Articles in 2021

Wang et al. use transcriptomic analysis to show that disruption of the transcription factor Lyl-1 in primitive macrophage progenitors results in defective differentiation that impacts on embryonic patterning and neurodevelopment. They also show that Lyl-1 disruption leads to a reduction in mature microglia, thus revealing its role in macrophage and microglial development

Olivieri et al. exploit floating properties of microdomain-associated proteins to investigate host proteins important for Plasmodium falciparum erythrocyte invasion. Using proteomic and bioinformatic approaches, they analyze clusters of protein abundance profiles from detergent resistant membranes (DRMs) of erythrocytes and identify a host protein, ART4, important for P. falciparum invasion into RBCs.

Sandhu et al. report that the synaptonemal complex (SC) protein, TEX12, localises to centrosomes independently of the SC during meiosis. They also show that it provokes centrosome amplification in somatic cells, a pathology associated with cancer development.

Yang et al. report a mechanism of restoration of tumor suppressor activity of mutant p53 by disrupting its binding to peptidase D, leading to posttranslational modification, refolding and reactivation of the protein and its inhibition of cancer cell growth in vivo and in vitro. This finding presents a new possibility of “reactivating” mutant p53 and reveals a new therapeutic approach for a large number of human tumors.

Harding et al. present a biophysical and structural characterization of the complex between huntingtin (HTT) and HAP40 proteins. They show that the abundance of HAP40 is coupled with that of HTT and that there is greater conformational variety in the exon 1 of the mutant HTT than WT, important for the future drug discovery studies targeting Huntington’s disease.

Huang et al. use a soil translocation experiment to test the effects of higher temperature and initial organic matter content on the stability of soil carbon. Their results demonstrate a link between microbial communities and soil carbon-dependent sensitivity to warming.

To advance our understanding of aberrant neuronal activity in Alzheimer’s disease (AD) Korzhova et al. use in vivo two-photon calcium imaging to record activity from cortical neurons of awake APPPS1 transgenic mice over four weeks, during the early phase of plaque deposition. They demonstrate that neuronal network pathology in models of cerebral amyloidosis is the consequence of persistent single cell aberrant neuronal activity, which could have diagnostic and therapeutic relevance for AD.

Xihua Yue et al. report that Tankyrase-1 controls poly-ADP-ribosylation of Golgin45, a Golgi structural protein, which has a profound influence on glycosyltransferase trafficking and protein glycosylation at the Golgi. This may shed new light onto mechanisms involved in development and oncogenic transformation.

Ito et al. demonstrate that murine gastric parietal cells produce estrogen using fatty acids as an energy source, and secrete estrogen in response to the blood triglyceride levels. The authors propose that the stomach is involved in the monitoring and the regulation of blood triglyceride levels.

Calvaresi et al. use hydrogen-deuterium exchange coupled to mass spectrometry to compare the conformational dynamics of the human heat shock protein Hsp70 when free and when associated with liposomes composed of common lysosomal lipids. They also investigate the conformational changes occuring in Hsp70 when transitioning from the pH of the cytosol to that of early and late lysosomes. This study provides new molecular insights into how Hsp70 can stabilize endo-lysosomal membranes and inhibit the uncontrolled release of degradative enzymes linked to lysosomal storage disorders.

Beaulieu et al. report on the distribution of bioactive ergot alkaloids produced by symbiotic fungi found primarily in four clades of morning glories. Their results identify the repeated evolution of this symbiosis in Convolvulaceae, and a correlation between ergot alkaloid presence and greater seed mass that is consistent with a defensive function.

Hoivik, Hodneland and colleagues employ convoluted neural networks alongside radiogenomic biomarkers to profile endometrial tumors. They identify an 11-gene high-risk signature validated with retrospective patient data.

Redweik et al. explore mechanisms underlying the effects of reserpine treatment on Salmonella-infected explants from chicken intestine as well as the effects on the intestine in vivo following oral treatment. They demonstrate that several signaling pathways (norepinephrine, mTOR, epidermal growth factor) contribute to these reserpine-induced antimicrobial responses, with MEK1/2 playing a central role.

Luo, Wu, et al. assess the ability of Cassiae Semen and its extracted components to alleviate non-alcoholic fatty liver disease (NAFLD) in mice. In addition to reducing the symptoms of NAFLD, the authors find that Cassiae Semen modifies the gut microbiome of mice, and that its effects on the symptoms of NAFLD can also be conferred by fecal microbiome transfer.

Ran Chen et al. report the crystal structure of human m3C methyltrasfease METTL6. They generate structure models of hMETTL6 in complex with substrates, providing important insight into the molecular recognition mechanism by METTL6 and may aid in the METTL-based rational drug design in the future.

Helness et al. show that GFI1/CHD4 complexes critically regulate chromatin accessibility and histone modifications to regulate target genes affecting diverse cellular processes in neutrophils. Their results provide further insight into the molecular network operated by GFI1 for neutrophil differentiation programs.

Tuffin et al. demonstrate a method for culturing conditionally immortalized human podocytes and GEnCs in 3D by forming spheroid cultures termed GlomSpheres, which are found to segregate in an organized manner. These are shown to establish a GBM-like extracellular matrix with increased cell differentiation and maturity when compared to 2D cultures and their use demonstrated in pharmaceutical screening using rapid imaging approaches.

Joern Pezoldt et al. analyze mouse spleen fibroblasts using single cell RNA sequencing, revealing 11 distinct clusters of fibroblastic cells or subtypes. Their results collectively provide further insight into the transcriptional identities of splenic fibroblasts and innate immune signatures of distinct stromal compartments.

Sanchón et al find that misfolded proteins formed in the ER can become associated with mitochondria, both in mammalian cells and in yeast, resulting in impaired mitochondrial function. They further discover that components of ERMES-mediated ER-mitochondria contacts are needed for this mechanism, which they name ERAMS, for ER-associated mitochondrial sequestration.

Kanako Shimizu et al. identify HLA-A24 high-binding epitopes in the SARS-CoV-2 spike region and investigate their cross-reactivity with CD8⁺ T cell receptors. These results provide further insight into CD8⁺ T cell cross-reactivity toward SARS-CoV-2 and may be useful in future strategies for vaccine development.