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Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and resume growth remains poorly understood. Here, we visualized budding yeast cells undergoing meiosis by cryo-electron tomography (cryoET) and discovered elaborate filamentous assemblies decorating the nucleus, cytoplasm, and mitochondria. To determine filament composition, we developed a "filament identification" (FilamentID) workflow that combines multiscale cryoET/cryo-electron microscopy (cryoEM) analyses of partially lysed cells or organelles. FilamentID identified the mitochondrial filaments as being composed of the conserved aldehyde dehydrogenase Ald4ALDH2 and the nucleoplasmic/cytoplasmic filaments as consisting of acetyl-coenzyme A (CoA) synthetase Acs1ACSS2. Structural characterization further revealed the mechanism underlying polymerization and enabled us to genetically perturb filament formation. Acs1 polymerization facilitates the recovery of chronologically aged spores and, more generally, the cell cycle re-entry of starved cells. FilamentID is broadly applicable to characterize filaments of unknown identity in diverse cellular contexts.
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Gametogénesis , Mitocondrias , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Aldehído Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa/química , Núcleo Celular/metabolismo , Núcleo Celular/ultraestructura , Coenzima A Ligasas/metabolismo , Microscopía por Crioelectrón , Citoplasma/metabolismo , Tomografía con Microscopio Electrónico , Meiosis , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestructura , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Esporas Fúngicas/metabolismo , Modelos Moleculares , Estructura Cuaternaria de ProteínaRESUMEN
Asgard archaea are considered to be the closest known relatives of eukaryotes. Their genomes contain hundreds of eukaryotic signature proteins (ESPs), which inspired hypotheses on the evolution of the eukaryotic cell1-3. A role of ESPs in the formation of an elaborate cytoskeleton and complex cellular structures has been postulated4-6, but never visualized. Here we describe a highly enriched culture of 'Candidatus Lokiarchaeum ossiferum', a member of the Asgard phylum, which thrives anaerobically at 20 °C on organic carbon sources. It divides every 7-14 days, reaches cell densities of up to 5 × 107 cells per ml and has a significantly larger genome compared with the single previously cultivated Asgard strain7. ESPs represent 5% of its protein-coding genes, including four actin homologues. We imaged the enrichment culture using cryo-electron tomography, identifying 'Ca. L. ossiferum' cells on the basis of characteristic expansion segments of their ribosomes. Cells exhibited coccoid cell bodies and a network of branched protrusions with frequent constrictions. The cell envelope consists of a single membrane and complex surface structures. A long-range cytoskeleton extends throughout the cell bodies, protrusions and constrictions. The twisted double-stranded architecture of the filaments is consistent with F-actin. Immunostaining indicates that the filaments comprise Lokiactin-one of the most highly conserved ESPs in Asgard archaea. We propose that a complex actin-based cytoskeleton predated the emergence of the first eukaryotes and was a crucial feature in the evolution of the Asgard phylum by scaffolding elaborate cellular structures.
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Citoesqueleto de Actina , Archaea , Eucariontes , Filogenia , Citoesqueleto de Actina/metabolismo , Actinas/clasificación , Actinas/genética , Actinas/metabolismo , Archaea/clasificación , Archaea/citología , Archaea/genética , Archaea/crecimiento & desarrollo , Eucariontes/clasificación , Eucariontes/citología , Eucariontes/metabolismo , Anaerobiosis , Ribosomas/metabolismo , Estructuras de la Membrana Celular/metabolismo , Proteínas Arqueales/clasificación , Proteínas Arqueales/genética , Proteínas Arqueales/metabolismo , Evolución MolecularRESUMEN
Tumor immunotherapy is refashioning traditional treatments in the clinic for certain tumors, especially by relying on the activation of T cells. However, the safety and effectiveness of many antitumor immunotherapeutic agents are suboptimal due to difficulties encountered in assessing T cell responses and adjusting treatment regimens accordingly. Here, we review advances in the clinical visualization of T cell activity in vivo, and focus particularly on molecular imaging probes and biomarkers of T cell activation. Current challenges and prospects are also discussed that aim to achieve a better strategy for real-time monitoring of T cell activity, predicting prognoses and responses to tumor immunotherapy, and assessing disease management.
