key reaction intermediate.
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Aminas , Cetonas , Acetatos , Acetona , Catálise , Óxidos N-Cíclicos , Imidazóis , Estresse OxidativoRESUMO
The Ser10 to Arg mutation in mouse γB-crystallin (MGB) has been associated with protein aggregation, dense nuclear opacity, and the degeneration of fiber cells in the lens core. Overexpression of the gap junction protein, connexin 46 (Cx46), was found to suppress the nuclear opacity and restore normal cell-cell contact. However, the molecular basis for the protein aggregation and related downstream effects were not evident from these studies. Here, we provide a comparison of the structures and solution properties of wild type MGB and the S10R mutant in vitro and show that, even though the mutation does not directly involve cysteine residues, some cysteines in the mutant protein are activated, leading to the enhanced formation of intermolecular disulfide-crosslinked protein aggregates relative to the wild-type. This occurs even as the protein structure is essentially unaltered. Thus, the primary event is enhanced protein aggregation due to the disulfide crosslinking of the mutant protein. We suggest that these aggregates eventually get deposited on fiber cell membranes. Since the gap junction protein, Cx46 is involved in the transport of reduced glutathione, we posit that these deposits interfere in Cx46-mediated glutathione transport and facilitate the oxidative stress-mediated downstream changes. Overexpression of Cx46 suppresses such oxidative aggregation. These studies provide a plausible explanation for the protein aggregation and other changes that accompany this mutation. If indeed cysteine oxidation is the primary event for protein aggregation also in vivo, then the S10R mutant mouse, which is currently available, could serve as a viable animal model for human age-onset cataract.