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.

摘要： Building scientific arguments is a central ability for all scientists regardless of their specific domain. In organic chemistry, building arguments is a necessary skill to estimate reaction processes in consideration of the reactivities of reaction centres or the chemical and physical properties. Moreover, building arguments for multiple reaction pathways might help students overcome the tendency toward one-reason decision-making and offer them an authentic perspective on organic processes. Reasoning about multiple alternative organic reaction pathways requires students to build arguments and then judge and weigh the plausibility of these pathways. However, students often struggle to build strong arguments and use scientific principles appropriately to justify their claims. In the present study, the argumentation patterns of 29 chemistry majors students were analysed using a simplified version of Toulmin's argumentation model (claim-evidence-reasoning). The students solved various tasks related to alternative reaction pathways of a substitution reaction. They supported their claims with evidence and justified the evidence through reasoning. We investigated (a) the extent to which the students use evidence and reasoning in their argumentation (referred to as their argumentation approach), (b) how students with different argumentation approaches rationalised changes in their initial claims, and (c) how students used reasoning to justify their arguments. The results indicate that students need further support to appropriately use evidence and reasoning and to apply conceptual knowledge to build well-grounded arguments.

关键词： 4-exo-dig   allenes   cascade reactions   cyclocarbopalladation   cyclooctatrienes  

摘要： The 4-exo-dig cyclocarbopalladation of vinyl bromides substituted with a triple or double bond resulted in impressive cascade reactions leading to different compounds under Suzuki cross-coupling conditions upon a slight modification of the starting material. When the starting compound carries a triple bond, a single cascade occurs providing a structure containing an allene, a tetrasubstituted cyclopropane, and a cyclobutene with complete stereoselectivity. When the related starting material possessing a double bond is reacted under the same conditions in the presence of various vinyl boronic esters or acids, an efficient 8 pi-electrocyclization provides tricyclic systems comprised of a cyclobutene unit, as well as a cyclooctatriene. Five carbons of the latter can be selectively decorated with different substituents depending on the choice of the starting material and the boronic coupling partner.

关键词： Biogas   Food waste   Pruning residues   Sewage   Bioelectricity   Waste-to-energy  

摘要： Decentralized power plants fueled with biogas from organic waste are a keystone for large waste producers responsible for their waste management to reduce the impact of waste generation and poor management, especially in the urban centers, alongside bioenergy and other value-added products generation. This work presents an assessment framework for the characterization quantification and assessment of the biogas potential using theoretical and lab-scale methodologies to evaluate the technical and economic bioelectricity potential from biogas using the organic residues and effluents produced in the main USP campus. The yearly costs to transport and dispose of these residues are around US$ 3,253,716.25, and the electricity consumption is about 8.6 million US$/y. As a large generator, USP is responsible for its residue management, and reduce its generation by the local use to produce bioelectricity is a feasible option. The results show a biogas potential up to 2,363,405.15 m(3), allowing for a bioelectricity generation of up to 4454 MWh/y. A potential to produce 3081.131 tones of dry biofertilizer was also estimated. The wasted resource could currently supply up to 5.6% of the Campus's electricity demand, with an investment of around US$ 1.5 million and a payback range between 3.64 and 7.5 years. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： Co-combustion of coal and biomass   Ilmenite   Fluidised bed combustion   Agglomeration   Combustion performance  

摘要： Co -firing coal and biomass has the potential to reduce GHG emissions. However, high levels of alkali and alkaline metals in biomass ash can bring additional issues to the operation of coal-fired boilers. This study investigates the effects of ilmenite as the bed material on CO and NOx emissions and combustion efficiency of a coal and biomass blend, and the agglomeration tendency of the bed material with a pilot scale (30 kWth) bubbling fluidised bed combustor. The experiments were carried out at 900 degrees C using a bituminous coal blended with wheat straw pellets at 40 wt% as the fuel and silica sand as the baseline bed material. Samples of agglomerates collected from the combustor and cyclone ash were characterised by SEM-EDS, XRD, and XRF. The results revealed that ilmenite could reduce the level of excess air required to achieve complete combustion due to lower CO emissions and less efficiency loss compared to silica sand. However, ilmenite increased NOx emissions. Furthermore, the characterisation of the obtained agglomerates and cyclone ash showed that ilmenite could hinder the K-rich molten substance attachment to the bed material, leading to significantly smaller agglomerates and hence less tendency towards defluidisation in comparison to silica sand. (C) 2021 Elsevier Ltd. All rights reserved.