QRB Discovery最新文献

Uncovering the hidden biology of fibrinaloid microclot complexes in complex, inflammatory diseases. 揭示纤维蛋白样微凝块复合物在复杂炎症性疾病中的隐藏生物学。

QRB Discovery Pub Date : 2026-07-31 eCollection Date: 2026-01-01 DOI: 10.1017/qrd.2026.10022

Justine Grixti, Etheresia Pretorius, Douglas B Kell

{"title":"Uncovering the hidden biology of fibrinaloid microclot complexes in complex, inflammatory diseases.","authors":"Justine Grixti, Etheresia Pretorius, Douglas B Kell","doi":"10.1017/qrd.2026.10022","DOIUrl":"10.1017/qrd.2026.10022","url":null,"abstract":"Blood can clot into anomalous, fibrinolysis-resistant forms that arise from prothrombotic seeding areas, including damaged cellular debris and membrane-derived surfaces, giving rise to what we have termed fibrinaloid microclot complexes (colloquially: microclots). Their proteolytic resistance is due in part to the fact that they are amyloid in nature, and they can also entrap inhibitors of proteolysis. They consist of a variety of proteins besides the expected fibrin, and are highly enriched for other amyloidogenic proteins (in contrast to normal clots, whose proteome largely reflects the soluble plasma proteome). They also contain DNA in the form of neutrophil extracellular traps (NETs). Importantly, fibrinaloid microclot complexes are heterogeneous structures comprising multiple phenotypic forms, including those that nucleate and grow on cellular debris such as damaged membranes, microparticles, and immune-derived material. We consider that these debris-associated complexes can act as catalytic scaffolds that recruit fibrin(ogen) and inflammatory molecules, thereby amplifying amyloidogenic transformation and prothrombotic activity. Fibrinaloid microclot complexes have been reported in a widening range of chronic inflammatory and thrombo-inflammatory diseases in which they have been sought, and are highly enriched for amyloidogenic proteins. Additionally, the thrombi extracted from ischaemic stroke also contain proteins in an amyloid form. One mechanism that explains how such macroclots can form and block arteries larger than any leading to them is that this occurs via the accretion of microclots that already contain amyloid. We here show that these microclots exhibit a classical 'apple-green' birefringence when stained with the dye Congo red. It is now important to determine whether inhibiting amyloid-forming clot transitions has therapeutic value.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"7 ","pages":"e9"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13434857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148674347","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

Recent advances of in situ and in vivo electrochemical analysis of brain chemistry at micro- and nanoscale. 微纳米尺度脑化学原位和体内电化学分析研究进展。

QRB Discovery Pub Date : 2026-05-29 eCollection Date: 2026-01-01 DOI: 10.1017/qrd.2025.10015

Jinger Chen, Lijiao Cao, Yuying Liu, Junlan Zhou, Xiaoke Nan, Chuqi Li, Meiping Xiong, Chao Yuan, Xianchan Li

引用次数: 0

Welcome editorial from the new Editor-in-Chief. 新主编的欢迎社论。

QRB Discovery Pub Date : 2026-05-06 eCollection Date: 2026-01-01 DOI: 10.1017/qrd.2026.10020

Carol V Robinson, Emma Lalande

引用次数: 0

Hole migration in cytochrome P450. 细胞色素P450的空穴迁移。

QRB Discovery Pub Date : 2026-05-04 eCollection Date: 2026-01-01 DOI: 10.1017/qrd.2026.10021

Harry Gray, Jay Winkler

引用次数: 0

Mass spectrometry integrates protein design into structural biology method development. 质谱法将蛋白质设计整合到结构生物学方法开发中。

QRB Discovery Pub Date : 2026-04-13 eCollection Date: 2026-01-01 DOI: 10.1017/qrd.2025.10018

Alexander Stevens, Hannah Osterholz, Vsevolod Viliuga, Thibault Vosselman, Surabhi Kokane, Erik G Marklund, Arne Elofsson, Axel Leppert, Michael Landreh

