关键词： reference strain   alternative strain   Pharmacopeia   microbial characteristic   Staphylococcus aureus  

摘要： The National Culture Collection of Pathogens (NCCP) is a microbial resource bank in Korea that collects pathogen resources causing infectious disease in human and distributes them for research and education. The NCCP bank attempts to discover strains with various characteristics and specific purposes to provide diverse resources to researchers. Staphylococcus aureus American Type Culture Collection (ATCC) 6538P is used as a reference strain in the microbial assay for antibiotics in the Korean and in the United States Pharmacopoeias. We aimed to analyze domestically isolated microbial resources from the NCCP to replace the S. aureus reference strain. Staphylococcus aureus strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the VITEK-2 system and characterized by multilocus sequence typing, 16S rRNA sequencing, and antibiotic susceptibility testing. Several candidate strains had similar characteristics as the reference strain. Among them, the nucleotide sequence of the 16S rRNA region of NCCP 16830 was 100% identical to that of the reference strain;it was sensitive to six types of antibiotics and showed results most similar to the reference strain. A validity evaluation was conducted using the cylinder-plate method. NCCP 16830 presented valid results and had the same performance as ATCC 6538P;therefore, it was selected as an alternative candidate strain.

关键词： heart failure   acute   iron   quality of life  

摘要： This commentary refers to ‘The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study’, by E.A. Jankowska et al. , https://***/10.1093/eurheartj/ehab234 and the discussion piece ‘Dilemmas on diagnosis and treatment of iron deficiency in patients after an episode of acute heart failure’, by E.A. Jankowska and P. Ponikowski, https://***/10.1093/eurheartj/ehab839 .

关键词： mRNA variants   5'UTR   Coat color   Gene expression   Alternative splicing  

摘要： The Agouti gene (ASIP) is one of the most important genes for coat color determination in mammals. It has a complex structure with several promoters and alternative non-coding first exons that are transcribed into mRNAs with different 5'UTR. These mRNA isoforms regulate the temporal and spatial expression of the gene, producing diverse pigmentation patterns. Here, we studied ASIP transcriptional variants and their expression in the skin of llamas with different coat color phenotypes. We also described the ASIP locus, including promoter usage and the splicing events that originate each transcript variant. Using 5'RACE-PCR we isolated seven ASIP transcripts with alternative 5'UTR, where exons 1A, 1A', 1C, 1D, and a novel non-coding exon 1A" were identified. Additionally, new alternative spliced forms were found. The diversity of ASIP 5'UTRs is originated by a complex pattern of alternative promoter usage, multiple transcription start sites and splicing events that include exon skipping and alternative 3' splicing site selection. We found that ASIP was highly expressed in llamas with white and brown phenotypes while black animals presented very low expression. The main responsible for this difference was a fusion transcript between ASIP and NCOA6 genes, which was present in the skin of white and brown llamas but not in the black ones. The rest of ASIP transcripts presented very low expression in the skin, indicating that the main regulation point for ASIP gene expression is at the transcriptional level. Nevertheless, the characteristics of the 5'UTRs sequences suggest that alternative transcripts could be regulated differently at the protein synthesis level.

关键词： Internet of things  

摘要： The arrival of 5G will usher in an era of "Internet of Everything." Massive Internet of Things data contains great value in the dynamic analysis of alternative elements of automated packaging systems. From the perspective of the realization of personalized customization functions, this article solves the problem of dynamic analysis of alternative elements in the automated packaging system. We analyze the connection mechanism and interaction method between the cloud service system layer and the mobile terminal service layer, and carry out the corresponding software design. From the perspective of the realization of the intelligent production of the system in this paper, this topic mainly studies the information interaction mechanism and production control mechanism of the cloud service system and the manufacturing system. Based on the hardware of the manufacturing system layer, a flexible production implementation mechanism is formulated to make it the basis for the implementation of intelligent production of the system. Based on the massive data processing capabilities of the cloud service system, the information processing mechanism and the production planning decision-making mechanism are formulated for it, so as to realize the intelligent adjustment of the manufacturing system layer in the production process. For the connection scenario of IoT group paging, based on the application of NB-IoT technology in the next-generation mobile communication network, the focus of network optimization is to ensure the random access performance of IoT devices as much as possible. To this end, this paper proposes a random access optimization strategy for IoT group paging based on time slot scattering. We establish a mathematical model based on queuing theory for the connection scenario of the Io T group paging, then use the mathematical formula to derive the number of IoT devices scattered to each time slot in the initial state, thereby deriving the specific time slot scattering

