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| Open AccessSynergistic insights into human health from aptamer- and antibody-based proteomic profiling
Broad-capture affinity-based proteomic technologies inform how the readout of our genes affects human health. Here, the authors integrate aptamer- and antibody-based profiling to understand the mechanisms underlying gene-protein-disease associations.
- Maik Pietzner
- , Eleanor Wheeler
- & Claudia Langenberg
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| Open AccessIdentification of the factor XII contact activation site enables sensitive coagulation diagnostics
Blood coagulation is started by contact to surfaces and this is the principle for a commonly used diagnostic clotting test, aPTT. Here, the authors identify the structure in coagulation factor XII that initiates surface-driven coagulation and use the information to develop improved aPTT assays.
- Marco Heestermans
- , Clément Naudin
- & Thomas Renné
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| Open AccessNext generation plasma proteome profiling to monitor health and disease
The proximity extension assay (PEA) is a popular tool to measure plasma protein levels. Here, the authors extend the proteome coverage of PEA by combining it with next-generation sequencing, enabling the analysis of nearly 1500 proteins from minute amounts of plasma.
- Wen Zhong
- , Fredrik Edfors
- & Mathias Uhlén
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| Open AccessActivation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module
Von Willebrand factor (VWF) is a large glycoprotein in the blood secreted from endothelial cells lining the blood vessel and activation of VWF leads to formation of VWF-platelet complexes or thrombi. Here authors use single-molecule force measurement, X-ray crystallography and functional measurements to monitor the activation of VWF via mechanical unfolding of the autoinhibitory module (AIM).
- Nicholas A. Arce
- , Wenpeng Cao
- & Renhao Li
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Article
| Open AccessFibrinogen function achieved through multiple covalent states
Disulfide bonds play critical roles in determining protein structure and function. Here, the authors show that fibrinogen exists in multiple disulfide-bonded states in human blood, and that these states change during fibrin polymerization and in response to fluid shear forces.
- Diego Butera
- & Philip J. Hogg
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| Open AccessRapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona
Large-scale, unbiased proteomics studies of biological samples like plasma are constrained by the complexity of the proteome. Herein, the authors develop a highly parallel protein quantitation platform leveraging multi nanoparticle protein coronas for deep proteome sampling and biomarker discovery.
- John E. Blume
- , William C. Manning
- & Omid C. Farokhzad
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Article
| Open AccessSynthetic molecular recognition nanosensor paint for microalbuminuria
Microalbuminuria, a clinical marker associated with cancer and hypertension, defined by low albumin levels in the urine, is normally detected by immunoassay. Herein, a nanosensor paint was developed using a polymer to mimic fatty acid binding to albumin, transduced by carbon nanotube fluorescence.
- Januka Budhathoki-Uprety
- , Janki Shah
- & Daniel A. Heller
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| Open AccessAnti-platelet factor 4/polyanion antibodies mediate a new mechanism of autoimmunity
Antibodies against the platelet factor 4 (PF4) support bacterial host defence but in some cases may lead to heparin-induced thrombocytopenia (HIT). Nguyenet al.show that in autoimmune HIT a subset of antibodies binds strongly to PF4 causing its conformational change that leads to association of non-pathogenic PF4 antibodies and thrombotic platelet activation.
- Thi-Huong Nguyen
- , Nikolay Medvedev
- & Andreas Greinacher
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| Open AccessHuman serum-derived protein removes the need for coating in defined human pluripotent stem cell culture
Improved culture methods are needed to reliably grow human pluripotent stem cells (hPSCs) on a large scale. Here, the authors identify a xeno-free medium with a supplement of Inter-α-inhibitor that supports long-term propagation and improved single-cell passaging of hPSCs on uncoated plastic.
- Sara Pijuan-Galitó
- , Christoffer Tamm
- & Cecilia Annerén
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Article
| Open AccessStructural basis for haem piracy from host haemopexin by Haemophilus influenzae
Haemophilus influenzae requires haem, and acquires it from host haemoproteins including haemopexin. Here, the authors examine the haem transport system consisting of HxuA, HxuB and HxuC via the structures of HxuA in complex with haemopexin.
- Silvia Zambolin
- , Bernard Clantin
- & Philippe Delepelaire
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| Open AccessBlood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells
Factor XII initiates the intrinsic blood coagulation cascade and the kinin system. Here the authors show that Factor XII is elevated in the blood of multiple sclerosis patients, activates dendritic cells via CD87 and cAMP, and its blockade inhibits immunopathology in a mouse model of the disease.
- Kerstin Göbel
- , Susann Pankratz
- & Sven G. Meuth
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Article
| Open AccessGlobal distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis
Sixty years ago it was suggested that the sickle cell disease mutation survives because the heterozygous genotype confers resistance to malaria, resulting in correlation of the two geographical distributions. The authors use a new global assembly of sickle allele frequencies to support this hypothesis at the global scale.
- Frédéric B. Piel
- , Anand P. Patil
- & Simon I. Hay