Molecular characterization, structural analysis and determination of host range of a novel bacteriophage LSB-1

<p>Abstract</p> <p>Background</p> <p>Bacteriophages (phages) are widespread in the environment and play a crucial role in the evolution of their bacterial hosts and the emergence of new pathogens.</p> <p>Results</p> <p>LSB-1, a reference coliphage strain, was classified as a member of the Podoviridae family with a cystic form (50 ± 5 nm diameter) and short tail (60 ± 5 nm long). The double stranded DNA was about 30 kilobase pairs in length. We identified its host range and determined the gp17 sequences and protein structure using shotgun analysis and bioinformatics technology.</p> <p>Conclusions</p> <p>Coliphage LSB-1 possesses a tailspike protein with endosialidase activity which is probably responsible for its specific enteroinvasive <it>E.coli </it>host range within the laboratory.</p

Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of H3K27 Deacetylation and Methylation

Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of brown adipocyte thermogenic program. HDAC1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing HDAC1 profoundly blocks, whereas deleting HDAC1 significantly enhances β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes. β-adrenergic activation in brown adipocytes results in a dissociation of HDAC1 from promoters of BAT-specific genes, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α), leading to increased acetylation of histone H3 lysine 27 (H3K27), an epigenetic mark of gene activation. This is followed by dissociation of the polycomb repressive complexes, including the H3K27 methyltransferase enhancer of zeste homologue (EZH2), suppressor of zeste 12 (SUZ12), and ring finger protein 2 (RNF2) from, and concomitant recruitment of H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) to UCP1 and PGC1α promoters, leading to decreased H3K27 trimethylation, a histone transcriptional repression mark. Thus, HDAC1 negatively regulates brown adipocyte thermogenic program, and inhibiting HDAC1 promotes BAT-specific gene expression through a coordinated control of increased acetylation and decreased methylation of H3K27, thereby switching transcriptional repressive state to active state at the promoters of UCP1 and PGC1α. Targeting HDAC1 may be beneficial in prevention and treatment of obesity by enhancing BAT thermogenesis

Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of H3K27 Deacetylation and Methylation

Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of brown adipocyte thermogenic program. HDAC1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing HDAC1 profoundly blocks, whereas deleting HDAC1 significantly enhances β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes. β-adrenergic activation in brown adipocytes results in a dissociation of HDAC1 from promoters of BAT-specific genes, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α), leading to increased acetylation of histone H3 lysine 27 (H3K27), an epigenetic mark of gene activation. This is followed by dissociation of the polycomb repressive complexes, including the H3K27 methyltransferase enhancer of zeste homologue (EZH2), suppressor of zeste 12 (SUZ12), and ring finger protein 2 (RNF2) from, and concomitant recruitment of H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) to UCP1 and PGC1α promoters, leading to decreased H3K27 trimethylation, a histone transcriptional repression mark. Thus, HDAC1 negatively regulates brown adipocyte thermogenic program, and inhibiting HDAC1 promotes BAT-specific gene expression through a coordinated control of increased acetylation and decreased methylation of H3K27, thereby switching transcriptional repressive state to active state at the promoters of UCP1 and PGC1α. Targeting HDAC1 may be beneficial in prevention and treatment of obesity by enhancing BAT thermogenesis

Effects of lncRNA PKD2-2-3 on cell proliferation, clone formation, migration, and invasion of lung adenocarcinoma