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Antineoplásicos , Neoplasias , Humanos , Linfocitos T , Neoplasias/terapia , Inmunoterapia/métodos , Imagen MolecularRESUMEN
Myeloid-derived suppressor cells (MDSCs) significantly hinder the immune response to tumor radiotherapy (RT) because of their massive accumulation in tumors after RT, resulting in immunosuppression and poor clinical prognosis. Herein, we developed an anti-PD-L1 antibody-conjugated iron oxide nanoprobe (Fe3O4-αPD-L1) to target and induce ferroptosis in MDSCs, thereby alleviating RT resistance. Overexpression of PD-L1 in MDSCs following RT enables noninvasive in vivo magnetic resonance and positron emission tomography imaging using 89Zr-labeled nanoprobes to track the movement of MDSCs and their infiltration into the tumor. After uptake by MDSCs that infiltrated the tumor, Fe3O4-αPD-L1 nanoprobes were mainly found within the lysosome and triggered the Fenton reaction, resulting in the generation of abundant reactive oxygen species. This process leads to ferroptosis of MDSCs, characterized by lipid peroxidation and mitochondrial dysfunction, and effectively reprograms the immunosuppressive environment within the tumor following RT. This study highlights a strategy for monitoring and regulating the fate of MDSCs to alleviate RT resistance and ultimately achieve improved treatment outcomes.
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Ferroptosis , Células Supresoras de Origen Mieloide , Ferroptosis/efectos de los fármacos , Células Supresoras de Origen Mieloide/inmunología , Animales , Humanos , Ratones , Antígeno B7-H1/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Neoplasias/patología , Compuestos Férricos/química , Línea Celular TumoralRESUMEN
BACKGROUND: Adding CDK4/6 inhibitor dalpiciclib to fulvestrant significantly prolonged progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer progressing after endocrine therapy. We aimed to assess the efficacy and safety of dalpiciclib plus letrozole or anastrozole in patients with hormone receptor-positive, HER2-negative advanced breast cancer who had no previous systemic therapy in the advanced setting. METHODS: DAWNA-2 is a randomised, double-blind, placebo-controlled, phase 3 trial done at 42 hospitals in China. Eligible patients were aged 18-75 years, of any menopausal status, had an ECOG performance status of 0-1, and had pathologically confirmed hormone receptor-positive, HER2-negative untreated advanced breast cancer. Patients were randomly assigned (2:1) to receive oral dalpiciclib (150 mg per day for 3 weeks, followed by 1 week off) or matching placebo. Both groups also received endocrine therapy: either 2·5 mg letrozole or 1 mg anastrozole orally once daily continuously. Randomisation was using an interactive web response system (block size of six) and stratified according to visceral metastasis, previous endocrine therapy in the adjuvant or neoadjuvant setting, and endocrine therapy partner. All investigators, patients, and the funders of the study were masked to group allocation. We present the results of the preplanned interim analyses for the primary endpoint of investigator-assessed progression-free survival, which was assessed in all randomly assigned patients who met the eligibility criteria by intention-to treat. Safety was analysed in all randomly assigned patients who received at least one dose of study treatment. The superiority boundary was calculated as a one-sided p value of 0·0076 or less. This trial is registered with ClinicalTrials.gov, NCT03966898, and is ongoing but closed to recruitment. FINDINGS: Between July 19, 2019, and Dec 25, 2020, 580 patients were screened and 456 were eligible and randomly assigned to the dalpiciclib group (n=303) or placebo group (n=153). At data cutoff (June 1, 2022), median follow-up was 21·6 months (IQR 18·3-25·9), and 103 (34%) of 303 patients in the dalpiciclib group and 83 (54%) of 153 patients in the placebo group had disease progression or died. Median progression-free survival was significantly longer in the dalpiciclib group than in the placebo group (30·6 months [95% CI 30·6-not reached] vs 18·2 months [16·5-22·5]; stratified hazard ratio 0·51 [95% CI 0·38-0·69]; one-sided log-rank p<0·0001). Adverse events of grade 3 or 4 were reported in 271 (90%) of 302 patients in the dalpiciclib group and 18 (12%) of 153 patients in the placebo group. The most common adverse events of grade 3 or 4 were neutropenia (259 [86%] in the dalpiciclib group vs none in the