Adenovirus cement proteins play crucial roles in virion assembly, disassembly, cell entry, and infection. Based on a refined crystal structure of the adenovirus virion at 3.8-Å resolution, we have ...determined the structures of all of the cement proteins (IIIa, VI, VIII, and IX) and their organization in two distinct layers. We have significantly revised the recent cryoelectron microscopy models for proteins IIIa and IX and show that both are located on the capsid exterior. Together, the cement proteins exclusively stabilize the hexon shell, thus rendering penton vertices the weakest links of the adenovirus capsid. We describe, for the first time to our knowledge, the structure of protein VI, a key membrane-lytic molecule, and unveil its associations with VIII and core protein V, which together glue peripentonal hexons beneath the vertex region and connect them to the rest of the capsid on the interior. Following virion maturation, the cleaved N-terminal propeptide of VI is observed, reaching deep into the peripentonal hexon cavity, detached from the membrane-lytic domain, so that the latter can be released. Our results thus provide the molecular basis for the requirement of maturation cleavage of protein VI. This process is essential for untethering and release of the membrane-lytic region, which is known to mediate endosome rupture and delivery of partially disassembled virions into the host cell cytoplasm.
Plaque brachytherapy - Radiating positivity Bansal, Rolika; Honavar, Santosh; P Reddy, Vijay ...
Indian journal of ophthalmology,
07/2023, Letnik:
71, Številka:
7
Journal Article
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Background: Plaque brachytherapy is an evolving, yet effective globe and vision-sparing modality for the treatment of intraocular tumors by transscleral irradiation of the tumor base with a ...radioactive implant. The American Brachytherapy Society (ABS) along with the collaboration of the international multicenter Ophthalmic Oncology Task Force (OOTF) was assembled to reach a consensus regarding establishing practice guidelines and setting standards of care for intraocular tumors. The advent of plaque brachytherapy has revolutionized the outcomes of intraocular tumors, thus ensuring globe salvage, reducing morbidity and mortality, and avoiding cosmetic disfigurement. A well-planned dosimetry for plaque brachytherapy results in achieving local tumor control and excellent prognosis. Purpose: This technique provides the advantage of focal radiation, thus eliminating the damage to the adjacent structures, minimal periorbital tissue damage, absence of cosmetic disfigurement owing to lack of retarded bone growth as seen in external beam radiotherapy. Thus, it reduces the risk of metastasis, and with the recent advances, it provides a shorter duration of treatment. Synopsis: In this video, we shall display the concept of plaque brachytherapy, the various types of plaques available, different radiations sources, planning dosimetry and calculations, target disease spectrum, surgical placement, and post-radiation outcomes in terms of local tumor control and prognosis. Highlights: This video highlights the history, basic principles and techniques of plaque brachytherapy and provides an understanding of its applications in the world of ocular oncology. Video link: https://youtu.be/7PX0mDQETRY
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adenoviruses are respiratory, ocular and enteric pathogens that form complex capsids, which are assembled from seven different structural proteins and composed of several core proteins that closely ...interact with the packaged dsDNA genome. The recent near-atomic resolution structures revealed that the interlacing continuous hexagonal network formed by the protein IX molecules is conserved among different human adenoviruses (HAdVs), but not in non-HAdVs. In this report, we propose a distinct role for the hexon protein as a “molecular mold” in enabling the formation of such hexagonal protein IX network that has been shown to preserve the stability and infectivity of HAdVs.
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Grain boundary (GB) migration and grain growth in nanocrystalline metals are major obstructions to exploit these materials to their fullest potential, thus limiting their utility as advanced ...structural materials. Here, we investigate the effect of Zr segregation to a Ni GB on migration and subsequent strengthening during shear deformation and high-temperature bending creep. Specifically, using molecular dynamics simulation, we simulate deformation of a Ni bicrystal specimen having a symmetric ∑5 grain boundary with and without segregated Zr. It is found that GB segregation up to 0.4 at.% pins the CSL boundary resulting in increased shear strength. Similar behavior is also observed in the case of bending creep deformation where the creep resistance increases only up to 0.4 at.%. This study indicates that larger amounts of GB segregation cause destabilization of the local atomic structure and consequently affect the GB stiffness. Moreover, we investigate the effect of Zr segregation on the interaction between the GB and a dislocation. We find that the preexisting dislocation is absorbed in the GB region for both clean and segregated specimens; however, the absorption path of the dislocation is different due to the change in GB stiffness caused by the Zr segregation.
The aim of the present study was to explore the relationship between satisfaction with life and mathematics achievement among a nationally representative sample of Grade 9 learners in South Africa.
...Using the Trends in Mathematics and Science Study (TIMSS 2019) based on a sample of 20,829 learners (females = 11,067 and males = 9,719), and employing structural equation modelling (SEM), we examined the nature of the relationship between satisfaction with life and mathematics achievement, considering the role of gender, parental involvement, and instructional clarity.
