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1.
Am J Hum Genet ; 110(12): 2092-2102, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38029743

RESUMEN

Aneuploidy frequently arises during human meiosis and is the primary cause of early miscarriage and in vitro fertilization (IVF) failure. Individuals undergoing IVF exhibit significant variability in aneuploidy rates, although the exact genetic causes of the variability in aneuploid egg production remain unclear. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing is a standard test for identifying and selecting IVF-derived euploid embryos. The wealth of embryo aneuploidy data and ultra-low coverage whole-genome sequencing (ulc-WGS) data from PGT-A have the potential to discover variants in parental genomes that are associated with aneuploidy risk in their embryos. Using ulc-WGS data from ∼10,000 PGT-A biopsies, we imputed genotype likelihoods of genetic variants in embryo genomes. We then used the imputed variants and embryo aneuploidy calls to perform a genome-wide association study of aneuploidy incidence. Finally, we carried out functional evaluation of the identified candidate gene in a mouse oocyte system. We identified one locus on chromosome 3 that is significantly associated with meiotic aneuploidy risk. One candidate gene, CCDC66, encompassed by this locus, is involved in chromosome segregation during meiosis. Using mouse oocytes, we showed that CCDC66 regulates meiotic progression and chromosome segregation fidelity, especially in older mice. Our work extended the research utility of PGT-A ulc-WGS data by allowing robust association testing and improved the understanding of the genetic contribution to maternal meiotic aneuploidy risk. Importantly, we introduce a generalizable method that has potential to be leveraged for similar association studies that use ulc-WGS data.


Asunto(s)
Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Animales , Ratones , Diagnóstico Preimplantación/métodos , Estudio de Asociación del Genoma Completo , Pruebas Genéticas/métodos , Fertilización In Vitro , Aneuploidia , Blastocisto , Proteínas del Ojo
2.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38797969

RESUMEN

In recent decades, antibodies have emerged as indispensable therapeutics for combating diseases, particularly viral infections. However, their development has been hindered by limited structural information and labor-intensive engineering processes. Fortunately, significant advancements in deep learning methods have facilitated the precise prediction of protein structure and function by leveraging co-evolution information from homologous proteins. Despite these advances, predicting the conformation of antibodies remains challenging due to their unique evolution and the high flexibility of their antigen-binding regions. Here, to address this challenge, we present the Bio-inspired Antibody Language Model (BALM). This model is trained on a vast dataset comprising 336 million 40% nonredundant unlabeled antibody sequences, capturing both unique and conserved properties specific to antibodies. Notably, BALM showcases exceptional performance across four antigen-binding prediction tasks. Moreover, we introduce BALMFold, an end-to-end method derived from BALM, capable of swiftly predicting full atomic antibody structures from individual sequences. Remarkably, BALMFold outperforms those well-established methods like AlphaFold2, IgFold, ESMFold and OmegaFold in the antibody benchmark, demonstrating significant potential to advance innovative engineering and streamline therapeutic antibody development by reducing the need for unnecessary trials. The BALMFold structure prediction server is freely available at https://beamlab-sh.com/models/BALMFold.


Asunto(s)
Anticuerpos , Anticuerpos/química , Anticuerpos/inmunología , Biología Computacional/métodos , Conformación Proteica , Humanos , Modelos Moleculares , Aprendizaje Profundo
3.
Mol Cell Proteomics ; 23(2): 100719, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38242438

RESUMEN

Although the human gene annotation has been continuously improved over the past 2 decades, numerous studies demonstrated the existence of a "dark proteome", consisting of proteins that were critical for biological processes but not included in widely used gene catalogs. The Genotype-Tissue Expression project generated more than 15,000 RNA-seq datasets from multiple tissues, which modeled 30 million transcripts in the human genome. To provide a resource of high-confidence novel proteins from the dark proteome, we screened 50,000 mass spectrometry runs from over 900 projects to identify proteins translated from the Genotype-Tissue Expression transcript model with proteomic support. We also integrated 3.8 million common genetic variants from the gnomAD database to improve peptide identification. As a result, we identified 170,529 novel peptides with proteomic evidence, of which 6048 passed the strictest standard we defined and were supported by PepQuery. We provided a user-friendly website (https://ncorf.genes.fun/) for researchers to check the evidence of novel peptides from their studies. The findings will improve our understanding of coding genes and facilitate genomic data interpretation in biomedical research.