placebo group) and leukopenia (201 [67%] vs none). Serious adverse events were reported for 36 (12%) patients in the dalpiciclib group and ten (7%) patients in the placebo group. Two treatment-related deaths occurred, both in the dalpiciclib group (deaths from unknown causes). INTERPRETATION: Our findings suggest that dalpiciclib plus letrozole or anastrozole could be a novel standard first-line treatment for patients with hormone receptor-positive, HER2-negative advanced breast cancer, and is an alternative option to the current treatment landscape. FUNDING: Jiangsu Hengrui Pharmaceuticals and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Letrozol , Anastrozol , Resultado del Tratamiento , Supervivencia sin Enfermedad , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Método Doble CiegoRESUMEN
BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer and primary resistance to trastuzumab have a poor clinical outcome and lack good evidence to inform clinical decision. This study investigated the efficacy and safety of pyrotinib plus capecitabine in this population. METHODS: This phase 2 trial was conducted at 16 sites in China. Patients received oral pyrotinib 400 mg once daily and capecitabine 1000 mg/m2 twice a day on days 1-14 of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: Between June 2019 and September 2021, 100 patients were enrolled with a median age of 51 years (range, 24-69). All patients had been treated with trastuzumab and 21 (21.0%) patients had prior use of pertuzumab. As of August 31, 2022, the median follow-up duration was 20.1 months (range, 1.3-38.2). The median PFS was 11.8 months (95% confidence interval [CI], 8.4-15.1), which crossed the pre-specified efficacy boundary of 8.0 months. The objective response rate was 70.0% (70/100), with a median duration of response of 13.8 months (95% CI, 10.2-19.3). The disease control rate was 87.0% (87/100). The median overall survival was not reached. The most common grade ≥ 3 treatment-emergent adverse event was diarrhea (24 [24.0%]). No treatment-related deaths occurred. CONCLUSIONS: Pyrotinib plus capecitabine can be considered to be a treatment option in HER2-positive advanced breast cancer patients who have shown primary resistance to trastuzumab. Even in the era of modern anti-HER2 treatments, this clinical setting warrants more investigations to meet unmet needs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04001621. Retrospectively registered on June 28, 2019.
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Neoplasias de la Mama , Capecitabina , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Acrilamidas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/etiología , Capecitabina/uso terapéutico , Receptor ErbB-2/genética , TrastuzumabRESUMEN
BACKGROUND: Non-small cell lung cancer is a heterogeneous disease driven by extensive molecular alterations. Exosomes are small vesicles with diameters ranging from 30 to 150 nm released by various cell types and are important mediators of information transmission in tumor cells. Exosomes contain proteins, lipids, and various types of nucleic acids, including miRNAs and even DNA and RNA. MFI2 Antisense RNA 1 (MFI2-AS1) is a long noncoding RNA known to promote cell proliferation, metastasis and invasion in a variety of malignancies. METHODS: The relative expression of MFI2-AS1 in NSCLC tissues was examined using RNA fluorescence in situ hybridization (FISH) staining. Transwell migration and wound healing assays were used to analyze cell migration and invasion abilities. Tube formation is used to assess angiogenic capacity. CCK8 was used to assess cell proliferation ability. RNA immunoprecipitation (RIP) experiments confirmed that MFI2-AS1 acts as a competing endogenous RNA (ceRNA) for miR-107. Dual-luciferase reporter assays were used to identify potential binding between MFI2-miRNA and target mRNA. In vivo experiments were performed by injecting exosomes into subcutaneous tumors to establish animal models. RESULT: Exosomal MFI2-AS1 increases NFAT5 expression by sponging miR-107, which in turn activates the PI3K/AKT pathway. We found that the MFI2-AS1/miR-107/NFAT5 axis plays an important role in exosome-mediated NSCLC progression, is involved in pre-metastatic niche formation, and can be used as a blood-based biomarker for NSCLC metastasis. CONCLUSION: We demonstrate that MFI2-AS1 is upregulated in exosomes secreted by metastatic NSCLC cells and can be transferred to HUVECs, promoting angiogenesis and migration.
