Background Phage therapy, reemerging as a promising approach to counter antimicrobial-resistant infections, relies on a comprehensive understanding of the specificity of individual phages. Yet the significant diversit...
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Background Phage therapy, reemerging as a promising approach to counter antimicrobial-resistant infections, relies on a comprehensive understanding of the specificity of individual phages. Yet the significant diversity within phage populations presents a considerable challenge. Currently, there is a notable lack of tools designed for large-scale characterization of phage receptor-binding proteins, which are crucial in determining the phage host *** In this study, we present SpikeHunter, a deep learning method based on the ESM-2 protein language model. With SpikeHunter, we identified 231,965 diverse phage-encoded tailspike proteins, a crucial determinant of phage specificity that targets bacterial polysaccharide receptors, across 787,566 bacterial genomes from 5 virulent, antibiotic-resistant pathogens. Notably, 86.60% (143,200) of these proteins exhibited strong associations with specific bacterial polysaccharides. We discovered that phages with identical tailspike proteins can infect different bacterial species with similar polysaccharide receptors, underscoring the pivotal role of tailspike proteins in determining host range. The specificity is mainly attributed to the protein's C-terminal domain, which strictly correlates with host specificity during domain swapping in tailspike proteins. Importantly, our dataset-driven predictions of phage-host specificity closely match the phage-host pairs observed in real-world phage therapy cases we *** Our research provides a rich resource, including both the method and a database derived from a large-scale genomics survey. This substantially enhances understanding of phage specificity determinants at the strain level and offers a valuable framework for guiding phage selection in therapeutic applications.
Ribosomes are produced in large quantities during oogenesis and are stored in the egg. However, the egg and early embryo are translationally repressed(1-4). Here, using mass spectrometry and cryo-electron microscopy a...
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Ribosomes are produced in large quantities during oogenesis and are stored in the egg. However, the egg and early embryo are translationally repressed(1-4). Here, using mass spectrometry and cryo-electron microscopy analyses of ribosomes isolated from zebrafish (Danio rerio) and Xenopus laevis eggs and embryos, we provide molecular evidence that ribosomes transition from a dormant state to an active state during the first hours of embryogenesis. Dormant ribosomes are associated with four conserved factors that form two modules, consisting of Habp4-eEF2 and death associated protein 1b (Dap1b) or Dap in complex with eIF5a. Both modules occupy functionally important sites and act together to stabilize ribosomes and repress translation. Dap1b (also known as Dapl1 in mammals) is a newly discovered translational inhibitor that stably inserts into the polypeptide exit tunnel. Addition of recombinant zebrafish Dap1b protein is sufficient to block translation and reconstitute the dormant egg ribosome state in a mammalian translation extract in vitro. Thus, a developmentally programmed, conserved ribosome state has a key role in ribosome storage and translational repression in the egg.
We describe Miconia burkeae, a new dioecious species of Miconia section Cremanium from the Peruvian Andes. The new species shares the presence of nearly sessile and glabrescent leaves with two other Andean species in ...
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We describe Miconia burkeae, a new dioecious species of Miconia section Cremanium from the Peruvian Andes. The new species shares the presence of nearly sessile and glabrescent leaves with two other Andean species in section Cremanium, M. lilacina and M. opacifolia, but dillers in leaf shape and texture, as well as other characters. The occurrence of dioecy in Miconia is discussed.
Human immunodeficiency virus type 1 (HIV-1) infection involves a selection bottleneck that leads to transmission of one or a few variants. C-C motif chemokine receptor 5 (CCR5) or C-X-C motif chemokine receptor 4 (CXC...
Human immunodeficiency virus type 1 (HIV-1) infection involves a selection bottleneck that leads to transmission of one or a few variants. C-C motif chemokine receptor 5 (CCR5) or C-X-C motif chemokine receptor 4 (CXCR4) can act as coreceptors for HIV-1 viral entry. However, initial infection mostly occurs via CCR5, despite abundant expression of CXCR4 on target cells. The host factors that influence HIV-1 susceptibility and selection during transmission are unclear. Here we conduct CRISPR-Cas9 screens and identify SLC35A2 (a transporter of UDP-galactose expressed in target cells in blood and mucosa) as a potent and specific CXCR4-tropic restriction factor in primary target CD4+ T cells. SLC35A2 inactivation, which resulted in truncated glycans, not only increased CXCR4-tropic infection levels but also decreased those of CCR5-tropic strains consistently. Single-cycle infections demonstrated that the effect is cell-intrinsic. These data support a role for a host protein that influences glycan structure in regulating HIV-1 infection. Host cell glycosylation may, therefore, affect HIV-1 selection during transmission in vivo. CRISPR-Cas9 screens in primary CD4+ T cells enable identification of SLC35A2 as a host factor that restricts CXCR4-tropic HIV-1 viral entry and promotes that of CCR5-tropic viruses.
