QRB Discovery最新文献_第3页

Mouth breathing, dry air, and low water permeation promote inflammation, and activate neural pathways, by osmotic stresses acting on airway lining mucus. 口呼吸，干燥的空气，低水渗透促进炎症，并激活神经通路，渗透应力作用于气道粘膜。

QRB Discovery Pub Date : 2023-01-01 DOI: 10.1017/qrd.2023.1

David A Edwards, Kian Fan Chung

{"title":"Mouth breathing, dry air, and low water permeation promote inflammation, and activate neural pathways, by osmotic stresses acting on airway lining mucus.","authors":"David A Edwards, Kian Fan Chung","doi":"10.1017/qrd.2023.1","DOIUrl":"https://doi.org/10.1017/qrd.2023.1","url":null,"abstract":"Respiratory disease and breathing abnormalities worsen with dehydration of the upper airways. We find that humidification of inhaled air occurs by evaporation of water over mucus lining the upper airways in such a way as to deliver an osmotic force on mucus, displacing it towards the epithelium. This displacement thins the periciliary layer of water beneath mucus while thickening topical water that is partially condensed from humid air on exhalation. With the rapid mouth breathing of dry air, this condensation layer, not previously reported while common to transpiring hydrogels in nature, can deliver an osmotic compressive force of up to around 100 cm H2O on underlying cilia, promoting adenosine triphosphate secretion and activating neural pathways. We derive expressions for the evolution of the thickness of the condensation layer, and its impact on cough frequency, inflammatory marker secretion, cilia beat frequency and respiratory droplet generation. We compare our predictions with human clinical data from multiple published sources and highlight the damaging impact of mouth breathing, dry, dirty air and high minute volume on upper airway function. We predict the hypertonic (or hypotonic) saline mass required to reduce (or amplify) dysfunction by restoration (or deterioration) of the structure of ciliated and condensation water layers in the upper airways and compare these predictions with published human clinical data. Preserving water balance in the upper airways appears critical in light of contemporary respiratory health challenges posed by the breathing of dirty and dry air.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"4 ","pages":"e3"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Origins of life: first came evolutionary dynamics. 生命的起源:首先是进化动力学。

QRB Discovery Pub Date : 2023-01-01 DOI: 10.1017/qrd.2023.2

Charles Kocher, Ken A Dill

引用次数: 1

Computer-aided comprehensive explorations of RNA structural polymorphism through complementary simulation methods. 通过互补模拟方法对 RNA 结构多态性进行计算机辅助综合探索。

QRB Discovery Pub Date : 2022-10-17 eCollection Date: 2022-01-01 DOI: 10.1017/qrd.2022.19

Konstantin Röder, Guillaume Stirnemann, Pietro Faccioli, Samuela Pasquali

引用次数: 0

Towards design of drugs and delivery systems with the Martini coarse-grained model. 利用马蒂尼粗粒度模型设计药物和输送系统。

QRB Discovery Pub Date : 2022-10-12 eCollection Date: 2022-01-01 DOI: 10.1017/qrd.2022.16

Lisbeth R Kjølbye, Gilberto P Pereira, Alessio Bartocci, Martina Pannuzzo, Simone Albani, Alessandro Marchetto, Brian Jiménez-García, Juliette Martin, Giulia Rossetti, Marco Cecchini, Sangwook Wu, Luca Monticelli, Paulo C T Souza

{"title":"Towards design of drugs and delivery systems with the Martini coarse-grained model.","authors":"Lisbeth R Kjølbye, Gilberto P Pereira, Alessio Bartocci, Martina Pannuzzo, Simone Albani, Alessandro Marchetto, Brian Jiménez-García, Juliette Martin, Giulia Rossetti, Marco Cecchini, Sangwook Wu, Luca Monticelli, Paulo C T Souza","doi":"10.1017/qrd.2022.16","DOIUrl":"10.1017/qrd.2022.16","url":null,"abstract":"Coarse-grained (CG) modelling with the Martini force field has come of age. By combining a variety of bead types and sizes with a new mapping approach, the newest version of the model is able to accurately simulate large biomolecular complexes at millisecond timescales. In this perspective, we discuss possible applications of the Martini 3 model in drug discovery and development pipelines and highlight areas for future development. Owing to its high simulation efficiency and extended chemical space, Martini 3 has great potential in the area of drug design and delivery. However, several aspects of the model should be improved before Martini 3 CG simulations can be routinely employed in academic and industrial settings. These include the development of automatic parameterisation protocols for a variety of molecule types, the improvement of backmapping procedures, the description of protein flexibility and the development of methodologies enabling efficient sampling. We illustrate our view with examples on key areas where Martini could give important contributions such as drugs targeting membrane proteins, cryptic pockets and protein-protein interactions and the development of soft drug delivery systems.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":"e19"},"PeriodicalIF":0.0,"publicationDate":"2022-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Applications of machine learning in computer-aided drug discovery. 机器学习在计算机辅助药物研发中的应用。

QRB Discovery Pub Date : 2022-09-01 eCollection Date: 2022-01-01 DOI: 10.1017/qrd.2022.12

Sm Bargeen Alam Turzo, Eric R Hantz, Steffen Lindert

引用次数: 0

Integrative structural modelling and visualisation of a cellular organelle. 细胞器的综合结构建模和可视化。

