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1.
Pest Manag Sci ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35527698

RESUMO

BACKGROUND: The gradually aggravated disease caused by phytopathogenic bacteria severely restricts food security and crop yield, and few pesticides can relieve this severe situation. Thus, development and excavation of new agrochemicals with high bioactivity and novel action mechanism may be a feasible strategy to control intractable bacterial diseases. As the private molecular framework, steroid molecules exhibit diversiform bioactivities. Herein, a series of novel androst-4-ene derivatives were designed, synthesized, and investigated for their antibacterial behaviour to excavate novel agrochemicals on the base of steroid molecules. RESULTS: Bioassay results indicated that target compounds displayed high bioactivities toward three destructive phytopathogenic bacteria including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa). Compound III19 displayed excellent in vitro antibacterial profiling (EC50  = 2.37 mg L-1 towards Xoo; EC50  = 2.10 mg L-1 towards Xac; EC50  = 9.50 mg L-1 towards Psa). Furthermore, compound III19 showed outstanding in vivo protective activities, with values of 81.81% and 58.75% towards kiwifruit bacterial canker and rice bacterial leaf blight, respectively. Analysis of the antibacterial mechanism disclosed that compound III19 enhanced host defence enzyme activities (SOD, POD, PAL, PPO, and CAT) and increased the salicylate synthase (SAS) content to induce host resistance. In addition, compound III19 increased the membrane permeability, destroyed the cell membrane, and killed the bacteria. CONCLUSION: Given these profiles of target compounds, we highlight a new strategy for controlling intractable plant bacterial diseases by inducing plant resistance and targeting the bacterial cell membrane. This article is protected by copyright. All rights reserved.

2.
Cell ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35568034

RESUMO

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

3.
J Eat Disord ; 10(1): 59, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35501911

RESUMO

BACKGROUND: This study examined the role of anxiety and coronavirus disease 2019 (COVID-19) burnout in the relationship between coronavirus stress and overeating among Chinese college students during the COVID-19 pandemic. METHODS: Chinese college students (N = 2926; Mage = 19.90, SD = 1.47, range = 18-25 years old; 54.34% female) completed self-reported online questionnaires regarding coronavirus stress, anxiety, COVID-19 burnout, and overeating. RESULTS: Anxiety showed partially indirect effect on the association between coronavirus stress and overeating. COVID-19 burnout exacerbated the indirect pathway between coronavirus stress and overeating via anxiety. DISCUSSION AND CONCLUSION: This is the first study, to our knowledge, that examines the underlying mechanisms of the coronavirus stress and overeating behavior association among Chinese college students. The results support several existing theories on stress and problematic eating behaviors and provide practical implications for prevention and intervention programs of overeating during the COVID-19 pandemic.


One's response is not arbitrary when confronted with the coronavirus disease 2019 (COVID-19). Previous research has found that individuals with coronavirus stress still be more prone to overeat. We also know from other research that anxiety is the most salient aspect of overeating. However, no research has investigated whether the coronavirus stress of college students is significantly associated with overeating and examine the potential indirect pathway and moderating mechanisms in this association. With the aid of 2926 participants, we found that, coronavirus stress was linked to college students' overeating. We also found that this relationship was partially explained by anxiety. In addition, the association between anxiety and overeating was stronger for those with higher COVID-19 burnout. This study is an important step in unpacking how coronavirus stress relates to overeating of Chinese college students. However, they are limited by the cross-sectional nature of the study, meaning we cannot imply causality. We recommend that further research replicate our findings in people with diagnosed feeding and eating disorders using a longitudinal design.

4.
J Agric Food Chem ; 70(16): 4899-4911, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35437986

RESUMO

Bacterial biofilms are the root cause of persistent and chronic phytopathogenic bacterial infections. Therefore, developing novel agrochemicals that target the biofilm of phytopathogenic bacteria has been regarded as an innovative tactic to suppress their invasive infection or decrease bacterial drug resistance. In this study, a series of natural pterostilbene (PTE) derivatives were designed, and their antibacterial potency and antibiofilm ability were assessed. Notably, compound C1 displayed excellent antibacterial potency in vitro, affording an EC50 value of 0.88 µg mL-1 against Xoo (Xanthomonas oryzae pv. oryzae). C1 could significantly reduce biofilm formation and extracellular polysaccharides (EPS). Furthermore, C1 also possessed remarkable inhibitory activity against bacterial extracellular enzymes, pathogenicity, and other virulence factors. Subsequently, pathogenicity experiments were further conducted to verify the above primary outcomes. More importantly, C1 with pesticide additives displayed excellent control efficiency. Given these promising profiles, these pterostilbene derivatives can serve as novel antibiofilm agents to suppress plant pathogenic bacteria.