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OBJECTIVES: During the development of systemic sclerosis (SSc), endothelial-mesenchymal transition (EndoMT) has been shown to be one of the mechanisms leading to pulmonary fibrosis. However, the correlation between hypoxia and EndoMT was mostly unknown. METHODS: R software was used to analyse differentially expressed genes (DEGs) in vascular endothelial cells under hypoxic conditions, and fibroblasts derived from SSc-related pulmonary fibrotic tissues, respectively. Using a web-based online Venn diagram tool, we analysed overlapping genes of DEGs between endothelial cells and fibroblasts. Finally, the protein-protein interaction network of EndoMT hub genes were constructed using the STRING database. The hub genes were knockdown by transfection of siRNAs in the hypoxia model of HULEC-5a cells constructed by liquid paraffin closure and then used to detect the effect on EndoMT-related biomarkers by western blot. RESULTS: In this study, we found that INHBA, DUSP1, NOX4, PLOD2, BHLHE40 were upregulated in SSc fibroblasts and hypoxic-treated endothelial cells, while VCAM1, RND3, CCL2, and TXNIP were downregulated. In the hypoxia model of HULEC-5a cells, the expression of these 9 hub genes was confirmed by western blot. In addition, through Spearman's correlation analysis and Western blot, we confirmed that these hub genes were closely related to the EndoMT-related markers. The mechanisms of these hypoxia-induced EndoMT hub genes may be related to TGF-ß, Notch, Wnt, NF-κ B, TNF and mTOR signalling pathways. CONCLUSIONS: Our study provides new insights into the occurrence and development of SSc-related pulmonary fibrosis resulting from hypoxia-induced EndoMT.
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Fibrosis Pulmonar , Esclerodermia Sistémica , Humanos , Células Endoteliales/metabolismo , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Transición Epitelial-Mesenquimal/genética , Esclerodermia Sistémica/patología , Hipoxia/genética , Hipoxia/metabolismo , Hipoxia/patologíaRESUMEN
In the electronic warfare environment, the performance of ground-based radar target search is seriously degraded due to the existence of smeared spectrum (SMSP) jamming. SMSP jamming is generated by the self-defense jammer on the platform, playing an important role in electronic warfare, making traditional radars based on linear frequency modulation (LFM) waveforms face great challenges in searching for targets. To solve this problem, an SMSP mainlobe jamming suppression method based on a frequency diverse array (FDA) multiple-input multiple-output (MIMO) radar is proposed. The proposed method first uses the maximum entropy algorithm to estimate the target angle and eliminate the interference signals from the sidelobe. Then, the range-angle dependence of the FDA-MIMO radar signal is utilized, and the blind source separation (BSS) algorithm is used to separate the mainlobe interference signal and the target signal, avoiding the impact of mainlobe interference on target search. The simulation verifies that the target echo signal can be effectively separated, the similarity coefficient can reach more than 90% and the detection probability of the radar is significantly enhanced at a low signal-to-noise ratio.