Asunto(s)
Proteogenómica , Humanos , Proteogenómica/métodos , Proteoma/metabolismo , Proteómica/métodos , Péptidos/genética , Genoma Humano
4.
Plant Cell ; 34(6): 2424-2448, 2022 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-35348751

RESUMEN

Membrane contact sites (MCSs) are interorganellar connections that allow for the direct exchange of molecules, such as lipids or Ca2+ between organelles, but can also serve to tether organelles at specific locations within cells. Here, we identified and characterized three proteins of Arabidopsis thaliana that form a lipid droplet (LD)-plasma membrane (PM) tethering complex in plant cells, namely LD-localized SEED LD PROTEIN (SLDP) 1 and SLDP2 and PM-localized LD-PLASMA MEMBRANE ADAPTOR (LIPA). Using proteomics and different protein-protein interaction assays, we show that both SLDPs associate with LIPA. Disruption of either SLDP1 and SLDP2 expression, or that of LIPA, leads to an aberrant clustering of LDs in Arabidopsis seedlings. Ectopic co-expression of one of the SLDPs with LIPA is sufficient to reconstitute LD-PM tethering in Nicotiana tabacum pollen tubes, a cell type characterized by dynamically moving LDs in the cytosolic streaming. Furthermore, confocal laser scanning microscopy revealed both SLDP2.1 and LIPA to be enriched at LD-PM contact sites in seedlings. These and other results suggest that SLDP and LIPA interact to form a tethering complex that anchors a subset of LDs to the PM during post-germinative seedling growth in Arabidopsis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Membrana Celular/metabolismo , Gotas Lipídicas/metabolismo , Plantones/genética , Plantones/metabolismo , Semillas/genética , Semillas/metabolismo
5.
Nano Lett ; 24(18): 5631-5638, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38669049

RESUMEN

Perovskite light-emitting diodes (PeLEDs) based on CsPb(Br/I)3 nanocrystals (NCs) usually suffer from severe spectral instability under operating voltage due to the poor-quality PeNCs. Herein, zeolite was utilized to prepare high-quality CsPb(Br/I)3 NCs via promoting the homogeneous nucleation and growth and suppressing the Ostwald ripening of PeNCs. In addition, the decomposed zeolite interacted strongly with PeNCs through Pb-O bonds and hydrogen bonds, which inhibited the formation of defects and suppressed halide ion migration, leading to an improved photoluminescence quantum yield (PLQY) and enhanced stability of PeNCs. Moreover, the strong binding affinity of decomposed zeolite to PeNCs contributed to the formation of homogeneous perovskite films with high PLQY. As a result, pure-red PeLEDs with Commission International de I'Eclairage (CIE) coordinates of (0.705, 0.291) were fabricated, approaching the Rec. 2020 red primary color. The devices achieved a peak external quantum efficiency of 23.0% and outstanding spectral stability.

6.
Fish Shellfish Immunol ; 149: 109578, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38670413

RESUMEN

MicroRNAs are increasingly recognized for their pivotal role in the immune system, yet the specific regulatory functions of fish-derived microRNAs remain largely unexplored. In this research, we discovered a novel miRNA, Cse-miR-144, in the Chinese tongue sole (Cynoglossus semilaevis), characterized by a 73-base pair precursor and a 21-nucleotide mature sequence. Our findings revealed that the expression of Cse-miR-144 was notably inhibited by various Vibrio species. Utilizing bioinformatics and dual-luciferase assay techniques, we established that the pro-inflammatory cytokine gene CsMAPK6 is a direct target of Cse-miR-144. Subsequent in vitro and in vivo western blotting analyses confirmed that Cse-miR-144 can effectively reduce the protein levels of CsMAPK6 post-transcriptionally. Moreover, CsMAPK6 is known to be involved in the activation of the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB). Additional investigations using qPCR and ELISA demonstrated that suppression of Cse-miR-144 leads to an upsurge in the liver mRNA levels of various immune genes (including MYD88, TRAF6, NF-κB, TRAF2, TRAF3, and TNF), alongside a marked increase in the production and secretion of pro-inflammatory cytokines (IL-1ß, IL-6, and IL-8) in the bloodstream of C. semilaevis. These findings collectively underscore the potential of Cse-miR-144 as a key inhibitor of CsMAPK and its crucial role in modulating the immune and inflammatory responses in teleost fish. Compared to the siRNA, miRNA is a better tool in controlling the expression of target gene with a lower cost.


