We are inviting submissions of articles on the role of mechanobiology in health and disease with the aim of publishing high quality research devoted to advance our understanding of mechanics shaping biological function. We are also happy to present a Collection of papers already published in our journal in this exciting field.

Balisi and Van Valkenburgh analyse the effect of body size and dietary specialization on extinction regimes in North American Canidae. They find that hypercarnivory, which evolved independently multiple times, does not increase species-level extinction but is associated with extinctions of clades.

Sherif Bayoumy et al. report a lateral flow immunoassay (LFIA) to quantify aberrantly glycosylated CA125 to diagnose epithelial ovarian cancer. Their method has a 30-minute read-out time, high sensitivity and specificity, and can distinguish ovarian cancer from benign endometriosis and other cancers.

Akira Meguro et al. report a genome-wide association study for sarcoidosis—a systemic inflammatory disease—in the Japanese population. They identify 3 non-HLA loci with genome-wide significance, 2 of which have not been previously associated with sarcoidosis in any population.

Sakthivel et al. report two natural genetic variants of galectin-11 in sheep and demonstrate that their ability to dimerise correlates with the differences in their anti-parasitic activity that triggers larval arrest. This study provides a basis for genetic studies toward selective breeding of animals to improve their resistance to parasites.

Park et al. identify Multiple Myeloma SET domain (MMSET/NSD2) in a large-scale CRISPR screen of genes whose depletion regulates hematopoietic differentiation and found it to interact with BRCA1. Thus regulation of MMSET/NSD2 stability BRCA1-mediated ubiquitination could be explored for potential therapeutic interventions in multiple myeloma.

Eeva Sliz et al. show an association between triacylglycerols species carrying 18-carbon unsaturated fatty acids and cortical thickness by combining serum lipidomics and brain imaging data. This association is more pronounced in cortical regions with higher expression of genes regulating fatty acid metabolism and cellular membranes.

Zhang et al present an integrated real-time imaging and flow field control platform based on water droplet evaporation on super-hydrophobic substrate (SHS) to enable amyloid fibril aggregation. They apply this methodology to observe structural polymorphism in PHF6 peptide and full length Tau441.

Oi et al. describe LIVE-PAINT, a new method to achieve superresolution fluorescent imaging within live cells. They demonstrate its efficacy by imaging a number of different proteins inside live S. cerevisiae cells. Their method is widely applicable, easily implemented with extended data acquisition times.

Xu, Tang et al. show that ω-transaminase CrmG is insensitive to the inhibition from by-products α-ketoglutarate or pyruvate. They find that these by-products cannot interact strongly with the flexible roof of the active site in CrmG. This study provides insights into the rational design of transaminase to eliminate by-product inhibition.

Torras-Llort et al. find that the chromatin binding protein Barrier-to-Autointegration Factor (BAF) associates with centromeres and is required for proper centromere assembly and function in Drosophila. They show that disruption of centromeric BAF localization prevents PP2A inactivation in mitosis compromising global BAF phosphorylation and leading to delayed anaphase onset and nuclear envelope defects.

Luo, Zhou et al. show that Bedaquiline (BDQ, Sirturo), approved to treat multi-drug-resistant tuberculosis, inhibits the yeast and human mitochondrial ATP synthases in addition to its intended target, the Mycobacterium tuberculosis ATP synthase. The structure of the mitochondrial ATP synthase bound to BDQ suggests a means to modify this inhibitor to increase its specificity for the M. tuberculosis  enzyme, thereby reducing its side effects for patients.

Habowski et al. develop a sorting protocol for purification and comparative analysis of mouse colon stem cells and their progeny. By proteomic and transcriptomic analysis, they determine that lineage commitment is accompanied by a greater change in mRNA splicing and polyadenylation than in gene expression and they characterise signalling pathways involved in differentiation.

Wikström and Springett analyze the thermodynamic efficiency of redox reactions and proton translocation by the complexes of mitochondrial respiratory chain. They report that the thermodynamic efficiency is about 80–90% and that the degree of coupling between the redox and proton translocation reactions is very high during active ATP synthesis, but decreases when ATP synthesis stops.

Deng-hai Zhang et al. report a network pharmacology analysis of the Traditional Chinese Medicine (TCM) lung-cleaning and toxicity-excluding (LCTE) soup. By exploring the chemical compounds that make up LCTE and the likely pathways and proteins that they target, the authors show that LCTE may have the potential to directly inhibit the SARS-CoV-2 virus and relieve inflammatory symptoms.

Koike et al. show that the 2-nitroimidazole doranidazole increases radiation-induced DNA damage in hypoxic glioma stem cells (GSCs). They further demonstrate that additional radiation-independent cytotoxicity of 2-nitroimidazoles is due to ferroptosis that occurs through blockade of mitochondrial complexes I and II leading to metabolic changes in the oxidative stress response.