Background and purpose: Long non-coding RNA (lncRNA) is abnormally expressed in lung adenocarcinoma patients, and closely related to tumor occurrence, development and chemotherapy resistance. In this study, we mainly investigated the biological function of lncRNA PKD2-2-3 and verified its effect on the proliferation, colony formation, migration and invasion in lung adenocarcinoma. Methods: Three pairs of lung adenocarcinoma tissues and adjacent tissues were analyzed based on expression profiling Affymetrix® GeneChip Human Transcriptome Array 2.0 (HTA2.0), and we focused on lncRNA PKD2-2-3 that showed most significant difference between lung adenocarcinoma issues and adjacent tissues. Besides, we found the upregulated expression of lncRNA PKD2-2-3 in lung adenocarcinoma tissues and suggested the relation of lncRNA PKD2-2-3 expression with prognosis by using GSE19188 and GSE30219 data in Gene Expression Omnibus (GEO) database. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression of lncRNA PKD2-2-3 in cell lines including HBE, A549 and PC9. After using siRNAs to decrease the expression of lncRNA PKD2-2-3 in A549 and PC9, we detected cell proliferation and colony formation by cell counting kit-8 (CCK-8) assay and colony formation assay. Effects of lncRNA PKD2-2-3 on migration and invasion in lung adenocarcinoma cells were detected by wound-healing assay and transwell assay, respectively. Moreover, we detected expression levels of E-cadherin and N-cadherin that were epithelial-mesenchymal transition (EMT) related genes by Western blot. The effect of lncRNA PKD2-2-3 on the formation and growth of lung adenocarcinoma in vivo was verified by subcutaneous transplantation tumor model. Results: LncRNA PKD2-2-3 was highly expressed in lung adenocarcinoma tissue, and was positively associated with poor prognosis of lung adenocarcinoma patients. Compared with human bronchial epithelial cells (HBE), lncRNA PKD2-2-3 was overexpressed in A549 and PC9. The proliferation, colony formation, migration and invasion of lung adenocarcinoma cells were significantly inhibited when decreasing the expression level of lncRNA PKD2-2-3. Western blot also showed that the expression level of E-cadherin was increased, while the level of N-cadherin was decreased after lncRNA PKD2-2-3 knockdown. Subcutaneous tumor transplantation experiments showed that lncRNA PKD2-2-3 knockdown inhibited the growth of lung adenocarcinoma in vivo. Conclusion: LncRNA PKD2-2-3 expression was upregulated in lung adenocarcinoma tissues, and it was associated with poor prognosis of lung adenocarcinoma patients. Overexpression of lncRNA PKD2-2-3 promoted the proliferation, colony formation, migration and invasion of lung adenocarcinoma cells. LncRNA PKD2-2-3 level was closely related to EMT process in lung adenocarcinoma in vitro and in vivo

The influence of employees' perception of over-qualification on career compromise: Mediated by role conflict and sense of relative deprivation

In the external environment with the increasing level of education, there is a general phenomenon of excess qualification in the employment market. This research discusses employee career compromise from the perspective of employee over-qualification based on resource conservation theory and self-regulation theory. Combined with the survey data, a structural equation model (SEM) is constructed, and the mediation effect of relative deprivation and role conflict is analyzed according to the causal mediation model. The research find that employees' perception of over-qualification has three ways to affect employees' career compromise. First, employees' perception of over-qualification has a significant positive impact on their career compromise behavior through employees' emotions and self-cognition. Second, role conflict plays a partial intermediary role between the perception of over-qualification and career compromise by positively affecting career compromise behavior. Third, the sense of relative deprivation plays a partial intermediary role between the perception of over-qualification and career compromise by negatively affecting career compromise behavior. According to the research conclusions, the following suggestions are put forward. Enterprises need to establish a scientific employment mechanism to achieve talent-post matching and fundamentally reduce the phenomenon of over-qualifications. The company should pay attention to employee training, actively guide employees' career planning, instruct employees to correctly understand the sense of over-qualification and play a positive role in guiding employees' career planning

Discrimination of Nasopharyngeal Carcinoma from Noncancerous Ex Vivo Tissue Using Reflectance Spectroscopy

Reflectance spectroscopy is a low-cost, nondestructive, and noninvasive method for detection of neoplastic lesions of mucosal tissue. This study aims to evaluate the capability of reflectance spectroscopy system under white light (400-700 nm) with a multivariate statistical analysis for distinguishing nasopharyngeal carcinoma (NPC) from nasopharyngeal benign ex vivo tissues. High quality reflectance spectra were acquired from nasopharyngeal ex vivo tissues belonging to 18 noncancerous and 19 cancerous subjects, and the combination of principal component analysis-linear discriminant analysis (PCA-LDA) along with leave-onespectrum-out cross-validation (LOOCV) diagnostic algorithm was subsequently employed to classify different types of tissue group, achieving a diagnostic sensitivity of 73.7% and a specificity of 72.2%. Furthermore, in order to distinguish NPC from nasopharyngeal benign ex vivo tissues based on reflectance spectra simply, spectral intensity ratios of oxyhemoglobin ( 540/ 576) were used as an indicator of the carcinogenesis associated transformation in the hemoglobin oxygenation. This tentative work demonstrated the potential of reflectance spectroscopy for NPC detection using ex vivo tissue and has significant experimental and clinical value for further in vivo NPC detection in the future

Low Cost Industrial Production of Coagulation Factor IX Bioencapsulated in Lettuce Cells for Oral Tolerance Induction in Hemophilia B

Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (~1mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ~2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP+ regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ~870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft2 per annum yielding 24,000–36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs

Photoluminescence properties of BaxSryLi zSiO4:Ce3+, Mn2+ phosphors for NUV-LED lighting