Asunto(s)
Enfermedades de los Peces , Proteínas de Peces , Peces Planos , Regulación de la Expresión Génica , Inmunidad Innata , MicroARNs , Vibriosis , Vibrio , Animales , MicroARNs/genética , MicroARNs/inmunología , Peces Planos/inmunología , Peces Planos/genética , Enfermedades de los Peces/inmunología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Vibrio/fisiología , Inmunidad Innata/genética , Regulación de la Expresión Génica/inmunología , Vibriosis/inmunología , Vibriosis/veterinaria , Inflamación/inmunología , Inflamación/veterinaria , Inflamación/genética , Citocinas/genética , Citocinas/inmunología , Citocinas/metabolismo
7.
Appl Opt ; 63(9): 2180-2186, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38568570

RESUMEN

In this paper, a methane detection sensor based on direct absorption spectroscopy and the self-heating effect of lasers is proposed, which abandons the traditional method of relying on a thermoelectric cooler (TEC) to ensure stable gas concentration detection. The sensor can achieve stable concentration measurement in the temperature range of -10∘ to 40°C without the need for a TEC, which greatly simplifies the structure of the sensor and reduces the cost. The results of gas concentration calibration experiments show that the sensor has a good linear correlation (R 2=0.9993). Long-term continuous detection experiments show that the sensor maintains a relative detection error between -2.667% and 4.3% over the full test temperature range. In addition, signal-to-noise ratio analysis experiments further determine that the minimum detection limit of the sensor for methane gas is 27.33p p m⋅m (1σ). Given its advantages of simple structure, low cost, high accuracy, and stability, this methane detection sensor is well suited for natural gas leakage monitoring in home environments and can also be widely used in industrial safety detection and environmental monitoring applications. This technology provides a cost-effective solution for domestic and industrial methane detection.

8.
Angew Chem Int Ed Engl ; 63(9): e202317376, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38229423

RESUMEN

Although colloidal perovskite nanocrystal (PNC) solution has exhibited near-unity photoluminescence quantum yield (PLQY), the luminance would be severely quenched when the PNC solution is assembled into thin films due to the agglomeration and fusion of NCs caused by the exfoliation of surface ligands and non-radiative Förster resonance energy transfer (FRET) from small to large particle sizes, which seriously affected the performances of light-emitting diodes (LEDs). Here, we used Guanidine thiocyanate (GASCN) and Sodium thiocyanate (NaSCN) to achieve effective CsPbI3 PNC surface reconstruction. Due to the strong coordination ability of these small molecules with the anions and cations on the surface of the PNCs, they can provide strong surface protection against PNC fusion during centrifugal purification process and repair the surface defects of PNCs, so that the original uniform size distribution of PNCs can be maintained and FRET between close-packed PNC films is effectively suppressed, which allows the emission characteristics of the films to be preserved. As a result, highly oriented, smooth and nearly defect-free high-quality PNC thin films are obtained, with PLQY as high as 95.1 %, far exceeding that of the original film, and corresponding LEDs exhibit a maximum external quantum efficiency of 24.5 %.

