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Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

A combined genomic and metabolomic approach sheds light on the consistency between genotypes, chemotypes, and toxico-ecotypes of European Microcystis strains, suggesting that different clades may induce different ecotoxicological threats.

The heterogenous nature of rheumatoid arthritis renders the prediction of responsiveness to biological treatments difficult. Here the authors analyze bulk RNA-seq data from the STRAP trial (n = 208) to build a machine-learning model for predicting responses to etanercept, tocilizumab and rituximab with AUCs around 0.75 to potentially assist in therapy planning.

Here the authors apply ZooMS, radiocarbon, and stable isotope analyses to whale bones from the Bay of Biscay. They find that humans were utilizing the remains of at least five species of whales from 20,000 years ago, and that those whale communities may have resembled today’s arctic waters.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Hodor, an intestinal zinc-gated chloride channel, controls systemic growth in Drosophila by promoting food intake and by modulating Tor signalling and lysosomal homeostasis within enterocytes.

An efficient computational pipeline starting from validated peptide assemblies has been used to design two families of α-helical barrel proteins with functionalizable channels. This rationally seeded computational protein design approach delivers soluble, monomeric proteins that match the design targets accurately and with high success rates.

The pre-autophagosomal structure in yeast is a liquid-like condensate of Atg proteins whose phase separation may have a critical, active role in autophagy.

Working memory requires the brain to switch between cognitive states and activity patterns. Here, the authors show that the steering of these neural network dynamics is influenced by dopamine D1- and D2-receptor function and altered in schizophrenia.

The role of the nuclear lamina (NL) in chromatin architecture is still poorly understood. Here, the authors provide evidence that disruption of the NL in Drosophila cells leads to overall chromatin compaction and repositioning from the nuclear envelope, whereas lamina-associated regions become less compacted and transcription within them is increased.

By experimentally sampling from sequence spaces larger than 10¹⁰ and using thermodynamic models, the genetic structure of at least some proteins can be well described, indicating that protein genetics is simpler than anticipated.

Analysis of the effects of more than 26,000 KRAS mutations on abundance and interactions with six other proteins is used to construct an energy landscape of KRAS and identify allosteric drug target sites.

Epistasis effects among amino acids at distal sites within binding pockets can have important impacts on protein fitness landscapes. Here the authors present BRIDGE, which matches non-overlapping sequence reads with their cognate DNA templates.

Biomarker analysis of the phase 4 R4RA trial identifies pretreatment synovial biopsy features selectively associated with response to rituximab or tocilizumab, and leads to the development of models that might predict treatment benefit in patients with rheumatoid arthritis

An approach that combines deep mutational scanning with neural network-based thermodynamic modelling is used to provide comprehensive maps of the energetic and allosteric effects of mutations in two common protein domains.

Mathematical models are used to predict malaria burden to inform disease control efforts. Here, Cameron et al. use Bayesian statistics to calibrate previous models against a data set of age-structured prevalence and incidence, generating stratified forecasts of the prevalence–incidence relationship.

Lombardo et al. find large-scale associations between the leukocyte transcriptome and neural responses to speech in toddlers, and these associations differ between toddlers with ASD who have good versus poor language outcomes.

Phylogeographical genomic analysis of Neisseria gonorrhoeae uncovers its recent emergence and current distribution into two distinct lineages that are differentially associated with antibiotic resistance and sexual networks.

A DNA-nanoassembly-based non-microscopy method is developed for ensemble analysis of membrane protein nanodomains.

The Mertz Glacier Polynya—a site of sea ice production and Antarctic Bottom Water formation—was strongly impacted following the calving of a massive iceberg in 2010. Here, the authors present a 250-year long sea ice reconstruction from the region and present evidence for a ~70-year calving cyclicity.

Protein glycosylation is an essential post-translational modification which analysis is complicated by the diversity of glycan composition and heterogeneity at individual attachment sites. Here the authors describe a method to selectively enrich N-linked glycopeptides to facilitate the detection of micro-heterogeneity in N-glycosylation.

An ultrafast, fragment-ion indexing–based database search tool, MSFragger, makes open searching practical and enables comprehensive identification of modified peptides in mass spectrometry–based proteomics data sets.

The sedimentary presence of the diatom lipid diene II (hereafter IPSO₂₅) has been proposed as a proxy for palaeo Antarctic sea ice. Here, the authors identify a source of IPSO₂₅and hypothesize that its sedimentary distribution may provide proxy evidence of landfast ice influenced by freshwater discharge.

Palmulli, Couty and colleagues show that the tetraspanin CD63 promotes accumulation of cholesterol in intraluminal vesicles (ILVs) at the expense of retrieval from endosomes; cholesterol stored in ILVs and exosomes is recovered in an NPC1-dependent manner.

The mechanism of iron-sulfur (Fe-S) cluster biosynthesis is not fully understood. Here, the authors develop a physiologically relevant in vitro model of Fe-S cluster assembly, allowing them to elucidate the sequence of Fe-S cluster synthesis along with the respective roles of ferredoxin-2 and frataxin.

Exploring the clonal expansion of somatically mutated hematopoietic stem cells with aging, Mack, Raddatz et al. quantify rates of clonal expansion in 4,370 individuals in the Trans-Omics for Precision Medicine cohort, observing epigenetic and proteomic patterns associated with clonal hematopoiesis of indeterminate potential.

Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimer´s disease. Here authors present the 3D- structure of an Aβ oligomer formed in a membrane mimicking environment and observe that Aβ tetramers and octamers inserted into lipid bilayers as well-defined pores.

A human binary protein interactome map that includes around 53,000 protein–protein interactions involving more than 8,000 proteins provides a reference for the study of human cellular function in health and disease.

Outbreak.info Research Library collects and integrates COVID-19 information from various repositories, enabling one-stop search for publications, clinical trials, datasets and other resources.

Crystallography companion agent enables autonomous characterization of powder X-ray diffraction data for organic and inorganic materials.