Assuntos
Infecções Bacterianas , Oryza , Xanthomonas , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana , Oryza/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Propanolaminas , Estilbenos
5.
Cell Res ; 32(5): 437-450, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35301440

RESUMO

Nuclear pore complexes (NPCs) mediate bidirectional nucleocytoplasmic transport of substances in eukaryotic cells. However, the accurate molecular arrangement of NPCs remains enigmatic owing to their huge size and highly dynamic nature. Here we determined the structure of the asymmetric unit of the inner ring (IR monomer) at 3.73 Å resolution by single-particle cryo-electron microscopy, and created an atomic model of the intact IR consisting of 192 molecules of 8 nucleoporins. In each IR monomer, the Z-shaped Nup188-Nup192 complex in the middle layer is sandwiched by two approximately parallel rhomboidal structures in the inner and outer layers, while Nup188, Nup192 and Nic96 link all subunits to constitute a relatively stable IR monomer. In contrast, the intact IR is assembled by loose and instable interactions between IR monomers. These structures, together with previously reported structural information of IR, reveal two distinct interaction modes between IR monomers and extensive flexible connections in IR assembly, providing a structural basis for the stability and malleability of IR.


Assuntos
Poro Nuclear , Proteínas de Saccharomyces cerevisiae , Microscopia Crioeletrônica , Modelos Moleculares , Poro Nuclear/química , Poro Nuclear/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/química , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química
6.
J Agric Food Chem ; 70(9): 2825-2838, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35201749

RESUMO

To unceasingly expand the molecular diversity of 1,3,4-oxadiazole-2-carbohydrazides, herein, small fragments (including -CH2-, -OCH2-, and -SCH2-) were incorporated into the target compounds to screen out the potential succinate dehydrogenase inhibitors (SDHIs). The bioassay results showed that the antifungal effects (expressed by EC50) against Sclerotinia sclerotiorum, Botryosphaeria dothidea, Fusarium oxysporum, and Colletotrichun higginsianum could reach 1.29 (10a), 0.63 (8h), 1.50 (10i), and 2.09 (10i) µg/mL, respectively, which were slightly lower than those of carbendazim (EC50 were 0.69, 0.13, 0.55, and 0.80 µg/mL, respectively). Especially, compound 10h was extremely bioactive against Gibberella zeae (G. z.) with an EC50 value of 0.45 µg/mL. This outcome was better than that of fluopyram (3.76 µg/mL) and was similar to prochloraz (0.47 µg/mL). In vivo trials against the corn scab (infected by G. z.) showed that compound 10h had control activity of 86.8% at 200 µg/mL, which was better than that of boscalid (79.6%). Further investigations found that compound 10h could inhibit the enzymatic activity of SDH in the G. z. strain with an IC50 value of 3.67 µM, indicating that potential SDHIs might be developed. Additionally, the other biological activities of these molecules were screened simultaneously. The anti-oomycete activity toward Phytophthora infestans afforded a minimal EC50 value of 3.22 µg/mL (10h); compound 4d could strongly suppress the growth of bacterial strains Xanthomonas axonopodis pv. citri and Xanthomonas oryzae pv. oryzae with EC50 values of 3.79 and 11.4 µg/mL, respectively; and compound 10a displayed some insecticidal activity toward Plutella xylostella. Given their multipurpose features, these frameworks could be actively studied as potential pesticide leads.


Assuntos
Phytophthora infestans , Xanthomonas , Antibacterianos/farmacologia , Hidrazinas , Testes de Sensibilidade Microbiana , Oxidiazóis/farmacologia , Doenças das Plantas , Relação Estrutura-Atividade
7.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35046043

RESUMO

Receptor usage defines cell tropism and contributes to cell entry and infection. Coxsackievirus B (CVB) engages coxsackievirus and adenovirus receptor (CAR), and selectively utilizes the decay-accelerating factor (DAF; CD55) to infect cells. However, the differential receptor usage mechanism for CVB remains elusive. This study identified VP3-234 residues (234Q/N/V/D/E) as critical population selection determinants during CVB3 virus evolution, contributing to diverse binding affinities to CD55. Cryoelectron microscopy (cryo-EM) structures of CD55-binding/nonbinding isolates and their complexes with CD55 or CAR were obtained under both neutral and acidic conditions, and the molecular mechanism of VP3-234 residues determining CD55 affinity/specificity for naturally occurring CVB3 strains was elucidated. Structural and biochemical studies in vitro revealed the dynamic entry process of CVB3 and the function of the uncoating receptor CAR with different pH preferences. This work provides detailed insight into the molecular mechanism of CVB infection and contributes to an in-depth understanding of enterovirus attachment receptor usage.


