
Roche's Tina-quant Lp(a) RxDx assay, a blood test that measures lipoprotein(a) levels, has received breakthrough device designation from the FDA to identify adults with elevated Lp(a) who may benefit from emerging lipid-lowering therapies.


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The Tina-quant Lp(a) RxDx assay identifies adults with elevated Lp(a) levels who might benefit from innovative lipid-lowering therapies currently in development.

Roche Blood Test for Lp(a) Designated Breakthrough Device

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Roche's Breakthrough Blood Test for Measuring Lipoprotein(a) Levels to Assess Cardiovascular Risk


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Introducing a causal graphical model to characterize dropout mechanisms for gene regulatory network inference.


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Gene Regulatory Network Inference in the Presence of Dropouts: A Causal View



Novel semantic data augmentation techniques, NaNa and MiGu, significantly improve protein classification tasks by incorporating biophysical and chemical features.


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Enhancing Protein Classification with NaNa and MiGu Semantic Data Augmentation Techniques



Advances in neural-network control methods offer a promising alternative for managing medical digital twins, especially in complex biomedical systems.


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Control of Medical Digital Twins with Neural Networks



Hsp110 plays a crucial role in stimulating protein disaggregation by enhancing Hsp70 activity, particularly with class B J-Domain proteins. The interaction between Hsp110 and Hsp70 is essential for efficient aggregate processing.


Hsp70 is a key cellular system counteracting protein misfolding and aggregation, associated with stress, ageing and disease. Hsp70 solubilizes aggregates and aids protein refolding through substrate binding and release cycles regulated by co-chaperones: J-domain proteins (JDPs) and Nucleotide Exchange Factors (NEFs). Here, we elucidate the collaborative impact of Hsp110 NEFs and different JDP classes throughout Hsp70-dependent aggregate processing. We show that Hsp110 plays a major role at initial stages of disaggregation, determining its final efficacy. The NEF catalyses the recruitment of thick Hsp70 assemblies onto aggregate surface, which modifies aggregates into smaller species more readily processed by chaperones. The stimulation is much limited with class A JDPs and requires the auxiliary interaction between class B JDP and the Hsp70 EEVD motif. Furthermore, we demonstrate for the first time that Hsp110 disrupts the JDP-Hsp70 interaction. We propose that the limited destabilisation of the chaperone complex improves disaggregation, but also leads to the inhibition above the substoichiometric Hsp110 optimum. This suggests that the tuned proportion between the co-chaperones of Hsp70 is critical to reach its disaggregating potential.

### Competing Interest Statement

The authors have declared no competing interest.

Balanced Interplay Between Hsp110, Hsp70 and Class B J-Domain Protein Improves Aggregate Disassembly

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Interplay Between Hsp110, Hsp70, and J-Domain Protein in Aggregate Disassembly



The author explores the heterogeneity of human aortic endothelial cells in response to various perturbations, highlighting distinct subtypes and their unique reactions. The study reveals that different perturbations have varied effects on different endothelial cell populations.


Objective Endothelial cells (ECs), macrophages, and vascular smooth muscle cells (VSMCs) are major cell types in atherosclerosis progression, and heterogeneity in EC sub-phenotypes are becoming increasingly appreciated. Still, studies quantifying EC heterogeneity across whole transcriptomes and epigenomes in both in vitro and in vivo models are lacking.

Approach and Results To create an in vitro dataset to study human EC heterogeneity, multiomic profiling concurrently measuring transcriptomes and accessible chromatin in the same single cells was performed on six distinct primary cultures of human aortic ECs (HAECs). To model pro-inflammatory and activating environments characteristic of the atherosclerotic microenvironment in vitro , HAECs from at least three donors were exposed to three distinct perturbations with their respective controls: transforming growth factor beta-2 (TGFB2), interleukin-1 beta (IL1B), and siRNA-mediated knock-down of the endothelial transcription factor ERG (siERG). To form a comprehensive in vivo/ex vivo dataset of human atherosclerotic cell types, meta-analysis of single cell transcriptomes across 17 human arterial specimens was performed. Two computational approaches quantitatively evaluated the similarity in molecular profiles between heterogeneous in vitro and in vivo cell profiles. HAEC cultures were reproducibly populated by 4 major clusters with distinct pathway enrichment profiles: EC1-angiogenic, EC2-proliferative, EC3-activated/mesenchymal-like, and EC4-mesenchymal. Exposure to siERG, IL1B or TGFB2 elicited mostly distinct transcriptional and accessible chromatin responses. EC1 and EC2, the most canonically ‘healthy’ EC populations, were affected predominantly by siERG; the activated cluster EC3 was most responsive to IL1B; and the mesenchymal population EC4 was most affected by TGFB2. Quantitative comparisons between in vitro and in vivo transcriptomes confirmed EC1 and EC2 as most canonically EC-like, and EC4 as most mesenchymal with minimal effects elicited by siERG and IL1B. Lastly, accessible chromatin regions unique to EC2 and EC4 were most enriched for coronary artery disease (CAD)-associated SNPs from GWAS, suggesting these cell phenotypes harbor CAD-modulating mechanisms.

Conclusion Primary EC cultures contain markedly heterogeneous cell subtypes defined by their molecular profiles. Surprisingly, the perturbations used here, which have been reported by others to be involved in the pathogenesis of atherosclerosis as well as induce endothelial-to-mesenchymal transition (EndMT), only modestly shifted cells between subpopulations, suggesting relatively stable molecular phenotypes in culture. Identifying consistently heterogeneous EC subpopulations between in vitro and in vivo models should pave the way for improving in vitro systems while enabling the mechanisms governing heterogeneous cell state decisions.

### Competing Interest Statement

The authors have declared no competing interest.

Single cell ‘omic profiles of human aortic endothelial cells in vitro and human atherosclerotic lesions ex vivo reveals heterogeneity of endothelial subtype and response to activating perturbations

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Heterogeneous Responses of Human Aortic Endothelial Cells to Perturbations