Our findings showed that satisfaction with life is positively related to mathematics achievement, but is not moderated by gender. Additionally, instructional clarity contributes to, and is a partial mediator of, the relationship between life satisfaction and mathematics achievement. This suggests that greater instructional clarity is positively associated with high achievement in mathematics, over and above the relationship with satisfaction with life. By contrast, parental involvement negatively mediates this relationship, suggesting that mathematics achievement is negatively associated with certain forms of parental involvement, such as setting time aside for homework; and checking if homework is done.
Given the tested linear relationship between life satisfaction, instructional clarity and mathematics achievement, the results of the study suggest that if wellbeing is improved and existing instructional practices are constantly reviewed, mathematics scores could be positively affected. In addition, the emerging finding on the negative role of parental involvement in the hypothesised mediated relationship suggests that learners could benefit from properly tailored, and government-sponsored, afterschool tutoring.
In this paper, we deal with a Bicopter drone that has two thrusters and two tilting servos. Both the position and attitude dynamics of Bicopter are globally expressed on the Special Euclidean group ...SE3. A simple control allocation method is proposed to map between the control wrench and actuator inputs for the Bicopter. A geometric nonlinear attitude and altitude tracking controller is developed for the Bicopter and the asymptotic stability analysis is performed using the Lyapunov method for the closed-loop nonlinear system. The performance of the proposed altitude and attitude stabilization controller is validated through experimental hardware developed in-house. The attitude controller performance is validated through simulations and shown to be comparable against an linear matrix inequality-based control law.
Proline-rich domains (PRDs) are among the most prevalent signaling modules of eukaryotes but often unexplored by biophysical techniques as their heterologous recombinant expression poses significant ...difficulties. Using a “divide-and-conquer” approach, we present a detailed investigation of a PRD (166 residues; ∼30% prolines) belonging to a human protein ALIX, a versatile adaptor protein involved in essential cellular processes including ESCRT-mediated membrane remodeling, cell adhesion, and apoptosis. In solution, the N-terminal fragment of ALIX-PRD is dynamically disordered. It contains three tandem sequentially similar proline-rich motifs that compete for a single binding site on its signaling partner, TSG101-UEV, as evidenced by heteronuclear NMR spectroscopy. Global fitting of relaxation dispersion data, measured as a function of TSG101-UEV concentration, allowed precise quantitation of these interactions. In contrast to the soluble N-terminal portion, the Cterminal tyrosine-rich fragment of ALIX-PRD forms amyloid fibrils and viscous gels validated using dye-binding assays with amyloidspecific probes, congo red and thioflavin T (ThT), and visualized by transmission electron microscopy. Remarkably, fibrils dissolve at low temperatures (2 to 6 °C) or upon hyperphosphorylation with Src kinase. Aggregation kinetics monitored by ThT fluorescence shows that charge repulsion dictates phosphorylation-mediated fibril dissolution and that the hydrophobic effect drives fibril formation. These data illuminate the mechanistic interplay between interactions of ALIX-PRD with TSG101-UEV and polymerization of ALIX-PRD and its central role in regulating ALIX function. This study also demonstrates the broad functional repertoires of PRDs and uncovers the impact of posttranslational modifications in the modulation of reversible amyloids.
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The antigenic epitope regions of pathogens (e.g., viruses) are recognized by antibodies (Abs) and subsequently cleared by the host immune system, thereby protecting us from disease. ...Some of these epitopes are conserved among different variants or subgroups of pathogens (e.g., Influenza (FLU) viruses, Coronaviruses), hence can be targeted for potential broad-neutralization. Here we report a web-based tool, Epitope Analyzer (EA), that rapidly identifies conformational epitope and paratope residues in an antigen–antibody complex structure. Furthermore, the tool provides the ways and means to analyze broadly neutralizing epitopes by comparing the equivalent epitope residues in similar antigen structures. The similarity in the epitope residues between (multiple) pairs of similar antigen molecules suggest the presence of conserved epitopes that can be targeted by broadly neutralizing antibodies. These details can be used as a guide in developing effective treatments, such as the design of novel vaccines and formulation of cocktail of broadly neutralizing antibodies, against multiple variants or subgroups of viruses. The web application can be freely accessed from the URL, http://viperdb.scripps.edu/ea.php.
Crystal Structure of Human Adenovirus at 3.5 Å Resolution Reddy, Vijay S; Natchiar, S. Kundhavai; Stewart, Phoebe L ...
Science (American Association for the Advancement of Science),
08/2010, Letnik:
329, Številka:
5995
Journal Article
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Rational development of adenovirus vectors for therapeutic gene transfer is hampered by the lack of accurate structural information. Here, we report the x-ray structure at 3.5 angstrom resolution of ...the 150-megadalton adenovirus capsid containing nearly 1 million amino acids. We describe interactions between the major capsid protein (hexon) and several accessory molecules that stabilize the capsid. The virus structure also reveals an altered association between the penton base and the trimeric fiber protein, perhaps reflecting an early event in cell entry. The high-resolution structure provides a substantial advance toward understanding the assembly and cell entry mechanisms of a large double-stranded DNA virus and provides new opportunities for improving adenovirus-mediated gene transfer.
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