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Algoritmos , Radar , Simulación por Computador , Electrónica , EntropíaRESUMEN
New pollutant pharmaceutical and personal care products (PPCPs), especially antiviral drugs, have received increasing attention not only due to their increase in usage after the outbreak of COVID-19 epidemics but also due to their adverse impacts on water ecological environment. Electro-Fenton technology is an effective method to remove PPCPs from water. Novel particle electrodes (MMT/rGO/Fe3O4) were synthesized by depositing Fe3O4 nanoparticles on reduced graphene oxide modified montmorillonite and acted as catalysts to promote oxidation performance in a three-dimensional Electro-Fenton (3D-EF) system. The electrodes combined the catalytic property of Fe3O4, hydrophilicity of montmorillonite and electrical conductivity of graphene oxides, and applied for the degradation of Acyclovir (ACV) with high efficiency and ease of operation. At optimal condition, the degradation rate of ACV reached 100% within 120 min, and the applicable pH range could be 3 to 11 in the 3D-EF system. The stability and reusability of MMT/rGO/Fe3O4 particle electrodes were also studied, the removal rate of ACV remained at 92% after 10 cycles, which was just slightly lower than that of the first cycle. Potential degradation mechanisms were also proposed by methanol quenching tests and FT-ICR-MS.
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BACKGROUND: Cuproptosis, a newly discovered mode of cell death, has been less studied in hepatocellular carcinoma (HCC). Exploring the molecular characteristics of different subtypes of HCC based on cuproptosis-related genes (CRGs) is meaningful to HCC. In addition, immunotherapy plays a pivotal role in treating HCC. Exploring the sensitivity of immunotherapy and building predictive models are critical for HCC. METHODS: The 357 HCC samples from the TCGA database were classified into three subtypes, Cluster 1, Cluster 2, and Cluster 3, based on the expression levels of ten CRGs genes using consensus clustering. Six machine learning algorithms were used to build models that identified the three subtypes. The molecular features of the three subtypes were analyzed and compared from some perspectives. Moreover, based on the differentially expressed genes (DEGs) between Cluster 1 and Cluster 3, a prognostic scoring model was constructed using LASSO regression and Cox regression, and the scoring model was used to predict the efficacy of immunotherapy in the IMvigor210 cohort. RESULTS: Cluster 3 had the worst overall survival compared to Cluster 1 and Cluster 2 (P = 0.0048). The AUC of the Catboost model used to identify Cluster 3 was 0.959. Cluster 3 was significantly different from the other two subtypes in gene mutation, tumor mutation burden, tumor microenvironment, the expression of immune checkpoint inhibitor genes and N6-methyladenosine regulatory genes, and the sensitivity to sorafenib. We believe Cluster 3 is more sensitive to immunotherapy from the above analysis results. Therefore, based on the DEGs between Cluster 1 and Cluster 3, we obtained a 7-gene scoring prognostic model, which achieved meaningful results in predicting immunotherapy efficacy in the IMvigor210 cohort (P = 0.013). CONCLUSIONS: Our study provides new ideas for molecular characterization and immunotherapy of HCC from machine learning and bioinformatics. Moreover, we successfully constructed a prognostic model of immunotherapy.
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Apoptosis , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Inmunoterapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Pronóstico , Microambiente Tumoral , CobreRESUMEN
The immune checkpoint programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) are biologically important immunosuppressive molecules, and the PD-L1/PD-1-mediated signalling pathway is currently considered one of the main mechanisms of tumour escape immune surveillance. PD-L1 is highly expressed on the cytomembrane of tumour cell and binds to PD-1 receptor of activated T cells. This interaction activates PD-L1/PD-1 downstream signal transduction, inhibiting T cells anti-tumour activity. Therefore, inhibitors of PD-L1/PD-1 activation, showing significant efficacy in some types of tumours, have been widely approved in clinical tumour therapy. Recent research on PD-L1/PD-1 signalling pathway regulation has shown post-translational modifications (PTMs) form of PD-L1 or PD-1, including glycosylation, ubiquitination, phosphorylation, and acetylation, which may play an important role in PD-L1/PD-1 signalling pathway regulation and anti-tumour function of T cells. In this review, we focused on PTMs of PD-L1/PD-1 research and potential applications in tumour immunotherapy.