Kazazian and colleagues identify FAM46C/TENT5C as an interactor and negative regulator of PLK4 activity in centriole duplication. The authors also find that FAM46C expression strongly reduces cancer cell invasion, uncovering a role for FAM46C as tumor suppressor.

David Baracchi et al. show that honey bees exposed to geraniol, a component of an attractant pheromone, exhibit improved olfactory learning and memory while the opposite effect was seen in honey bees exposed to the aversive pheromone, 2- heptanone. These changes occurred through a modulation of appetitive motivation without affecting odor processing, suggesting an important role for pheromones as modulators of motivational and learning processes.

Thomas Conrad et al. identify sequences downstream of transcription start sites that affect T7 promoter activity and use this to generate promoter variants with enhanced transcriptional output. They use the optimized promoters to prepare cDNA libraries for single-cell RNA sequencing with increased complexity compared to those prepared with standard T7 promoters.

Tanabe, Fujii, Okada-Iwabu, Iwabu et al. report the crystal structures of the D208A variant of human adiponectin receptor AdipoR1 as well as the revised structures of the wild-type AdipoR1. These structures clarify the interconversion between the open and closed states of this protein, which may be relevant to its function.

Wu et al. provide insight to the role of acetyl coenzyme A in regulating N-acetylation in insect AANAT using ITC and NMR methods. These results provide useful data on the structural function of insect AANATs.

Kim et al. use RNAseq of two watermelons to select candidate genes coding for enzymes that catalyze modifications of cucurbitacins. They characterise four of the 16 candidate enzymes (3 different acetyltransferases and one UDP-glucosyltransferase) by HPLC, LC-MS, NMR, and in vitro enzymatic assay. They further show with in vivo assay in Drosophila, that acetylation of cucurbitacin increases neuronal activity in insects.

Benjamin Simpson et al. use publicly available cancer genomic data to investigate copy number changes at the 3q26.31–32 locus, which has been associated with aggressive prostate cancer based on single-nucleotide polymorphisms. They find that gains of NAALADL2 and TBL1XR1 in this locus are associated with more aggressive subtypes of prostate cancer and the transcription of pro-proliferative signalling processes.

Ergal et al. report that biohydrogen production from glucose by an engineered microbial consortium of Clostridium acetobutylicum and Enterobacter aerogenes can be 40% higher than the “Thauer limit”. They further show that the volumetric H₂ production rates of their system are superior compared to any mono-, co- or multi-culture system reported to date.

Pedro R. Frade et al. analyze published bacterial data and environmental data from the eReefs platform to study bacterioplankton community dynamics across the Great Barrier Reef. They identify communities within inshore and outershelf reefs that are susceptible to nutrient and temperature changes, highlighting the importance of understanding microbial ecosystems dynamics informing reef health.

Rugema, Garland-Kuntz et al. report the 2.7 Å crystal structure of a fragment of a catalytically active PLCε in which the RA1 domain is integrated into the core. They find that a conserved amphipathic helix in the autoregulatory X–Y linker of PLCε modulates its catalytic activity in cells. This study provides structural insights into the regulation of this essential cardiovascular enzyme.

Marc A. Beal, Matt J. Meier et al. use a transgenic rodent model with NGS to inform mutational signature analyses. They analyze lacZ mutations from the bone marrow of MutaMouse animals exposed to chemical mutagens. They report that lacZ sequencing generates chemical-specific mutation signatures observed in human cancers with established environmental causes.

Danyang Wang and Yina Ma measure the amount of money participants are willing to forgo for the opportunity to access social or non-social evaluations of the self. They show that subjective values on knowing social evaluation is valence-dependent whereas that on non-social evaluation is valence-insensitive. Moreover, oxytocin contributes to valence-dependent valuation on social evaluation.

Kuwabara et al. identify a novel long intergenic noncoding RNA (lincRNA), termed Lionheart, upregulated in pressure overloaded hearts in mice. Deleting this gene results in decreased systolic function and reduction in MYH6 protein levels following pressure overload. They demonstrate that Lionheart interacts with PURA, preventing its binding to the promoter region of Myh6 locus, leading to reduced MYH6 protein expression.

Ravindran et al. report the construction of synthetic immediate-early genes (SynIEGs), target genes of the Erk signaling pathway. SynIEGs implement user-defined regulation while tracking transcription and translation. This study underscores post-transcriptional regulation in signal decoding that may be masked by analyses of RNA abundance alone.

Limbocker et al. show that trodusquemine, an aminosterol, reduces the cytotoxicity of protein misfolded oligomers by displacing them from cell membranes in the absence of any overt structural/ morphological changes in them. This mechanism appears to be general, as they test it for oligomers of αS, Aβ and the model protein HypF-N to human neuroblastoma cells.

