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1.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35177473

RESUMO

Researchers commonly anneal metals, alloys, and semiconductors to repair defects and improve microstructures via recrystallization. Theoretical studies indicate that simulated annealing on biological macromolecules helps predict the final structures with minimum free energy. Experimental validation of this homogenizing effect and further exploration of its applications are fascinating scientific questions that remain elusive. Here, we chose the apo-state 70S ribosome from Escherichia coli as a model, wherein the 30S subunit undergoes a thermally driven intersubunit rotation and exhibits substantial structural flexibility as well as distinct free energy. We experimentally demonstrate that annealing at a fast cooling rate enhances the 70S ribosome homogeneity and improves local resolution on the 30S subunit. After annealing, the 70S ribosome is in a nonrotated state with respect to corresponding intermediate structures in unannealed or heated ribosomes. Manifold-based analysis further indicates that the annealed 70S ribosome takes a narrow conformational distribution and exhibits a minimum-energy state in the free-energy landscape. Our experimental results offer a facile yet robust approach to enhance protein stability, which is ideal for high-resolution cryogenic electron microscopy. Beyond structure determination, annealing shows great potential for synchronizing proteins on a single-molecule level and can be extended to study protein folding and explore conformational and energy landscapes.


Assuntos
Conformação Proteica , Proteínas Ribossômicas/ultraestrutura , Ribossomos/fisiologia , Microscopia Crioeletrônica , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Modelos Moleculares , RNA Ribossômico/metabolismo , RNA Ribossômico/ultraestrutura , Proteínas Ribossômicas/metabolismo , Ribossomos/ultraestrutura
2.
Am J Rhinol Allergy ; : 19458924241259333, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38881270

RESUMO

BACKGROUND: Subtypes of sinusitis have different symptoms and prognoses due to different pathogens. Odontogenic maxillary sinusitis (OMS) mainly occurs unilaterally and is different from chronic rhinosinusitis (CRS) usually occurring bilaterally in terms of clinical characteristics. However, comprehensive microbiological comparisons between OMS and CRS have never been systematically conducted and most comparisons are methodologically biased. This study aims to provide a comprehensive analysis of the microbiology associated with OMS and CRS through a meta-analysis approach in order to provide evidence for differential diagnosis of OMS and CRS from a microbiological perspective. METHODS: The databases PubMed and CNKI were searched from their inception to July 2023. A random-effects model was employed to derive the pooled prevalence estimates of the identified bacterial species or genera. RESULTS: The 17 represented studies included 6 concerning OMS, 12 concerning CRS, and 4 concerning normal sinus, yielding 191, 610, and 92 samples, respectively. Though not statistically significant, the prevalence of Peptostreptococcus and Prevotella was generally higher in OMS compared to CRS. Notably, Fusobacterium was identified as the only genus with a significantly higher prevalence in OMS compared to CRS. CONCLUSION: Fusobacterium was significantly more prevalent in OMS compared with CRS, while Staphylococcus aureus was more prevalent in CRS than in OMS. Such differences in bacterial profile may partly explain the distinct pathology observed and contribute to the development of novel strategies for diagnosis and therapeutic interventions in OMS.

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