QRB Discovery Pub Date : 2022-08-09 eCollection Date: 2022-01-01 DOI: 10.1017/qrd.2022.10

Ludovic Autin, Brett A Barbaro, Andrew I Jewett, Axel Ekman, Shruti Verma, Arthur J Olson, David S Goodsell

引用次数: 0

Erratum: Comparing 2 crystal structures and 12 AlphaFold2-predicted human membrane glucose transporters and their water-soluble glutamine, threonine and tyrosine variants - CORRIGENDUM. 勘误：比较 2 个晶体结构和 12 个 AlphaFold2 预测的人类膜葡萄糖转运体及其水溶性谷氨酰胺、苏氨酸和酪氨酸变体 - CORRIGENDUM。

QRB Discovery Pub Date : 2022-07-21 eCollection Date: 2022-01-01 DOI: 10.1017/qrd.2022.8

Eva Smorodina, Fei Tao, Rui Qing, David Jin, Steve Yang, Shuguang Zhang

引用次数: 0

Refinement of AlphaFold2 models against experimental and hybrid cryo-EM density maps. 针对实验和混合低温电镜密度图的AlphaFold2模型的改进。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.13

Maytha Alshammari, Willy Wriggers, Jiangwen Sun, Jing He

{"title":"Refinement of AlphaFold2 models against experimental and hybrid cryo-EM density maps.","authors":"Maytha Alshammari, Willy Wriggers, Jiangwen Sun, Jing He","doi":"10.1017/qrd.2022.13","DOIUrl":"https://doi.org/10.1017/qrd.2022.13","url":null,"abstract":"Recent breakthroughs in deep learning-based protein structure prediction show that it is possible to obtain highly accurate models for a wide range of difficult protein targets for which only the amino acid sequence is known. The availability of accurately predicted models from sequences can potentially revolutionise many modelling approaches in structural biology, including the interpretation of cryo-EM density maps. Although atomic structures can be readily solved from cryo-EM maps of better than 4 Å resolution, it is still challenging to determine accurate models from lower-resolution density maps. Here, we report on the benefits of models predicted by AlphaFold2 (the best-performing structure prediction method at CASP14) on cryo-EM refinement using the Phenix refinement suite for AlphaFold2 models. To study the robustness of model refinement at a lower resolution of interest, we introduced hybrid maps (i.e. experimental cryo-EM maps) filtered to lower resolutions by real-space convolution. The AlphaFold2 models were refined to attain good accuracies above 0.8 TM scores for 9 of the 13 cryo-EM maps. TM scores improved for AlphaFold2 models refined against all 13 cryo-EM maps of better than 4.5 Å resolution, 8 hybrid maps of 6 Å resolution, and 3 hybrid maps of 8 Å resolution. The results show that it is possible (at least with the Phenix protocol) to extend the refinement success below 4.5 Å resolution. We even found isolated cases in which resolution lowering was slightly beneficial for refinement, suggesting that high-resolution cryo-EM maps might sometimes trap AlphaFold2 models in local optima.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/a8/S2633289222000138a.PMC10361706.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9905304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Inconsistent treatments of the kinetics of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) impair assessment of its diagnostic potential. 聚类规则间隔短回文重复序列(CRISPR)动力学的不一致处理损害了其诊断潜力的评估。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.7

Juan G Santiago

{"title":"Inconsistent treatments of the kinetics of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) impair assessment of its diagnostic potential.","authors":"Juan G Santiago","doi":"10.1017/qrd.2022.7","DOIUrl":"https://doi.org/10.1017/qrd.2022.7","url":null,"abstract":"The scientific and technological advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is one of the most exciting developments of the past decade, particularly in the field of gene editing. The technology has two essential components, (1) a guide RNA to match a targeted gene and (2) a CRISPR-associated protein (e.g. Cas 9, Cas12 or Cas13) that acts as an endonuclease to specifically cut DNA. This specificity and reconfigurable nature of CRISPR has also spurred intense academic and commercial interest in the development of CRISPR-based molecular diagnostics. CRISPR Cas12 and Cas13 orthologs are most commonly applied to diagnostics, and these cleave and become activated by DNA and RNA targets, respectively. Despite the intense research interest, the limits of detection (LoDs) and applications of CRISP-based diagnostics remain an open question. A major reason for this is that reports of kinetic rates have been widely inconsistent, and the vast majority of these reports contain gross errors including violations of basic conservation and kinetic rate laws. It is the intent of this Perspective to bring attention to these issues and to identify potential improvements in the manner in which CRISPR kinetic rates and assay LoDs are reported and compared. The CRISPR field would benefit from verifications of self-consistency of data, providing sufficient data for reproduction of experiments, and, in the case of reports of novel assay LoDs, concurrent reporting of the associated kinetic rate constants. The early development of CRISPR-based diagnostics calls for self-reflection and urges us to proceed with caution.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":"e9"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10283211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Challenges and frontiers of computational modelling of biomolecular recognition. 生物分子识别计算建模的挑战与前沿。

QRB Discovery Pub Date : 2022-01-01 Epub Date: 2022-08-19 DOI: 10.1017/qrd.2022.11

Jinan Wang, Apurba Bhattarai, Hung Nguyen Do, Yinglong Miao

引用次数: 0