Assuntos
Antígenos CD55/metabolismo , Infecções por Coxsackievirus/metabolismo , Infecções por Coxsackievirus/virologia , Enterovirus Humano B/fisiologia , Interações Hospedeiro-Patógeno , Receptores Virais/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Enterovirus Humano B/ultraestrutura , Humanos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Receptores Virais/química , Relação Estrutura-Atividade , Ligação Viral
8.
ACS Appl Mater Interfaces ; 14(2): 2564-2577, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34981928

RESUMO

Supramolecular chemistry provides huge potentials and opportunities in agricultural pest management. In an attempt to develop highly bioactive, eco-friendly, and biocompatible supramolecular complexes for managing intractable plant bacterial diseases, herein, a type of interesting adamantane-functionalized 1,3,4-oxadiazole was rationally prepared to facilitate the formation of supramolecular complexes via ß-cyclodextrin-adamantane host-guest interactions. Initial antibacterial screening revealed that most of these adamantane-decorated 1,3,4-oxadiazoles were obviously bioactive against three typically destructive phytopathogens. The lowest EC50 values could reach 0.936 (III18), 0.889 (III18), and 2.10 (III19) µg/mL against the corresponding Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). Next, the representative supramolecular binary complex III18@ß-CD (binding mode 1:1) was successfully fabricated and characterized by 1H nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), high-resolution mass spectrometry (HRMS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Eventually, correlative water solubility and foliar surface wettability were significantly improved after the formation of host-guest assemblies. In vivo antibacterial evaluation found that the achieved supramolecular complex could distinctly alleviate the disease symptoms and promote the control efficiencies against rice bacterial blight (from 34.6-35.7% (III18) to 40.3-43.6% (III18@ß-CD)) and kiwi canker diseases (from 41.0-42.3% (III18) to 53.9-68.0% (III18@ß-CD)) at 200 µg/mL (active ingredient). The current study can provide a feasible platform and insight for constructing biocompatible supramolecular assemblies for managing destructive bacterial infections in agriculture.


Assuntos
Adamantano/farmacologia , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Materiais Biocompatíveis/farmacologia , Oxidiazóis/farmacologia , beta-Ciclodextrinas/farmacologia , Adamantano/química , Antibacterianos/síntese química , Antibacterianos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Teste de Materiais , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oryza/microbiologia , Oxidiazóis/química , Pseudomonas/efeitos dos fármacos , Xanthomonas/efeitos dos fármacos , beta-Ciclodextrinas/química
9.
Cell ; 185(4): 630-640.e10, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35093192

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here, we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryoelectron microscopy structures of the omicron RBD-hACE2 complex as well as the crystal structure of the delta RBD-hACE2 complex. We found that, unlike alpha, beta, and gamma, omicron RBD binds to hACE2 at a similar affinity to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of omicron RBD-hACE2 and delta RBD-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.


Assuntos
Enzima de Conversão de Angiotensina 2/química , Receptores Virais/química , SARS-CoV-2/química , Sequência de Aminoácidos , Microscopia Crioeletrônica , Humanos , Modelos Moleculares , Mutação/genética , Filogenia , Ligação Proteica , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Eletricidade Estática , Homologia Estrutural de Proteína
10.
Appetite ; 169: 105826, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34826527

RESUMO

Acculturative stress is associated with health behaviors that have downstream consequences for health outcomes. Eating disinhibition, a behavior characterized by eating emotionally and uncontrollably in the presence of disinhibiting stimuli, has been consistently associated with acculturative stress, but the underlying mechanism is not well-understood. The current study sought to test the role of depressive symptoms and gender on these associations. Asian undergraduate students (N = 477; 78% female) participated in an online cross-sectional study. Higher acculturative stress was associated with higher eating disinhibition (b = 3.45, 95% CI = [0.75, 6.15]), and depressive symptoms showed a partial indirect effect on this association (indirect effect = 0.57, 95% CIboot = [0.13, 1.34]). Among male young adults (b = 0.98, 95% CIboot = [0.24, 2.39]), the indirect correlation was stronger than among female young adults (b = 0.44, 95% CIboot = [0.05, 1.20]; non-significant trend), implying individual differences underlying the indirect effect of depressive symptoms in the acculturative stress and eating disinhibition correlation. The Intercultural Relations dimension of acculturative stress appeared to drive the observed associations. This study is among the first highlighting the role of acculturative stress, depressive symptoms, and gender in eating disinhibition and provides evidence that can inform health professionals to target at-risk Asian individuals with eating problems.


