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Xuejing Wen et al. present a new method, Reverse Chromatin Immunoprecipitation (R-ChIP), for analyzing DNA-protein interactions specifically in plant cells. They apply R-ChIP to identify proteins binding to the promoter of the Arabidopsis gene AtCAT3 and optimize the method using transient transformation of the target promoter to increase efficiency.
Simon Bachler et al. present a new microfluidic platform to control the precise position and patterns of nanoliter droplets with various lipid materials. They show their platform enables monitoring of droplets and subsequent label-free mass spectrometry, which represents an important advance for the synthetic biology community.
With cryo-EM, single-molecule FRET and MD simulations, Iadanza et al. characterise the membrane protein insertase complex BAM in lipid bilayer nanodiscs. They show that the β-barrel domain of BamA is in a ‘lateral open’ conformation, and that BAM-containing lipid nanodisc deform around BAM’s lateral gate, giving structural evidence for lipid ‘disruptase’ activity of BAM.
Eric Jorgenson and Hélène Choquet et al. find that northwestern European genetic ancestry is associated with increased risk of cutaneous squamous cell carcinoma (cSCC) in non-Hispanic whites, and more so in Hispanic/Latinos of the US. The ancestry effect is largely, but not entirely explained by genetic determinants of skin pigmentation in both populations.
Lili Ren et al. investigate antibody response from 176 COVID-19 patients who presented different stages of their disease. This study suggests the late onset of antibody response as a risk factor for disease severity and a limited role of antibody titers in predicting the disease severity of COVID-19.
Peterle et al. show that a subtilisin like serine protease secreted from gut microbiota Bacillus subtilis cleaves the wild-type human transthyretin (hTTR) to generate an amyloidogenic peptide. High propensity of the hTTR fragment to form pathogenic protein aggregates implicates the serine protease in the pathogenesis of acquired senile systemic amyloidosis.
Aluthge et al. evaluated the establishment of human fecal bacterial communities in human microbiota-associated (HMA) piglet and mouse models under identical dietary conditions. They find that human fecal bacterial communities from mature microbiotas establish more successfully in the HMA porcine model than mice, suggesting the broader applicability of the piglet model for human microbiome studies.
Ella Gabitov et al. use functional magnetic resonance imaging to identify changes in neural activity when participants commit an error in a motor sequence task. Their results suggest that two distinct neural circuits are involved in the processing of action errors: (1) the salience network that signals surprise and novelty, and (2) the reward pathway that plays a central role in motivation and incentive drive.
Matiar Jafari, Tyson Aflalo et al. show that the human primary somatosensory cortex is activated when subjects imagine reaches in a cognitive motor task, but not when they plan movement or imagine a static limb position. These results highlight a role for this region in cognitive imagery and motor control in the absence of sensory information.
Han Zhang et al. report molecular dynamics simulations and mutational analysis of a key process of the E. coli glycine cleavage system, an important enzyme complex in C1 metabolism. They identify a key amino acid residue controlling the release of the swinging aminomethyl lipoate arm and increase the overall reaction rate of glycine cleavage by more than twice, providing a strategy for manipulating this reaction system for use in synthetic biology.
Here the authors report a major histocompatibility complex (MHC) association analysis for nasopharyngeal carcinoma in Chinese individuals from Hong Kong, finding 8 independent associated loci associated with lower risk for developing nasopharyngeal carcinoma. Two non-human leukocyte antigen (HLA) genes are E3 ubiquitin ligases, TRIM31 and TRIM39, having a role in the innate immune response and implicating the importance of host Epstein-Barr virus interactions in this cancer.
Here, the authors screen for feedback regulation of ribosomal proteins by overexpressing a non- regulatable version of a gene and observing its effects on the expression of the GFP-fused version. They find that 30% show at least a 3-fold reduction in expression and two genes show a 10-fold reduction with the regulatory site being in the 5’ untranslated region of the gene.
Here, the authors report a multi-ethnic genome wide association meta-analysis of 12 studies from the International Cataract Genetics Consortium. They find six new loci associated with age-related nuclear cataract, in addition to replicating the association at CRYAA, and suggest a strong genetic link between age-related nuclear and congenital cataracts.
Here, the authors report a genome-wide association analysis for corneal resistance factor (CRF), a measure of corneal biomechanical properties relevant to a number of corneal diseases. They identify 135 loci associated with CRF and use fine-mapping and ATAC-seq in human cornea cell lines to identify putative causal variants affecting gene expression.
Reyes et al. identified and characterized dominant mutations in the MutL homolog MLH2 (in S. cerevisiae) and PMS1 (in humans) causing an increased mutator phenotype. Based on their findings, they propose that Mlh2/hPMS1-Mlh1 mutant complexes can act as roadblocks on DNA preventing mismatch repair function.
Miklós Kecskés et al. show that somatostatin-expressing interneurons in the medial entorhinal cortex regulate deep-layer pyramidal neurons and impact short-term memory in mice.
Ye, Xiong et al. present crystal structures of bacterial E3 ubiquitin ligase IpaH9.8 and IpaH9.8LRR–hGBP1. They find that substrate-binding destabilizes the hydrophobic cluster to relieve the autoinhibition of IpaH9.8. This study provides insights into the mechanisms underlying substrate-induced activation of IpaH9.8.
In this work, the authors demonstrate that a coral thermostable GFP (TGP) is an improved tag compared to conventional GFPs. In addition to reporting melting point stability at temperatures near 90 °C, its fusion also helps increase expression levels of test membrane proteins. They further generated synthetic nanobodies against TGP to facilitate purification.
Ren et al. investigated how the obligate intracellular pathogen Toxoplasma gondii satisfies its requirement of phosphatidylinositol (PtdIns). They show that this parasite can synthesize certain PtdIns species de novo and salvages others from human host cells. Endogenous production of PtdIns in the Golgi complex is critical for the acute infection, and its loss perturbs homeostasis of selected anionic phospholipids.
de Medeiros and Farrell test how insect-host interactions influence species divergence in phytophagous insects. Using ddRAD-seq data and hierarchical modelling, they demonstrate, surprisingly, that antagonistic interactions between insect and host do not lead to greater species diversification.