9.
J Med Virol ; 95(12): e29278, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38088537

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22,995 and 28,866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Humanos , SARS-CoV-2/genética , Células CACO-2 , Recombinación Homóloga , Glicoproteína de la Espiga del Coronavirus
10.
Neurochem Res ; 48(3): 956-966, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36402927

RESUMEN

Ferroptosis is characterized by excessive accumulation of iron and lipid peroxides, which are involved in ischemia, reperfusion-induced organ injury, and stroke. Propofol, an anesthetic agent, has neuroprotective effects due to its potent antioxidant, anti-ischemic, and anti-inflammatory properties. However, the relationship between propofol and ferroptosis is still unclear. In the current study, we elucidated the role of ferroptosis in the neuroprotective effect of propofol in mouse brains subjected to cerebral ischemia reperfusion injury (CIRI). Ferroptosis was confirmed by Western blotting assays, transmission electron microscopy, and glutathione assays. Propofol regulated Nrf2/Gpx4 signaling, enhanced antioxidant potential, inhibited the accumulation of lipid peroxides in CIRI-affected neurons, and significantly reversed CIRI-induced ferroptosis. Additionally, Gpx4 inhibitor RSL3 and Nrf2 inhibitor ML385 attenuated the effects of propofol on antioxidant capacity, lipid peroxidation, and ferroptosis in CIRI-affected neurons. Our data support a protective role of propofol against ferroptosis as a cause of cell death in mice with CIRI. Propofol protected against CIRI-induced ferroptosis partly by regulating the Nrf2/Gpx4 signaling pathway. These findings may contribute to the development of future therapies targeting ferroptosis induced by CIRI.


Asunto(s)
Propofol , Daño por Reperfusión , Animales , Ratones , Propofol/farmacología , Propofol/uso terapéutico , Factor 2 Relacionado con NF-E2 , Antioxidantes , Peróxidos Lipídicos , Daño por Reperfusión/tratamiento farmacológico , Modelos Animales de Enfermedad , Transducción de Señal , Muerte Celular
11.
Psychiatry Clin Neurosci ; 77(12): 653-664, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37675893

RESUMEN

AIM: The current study aimed to investigate the neuroinflammatory hypothesis of depression and the potential anti-inflammatory effect of electroconvulsive therapy (ECT) in vivo, utilizing astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma. METHODS: A total of 40 patients with treatment-resistant depression (TRD) and 35 matched healthy controls were recruited at baseline, and 34 patients with TRD completed the post-ECT visits. Blood samples were collected at baseline and post-ECT. Plasma ADEVs were isolated and confirmed, and the concentrations of two astrocyte markers (glial fibrillary acidic protein [GFAP] and S100ß), an extracellular vesicle marker cluster of differentiation 81 (CD81), and nine inflammatory markers in ADEVs were measured as main analyses. In addition, correlation analysis was conducted between clinical features and ADEV protein levels as exploratory analysis. RESULTS: At baseline, the TRD group exhibited significantly higher levels of two astrocyte markers GFAP and S100ß, as well as CD81 compared with the healthy controls. Inflammatory markers interferon γ (IFN-γ), interleukin (IL) 1ß, IL-4, IL-6, tumor necrosis factor α, IL-10, and IL-17A were also significantly higher in the TRD group. After ECT, there was a significant reduction in the levels of GFAP, S100ß, and CD81, along with a significant decrease in the levels of IFN-γ and IL-4. Furthermore, higher levels of GFAP, S100ß, CD81, and inflammatory cytokines were associated with more severe depressive symptoms and poorer cognitive function. CONCLUSION: This study provides direct insight supporting the astrocyte activation and neuroinflammatory hypothesis of depression using ADEVs. ECT may exert an anti-inflammatory effect through inhibition of such activation of astrocytes.


Asunto(s)
Terapia Electroconvulsiva , Humanos , Astrocitos/metabolismo , Depresión/terapia , Enfermedades Neuroinflamatorias , Interleucina-4/metabolismo , Interleucina-4/farmacología , Antiinflamatorios/farmacología
12.
Hum Genet ; 141(10): 1615-1627, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35347416