Assuntos
Depressão , Estresse Psicológico , Aculturação , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Masculino , Estresse Psicológico/psicologia , Estudantes/psicologia , Adulto Jovem
12.
J Biol Chem ; 298(1): 101430, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34801553

RESUMO

Various plants use antimicrobial proteins/peptides to resist phytopathogens. In the potato, Solanum tuberosum, the plant-specific insert (PSI) domain of an aspartic protease performs this role by disrupting phytopathogen plasma membranes. However, the mechanism by which PSI selects target membranes has not been elucidated. Here, we studied PSI-induced membrane fusion, focusing on the effects of lipid composition on fusion efficiency. Membrane fusion by the PSI involves an intermediate state whereby adjacent liposomes share their bilayers. We found that increasing the concentration of negatively charged phosphatidylserine (PS) phospholipids substantially accelerated PSI-mediated membrane fusion. NMR data demonstrated that PS did not affect the binding between the PSI and liposomes but had seminal effects on the dynamics of PSI interaction with liposomes. In PS-free liposomes, the PSI underwent significant motion, which was suppressed on PS-contained liposomes. Molecular dynamics simulations showed that the PSI binds to PS-containing membranes with a dominant angle ranging from -31° to 30°, with respect to the bilayer, and is closer to the membrane surfaces. In contrast, PSI is mobile and exhibits multiple topological states on the surface of PS-free membranes. Taken together, our data suggested that PS lipids limit the motion of the anchored PSI, bringing it closer to the membrane surface and efficiently bridging different liposomes to accelerate fusion. As most phytopathogens have a higher content of negatively charged lipids as compared with host cells, these results indicate that the PSI selectively targets negatively charged lipids, which likely represents a way of distinguishing the pathogen from the host.


Assuntos
Ácido Aspártico Proteases , Solanum tuberosum , Ácido Aspártico Proteases/metabolismo , Membrana Celular/metabolismo , Lipossomos/química , Fusão de Membrana , Fosfatidilserinas/química , Fosfolipídeos/farmacologia , Solanum tuberosum/química
13.
Cell ; 185(1): 204-217.e14, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34965378

RESUMO

Conifers dominate the world's forest ecosystems and are the most widely planted tree species. Their giant and complex genomes present great challenges for assembling a complete reference genome for evolutionary and genomic studies. We present a 25.4-Gb chromosome-level assembly of Chinese pine (Pinus tabuliformis) and revealed that its genome size is mostly attributable to huge intergenic regions and long introns with high transposable element (TE) content. Large genes with long introns exhibited higher expressions levels. Despite a lack of recent whole-genome duplication, 91.2% of genes were duplicated through dispersed duplication, and expanded gene families are mainly related to stress responses, which may underpin conifers' adaptation, particularly in cold and/or arid conditions. The reproductive regulation network is distinct compared with angiosperms. Slow removal of TEs with high-level methylation may have contributed to genomic expansion. This study provides insights into conifer evolution and resources for advancing research on conifer adaptation and development.


Assuntos
Epigenoma , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Pinus/genética , Aclimatação/genética , Cromossomos de Plantas/genética , Cycadopsida/genética , Elementos de DNA Transponíveis/genética , Florestas , Redes Reguladoras de Genes , Tamanho do Genoma , Genômica/métodos , Íntrons , Magnoliopsida/genética
14.
J Agric Food Chem ; 69(50): 15108-15122, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34905356