{"title":"Mass spectrometry integrates protein design into structural biology method development.","authors":"Alexander Stevens, Hannah Osterholz, Vsevolod Viliuga, Thibault Vosselman, Surabhi Kokane, Erik G Marklund, Arne Elofsson, Axel Leppert, Michael Landreh","doi":"10.1017/qrd.2025.10018","DOIUrl":"10.1017/qrd.2025.10018","url":null,"abstract":"Recent advances in machine learning (ML) have transformed protein science, enabling engineering and de novo design of artificial proteins with novel structures and functions. However, experimental analysis of key design features, such as oligomerization, folding, ligand binding, and dynamic conformational changes, remains critical. Here, we outline how mass spectrometry (MS) complements protein design through its ability to corroborate a wide range of design objectives. Furthermore, engineered proteins have become valuable tools for exploring the use of MS in detecting structural features, charge effects, and weak interactions by serving as testbeds for method development. Integrating ML and native MS thus creates a feedback loop: new designs challenge analytical techniques, while improved methods provide richer data to guide and improve future predictions. This synergy is vital for expanding the capabilities of protein engineering, including toward applications in synthetic biology and artificial protocell development.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"7 ","pages":"e4"},"PeriodicalIF":0.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820912","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

Electrochemical measurements at human iPSC-derived FOXA2 dopaminergic neurons suggest a role for partial release in presynaptic plasticity. 人类ipsc衍生的FOXA2多巴胺能神经元的电化学测量表明，部分释放在突触前可塑性中起作用。

QRB Discovery Pub Date : 2026-03-23 eCollection Date: 2026-01-01 DOI: 10.1017/qrd.2026.10019

Chaoyi Gu, Alicia Lork, Soodabeh Majdi, Stefania Rabasco, Huashan Peng, Anjie Ni, Carl Ernst, Andrew G Ewing

{"title":"Electrochemical measurements at human iPSC-derived FOXA2 dopaminergic neurons suggest a role for partial release in presynaptic plasticity.","authors":"Chaoyi Gu, Alicia Lork, Soodabeh Majdi, Stefania Rabasco, Huashan Peng, Anjie Ni, Carl Ernst, Andrew G Ewing","doi":"10.1017/qrd.2026.10019","DOIUrl":"10.1017/qrd.2026.10019","url":null,"abstract":"During the past decade, emerging studies using electrochemistry and nanoscale imaging have demonstrated that partial exocytotic release is prevailing in neuroendocrine cell models. However, due to complicated structure and culture process, few studies have been carried out using neurons, especially human neurons. Here, dopamine (DA) release from individual vesicles and DA content stored within vesicles were quantified from induced pluripotent stem cell-derived DA neurons with electrochemical techniques. The results indicate that around 61% of the total vesicular DA content is released from these neurons during exocytosis. The vesicular content quantified in DA neurons is significantly higher than that in undifferentiated neural progenitor cells, owing to the increased appearance of dense-core vesicles that are able to store more DA molecules than the clear vesicles. When the neurons are differentiated with BAY-K8644, which stimulates neuronal maturation as well as DA release, the release fraction rises to 91%. The use of BAY-K8644 can be considered as chronic stimulation and leads to similar effects on exocytosis as repetitive stimulation, which triggers short-term plasticity. This study demonstrates partial release in DA transmission in human neurons and provides a link between neuronal maturation and the formation of plasticity. Furthermore, this work suggests that the fraction of release in exocytosis at human neurons may be a factor in determining plasticity.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"7 ","pages":"e3"},"PeriodicalIF":0.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821737","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

Infrared nanoscopy for subcellular chemical imaging. 用于亚细胞化学成像的红外纳米显微镜。

QRB Discovery Pub Date : 2026-01-19 eCollection Date: 2026-01-01 DOI: 10.1017/qrd.2025.10014

Katerina Kanevche, David Joll Burr, Janina Drauschke, Jacek Kozuch, Carlos Baiz, Andreas Elsaesser, Joachim Heberle

{"title":"Infrared nanoscopy for subcellular chemical imaging.","authors":"Katerina Kanevche, David Joll Burr, Janina Drauschke, Jacek Kozuch, Carlos Baiz, Andreas Elsaesser, Joachim Heberle","doi":"10.1017/qrd.2025.10014","DOIUrl":"10.1017/qrd.2025.10014","url":null,"abstract":"Infrared (IR) nanoscopy represents a collection of imaging and spectroscopy techniques capable of resolving IR absorption on the nanometer scale. Chemical specificity is leveraged from vibrational spectroscopy, while light-matter interactions are detected by observing perturbations in the optical near field with an atomic force microscopy probe. Therefore, imaging is wavelength independent and has a spatial resolution on the nanometer scale, well beyond the classical diffraction limit. In this perspective, we outline the recent biological applications of scattering type scanning near-field optical microscopy and nanoscale Fourier-transform IR spectroscopy. These techniques are uniquely suited to resolving subcellular ultrastructure from a variety of cell types, as well as studying biological processes such as metabolic activity on the single-cell level. Furthermore, this review describes recent technical advances in IR nanoscopy, and emerging machine learning supported approaches to sampling, signal enhancement, and data processing. This emphasizes that label-free IR nanoscopy holds significant potential for ongoing and future biological applications.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"7 ","pages":"e2"},"PeriodicalIF":0.0,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12823213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031126","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