Ryoichi Yano et al. report a Nanopore-based reference genome assembly of muskmelon—a fruit known for its many cultivated varieties, including cantaloupe and honeydew—using the Japanese Harukei-3 cultivar. They identify structural genetic variation by comparing the reference to several melon genome assemblies and investigate tissue-wide gene expression patterns by RNA sequencing.

From a fermenting bacterium, Thermotoga maritima, Kuhns, Trifunovi ć et al. purify a complex that includes a respiratory enzyme, Rnf. They find that the Rnf complex requires Na⁺ for activity and that it catalyzes Na⁺ transport in liposomes. This study shows that the Rnf complex is indeed an ion translocating, respiratory enzyme.

Radford et al. monitored cattle marked with artificial eyespots in non-commercial cattle farms in northern Botswana, and demonstrate that cattle with these eyespot markings were more likely to avoid predation by large carnivores. Their findings have applications as a cost-effective tool to reduce livestock predation by ambush predators.

Ravasio et al. develop an assay to quantify the clustering of Eph receptor EphA2 upon ligand binding, based on the scoring of single cells. They discover that clustering phenotype predicts cell and population migration potential in cancer cells and reflects Eph associated gene expression profiles in cancer cell lines.

Shinzawa et al. develop a method that improves the transfection efficiency for Plasmodium parasites that cause malaria by transfecting Cas9-expressing parasites with linear donor templates. This method allows efficient integration of the donor template while preventing unexpected recombination.

Mochizuki, Fukumoto, Ohara, et al. study the protective role of the rare sugar d-tagatose against plant disease. They focus on its effects against the downy mildews and delineate the metabolic pathway that blocks the initial infection. Their work paves the way for the development of safe fungicidal agrochemicals using natural products.

Hwang et al. show that the activity of PRMT5 methyltransferase is regulated by Src kinase-mediated phosphorylation at Y324 in response to DNA damage. They also show that PRMT5 participates in NHEJ repair by regulating 53BP1 protein levels and is critical for cellular survival after DNA damage.

Ausar et al. show that the crystal structure of gdPT, a mutant pertussis toxin (PTx), is nearly identical to that of PTx. They also find that gdPT exhibits broader immunogenicity than the pertussis toxoid antigen. This study suggests a promising potential of gdPT as an improved acellular pertussis vaccine candidate due to its reduced toxicity and greater immunogenicity.

Maxwell Scott et al. report the genome of the New World screwworm, a devastating livestock pest in South America and the Caribbean. Using transcriptomic analysis of the insect’s developmental stages combined with genomic analyses, the authors identify genes that may be important for its parasitic lifestyle.

Wang et al. describe a strategy for quantitatively performing composition analysis of heparan sulfate using ¹³C-labeled disaccharides and polysaccharides that mimic the glycosaminoglycan chemical structure. They further show that these isotopically labelled small molecules can be used as internal standards for mass spectrometry analysis of heparan sulfate derived from mouse tissue and plasma.

Yandong Zhang, et al. develop iDentification and qUantification sEparaTion (DUET) to quantify target protein and its post-translational modification isoforms in single cells. Using their method, they report heterogeneities in the ubiquitination levels of histone H2B in single yeast cells and reveal the cell-cycle dynamics of H2B monoubiquitination.

Zhang, Wu, Feng et al. show that ligand-bound glutamine binding protein assumes multiple metastable binding sites, presenting a more dynamic energy landscape than its ligand-free form. This study provides insights into the ligand-binding mechanisms coupled with protein dynamics that underly the apparent binding affinity.

Tao Li et al. report crystal structure of MucA-MucB complex and identify a cavity region of MucB that binds PEG molecule. They further show that this hydrophobic cavity of MucB is a primary site for sensing lipid molecules and that lipid A stimulates MucB to release MucA for AlgW cleavage, helping to understand the regulation mechanism of alginate biosynthesis.

Vinod Kumar Singh, Arnav Rastogi, et al. study etiology of mutational signature 8 (SBS8) in human cancers. They develop genome-wide composite epigenomic context maps related to mutagenesis and DNA repair. They report that SBS8 preferentially occurs in heterochromatin and likely arises from late replication errors during cancer progression.

Douglas Arneson et al. develop MethylResolver that enables the deconvolution of cellular fractions from bulk DNA methylation data. Using this method, the authors resolve tumor purity-scaled immune cell-type fractions without requiring cancer-specific signatures and identify cellular fractions as prognostic factors of multiple human cancers.

Hao, Qiao, Gao et al. show that over ten thousand oligonucleotides encoding 445 KB of digital data can be stored in cultured bacterial cells. Data storage in living cells increases the information storage capacity while enabling its economical propagation.