Search

Using a non-human primate model, the authors identified the tissue sites of initial viral rebound after discontinuation of antiretroviral therapy, demonstrating that such rebound preferentially occurs in the gastrointestinal tract-associated lymphoid tissues.

Two-dimensional polyaramid polymers are synthesized to form nanofilms that exhibit the lowest gas permeability of any polymer by orders of magnitude, despite lacking crystallinity, enabling molecular-scale nanomechanical resonators and barrier materials.

Accurate spectral libraries are essential for analyzing data-independent acquisition (DIA) proteomics data. Here, the authors present Carafe, which trains on DIA data to build experiment-specific spectral libraries, boosting peptide detection across diverse datasets.

The nucleoporin RanBP2 functions in cellular transport, mitosis and SUMO conjugation. Here, the authors determine cryo-EM structures of RanBP2 complexed with SUMO1-RanGAP1, Ubc9, Crm1, Ran and use cell and biochemical assays to probe its functions.

Kozai, Fernandez-Martinez et al. use high-speed atomic force microscopy to study the permeability barrier of yeast nuclear pore complexes. They show that karyopherins remodel a central plug that shapes barrier dynamics and disorder within the pore.

PU.1 is a master TF of hematopoietic lineage differentiation. Here the authors analyse properties of PU.1 DNA-binding in vitro and genome-wide in vivo across different cell types with native or ectopic PU.1 expression, and uncover the mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1.

Mass spectrometry-based proteomic studies involve tissue lysis. Herein, we updated our 2018 protocol¹ by implementing a sonication step into urea-based tissue lysis to improve the detection of membrane-bound and DNA-binding proteins.

Proteins FtsZ, ZipA, and either PBP1A or PBP1B are required for the synthesis of preseptal peptidoglycan at the future cell division site in E. coli. Here, Pazos et al. provide evidence that ZipA and FtsA-FtsN connect the cytosolic FtsZ ring with the membrane-anchored PBPs.

Aberrant redox homeostasis links lipid metabolism and cell death programs. Here, authors reveal how cell stress reduces growth factor signaling, enriching polyunsaturated fatty acids in phospholipids and sensitizing membranes to oxidative damage.

RNA polymerase I (Pol I) catalyses the transcription of ribosomal RNA precursors, and its transcription initiation mechanism differs from that of Pol II and Pol III. Here the authors present the cryo-EM structure of a trapped early intermediate stage of promoter-recruited Pol I, which reveals the interactions of the basal rDNA transcription machinery with the native promoter, and discuss the mechanistic implications.

Applying modern machine-vision techniques to the study of animal behavior, two groups developed systems that quantify many aspects of the complex social behaviors of Drosophila melanogaster. These software tools will enable high-throughput screens that seek to uncover the cellular and molecular underpinnings of behavior.

Viruses generally have compact genomes, resulting in many viral mRNAs with short 5’ untranslated regions. An antiviral complex exploits this feature of viral mRNAs to selectively inhibit viral protein synthesis and repress viral replication.

Rab3GAP, a guanine nucleotide exchange factor for Rab18, regulates membrane trafficking and lipid droplet metabolism. The authors elucidated its molecular structure, mapped its potential substrate binding interface, and uncovered that disease-associated mutations likely impair Rab18 binding.

A class of cationic—amidine-based degradable—lipids can now be readily synthesized through a tandem multi-component amine–thiol–acrylate conjugation reaction. Mechanistic studies provided key insights, from which the observed lead lipid enabled mRNA delivery to multiple organs, highlighting the potential for developing mRNA vaccines and therapeutics to treat various diseases.

A preclinical covalent compound, CMX410, contains a aryl fluorosulfate warhead that targets the acyltransferase domain of Mtb Pks13, an essential enzyme in cell-wall biosynthesis, making it a promising candidate for tuberculosis treatment regimens.

Design of cysteine-targeting analogs of a reversible SETDB1 triple Tudor domain (3TD) ligand, UNC6535, led to UNC10013, a potent covalent ligand with high selectivity. UNC10013 demonstrated allosteric inhibition of SETDB1-mediated Akt methylation in cells, a promising approach to SETDB1 therapeutics.

DNA methylation turnover is an essential epigenetic process during development. Here, the authors look at the changes in DNA methylation during the differentiation of post-mitotic human monocytes (MO), and find that EGR2 interacts with TET2 and is required for DNA demethylation at its binding sites; revealing EGR2 as an epigenetic pioneer factor in human MO.

Sperm–egg adhesion is crucial for mammalian reproduction. Here, authors report the human Izumo1:Juno complex, a key regulator of sperm-egg adhesion, forms an unusually strong bond through a secondary binding site, which is impaired in an infertility-associated Juno mutant.

A deep chemical proteomic investigation of diverse aminophilic electrophiles has identified ligandable lysines across a wide range of human proteins. The proteins cover different functional and structural classes, and the aminophilic electrophiles include compounds that disrupt protein–protein and protein–RNA interactions. This dataset provides a proteome-wide atlas of lysine-reactive chemistry.

Using a biofilm evolution assay, this study improves the antimicrobial and antibiofilm efficacy of Pseudomonas aeruginosa bacteriophages, while a two-phage cocktail shows further improved antimicrobial efficacy without incurring dual-bacteriophage-resistance.

Cohesin plays a crucial role in both chromosome organization and DNA repair. Here the authors find that cohesin mediated genome architecture prevents interactions between damaged chromatin. In contrast cohesin phosphorylation  appears to primarily impact DNA repair speed.