RESUMEN

Infertility is a major reproductive health issue that affects about 12% of women of reproductive age in the United States. Aneuploidy in eggs accounts for a significant proportion of early miscarriage and in vitro fertilization failure. Recent studies have shown that genetic variants in several genes affect chromosome segregation fidelity and predispose women to a higher incidence of egg aneuploidy. However, the exact genetic causes of aneuploid egg production remain unclear, making it difficult to diagnose infertility based on individual genetic variants in mother's genome. In this study, we evaluated machine learning-based classifiers for predicting the embryonic aneuploidy risk in female IVF patients using whole-exome sequencing data. Using two exome datasets, we obtained an area under the receiver operating curve of 0.77 and 0.68, respectively. High precision could be traded off for high specificity in classifying patients by selecting different prediction score cutoffs. For example, a strict prediction score cutoff of 0.7 identified 29% of patients as high-risk with 94% precision. In addition, we identified MCM5, FGGY, and DDX60L as potential aneuploidy risk genes that contribute the most to the predictive power of the model. These candidate genes and their molecular interaction partners are enriched for meiotic-related gene ontology categories and pathways, such as microtubule organizing center and DNA recombination. In summary, we demonstrate that sequencing data can be mined to predict patients' aneuploidy risk thus improving clinical diagnosis. The candidate genes and pathways we identified are promising targets for future aneuploidy studies.


Asunto(s)
Infertilidad , Diagnóstico Preimplantación , Aneuploidia , ADN , Femenino , Fertilización In Vitro , Humanos , Embarazo , Secuenciación del Exoma
13.
Opt Lett ; 47(5): 1033-1036, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35230283

RESUMEN

We measure the molecular alignment induced in gas using molecular rotational echo spectroscopy. Our results show that the echo intensity and the time interval between the local extremas of the echo responses depend sensitively on the pump intensities and the initial molecular rotational temperature, respectively. This allows us to accurately extract these experimental parameters from the echo signals and then further determine the molecular alignment in experiments. The accuracy of our method has been verified by comparing the simulation with the extracted parameters from the molecular alignment experiment performed with a femtosecond pump pulse.

14.
Int J Mol Sci ; 23(17)2022 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-36077140

RESUMEN

Kiwifruit bacterial canker is a recent epidemic disease caused by Pseudomonas syringae pv. actinidiae (Psa), which has undergone worldwide expansion in a short time and resulted in significant economic losses. 'Hongyang' (Actinidia chinensis), a widely grown cultivar because of its health-beneficial nutrients and appreciated red-centered inner pericarp, is highly sensitive to Psa. In this work, ten Psa strains were isolated from 'Hongyang' and sequenced for genome analysis. The results indicated divergences in pathogenicity and pathogenic-related genes among the Psa strains. Significantly, the interruption at the 596 bp of HrpR in two low-pathogenicity strains reemphasized this gene, expressing a transcriptional regulator for the effector secretion system, as an important pathogenicity-associated locus of Psa. The transcriptome analysis of 'Hongyang' infected with different Psa strains was performed by RNA-seq of stem tissues locally (at the inoculation site) and systemically. Psa infection re-programmed the host genes expression, and the susceptibility to Psa might be attributed to the down-regulation of several genes involved in plant-pathogen interactions, especially calcium signaling transduction, as well as fatty acid elongation. This suppression was found in both low- and high-pathogenicity Psa inoculated tissues, but the effect was stronger with more virulent strains. Taken together, the divergences of P. syringae pv. actinidiae in pathogenicity, genome, and resulting transcriptomic response of A. chinensis provide insights into unraveling the molecular mechanism of Psa-kiwifruit interactions and resistance improvement in the kiwifruit crop.


Asunto(s)
Actinidia , Pseudomonas syringae , Actinidia/metabolismo , Genómica , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Virulencia/genética
15.
J Environ Manage ; 301: 113932, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34731963

RESUMEN

Over the last four decades, China has experienced rapid parallel economic development and urbanization, leading to internal mass -migrations of its people from increasingly marginalized rural areas to urban centers where job opportunities and wealth are now concentrated. We compare the relative temporal growth trends in population-related and land-(i.e., area-) related urbanization systems to evaluate China's urbanization in the context of the 'New-Type' Urbanization Program (2014-2020). Based on coupling coordination models, we observed that the two systems were overall slightly decoupled since spatial urban expansion commonly outgrew urban population growth, but the degree of coordination between the two parameters was increasing. Employing exploratory spatial data analysis, we revealed that a high degree of coupling coordination has spread from Eastern to Western provinces. Urban planning and land policies have contributed to an increasing urban vegetation cover and the control of excessive urban land expansions. While China's urbanization appears to have become increasingly sustainable due to the increasing degree of coupling coordination between its subsystems, ongoing urban expansions require strong oversight to limit the environmental impacts of the country's sprawling mega-cities.