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Antígeno B7-H1 , Neoplasias , Humanos , Receptor de Muerte Celular Programada 1 , Inmunoterapia , Procesamiento Proteico-PostraduccionalRESUMEN
As an important theoretical concept, temporal boundaries provide researchers with new insights for tailoring electromagnetic waves in the time domain. Because a temporal boundary breaks the time translation symmetry, a source is necessary to satisfy energy conservation. In this Letter, we quantify the relationship between refractive index contrast and the required energy exchange. More specifically, to realize a temporal boundary with a large refractive index contrast, a correspondingly large and abrupt energy exchange is required. Considering this practical difficulty, we propose to mimic a large-contrast temporal boundary by staggering a series of small-contrast temporal boundaries separated by carefully designed durations. In this way, the process of energy input/output is distributed over an elongated duration, but their effect can still be cumulative. This process is analogous to a multi-resonant system with a periodic energy input. Based on this design principle, we discuss several scenarios for different temporal profiles of refractive index and their corresponding energy requirements.
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Most bacteriophages are tailed bacteriophages with an isometric or a prolate head attached to a long contractile, long non-contractile, or short non-contractile tail. The tail is a complex machine that plays a central role in host cell recognition and attachment, cell wall and membrane penetration, and viral genome ejection. The mechanisms involved in the penetration of the inner host cell membrane by bacteriophage tails are not well understood. Here we describe structural and functional studies of the bacteriophage Ï29 tail knob protein gene product 9 (gp9). The 2.0 Å crystal structure of gp9 shows that six gp9 molecules form a hexameric tube structure with six flexible hydrophobic loops blocking one end of the tube before DNA ejection. Sequence and structural analyses suggest that the loops in the tube could be membrane active. Further biochemical assays and electron microscopy structural analyses show that the six hydrophobic loops in the tube exit upon DNA ejection and form a channel that spans the lipid bilayer of the membrane and allows the release of the bacteriophage genomic DNA, suggesting that cell membrane penetration involves a pore-forming mechanism similar to that of certain non-enveloped eukaryotic viruses. A search of other phage tail proteins identified similar hydrophobic loops, which indicates that a common mechanism might be used for membrane penetration by prokaryotic viruses. These findings suggest that although prokaryotic and eukaryotic viruses use apparently very different mechanisms for infection, they have evolved similar mechanisms for breaching the cell membrane.
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Fagos de Bacillus/química , Fagos de Bacillus/metabolismo , Membrana Celular/metabolismo , Proteínas de la Cola de los Virus/química , Proteínas de la Cola de los Virus/metabolismo , Secuencia de Aminoácidos , Fagos de Bacillus/genética , Fagos de Bacillus/ultraestructura , Microscopía por Crioelectrón , Cristalografía por Rayos X , ADN Viral/metabolismo , Genoma Viral/fisiología , Proteínas del Virus de la Inmunodeficiencia Humana/química , Interacciones Hidrofóbicas e Hidrofílicas , Membrana Dobles de Lípidos/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Porosidad , Estructura Cuaternaria de Proteína , Proteínas de la Cola de los Virus/ultraestructura , Virión/genética , Virión/ultraestructuraRESUMEN
BACKGROUND: Surfactant protein D (SP-D) is a critical component of the innate immune system intrinsically linked to energy metabolism. However, the relationship of SP-D gene polymorphisms and gestational diabetes mellitus (GDM) remains unclear. In this study, we analyzed SP-D gene polymorphisms in GDM patients and nondiabetic controls and then determined the association of SP-D gene polymorphisms with GDM. METHODS: We examined a common genetic polymorphism located in the SP-D coding region (rs721917, Met31Thr) in GDM patients (n = 147) and healthy pregnant controls (n = 97) by using a cleaved amplification polymorphism sequence-tagged sites (PCR-RFLP) technique. The level of SP-D protein in the serum of GDM patients and nondiabetic controls was determined by ELISA. The gene and allele frequencies of SP-D and their association with GDM as well as SP-D protein levels were analyzed and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: We found that there was a significant association of the SP-D polymorphism (rs721917) with GDM. The SP-D (T/T) genotype was found in 11.6% and 21.6% of GDM patients and matched healthy controls, respectively (odds ratio, 0.473; 95% confidence interval, 0.235-0.952; P = 0.033), indicating that women with the (T/T) genotype had a lower prevalence of GDM (OR = 0.473). Women with the T/C genotype showed an increased risk of GDM (odds ratio, 2.440; 95% confidence interval, 1.162-5.123; P = 0.017). We did not observe corrections between glucose homeostasis markers and SP-D genotypes in women with GDM. Furthermore, serum SP-D levels were higher in GDM patients than in matched healthy controls. CONCLUSIONS: This study found the first evidence that an SP-D gene polymorphism (rs721917) was associated with GDM, which may provide the basis for further study on how SP-D plays a regulatory role in GDM.