DNA methylation is a critical component for repression of fetal haemoglobin in adult blood cells. Removing DNA methylation from the fetal haemoglobin promoter effectively upregulates the gene, opening avenues for the treatment of blood disorders.

Catheter-associated urinary tract infections can often lead to secondary bloodstream infections, and catheter-induced bladder inflammation. In this work, authors utilise murine models to probe defective fibrinolysis drives extravascular fibrin formation, potentially predisposing hosts to severe CAUTI.

Harmful algal blooms (HABs) pose negative worldwide impacts that could be minimized through the development of a forecasting tool. Quantitative analysis of peptides produced by a coastal microbiome prior to a HAB reveals predictive biomarkers that can forecast bloom events over 24 hours in advance.

Azetidine-2-carboxylic acid synthases catalyse the formation of the proline analogue azetidine-2-carboxylic acid (AZE) in bacteria. In this work, the authors combine structural and biochemical analyses with quantum mechanical calculations and mutagenesis studies to obtain catalytic insights into AZE synthases.

Nshanian et al. investigate the differential effects of the short-chain fatty acids propionate and butyrate on chromatin remodelling and gain insight into the mechanisms that drive selective histone acylation.

Cells respond to DNA damage by activating cell cycle checkpoints. Here, the authors show that the F-box protein cyclin F suppresses the B-Myb/cyclin A pathway to ensure a DNA damage-induced checkpoint response in the G2 phase of the cell cycle.

Multiple types of cell elongation have been described in bacteria, but little is known about how these strategies vary across species. Here, the authors use fluorescent D-amino acids to track the spatiotemporal dynamics of bacterial cell elongation, revealing unsuspected diversity of elongation modes among closely related species of the family Caulobacteraceae.

Massively parallel but cost-effective testing is essential to monitor the spread of pathogenic agents. Here the authors present SARSseq, which uses a dual indexing strategy in a multiplexed RT-PCR reaction to diagnose SARS-CoV-2 at scale.

Activation of ESCRT prevents potentially lethal outcomes of minor perturbations in lysosomal integrity. Here authors show that Ca2 + -activated scrambling of sphingomyelin and its cytosolic turnover drives lysosomal repair independently of ESCRT.

Inositol pyrophosphates are key nutrient messengers in fungi, plants and animals. This study uncovers the structure and function of a critical enzyme involved in their production and breakdown, revealing how cells control inositol pyrophosphate levels to regulate nutrient signaling.

During spermatogenesis most histones are replaced with protamines. The distribution of the products of Trithorax and Polycomb histone modifications are now examined in both mouse and human sperm, showing conservation of histone methylation distribution across species. The authors propose a role for the Polycomb complex in transgenerational inheritance.

Mcl-1 is an important survival factor for several hematopoietic lineages including B and T lymphocytes, but its role in the Natural Killer (NK) cells has not been previously tested. Here, the authors report that deletion of Mcl-1 in the NK cell lineage leads to the loss of NK cells from all tissues.

Little is known about how climate change impacts glacier-fed streams (GFSs) microbiomes. Here, using a modelling framework based on global GFS metagenomic, climatic and environmental data the authors predict future increases in GFS bacterial biomass and diversity, but potential loss of clades adapted to extreme conditions.

Here, the authors identify a conformational switch in the amino-terminal transactivation domain of c-MYC, termed coreMYC, which cycles between a closed, inactive state and an open, active conformation. Polyphenol epigallocatechin gallate (EGCG) is used to modulate the conformational landscape of coreMYC, stabilizing the closed and inactive conformation.

In tauopathies, the microtubule-associated protein tau is hyperphosphorylated and aggregated. Here the authors identified a polypharmacological small molecule that inhibits aggregation, reduces phosphorylation, and restores microtubule interaction of tau.

In this work, authors develop a live vaccine candidate against Pseudomonas aeruginosa using an unnatural amino acid-based auxotrophic strategy. They provide insight on the vaccine’s in vivo safety profile and protection of mice against lethal P. aeruginosa challenge.

Tisza et al. carry out a sequencing-based analysis of wastewater samples from major cities, to detect and quantify hundreds of distinct pathogenic viruses, finding striking correlations between virus abundance and local clinical cases.

Lipid nanoparticles (LNPs) are the preeminent drug delivery vehicle for mRNA therapies, partially due to the ionizable lipid (IL) components that facilitate endosomal escape. Here, authors devise terminally branched ILs that enhance endosome escape, resulting in increased liver and T cell delivery.

Isotopic analysis of six giant clam species reveals trophic niche partitioning along a heterotrophy-autotrophy continuum. The most autotrophic species had the fastest growth rates, but may be more susceptible to environmental disturbances.

The metal-dependent, bifunctional isoprenyl diphosphate synthase PcIDS1 from the leaf beetle Phaedon cochleariae integrates substrate, product and metal-ion concentrations to tune its dynamic reactivity. Now structural and functional analyses reveal that this enzyme uses both catalytic centres to form geranyl pyrophosphate, while one domain is inactivated during farnesyl pyrophosphate production.

Discovery of full-length antibodies can be slow and labor intensive. Here, the authors describe a robust genetic assay for facile isolation of IgG antibodies from combinatorial libraries expressed in the cytoplasm of redox-engineered bacteria.

The MHz repetition rates available at second-generation X-ray free-electron lasers enable the collection of microsecond time-resolved X-ray scattering data with exceptionally low noise, providing insights into protein structural dynamics.

A lag in nascent strand DNA methylation contributes to heterogeneous methylation in asynchronous cell populations, but cancer cells and active transcription factor binding sites preserve heterogeneity even after cell cycle arrest.