Comments from the leaving Editor-in-Chief. 即将离职的总编辑的评论。

QRB Discovery Pub Date : 2026-01-05 eCollection Date: 2026-01-01 DOI: 10.1017/qrd.2025.10017

Bengt Nordén

引用次数: 0

The low complexity linker of DNAJB6b is key to its anti-amyloid function. DNAJB6b的低复杂性连接体是其抗淀粉样蛋白功能的关键。

QRB Discovery Pub Date : 2025-12-02 eCollection Date: 2025-01-01 DOI: 10.1017/qrd.2025.10016

Timas Merkelis, Ulf Olsson, Sara Linse

{"title":"The low complexity linker of DNAJB6b is key to its anti-amyloid function.","authors":"Timas Merkelis, Ulf Olsson, Sara Linse","doi":"10.1017/qrd.2025.10016","DOIUrl":"10.1017/qrd.2025.10016","url":null,"abstract":"Neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, are associated with the formation of amyloid fibrils. The DNAJB6b (JB6) chaperone greatly inhibits the disease-related self-assembly of amyloid peptides in an ATP-independent manner. The molecular basis of this process is, however, not understood. Here, we studied the low complexity linker between the N- and C-terminal domains of JB6 as an isolated 110 amino acid residue construct, to get a better understanding of the role of the composition of the intact protein. We investigate the structure and aggregation behaviour of the linker and its anti-amyloid activity in comparison with the full-length chaperone. We find that the linker contains ca. 45% α-helix and 20% β-sheet and is in itself an amyloid-like peptide that self-assembles into different structures, which are bigger than those formed by the intact chaperone, including fibrils. The isolated linker protects against fibril formation of Aβ42 as well as α-synuclein, but is less potent than the intact chaperone. Based on our results, we propose a possible mechanism behind JB6 and linker amyloid suppression relating to their self-assembly behaviour. In the intact protein, the domains serve to solubilize the linker such that the solution concentration of exposed linker is high enough to sustain its high potency against amyloid formation.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"6 ","pages":"e25"},"PeriodicalIF":0.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828619","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

Continuous-time random walk model for the diffusive motion of helicases. 解旋酶扩散运动的连续时间随机游走模型。

QRB Discovery Pub Date : 2025-10-09 eCollection Date: 2025-01-01 DOI: 10.1017/qrd.2025.10011

Victor Rodríguez-Franco, Michelle Marie Spiering, Piero Bianco, Felix Ritort, Maria Manosas

{"title":"Continuous-time random walk model for the diffusive motion of helicases.","authors":"Victor Rodríguez-Franco, Michelle Marie Spiering, Piero Bianco, Felix Ritort, Maria Manosas","doi":"10.1017/qrd.2025.10011","DOIUrl":"10.1017/qrd.2025.10011","url":null,"abstract":"DNA helicases are molecular motors that use the energy from nucleotide hydrolysis to move along DNA, promoting the unwinding or rewinding of the double helix. Here, we use magnetic and optical tweezers to track the motion of three helicases, gp41, RecQ, and RecG, while they unwind or rewind a DNA hairpin. Their activity is characterized by measuring the helicase velocity and diffusivity under different force and ATP conditions. We use a continuous-time random walk framework that allows us to compute the mean helicase displacement and its fluctuations analytically. Fitting the model to the measured helicase velocity and diffusivity allows us to determine the main states and transitions in the helicase mechanochemical cycle. A general feature for all helicases is the need to incorporate an off-pathway pausing state to reproduce the data, raising the question of whether pauses play a regulatory role. Diffusivity measurements also lead to estimations of the thermodynamic uncertainty factor related to the motor efficiency. Assuming a tight mechano-chemical coupling, we find that the RecG helicase reaches a high efficiency when operating uphill, whereas the unwinding gp41 and RecQ helicases display much lower efficiencies. Incorporating the analysis of fluctuations allows for better characterization of the activity of molecular machines, which represents an advance in the field.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"6 ","pages":"e26"},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12722086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828609","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