Research articles

Nagai et al. show that mice fed high-fat diet (HFD) accumulate oxidized low-density lipoprotein in macrophages through the renin–angiotensin system, which impairs visual function. They find that angiotensin II type 1 receptor (AT1R) improves the visual function of HFD mice, suggesting AT1R signaling as a potential therapeutic target for age-related macular degeneration.

Thomas Kaye et al. use Laser-Stimulated Fluorescence and fossil evidence from the oldest known bird, Archaeopteryx, to document the oldest record of molting, demonstrating that a sophisticated molting strategy developed unexpectedly early on in the evolution of avian flight. This discovery provides important insights into the flight capabilities of the earliest birds and predates other major flight adaptations.

Using imaging and molecular dynamics simulations, Joseph et al characterize the tension-responsive recruitment of the membrane bending protein epsin and its stabilization of clathrin-coated structures (CCSs) to form clathrin-coated pits. They find epsin’s ENTH- and unstructured IDP domains play complementary roles in CCS maturation under high tension.

Chung-Yi Wu et al. demonstrate a role of neuraminidase (NA) for Influenza A viruse (IAV)-specific CD8⁺ T-cell response and virion assembly. When mice are vaccinated with the live attenuated NA-defective IAV, they are protected from the upcoming IAV infection. This study provides insights into the development strategies of universal influenza vaccines.

Megan Shand et al. present Lineage derived Somatic Truth (LinST), a validated data set of somatic mutations from a colon cancer cell line with a known lineage tree structure. They show that LinST can be used to benchmark true-positive and false-positive rates in somatic variant-calling pipelines applied to cancer genomic data.

Batchelder et al. report a new penem class antibiotic, T405, which exhibits potent activity against M. abscessus and clinical isolates from cystic fibrosis patients. The development of resistance to T405 is inhibited with the addition of a β-lactamase inhibitor, avibactam. Its clinical potential is further demonstrated by T405 displaying a favourable pharmacokinetic profile in mice with an absence of toxicity.

Di Domenico et al., provide a comprehensive assessment of DNA methylation in a large cohort of pancreatic neuroendocrine tumors. This work provides new insights into the epigenetic heterogeneity of the disease and cellular basis.

Noriaki Miyanaga and Hideaki Takagi et al. identify an essential role for migratory dendritic cells in mediating immunotherapy treatment against allergies in mice. They show that submandibular lymph node dendritic cells induce regulatory T cells, and their absence abrogates the effectiveness of immunotherapy treatment.

Tinguely et al. develop a photonic chip-based correlative light-electron microscopy system to generate co-registered multi-modal total internal reflection fluorescence microscopy (TIRF) and electron microscopy (EM) images of biological samples at nanometer scale.

Stratman et al. provide evidence linking the cxcl12b/cxcr4a signaling axis in endothelial cells to an increased release of platelet-derived growth factor b, leading to the recruitment of smooth muscle cells to developing arteries. This signalling axis is suppressed in the venous endothelium during early development by the high expression of blood flow-regulated transcription factor klf2a.

Bergmann et al. employ resting state fMRI to understand how individual variation affects the functional architecture of the mouse cortex. The results of this study lay the foundation for precision fMRI use in mice investigating individual brain organization.

Qi Zhang, Zhenyan Zhang et al. show that the numbers and relative abundance of antibiotics-resistance genes increase during a cyanobacterial bloom in Lake Taihu of China. This correlation provides insights to the ecologists and the policy makers who manage the quality of fresh water.

Patrick Stumpf et al. use a machine learning technique called transfer learning to compare bone marrow cell-type information between mice and humans, based on single-cell RNA-seq data. Using their model, they identify aspects of cellular expression profiles that transfer and those that don’t, which can be used to understand when mouse models of human disease are appropriate.

Here the authors reveal unique structural organization of the mammalian TRAPPII complex, which is critical in regulating membrane trafficking. They find that TRAPPII serves as a guanine nucleotide exchange factor for unexpected Rab GTPases such as Rab43 and Rab19.

Forcato et al. show that incomplete reminder cues rather than complete ones stabilize human memories during sleep. This study suggests that only incomplete reminders initiate long-term memory stabilization via mismatch detection during sleep.

Hendus-Altenburger et al. provide biochemical, structural and functional information on the lipid interaction domain (LID) of the Na+/H+ Exchanger 1 (NHE1). They find that NHE1-LID is intrinsically disordered, but, when allowed to interact with a lipid membrane, forms a helical αα-hairpin, stabilized by hydrophobic and electrostatic interactions. This co-structure is fundamental for NHE1 activity, giving insight into membrane protein regulation via disordered domains.

Wang et al. report on the role of a novel E3 ubiquitin ligase, Plastid Protein Sensing RING E3 ligase 1 (PPSR1), during tomato fruit ripening and find that it interacts with phytoene synthase 1 (PSY1) precursor protein and mediates its degradation via ubiquitination. This affects the steady-state level of PSY1 protein, the key rate-limiting enzyme in the carotenoid biosynthetic pathway. This study may provide a strategy for developing carotenoid-enriched horticultural crops.

Using a rodent model of ischemic stroke, Zahgmi et al. report on the neuro-protective effects of a bioconjugate form of the glutamate scavenger, glutamate-oxaloacetate transaminase (GOT). They found that a single dose of the bioconjugate was more effective in reducing the infarct size and improving motor function than the native GOT due to its higher and long lasting blood activity.

Gajendran et al. show that a C21-steroidal derivative called A671, 3-O-chloroacetyl-gagamine, suppresses the growth of T-cell lymphoma in mice. They find that A671 activates SAP18 to suppress the transcription of SIRT3, inhibiting cell growth. This study presents a new pharmacological target pathway for T-cell lymphoma.

Liu et al find that mesothelin (MSLN), a candidate target for antibody-based cancer therapy, is targeted by several proteases, and that inhibition of shedding facilitates killing of cells by an immunotoxin targeting MSLN.