RESUMO

Targeting the virulence factors of phytopathogenic bacteria is an innovative strategy for alleviating or eliminating the pathogenicity and rapid outbreak of plant microbial diseases. Therefore, several types of 1,2,4-triazole thioethers bearing an amide linkage were prepared and screened to develop virulence factor inhibitors. Besides, the 1,2,4-triazole scaffold was exchanged by a versatile 1,3,4-oxadiazole core to expand molecular diversity. Bioassay results revealed that a 1,2,4-triazole thioether A10 bearing a privileged N-(3-nitrophenyl)acetamide fragment was extremely bioactive against Xanthomonas oryzae pv. oryzae (Xoo) with an EC50 value of 5.01 µg/mL. Label-free quantitative proteomics found that compound A10 could significantly downregulate the expression of Xoo's type III secretion system (T3SS) and transcription activator-like effector (TALE) correlative proteins. Meanwhile, qRT-PCR detection revealed that the corresponding gene transcription levels of these virulence factor-associated proteins were substantially inhibited after being triggered by compound A10. As a result, the hypersensitive response and pathogenicity were strongly depressed, indicating that a novel virulence factor inhibitor (A10) was probably discovered. In vivo anti-Xoo trials displayed that compound A10 yielded practicable control efficiency (54.2-59.6%), which was superior to thiadiazole-copper and bismerthiazol (38.1-44.9%). Additionally, compound A10 showed an appreciable antiviral activity toward tobacco mosaic virus (TMV) with the curative and protective activities of 54.6 and 76.4%, respectively, which were comparable to ningnanmycin (55.2 and 60.9%). This effect was further validated and visualized by the inoculation test using GFP-labeled TMV, thereby leading to the reduced biosynthesis of green-fluorescent TMV on Nicotiana benthamiana. Given the outstanding features of compound A10, it should be deeply developed as a versatile agricultural chemical.


Assuntos
Infecções Bacterianas , Oryza , Vírus do Mosaico do Tabaco , Xanthomonas , Antibacterianos/farmacologia , Antivirais/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Doenças das Plantas , Sulfetos , Triazóis , Fatores de Virulência/genética
15.
Cell Discov ; 7(1): 106, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728622

RESUMO

Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2.

16.
Nat Commun ; 12(1): 6966, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845226

RESUMO

The membrane protein Dispatched (Disp), which belongs to the RND family of small molecule transporters, is essential for Hedgehog (Hh) signaling, by catalyzing the extracellular release of palmitate- and cholesterol-modified Hh ligands from producing cells. Disp function requires Furin-mediated proteolytic cleavage of its extracellular domain, but how this activates Disp remains obscure. Here, we employ cryo-electron microscopy to determine atomic structures of human Disp1 (hDisp1), before and after cleavage, and in complex with lipid-modified Sonic hedgehog (Shh) ligand. These structures, together with biochemical data, reveal that proteolytic cleavage opens the extracellular domain of hDisp1, removing steric hindrance to Shh binding. Structure-guided functional experiments demonstrate the role of hDisp1-Shh interactions in ligand release. Our results clarify the mechanisms of hDisp1 activation and Shh morphogen release, and highlight how a unique proteolytic cleavage event enabled acquisition of a protein substrate by a member of a family of small molecule transporters.


Assuntos
Proteínas Hedgehog/química , Proteínas de Membrana Transportadoras/química , Sequência de Aminoácidos , Sítios de Ligação , Microscopia Crioeletrônica , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Células HEK293 , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Ligantes , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Modelos Moleculares , Mutação , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteólise , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade por Substrato
17.
Int J Behav Med ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581977

RESUMO

BACKGROUND: The global spread of COVID-19 has brought immense psychological distress and sleep problems to those affected. This study examined the mediating role of rumination in the direct association between COVID-19 stressors and poor sleep quality and the moderating roles of emotion regulation strategies. METHOD: A cross-sectional online survey study was conducted in China during the early outbreak of the pandemic. A total of 1106 Chinese college students (Mage = 19.58, SD = 1.61) completed measures of COVID-19 stressors, rumination, emotion regulation strategies (i.e., cognitive reappraisal and expressive suppression), and poor sleep quality. RESULTS: COVID-19 stressors were positively associated with poor sleep quality (ß = .431, p < .001), and rumination partially mediated this association. The mediation effect accounted for 70.93% of the total effect of COVID-19 stressors on poor sleep quality. Moreover, cognitive reappraisal moderated the relation between COVID-19 stressors and rumination, and expressive suppression moderated the association between rumination and poor sleep quality. CONCLUSION: Rumination could be a mechanism by which COVID-19 stressors are linked with poor sleep quality. Cognitive reappraisal might provide desired benefits to improving sleep quality while expressive suppression may do the opposite. Implications for future steps and health interventions are discussed.