The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obt...
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The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 +/- 13.1 mg/L) than subjects with overweight (87.0 +/- 12.8 mg/L) and obesity (83.1 +/- 6.6 mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323;p = 0.031) and a negative correlation with body mass index (r = - 0.358;p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012);however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin.
This paper is concerned with the study of global attractors for a new semilinear Timoshenko-Ehrenfest type system. Firstly we establish the well-posedness of the system using Faedo-Galerkin method. By considering only...
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This paper is concerned with the study of global attractors for a new semilinear Timoshenko-Ehrenfest type system. Firstly we establish the well-posedness of the system using Faedo-Galerkin method. By considering only one damping term acting on the vertical displacement, we prove the existence of a smooth finite dimensional global attractor using the recent quasi-stability theory. Our results holds for any parameters of the system.
This paper presents an approach to designing editing workshops related to digital public history projects based on archival materials at institutions of higher learning. These events engage campus communities in the p...
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This paper presents an approach to designing editing workshops related to digital public history projects based on archival materials at institutions of higher learning. These events engage campus communities in the practice of public history and create opportunities for students interested in archives and digital humanities to develop professional skills. The model draws on the experiences of faculty, staff, and students who have contributed to Editing the Eartha M. M. White Collection, a pedagogically focused project that explores methods for the collaborative online publication of selected personal papers and correspondence of local African American leader Eartha M. M. White (1876-1974), held in the Special Collections of the Thomas G. Carpenter Library at the University of North Florida. Although this article focuses on designing workshops in the context of higher education, the model discussed can potentially be extended to other contexts beyond the campus.
Objective: The objective of this study was to assess the influence of immediate dentin sealing (IDS) on the fatigue behavior of laminate occlusal veneers fabricated with CAD/CAM lithium disilicate ceramic and resin **...
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Objective: The objective of this study was to assess the influence of immediate dentin sealing (IDS) on the fatigue behavior of laminate occlusal veneers fabricated with CAD/CAM lithium disilicate ceramic and resin ***: Forty sound human molars were prepared and randomly divided into 4 groups (n = 10): RC-IDS + (IDS and resin composite occlusal laminate veneer);RC-IDS-(resin composite occlusal laminate veneer without IDS);LD-IDS+ (IDS and lithium disilicate laminate veneer);LD-IDS-(lithium disilicate occlusal la-minate veneer without IDS). The restorations were obtained using a digital workflow. After surface conditioning and bonding, thermocycling and accelerated fatigue tests (20 Hz, 5000 cycles with an initial load of 300 N, step -size of 100 N for 10,000 cycles, up to 1000 N, and then a step-size of 50 N until failure) were conducted. Fatigue data were recorded for both outcomes (crack or fracture) and statistically analyzed. Fractographic and adhesive interface analysis were ***: The indirect resin composite groups showed better fatigue behavior compared to lithium disilicate. IDS only had a positive effect for the survival of resin composite restorations for the 'fracture' outcome. Evident presence of micro-gaps at the adhesive interface in the LD-IDS-group could be ***: Immediate dentin sealing improved fatigue resistance behavior of resin composite occlusal veneers. However, this effect was not observed in lithium disilicate veneers.
One critical aspect of cell proliferation is increased nucleotide synthesis, including pyrimidines. Pyrimidines are synthesized through de novo and salvage pathways. Prior studies established that the mammalian target...
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One critical aspect of cell proliferation is increased nucleotide synthesis, including pyrimidines. Pyrimidines are synthesized through de novo and salvage pathways. Prior studies established that the mammalian target of rapamycin complex 1 (mTORC1) promotes pyrimidine synthesis by activating the de novo pathway for cell proliferation. However, the involvement of mTORC1 in regulating the salvage pathway remains unclear. Here, we report that mTORC1 controls the half-life of uridine cytidine kinase 2 (UCK2), the rate-limiting enzyme in the salvage pathway. Specifically, UCK2 is degraded via the CTLH-WDR26 E3 complex during mTORC1 inhibition, which is prevented when mTORC1 is active. We also find that UCK1, an isoform of UCK2, affects the turnover of UCK2 by influencing its cellular localization. Importantly, altered UCK2 levels through the mTORC1-CTLH E3 pathway affect pyrimidine salvage and the efficacy of pyrimidine analog prodrugs. Therefore, mTORC1-CTLH E3-mediated degradation of UCK2 adds another layer of complexity to mTORC1's role in regulating pyrimidine metabolism.
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