Research articles

By integrating transcriptome, regulatory element and chromosome topology profiles, Schwartz et al identify redistribution of p53 and CTCF genomic binding to be associated with transcriptional and phenotypical changes during Ras-induced transformation of mammary epithelial cells.

Pinotsis and Miller present a simplified neural mass model for estimating the laminar dynamics that contribute to non-invasively recorded time frequency data. Using two independent MEG datasets, they give evidence for deep cortical layers contributing to inter-individual variability in visually induced oscillations. Their study links non-invasive brain imaging data, laminar dynamics and top-down control.

Using genetic code expansion, Zhao, Shi et al. generate light-sensitive tyrosine analogues to obtain insights into the activation of the NGF receptor, TrkA. They identify light-sensitive and NGF-insensitive phosphorylation sites, validating the approach and providing insights into TrkA signaling

Pitzalis et al. use replicative RNAseq, small RNA (sRNA)seq, and parallel analysis of RNA ends (PARE)seq analysis to identify networks of sRNAs-guided post-transcriptional regulation within local Turnip mosaic virus infection sites. This study provides insights into the complex regulatory networking at the plantvirus interface within cells undergoing early stages of infection.

Wright et al. report the first structure of a human TRPC1/4/5 channel in complex with a xanthine-based TRPC5 inhibitor Pico145. They find that Pico145 binds to a conserved lipid binding site of TRPC5, where it displaces a phospholipid. This study provides insights into the mechanism-of-action of xanthine-based TRPC1/4/5 modulators.

Pranam Chatterjee et al. present a novel computational platform for engineering peptide fusions that bind to the SARS-CoV-2 spike protein and tag it for proteasomal degradation. They experimentally validate an optimal variant in human cells, showing that it inhibits production of infection-competent virus.

Morahan et al. investigate inhibitors of human mitotic kinases in P. falciparum and show a resistance mechanism to the drug Hesperadin through an epistatic interaction between the PfArk1 and PfNek1 kinases. This study demonstrates that existing inhibitors can be used to validate additional essential and druggable kinase functions in the parasite.

Joseph Angeloni et al. show that Caenorhabditis elegans can detect and are attracted to multiple signal molecules produced by the bacterium Vibrio cholerae, specifically the 3′,5′-cyclic diguanylate (c-di-GMP), even though this bacterium kills the host at a high rate. This study reveals how bacterial c-di-GMP may serve as a cue for C. elegans that they can use to detect food or alternatively, impair their immune response, which could facilitate bacterial invasion and survival.

Tindell et al. identify glial granules in the adult Drosophila brain. The glial granules contain polypeptides known to function in germ cells, including Tudor. They find that Tudor in glial granules silences transposable elements and regulates the biogenesis of piRNA. This study uncovers previously unknown glial granules that regulate brain transcriptome.

Nega et al. shed light on the interplay of the two domain enzymes of the major autolysin, AmiA and GlcA, in S. aureus for peptidoglycan hydrolysis during bacterial cell division. They show that GlcA requires the prior removal of the stem peptide by AmiA for its activity and that GlcA is not an endo-enzyme as previously thought, but an exo-enzyme that chops down the glycan backbone to disaccharides independent of its O-acetylation modification.

Christian Kappel et al. examine the genetic composition of fairy circles, regular circular patterns of grasses in the Namib Desert, using ddRAD-seq. They find that these grasses are made up of multiple unrelated genets rather than genetically identical grasses, suggesting non-clonality.

Ke Shi et al. perform a structural and biochemical characterization of the complex formed between Spackle, an early gene product of T4 and the gp5 lysozyme located in the tail of T4, thereby revealing a new mode of inhibition of the well-known lysozyme enzyme. This study provides structural insight into the phenomenon of superinfection exclusion, phenomenon by which bacterial cells infected with a T4 phage become resistant to secondary infections by the same or closely related phages.

Sonali Setua et al. identify a small molecule which is capable of disrupting the interaction between the plasmodium-derived protein UIS3 and the host protein LC3. Disruption of this interaction by this small molecule triggers parasite elimination from host cells in an autophagy-dependent manner, without affecting the cells’ normal autophagy pathway.

Ana Chucair-Elliott, Sarah Ocaňas et al. present a NuTRAP approach for simultaneous analysis of transcript expression and DNA modifications in two specific mouse brain cell types, astrocytes and microglia. They further apply this approach to identify molecular changes in microglia following LPS treatment and identify both transcriptomic and epigenomic alterations not apparent in tissue-level analyses.

Sarah E. Donohue et al. characterize the spatiotemporal propagation of target and distractor processing in the human visual cortex. They show that these signals propagate in parallel as fast and slow sweeps from higher to lower hierarchical levels, and that the fast target processing signal can bypass intermediate levels correlating with behavioral performance.

AhYoung, Eckard et al. show that the expression of Neutrophil Serine Protease 4 (NSP4) during the early stages of mast cell development regulates the levels of histamine and serotonin in mast cell granules. This study reveals an important physiological function of NSP4 in mast cell-mediated vascular leakage in mice, establishing NSP4 as a potential therapeutic target for mast cell-dependent immune disorders.

Neil Burns et al. use a continuous-surface otolith microchemistry approach to geolocate whiting across the west coast of the UK and show connectivity across existing stock boundaries, highlighting the importance of the Firth of Clyde nursery area. This study is important for fisheries management and will have an influence on methods used to infer connectivity from otolith microchemistry.

Using hyperpolarized 13C magnetic resonance imaging (MRI), Timm et al. show that a change in oxidative mitochondrial carbohydrate metabolism precedes cardiac decline in a rat model of heart failure induced by doxorubicin (DOX), a widely used chemotherapeutic agent. This study suggests the possibility of using hyperpolarized MRI to test cancer patients receiving DOX for early signs of cardiotoxicity.

Neville et al. investigate how Streptococcus pneumoniae mitigates metal ion stress. Despite cadmium induced dysregulation of central carbon metabolism and lipid membrane homeostasis, they find that S. pneumoniae can remain viable by selectively utilizing predominately metal-independent cellular pathways. This study provides insights into how bacteria overcome metal ion toxicity.

Holman et al. develop a grid-less autonomous adaptive sampling method to explore high-dimensional spatiochemical experimental systems. Their method greatly decreases image acquisition time while improving spatial resolution, and when implemented with FTIR, it outperforms existing standard grid sampling approaches. They further show its utility for a complex biological sample, C. elegans.