Asunto(s)
Urbanización , China , Ciudades , Humanos , Análisis Espacial , Población Urbana
16.
Ocean Coast Manag ; 217: 105995, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-34955616

RESUMEN

International cruises have drawn worldwide attention since the outbreak of coronavirus (COVID-19). This article first examines the legal issues, challenges and impact of the pandemic on large cruise ships, like the Diamond Princess, and then probes into corresponding pandemic preventive measures which port states employ. A State is obliged under the International Health Regulations 2005 (IHR) to grant foreign cruise ships free pratique, but there is an exception when public health emergencies of international concern occur. Therefore, this article argues that a port state is not obliged to allow foreign cruise ships to dock at its port at the cost of its domestic public health safety. Regarding the Diamond Princess, the Japanese government has undertaken pandemic preventive measures upon passengers on board the ship and complied with its domestic laws, including the Japanese Quarantine Act. This article further evaluates whether a port state's pandemic preventive measures concerning cruise ships are appropriate from the perspective of law. More importantly, it is necessary to consider the characteristics and specialities of international cruise ships to improve future pandemic preventive measures against large passenger ships and cruise passengers.

17.
J Virol ; 94(13)2020 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-32321806

RESUMEN

Porcine circovirus type 2 (PCV2) is an important swine pathogen that causes significant economic losses to the pig industry. PCV2 interacts with host cellular factors to regulate its replication. High-mobility-group box 1 (HMGB1) protein, a major nonhistone protein in the nucleus, was recently discovered to participate in viral infections. Here, we demonstrate that nuclear HMGB1 negatively regulated PCV2 replication as shown by overexpression of HMGB1 or blockage of its nucleocytoplasmic translocation with ethyl pyruvate. The B box domain was essential in restricting PCV2 replication. Nuclear HMGB1 restricted PCV2 replication by sequestering the viral genome via binding to the Ori region. However, PCV2 infection induced translocation of HMGB1 from cell nuclei to the cytoplasmic compartment. Elevation of reactive oxygen species (ROS) induced by PCV2 infection was closely associated with cytosolic translocation of nuclear HMGB1. Treatment of PCV2-infected cells with ethyl pyruvate or N-acetylcysteine downregulated PCV2-induced ROS production, suppressed nucleocytoplasmic HMGB1 translocation, and decreased PCV2 replication. Collectively, these findings offer new insight into the mechanism of the PCV2 evasion strategy: PCV2 manages to escape restriction of its replication by nuclear HMGB1 by inducing ROS to trigger the nuclear-to-cytoplasmic translocation of HMGB1.IMPORTANCE Porcine circovirus type 2 (PCV2) is a small DNA virus that depends heavily on host cells for its infection. This study reports the close relationship between subcellular localization of host high-mobility-group box 1 (HMGB1) protein and viral replication during PCV2 infection. Restriction of PCV2 replication by nuclear HMGB1 is the early step of host defense at the host-pathogen interface. PCV2 then upregulates host reactive oxygen species (ROS) to prevent sequestration of its genome by expelling nuclear HMGB1 into the cytosol. It will be interesting to study if a similar evasion strategy is employed by other circoviruses such as beak and feather disease virus, recently discovered PCV3, and geminiviruses in plants. This study also provides insight into the justification and pharmacological basis of antioxidants as an adjunct therapy in PCV2 infection or possibly other diseases caused by the viruses that deploy the ROS-HMGB1 interaction favoring their replication.