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Diabetes Gestacional/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteína D Asociada a Surfactante Pulmonar/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Diabetes Gestacional/sangre , Femenino , Humanos , Embarazo , Proteína D Asociada a Surfactante Pulmonar/sangre , Adulto JovenRESUMEN
The filamentous bacteriophage IKe infects Escherichia coli cells bearing IncN pili. We report the cryo-electron microscopy structure of the micrometer-long IKe viral particle at a resolution of 3.4 Å. The major coat protein [protein 8 (p8)] consists of 47 residues that fold into a â¼68-Å-long helix. An atomic model of the coat protein was built. Five p8 helices in a horizontal layer form a pentamer, and symmetrically neighboring p8 layers form a right-handed helical cylinder having a rise per pentamer of 16.77 Å and a twist of 38.52°. The inner surface of the capsid cylinder is positively charged and has direct interactions with the encapsulated circular single-stranded DNA genome, which has an electron density consistent with an unusual left-handed helix structure. Similar to capsid structures of other filamentous viruses, strong capsid packing in the IKe particle is maintained by hydrophobic residues. Despite having a different length and large sequence differences from other filamentous phages, π-π interactions were found between Tyr9 of one p8 and Trp29 of a neighboring p8 in IKe that are similar to interactions observed in phage M13, suggesting that, despite sequence divergence, overall structural features are maintained.
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Bacteriófago IKe/ultraestructura , Bacteriófago IKe/genética , Bacteriófago IKe/fisiología , Proteínas de la Cápside/genética , Proteínas de la Cápside/ultraestructura , Microscopía por Crioelectrón , ADN de Cadena Simple/genética , ADN de Cadena Simple/ultraestructura , Modelos Moleculares , Alineación de Secuencia , Ensamble de VirusRESUMEN
Phytoremediation technology based on living green plants would clean up water pollution. Through hydroponic experiment, the effects of different concentration of 2, 4-dinitrophenol (2, 4-DNP) on the photosynthetic and chlorophyll fluorescence parameters of Salix babylonica, and the absorption and purification effect of S. babylonica on 2, 4-DNP were measured to explore the tolerance of S. babylonica to 2, 4-DNP and the feasibility to purify dinitrophenol waste water by it. The biomass, actual photochemical efficiency (PSII), net photosynthetic rate (Pn), photochemical quenching coefficient (qP), stomatal conductance (Gs), transpiration rate (Tr), maximum photochemical efficiency (Fv/Fm) and chlorophyll content of the S. babylonica showed downward trend with the increasing exposure concentrations of 2,4-DNP, but the intercellular CO2 concentration (Ci) appeared upward trend. Non-photochemical quenching coefficient (NPQ) increased at 5 mg L-1, then declined with the increase concentrations of 2, 4-DNP. In addition, the percent removal of 2, 4-DNP in 20 mg L-1 waste water was 91.4%. In conclusion, 2, 4-DNP significantly inhibits Pn of S. babylonica and the reduction of Pn was caused by decreasing Gs, carboxylation efficiency and chlorophyll content. When the concentration of 2, 4-DNP is not more than 20 mg L-1, S. babylonica can remove 2, 4-DNP efficiently.