关键词： Mechanisms of disease   Proteomic analysis   Life Sciences   general   Cell Biology  

摘要： Host cellular receptors play key roles in the determination of virus tropism and ***,little is known about SARS-CoV-2 host receptors with the exception of ***,ACE2 alone cannot explain the multi-organ tropism of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV,suggesting the involvement of other receptor(s).Here,we performed genomic receptor profiling to screen 5054 human membrane proteins individually for interaction with the SARS-CoV-2 capsid spike (S) *** proteins,including ACE2,ASGR1,and KREMEN1,were identified with diverse S-binding affinities and ***1 or KREMEN1 is sufficient for the entry of SARS-CoV-2 but not SARS-CoV in vitro and in ***-CoV-2 utilizes distinct ACE2/ASGR1/KREMEN1 (ASK) receptor combinations to enter different cell types,and the expression of ASK together displays a markedly stronger correlation with Virus susceptibility than that of any individual receptor at both the cell and tissue *** cocktail of ASK-related neutralizing antibodies provides the most substantial blockage of SARS-CoV-2 infection in human lung organoids when compared to individual *** study revealed an interacting host receptome of SARS-CoV-2,and identified ASGR1 and KREMEN1 as alternative functional receptors that play essential roles in ACE2-independent virus entry,providing insight into SARS-CoV-2 tropism and pathogenesis,as well as a community resource and potential therapeutic strategies for further COVID-19 investigations.

关键词： Passifloraceae   Physical and chemical descriptors   RGB   Genotypes   Regression analysis  

摘要： The present study provides an assessment of the genetic variability of different genotypes of Passiflora using physical and chemical descriptors and digital image analysis to quantify leaf, flower and fruit coloration as well as to develop and validate mathematical models for the prediction of passion fruit pulp weight without seeds by regression analysis. A total of 132 Passiflora genotypes belonging to different species were evaluated. Eleven quantitative physical and chemical descriptors were submitted to principal component and cluster analysis. The coloration was determined through RGB color space by digital images analysis. The equations were developed through multiple linear regression and cross-validation was used to validate the models. The first principal component (50.6% of total variance) was associated with fruit weight, diameter and length and peel weight, while the second (22.4%) was associated with fruit weight, fruit length, peel weight, peel thickness, soluble solids, fruit length/fruit diameter ratio and fruit length and diameter. Physical and chemical descriptors showed significant diversity among genotypes. In the cluster analysis, the genotypes BGP007 and BGP009 were most closely related, while BGP349 and BGP177 were distinct. The analysis of coloration using digital images allowed detecting greater variability in the color of leaves, flowers, fruits, and pulp. The analysis of digital images is a practical method for ascertaining the color of plant parts in the field or laboratory. The high phenotypic diversity detected in the present study can be used in passion fruit breeding programs through hybridizations. Regression analysis of physical traits revealed five models that could be used to estimate the pulp weight in two equations (13 and 15), which showed the highest R2 values and lowest RMSE and MAE. This model can be reliably adopted for estimation of the pulp weight without seeds of passion fruits (P. edulis Sims).

摘要： Covering: up to 2021 Terpenoids are a diverse group of chemicals used in a wide range of industries. Microbial terpenoid production has the potential to displace traditional manufacturing of these compounds with renewable processes, but further titre improvements are needed to reach cost competitiveness. This review discusses strategies to increase terpenoid titres in Escherichia coli with a focus on alternative metabolic pathways. Alternative pathways can lead to improved titres by providing higher orthogonality to native metabolism that redirects carbon flux, by avoiding toxic intermediates, by bypassing highly-regulated or bottleneck steps, or by being shorter and thus more efficient and easier to manipulate. The canonical 2-C-methyl-d-erythritol 4-phosphate (MEP) and mevalonate (MVA) pathways are engineered to increase titres, sometimes using homologs from different species to address bottlenecks. Further, alternative terpenoid pathways, including additional entry points into the MEP and MVA pathways, archaeal MVA pathways, and new artificial pathways provide new tools to increase titres. Prenyl diphosphate synthases elongate terpenoid chains, and alternative homologs create orthogonal pathways and increase product diversity. Alternative sources of terpenoid synthases and modifying enzymes can also be better suited for E. coli expression. Mining the growing number of bacterial genomes for new bacterial terpenoid synthases and modifying enzymes identifies enzymes that outperform eukaryotic ones and expand microbial terpenoid production diversity. Terpenoid removal from cells is also crucial in production, and so terpenoid recovery and approaches to handle end-product toxicity increase titres. Combined, these strategies are contributing to current efforts to increase microbial terpenoid production towards commercial feasibility.

