Research articles

Lisa Schwetlick et al. present a computational model linking visual scan path generation in scene viewing to physiological and experimental work on perisaccadic covert attention, the act of attending to an object visually without obviously moving the eyes toward it. They find that integrating covert attention into predictive models of visual scan paths greatly improves the model’s agreement with experimental data.

Bouyer et al. report that the new permeation pathways (NPP), responsible of modulating erythrocyte permeability to diverse solutes and considered only to be in pathogenic asexual stages of P. falciparum, are also active in erythrocytes infected with immature gametocytes and this activity declines with gametocyte maturation. NPPs are regulated by the cAMP signalling cascade, and the decrease in cAMP levels in mature stages slows NPP activity.

Higashijima et al show that mice lacking the Kdm7a demethylase exhibits anterior homeotic transformation of the axial skeleton and downregulation of posterior Hox gene transcription and these changes are associated with increased H3K9me2 at posterior Hox loci. These findings provide insights into the epigenetic control of Hox-mediated patterning in embryogenesis.

Momen-Roknabadi and colleagues present an inducible genome-wide CRISPRi library for yeast. This library will enable comprehensive transcriptional perturbations of the yeast genome, facilitating more directed exploration of this model organism’s functional biology.

Peltier et al. report additional type I toxin-antitoxin (TA) systems within phiCD630-1 and phiCD630-2 prophage regions of Clostridioides difficile strain 630. They find that type I TA modules within the phiCD630-1 prophage increase the stability and heritability of this prophage, uncovering the role of TA in prophage maintenance.

Using small-angle X-ray scattering, Hajdú et al. show that Rho-associated protein kinase 2 population is a mixture of folded and partially extended conformers. They find that the binding of natural protein substrates to the kinase domain breaks up the interaction between the N-terminal kinase and C-terminal regulatory domains. This study identifies a dynamic behavior of this long, dimeric molecule in solution.

Yuki Shibayama et al. find that high expression of (pro)renin receptor [(P)RR] in human pancreatic ductal cells causes increased genomic instability, leading to the development of pancreatic ductal adenocarcinoma. They show that (P)RR exerts its carcinogenic effects through direct binding and activation of the chromatin regulator SMARCA5.

Investigating signalling induced by the cytokine CCL2 as a therapeutic target, Tu et al demonstrate that blockade of the CCL2 receptor, CCR2 enhances CD8+ T cell recruitment and activation and the therapeutic efficacy of PD-1 inhibition in tumours.

Manzo et al. describe the development of multiple pleurocidin analogues with substantially improved antibacterial properties, conformational flexibility and therapeutic efficacy against murine models of bacterial lung infection. The most promising analogue is as effective as vancomycin in an in vivo mouse EMRSA lung model.

Avet et al. characterize I-287, an inhibitor to protease-activated receptor 2 using BRET-assays. They find that I-287 selectively inhibits Gα_q and Gα_12/13 without affecting the activation of G_i/o or the recruitment of βarrestin2 and that it blocks inflammation in vitro and in vivo.

Rico et al. propose a simple approach based on borax stimulation of NaBC1 transporter, which enhances FN-binding integrin-dependent mesenchymal stem cell adhesion and contractility, promotes osteogenesis and inhibits adipogenesis. Osteogenic differentiation depends on activation of the BMP pathway through a mechanism that involves simultaneous co-localization of NaBC1 with FN-binding integrins and BMPR1A.

Stoddart et al. propose rational design of a covalent and selective ligand probe to fluorescently label GPCR in transiently transfected and endogenous systems. Using the adenosine A_2A receptor as a model system, they show fluorescent labelling in an endogenous system, without impeding access to the orthosteric binding site. This study is useful to selectively and non-invasively study localisation and functions of GPCRs.

Feng et al. report that TRPV4 plays an important role in Schwann cells (SCs) during nerve demyelination and remyelination in mice. Using sciatic nerve cut injury mouse models, they find that TRPV4 expression is remarkably increased in demyelinating SCs during sciatic nerve injury; and ablation of TRPV4 expression impairs the demyelinating process after nerve injury, resulting in their delayed remyelination and functional recovery.

Kohno, Kobayashi, Yamamoto et al. use a recent mouse model where the affinity of the cardiac ryanodine receptor (RyR2) to Calmodulin has been enhanced through a point mutation. They show that this mutation inhibits hypertrophic signaling and improves survival after pressure-induced overload, providing insights into the mechanisms of cardiac hypertrophy

Karkman et al. explore how well available global sewage metagenomic data can predict clinical resistance prevalence using different models. A combination of sewage metagenomic data with socioeconomic factors predicts overall clinical resistance well, but still has limited ability to discriminate between resistance to different classes of antibiotics.

Generating mice lacking protein kinase N1 (PKN1), Yasuda et al. find that PKN1 loss leads to abnormal input-nonspecific mGluR-dependent long-term depression. The authors also observe reduced glutamate uptake and immature synaptic transmission, suggesting an important role for PKN1 in synapse maturation.

Darwisch, von Spangenberg et al. show that ACBD5‐deficient mice exhibit elevated levels of very long‐chain fatty acids and a progressive cerebellar pathology. A complex metabolic phenotype suggests that ACBD5 with its acyl‐CoA binding and peroxisome‐ER tethering functions might contribute to the regulation of anabolic and catabolic cellular lipid pathways.

Brinton, Uauy and colleagues utilize genomic data from the 10+ Wheat Genome Project to develop a useful tool for studying and generating new wheat cultivars. This framework uses advanced exploitation of wheat haplotypes to bring newfound precision and efficiency to wheat breeding.

Didriksen, Nawaz, et al. identify three novel genetic risk variants for restless legs syndrome and confirm 19 out of 20 previously reported variants through a genome-wide association meta-analysis including nearly half a million individuals. Using expression QTL analysis, they also find that a subset of these loci may have a causal effect on nearby gene expression.

Michael Donovan et al. examine well-preserved remains of diverse insect-feeding and fungal damage on Patagonian fossil and extant material of the conifer Agathis. They report a suite of blotch mines, galls, scale-insect covers, and rust fungus that re-occur on the same host genus through time and space, showing the persistence of ecological guilds and possible host-tracking across major plate movements since the late Mesozoic.