Conference Name:2011 International Symposium on Advanced Packaging Materials, APM 2011. Conference Address: Xiamen, China. Time:October 25, 2011 - October 28, 2011.A series of Ce3+, Mn2+ codoped BaxSr yLizSiO4:Ce3+, Mn2+ phosphors were synthesized by partially liquid-phase method. The effects of Ba/Sr ratio, Ce/Mn ratio and lithium content on the emission spectra of the BaxSryLizSiO4:Ce3+, Mn2+ (BSLS:Ce, Mn) phosphors were investigated in details, which showed blue emission around 410nm wavelength and red emission at about 620nm wavelength, respectively. With the increasing of Sr/Ba ratio, the color of BSLS:Ce, Mn was changed from orange to red. However, the intensity of blue emission was reduced and red emission was enhanced with an incensement of Mn/Ce ratio. The strongest intensity of emission for the phosphor was obtained at Li content of 15 mol%. ? 2011 IEEE

Mixing state and particle hygroscopicity of organic-dominated aerosols over the Pearl River Delta region in China

Simultaneous measurements of aerosol hygroscopicity and particle-phase chemical composition were performed at a suburban site over the Pearl River Delta region in the late summer of 2016 using a self-assembled hygroscopic tandem differential mobility analyzer (HTDMA) and an Aerodyne quadruple aerosol chemical speciation monitor (ACSM), respectively. The hygroscopic growth factor (HGF) of the Aitken mode (30 nm, 60 nm) and accumulation mode (100 nm, 145 nm) particles were obtained under 90% relative humidity (RH). An external mixture was observed for particles of every size during this study, with a dominant mode of more-hygroscopic (MH) particles, as aged aerosols dominated due to the anthropogenic influence. The HGF of lesshygroscopic (LH) mode particles increased, while their number fractions decreased during the daytime due to a reduced degree of external mixing that probably resulted from the condensation of gaseous species. These LH mode particles in the early morning or late afternoon could be possibly dominated by carbonaceous material emitted from local automobile exhaust during rush hours. During polluted days with air masses flowing mainly from the coastal areas, the chemical composition of aerosols had a clear diurnal variation and a strong correlation with the mean HGF. Closure analysis was carried out between the HTDMA-measured HGF and the ACSM-derived hygroscopicity using various approximations for the hygroscopic growth factor of organic compounds (HGF(org)). Considering the assumptions regarding the differences in the mass fraction of each component between PM1 and 145 nm particles, the hygroscopicity-composition closure was achieved using an HGF(org) of 1.26 for the organic material in the 145 nm particles and a simple linear relationship between the HGForg and the oxidation level inferred from the O : C ratio of the organic material was suggested. Compared with the results from other environments, HGF(org) obtained from our measurements appeared to be less sensitive to the variation of its oxidation level, which is, however, similar to the observations in the urban atmosphere of other megacities in China. This finding suggests that the anthropogenic precursors or the photooxidation mechanisms might differ significantly between the suburban and urban atmosphere in China and those in other background environments. This may lead to different characteristics of the oxidation products in secondary organic aerosols (SOA) and therefore to a different relationship between the HGF(org) and its O : C ratio.Peer reviewe

Development of China’s first space-borne aerosol-cloud high-spectral-resolution lidar: retrieval algorithm and airborne demonstration

Aerosols and clouds greatly affect the Earth’s radiation budget and global climate. Light detection and ranging (lidar) has been recognized as a promising active remote sensing technique for the vertical observations of aerosols and clouds. China launched its first space-borne aerosol-cloud high-spectral-resolution lidar (ACHSRL) on April 16, 2022, which is capable for high accuracy profiling of aerosols and clouds around the globe. This study presents a retrieval algorithm for aerosol and cloud optical properties from ACHSRL which were compared with the end-to-end Monte-Carlo simulations and validated with the data from an airborne flight with the ACHSRL prototype (A2P) instrument. Using imaging denoising, threshold discrimination, and iterative reconstruction methods, this algorithm was developed for calibration, feature detection, and extinction coefficient (EC) retrievals. The simulation results show that 95.4% of the backscatter coefficient (BSC) have an error less than 12% while 95.4% of EC have an error less than 24%. Cirrus and marine and urban aerosols were identified based on the airborne measurements over different surface types. Then, comparisons were made with U.S. Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) profiles, Moderate-resolution Imaging Spectroradiometer (MODIS), and the ground-based sun photometers. High correlations (R > 0.79) were found between BSC (EC) profiles of A2P and CALIOP over forest and town cover, while the correlation coefficients are 0.57 for BSC and 0.58 for EC over ocean cover; the aerosol optical depth retrievals have correlation coefficient of 0.71 with MODIS data and show spatial variations consistent with those from the sun photometers. The algorithm developed for ACHSRL in this study can be directly employed for future space-borne high-spectral-resolution lidar (HSRL) and its data products will also supplement CALIOP data coverage for global observations of aerosol and cloud properties