关键词： PSMA   prostate cancer   glutamate-ureido-lysine   molecular imaging   PET  

摘要： Prostate-specific membrane antigen (PSMA) is highly overexpressed in most prostate cancers and is clinically visualized using PSMAspecific probes incorporating glutamate-ureido-lysine (GUL). PSMA is effectively absent from certain high-mortality, treatment-resistant subsets of prostate cancers, such as neuroendocrine prostate cancer (NEPC);however, GUL-based PSMA tracers are still reported to have the potential to identify NEPC metastatic tumors. These probes may bind unknown proteins associated with PSMA-suppressed cancers. We have identified the up-regulation of PSMA-like aminopeptidase NAALADaseL and the metabotropic glutamate receptors (mGluRs) in PSMA-suppressed prostate cancers and find that their expression levels inversely correlate with PSMA expression and are associated with GUL-based radiotracer uptake. Furthermore, we identify that NAALADaseL and mGluR expression correlates with a unique cell cycle signature. This provides an opportunity for the future study of the biology of NEPC and potential therapeutic directions. Computationally predicting that GUL-based probes bind well to these targets, we designed and synthesized a fluorescent PSMA tracer to investigate these proteins in vitro, where it shows excellent affinity for PSMA, NAALADaseL, and specific mGluRs associated with poor prognosis.

摘要： Posttranscriptional regulation has emerged as a driver for leukemia development and an avenue for therapeutic targeting. Among posttranscriptional processes, alternative polyadenylation (APA) is globally dysregulated across cancer types. However, limited studies have focused on the prevalence and role of APA in myeloid leukemia. Furthermore, it is poorly understood how altered poly(A) site usage of individual genes contributes to malignancy or whether targeting global APA patterns might alter oncogenic potential. In this study, we examined global APA dysregulation in patients with acute myeloid leukemia (AML) by performing 3' region extraction and deep sequencing (3'READS) on a subset of AML patient samples along with healthy hemato-poietic stem and progenitor cells (HSPCs) and by analyzing publicly available data from a broad AML patient cohort. We show that patient cells exhibit global 3' untranslated region (UTR) shortening and coding sequence lengthening due to differences in poly(A) site (PAS) usage. Among APA regulators, expression of FIP1L1, one of the core deavage and polyadenylation factors, correlated with the degree of APA dysregulation in our 3'READS data set. Targeting global APA FIP1L1 knockdown reversed the global trends seen in patients. Importantly, FIP1L1 knock down induced differentiation of t(8;21) cells by promoting 3'UTR lengthening and downregulation of the fusion oncoprotein AML1-ETO. In non-t(8;21) cells, FIP1L1 knockdown also promoted differentiation by attenuating mechanistic target of rapamydn complex 1 (mTORC1) signaling and reducing MYC protein levels. Our study provides mechanistic insights into the role of APA in AML pathogenesis and indicates that targeting global APA patterns can overcome the differentiation block in patients with AML.

摘要： Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy affecting adults. The NF-kappa B transcription factor family is activated by 2 main pathways, the canonical and the alternative NF-kappa B activation pathway, with different functions. The alternative NF-kappa B pathway leads to activation of the transcriptionally active RelB NF-kappa B subunit. Alternative NF-kappa B activation status and its role in DLBCL pathogenesis remain undefined. Here, we reveal a frequent activation of RelB in a large cohort of DLBCL patients and cell lines, independently of their activated B-cell-like or germinal center B-cell-like subtype. RelB activity defines a new subset of patients with DLBCL and a peculiar gene expression profile and mutational pattern. Importantly, RelB activation does not correlate with the MCD genetic subtype, enriched for activated B-cell-like tumors carrying MYD88(L265P) and CD79B mutations that cooperatively activate canonical NF-kappa B, thus indicating that current genetic tools to evaluate NF-kappa B activity in DLBCL do not provide information on the alternative NF-kappa B activation. Furthermore, the newly defined RelB-positive subgroup of patients with DLBCL exhibits a dismal outcome after immunochemotherapy. Functional studies revealed that RelB confers DLBCL cell resistance to DNA damage-induced apoptosis in response to doxorubicin, a genotoxic agent used in the front-line treatment of DLBCL. We also show that RelB positivity is associated with high expression of cellular inhibitor of apoptosis protein 2 (cIAP2). Altogether, RelB activation can be used to refine the prognostic stratification of DLBCL and may contribute to subvert the therapeutic DNA damage response in a segment of patients with DLBCL.