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The development of catalysts that operate under low concentration CO₂ resembling industrial waste gases holds promise for CO₂ reduction. Here, the authors report a vacuum calcination approach for regulating the Cu⁰/Cu¹⁺ density on Cu-based catalysts that can electro-catalyze low-concentration CO₂.

The interaction between the host immune response and the component organisms forming the microbiota is critical during homeostatic but all pathological contexts. Here the authors use a multi-omics spatial approach to dissect and characterise host and microbiome in a murine model of intestinal inflammation.

VCP/p97 is identified as a co-factor to the fusion oncoprotein ASPSCR1::TFE3. They co-localize on chromatin, co-dependent for enhancer looping and transcriptional regulation in alveolar soft part sarcomas and Xp11- rearranged renal cell carcinomas.

HORNET, a method that uses unsupervised machine learning and deep neural networks to analyse atomic force microscopy data enables structural determination of RNA molecules in multiple conformations.

A genetically encoded FRET-based optical sensor generated from a computational design approach can monitor hippocampal glycine levels in brain tissue to determine differences between spines and shafts and changes induced by high- and low-frequency stimulation.

Photosynthetic bacteria growing in low light environments have evolved to use small amounts of light with high efficiency. Here, Coles et al. demonstrate strong exciton–photon coupling of about 1,000 chlorosomes to a confined cavity mode thus modifying the energy levels of the light-harvesting process.

The performance of energy materials is affected by structural defects, as well as physicochemical heterogeneity over different length scales. Here the authors map nanoscale correlations between morphological and functional heterogeneity, quantifying the trap states limiting electronic transport in bismuth vanadate thin films.

Pose estimation in combination with an anatomically constrained model allows inferring skeletal kinematics in rodents.

Optical pooled screening is enhanced by amplification of barcodes before in situ sequencing.

The authors present a microwave imaging system that can operate in continuous transmit-receive mode. Using an array of transmitters, a single receiver and a reconstruction matrix that correlate random time patterns with the captured signal, they demonstrate real-time imaging and tracking through a wall.

Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.

Controlling urination is a fundamental social need. Keller et al. develop a voluntary urination assay and uncover a subset of brainstem neurons that relax the urethral sphincter, providing insight into urinary control and its dysfunction.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

Multi-Omic approaches are a powerful way for obtaining in-depth understanding of a cell’s state. Here the authors present DISCO, combining digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to analyze single-cell genomes, transcriptomes and proteomes in a mixed population.

Using the lifespan brain chart and two large-scale cross-cultural consortia (ABIDE and CABIC), we disentangle the heterogeneity of brain morphology in ASD into two structural impairment pathways that could disrupt sensory to association functions.

Predicting binding specificity of T-cell receptors (TCRs) and putative antigens can help improve cancer immunotherapy. Lin et al. propose RACER, which efficiently makes use of supervised machine learning to learn important molecular interactions contributing to TCR–peptide binding.

A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

Recent evidence has suggested that blood type may be associated with severe COVID-19. Here, the authors use data from ~14,000 individuals tested for SARS-CoV-2 at a New York City hospital, and find that certain ABO and Rh blood types are associated with infection, intubation, and death.

Computationally designed genetically encoded proteins can be used to target surface proteins, thereby triggering endocytosis and subsequent intracellular degradation, activating signalling or increasing cellular uptake in specific tissues.

Two-step Mendelian randomization, combined with multiple layers of omics evidence, implicates COL6A3-derived endotrophin as a mediator of coronary artery disease risk in the context of obesity.

Using advanced brain imaging in male macaques, the authors show that both motor and higher-order brain regions, such as those involved in emotion and cognition, show significant changes after stroke, which are linked to better recovery.

Using in situ single cell lineage tracing technology DRAG, we show that, unlike emergency myelopoiesis post-transplantation, aged HSPCs do not functionally decline in the number of myeloid cells that they produce.