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Salix , Aguas Residuales , Biodegradación Ambiental , Clorofila/análisis , Clorofila/farmacología , Dinitrofenoles/farmacología , Fotosíntesis , Hojas de la Planta/químicaRESUMEN
Frequency diverse array (FDA)-multiple-input multiple-output (MIMO) radars can generate a range-angle two-dimensional transmit steering vector (SV), which is capable of suppressing mainbeam deceptive jamming in the transmit-receive frequency domain by utilizing additional degrees of freedom (DOFs) in the range dimension. However, when there are target SV mismatch, covariance matrix estimation error and target contamination, the jamming suppression performance degrades severely. In this paper, a robust adaptive beamforming algorithm for anti-jammer application based on covariance matrix reconstruction is proposed in FDA-MIMO radar. In this method, the residual noise is further determined by using the spatial power spectrum estimation approach, which results in improved estimation accuracy of the signal covariance matrix and the desired target SV. The jamming SV is obtained from vectors in the intersection of two subspaces (namely, the signal-jamming subspace derived from the sample covariance matrix (SCM) and the jamming subspace generated from the jamming covariance matrix) by an alternating projection algorithm. Furthermore, the jamming power is obtained by exploiting the orthogonality between the different SVs. With the obtained parameters of target and jamming, the optimal adaptive beamformer weight vector is calculated. Simulation results demonstrate that the proposed algorithm can cope with the mainbeam deceptive jamming suppression under various model mismatches and has excellent performance over a wide range of signal-to-noise ratios (SNRs).
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While many technologies rely on multilayer heterostructures, most of the studies on chemical functionalization have been limited to monolayer graphene. In order to use functionalization in multilayer systems, we must first understand the interlayer interactions between functionalized and nonfunctionalized (intact) layers and how to selectively functionalize one layer at a time. Here, we demonstrate a method to fabricate single- or double-sided fluorinated bilayer graphene (FBG) by tailoring substrate interactions. Both the top and bottom surfaces of bilayer graphene on the rough silicon dioxide (SiO2) are fluorinated; meanwhile, only the top surface of graphene on hexagonal boron nitride (hBN) is fluorinated. The functionalization type affects electronic properties; double-sided FBG on SiO2 is insulating, whereas single-sided FBG on hBN maintains conducting, showing that the intact bottom layer becomes electrically decoupled from the fluorinated top insulating layer. Our results define a straightforward method to selectively functionalize the top and bottom surfaces of bilayer graphene.
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Soil organic carbon (SOC), total nitrogen (TN) and total phosphorus (TP) are important indicators reflecting soil quality, and they can be used to effectively evaluate the effect of soil remediation. Many studies have evaluated the content of SOC, TN and TP in different ecosystems. However, after constructing protected forests for ecological restoration in the ecologically fragile coastal zone, the spatial distribution and influencing mechanism of SOC, TN and TP content is still uncertain. In this study, the spatial heterogeneity and influencing factors of SOC, TN and TP in surface (0-20 cm) soil were analyzed by traditional analysis and geostatistics. A total of 39 soil samples were collected under the coastal zone protected forest types including Quercus acutissima Carruth (QAC), Pinus thunbergii Parl (PTP), mixed PTP and QAC (QP) and Castanea mollissima BL (CMB) in the coastal zone protected forests in northern China. The results show that SOC, TN and TP content were defined as moderate variation, and they also show significant changes under different protected forest types (P < 0.05). The semivariance results indicate that SOC, TN and TP all exhibited strong spatial dependence class, with Range of 224 m, 229 m and 282 m respectively, which were more than the sampling scale of 200 m. The spatial prediction results showed that SOC, TN and TP content all appear in large areas of extremely low value in CMB, and its cross validation results showed that using vegetation and terrain factors as covariates in the spatial prediction of SOC, TN and TP can improve the prediction accuracy. The results of correlation analysis showed that the influencing factor for SOC and TN, and TP were NDVI and topographical changes, respectively. In general, vegetation and terrain factors as auxiliary factors can improved the accuracy of soil C-N-P spatial distribution prediction after afforestation in coastal zone.