18.
Nucleic Acids Res ; 49(17): 10178-10191, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34432044

RESUMO

CRISPR-Cas systems are bacterial adaptive immune systems, and phages counteract these systems using many approaches such as producing anti-CRISPR (Acr) proteins. Here, we report the structures of both AcrIF14 and its complex with the crRNA-guided surveillance (Csy) complex. Our study demonstrates that apart from interacting with the Csy complex to block the hybridization of target DNA to the crRNA, AcrIF14 also endows the Csy complex with the ability to interact with non-sequence-specific dsDNA as AcrIF9 does. Further structural studies of the Csy-AcrIF14-dsDNA complex and biochemical studies uncover that the PAM recognition loop of the Cas8f subunit of the Csy complex and electropositive patches within the N-terminal domain of AcrIF14 are essential for the non-sequence-specific dsDNA binding to the Csy-AcrIF14 complex, which is different from the mechanism of AcrIF9. Our findings highlight the prevalence of Acr-induced non-specific DNA binding and shed light on future studies into the mechanisms of such Acr proteins.


Assuntos
Sistemas CRISPR-Cas/genética , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Endodesoxirribonucleases/metabolismo , Pseudomonas aeruginosa/genética , Bacteriófagos/genética , Bacteriófagos/crescimento & desenvolvimento , Proteínas Associadas a CRISPR/metabolismo , DNA/genética , Proteínas de Ligação a DNA/antagonistas & inibidores , Conformação Proteica , Pseudomonas aeruginosa/virologia , Proteínas Virais/genética , Proteínas Virais/metabolismo
19.
Front Psychol ; 12: 589579, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456776

RESUMO

Federal and local government agencies were quick to issue orders for residents to shelter-in-place in response to the COVID-19 outbreak. This study utilized data collected from Unacast Inc., spanning observations of 3,142 counties across 50 states and the District of Columbia (N = 230,846) from March 8, 2020 to April 13, 2020 (n = 104,930) and from April 14, 2020 to May 24, 2020 (n = 131,912) in a 3-level multilevel model to examine the correlates of social distancing behavior, as measured by the relative reduction in (1) distance traveled and (2) non-essential visitations since baseline pre-COVID-19 times. Results showed that educational attainment and political partisanship were the most consistent correlates of social distancing. State-level indicators of culture appeared to have differentiated effects depending on whether the model outcomes were reduction in general mobility or to non-essential venues. State-level neuroticism was generally positively related to social distancing, but states marked by high neuroticism were slower to engage in such behaviors. Counties and states characterized as already engaging in preventive health measures (e.g., vaccination rates, preparedness for at-risk populations) enjoyed quicker engagement in social distancing. Specific implications of findings and future directions are discussed.

20.
J Agric Food Chem ; 69(30): 8380-8393, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34296859

RESUMO

Developing multipurpose agricultural chemicals is appealing in crop protection, thus eventually realizing the reduction and efficient usage of pesticides. Herein, an array of versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized and biologically evaluated the antifungal, antioomycetes, and antibacterial activities. In addition, the pyrazole ring was replaced by the correlative pyrrole, thiazole, and indole scaffolds to extend the molecular diversity. The results showed that most of these hybrid compounds were empowered with multifunctional bioactivities, which are exemplified by compounds a1-a6, b1-b3, b7, b10, b13, and b18. For the antifungal activity, the minimal EC50 values could afford 0.47 (a2), 1.05 (a2), 0.65 (a1), and 1.32 µg/mL (b3) against the corresponding fungi Gibberella zeae (G. z.), Fusarium oxysporum, Botryosphaeria dothidea, and Rhizoctonia solani. In vivo pot experiments against corn scab (caused by G. z.) revealed that the compound a2 was effective with protective and curative activities of 90.2 and 86.3% at 200 µg/mL, which was comparable to those of fungicides boscalid and fluopyram. Further molecular docking study and enzymatic activity analysis (IC50 = 3.21 µM, a2) indicated that target compounds were promising succinate dehydrogenase inhibitors. Additionally, compounds b2 and a4 yielded superior anti-oomycete and antibacterial activities toward Phytophora infestins and Xanthomonas oryzae pv. oryzae with EC50 values of 2.92 and 8.43 µg/mL, respectively. In vivo trials against rice bacterial blight provided the control efficiency within 51.2-55.3% (a4) at 200 µg/mL, which were better than that of bismerthiazol. Given their multipurpose characteristics, these structures should be positively explored as agricultural chemicals.


Assuntos
Infecções Bacterianas , Oomicetos , Xanthomonas , Agroquímicos , Antibacterianos/farmacologia , Ascomicetos , Fusarium , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Oxidiazóis , Doenças das Plantas , Pirazóis/farmacologia , Rhizoctonia , Relação Estrutura-Atividade
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