Here, Hiatt et al. report the knock-out of over 400 genes in primary CD4+ T cells to assess their functional role in HIV replication, finding 86 initial candidates of which 47 are validated as HIV host factors, including 23 with restrictive activity.

Improved cytosine base editors are generated by directed evolution of an adenosine deaminase.

ATAC-seq measures chromatin accessibility as a proxy for the activity of DNA regulatory regions across the genome. Here the authors present AtacWorks, a deep learning tool to denoise and identify accessible chromatin regions from low cell count, low-coverage, or low-quality ATAC-seq data.

The success of HER2-targeted cancer therapy is limited by treatment resistance. Here, the authors engineer an anti-HER2 biparatopic antibody with multiple mechanisms of action including induction of HER2 clustering to trigger complement dependent cytotoxicity, signal inhibition, antibody dependent cellular cytotoxicity and phagocytosis.

This Perspective reviews tools developed over the past five years in the macromolecular modeling, docking and design software Rosetta.

Amyloids may have played an important role in prebiotic molecular evolution but understanding replication of such information-coding molecules is still a problem. Here the authors design a model amyloid substrate and demonstrate sequence regio- and stereoselectivity during template-based replication.

This study elucidates how long-range chromatin loops are altered during short- and long-term changes in neural activity, and analyzes the interplay between the 3D genome and the linear epigenome during activity-dependent transcriptional responses.

Here the authors describe a 3D genomic strategy that uncovers novel enhancer hijacking events, including a MYC-ERBB2 chimeric ecDNA, providing new insights into oncogene activation and potential therapeutic targets.

The RNA endonuclease CPSF3 was identified as the cellular efficacy target of the small molecule JTE-607, revealing pre-mRNA processing as a vulnerability in cancers such as Ewing’s sarcoma that are characterized by aberrant transcription.

Multidrug-resistant (MDR) tuberculosis threatens global control of tuberculosis disease. Here, the authors investigate mechanisms underlying the collateral sensitivity of MDR Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

The third variable (V3) loop on the HIV-1 Env glycoprotein is required for viral entry. Here, the authors applied DARPin technology to produce broadly neutralizing inhibitors targeting a region of V3 that becomes accessible after binding to the CD4 receptor.

Crystal structures of HIV-1 Env V1V2 in complex with human broadly neutralizing antibodies and ontogeny analyses allow the engineering of Env trimers that are recognized by ancestor and intermediate antibody forms.

Photoselective sequencing combines targeted illumination and photocaged fragment libraries to enable the spatial analysis of genomic sequence and chromatin accessibility profiles with subcellular resolution in the context of complex tissues.

Controversy exists over the function of plasma membrane versus intracellular vesicular LAT in T-cell receptor signaling. Here the authors use high resolution imaging of the temporal dynamics of LAT involvement to show that both sources of LAT are required, but at distinct stages.

MaizeCODE maps active regulatory regions tied to maize domestication traits in a diverse panel of tissues and inbreds. It reveals bi-directional enhancer RNAs and the molecular conflicts between activity and silencing of non-coding regions.

Differential carbohydrate metabolism elicits distinct pyrazine and pyrazinone autoinducer signalling pathways in Klebsiella oxytoca, which impact bacterial virulence programs.

The authors perform cryo-EM of pre-tRNA in complex with the human tRNA splicing endonuclease complex TSEN to understand the basis of pre-tRNA recognition and processing by TSEN.

Jacks and colleagues demonstrate the effects of neoantigen expression level on T-cell priming and immune surveillance during tumor development and progression and explore implications for immunotherapies, using in vivo models of colorectal cancer.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may be able to elicit a durable antibody response.

Respirovirus 3 is a major cause of respiratory infection. Here authors generate and explore heavy-chain antibody fragments that target the fusion protein and test these in vitro and in an animal model.

Orthogonal aminoacyl-tRNA synthetase–tRNA pairs are discovered by analyzing millions of sequences.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.