Asunto(s)
Circovirus/metabolismo , Proteína HMGB1/metabolismo , Acetilcisteína/farmacología , Animales , Antioxidantes/metabolismo , Proteínas de la Cápside/genética , Línea Celular , Núcleo Celular/metabolismo , Infecciones por Circoviridae/virología , Circovirus/genética , Citosol/metabolismo , ADN Viral/metabolismo , Genoma Viral/efectos de los fármacos , Proteína HMGB1/genética , Piruvatos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Porcinos , Enfermedades de los Porcinos/virología , Replicación Viral/fisiología
18.
Appl Environ Microbiol ; 87(8)2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33579684

RESUMEN

Halolysins, which are subtilisin-like serine proteases of haloarchaea, are usually secreted into the extracellular matrix via the twin-arginine translocation pathway. A small number of activated molecules can greatly affect cell growth owing to their proteolytic activity. It is, however, unclear as to whether this proteolysis-based growth inhibition by halolysins conveys antagonistic or defensive effects against other resident abd potentially competitive microorganisms. Here, we report that halolysin R4 (HlyR4), encoded by the hlyR4 gene, is the key enzyme in the initial steps of extracellular protein utilization in Haloferax mediterranei HlyR4 shows significant antagonistic activity against other haloarchaeal strains. Deletion of hlyR4 completely halts the inhibition activity of Hfx. mediterranei towards other haloarchaea, while correspondingly, complementation of hlyR4 almost completely restores the inhibition activity. Furthermore, Hfx. mediterranei strains containing hlyR4 showed a certain amount of resistance to halocins and halolysins in milieu, and this function of hlyR4 is reproducible in Haloarcula hispanica The versatility of HlyR4 enables its host to outcompete other haloarchaea living in the same hypersaline environment. Intriguingly, unlike the growth phase-dependent halolysins SptA and Nep, it is likely that HlyR4 may be secreted independent of growth phase. This study provides a new peptide antibiotics candidate in haloarchaea, as well as new insight towards a better understanding of the ecological roles of halolysins.Importance: This study shows that halolysin R4 from Haloferax mediterranei provides its host antagonistic and defensive activities against other haloarchaea, which expands our knowledge on the traditional function of haloarchaeal extracellular proteases. Haloarchaeal extracellular serine proteases have been previously discussed as growth-phase-dependent proteins, whereas our study reports constitutive expression of halolysin R4. This work also clearly reveals a hidden diversity of extracellular proteases from haloarchaea. Studies on multifunctional halolysins reveal that they play an important ecological role in shaping microbial community composition and provide a new perspective towards understanding the intricate interactions between haloarchaeal cells in hypersaline environments. HlyR4 can lyse competing cells living in the same environment, and the cell debris may probably be utilized as nutrients, which may constitute an important part of nutrient cycling in extremely hypersaline environments.

19.
Opt Express ; 29(2): 663-673, 2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33726297

RESUMEN

We theoretically investigate the formation of the high-order fractional alignment echo in OCS molecule and systematically study the dependence of echo intensity on the intensities and time delay of the two excitation pulses. Our simulations reveal an intricate dependence of the intensity of high-order fractional alignment echo on the laser conditions. Based on the analysis with rotational density matrix, this intricate dependence is further demonstrated to arise from the interference of multiple quantum pathways that involve multilevel rotational transitions. Our result provides a comprehensive multilevel picture of the quantum dynamics of high-order fractional alignment echo in molecular ensembles, which will facilitate the development of "rotational echo spectroscopy."

20.
Nano Lett ; 20(4): 2829-2836, 2020 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-32223199

RESUMEN

Zirconium acetylacetonate used as a co-precursor in the synthesis of CsPbI3 quantum dots (QDs) increased their photoluminescence quantum efficiency to values over 90%. The top-emitting device structure on a Si substrate with high thermal conductivity (to better dissipate Joule heat generated at high current density) was designed to improve the light extraction efficiency making use of a strong microcavity resonance between the bottom and top electrodes. As a result of these improvements, light-emitting diodes (LEDs) utilizing Zr-modified CsPbI3 QDs with an electroluminescence at 686 nm showed external quantum efficiency (EQE) of 13.7% at a current density of 108 mA cm-2, which was combined with low efficiency roll-off (maintaining an EQE of 12.5% at a high current density of 500 mA cm-2) and a high luminance of 14 725 cd m-2, and the stability of the devices being repeatedly lit (cycled on and off at high drive current density) has been greatly enhanced.

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