Search

In vivo chimeric antigen receptor (CAR)-T cell engineering uses targeted delivery systems to generate CAR-T cells directly in patients, bypassing ex vivo manufacturing. This Review examines emerging viral and lipid nanoparticle platforms, early clinical proof of concept and potential applications beyond cancer.

The Heisenberg uncertainty principle bounds the uncertainties about the outcomes of two incompatible measurements on a quantum particle. This bound, however, changes if a memory device is involved that stores quantum information. New work now extends the uncertainty principle to include the case of quantum memories, and should provide a guide for quantum information applications.

Task paradigms allowing studies on the core ethological function of the whiskers are lacking. Authors here present a task for freely moving mice that enables the study of how the brain processes touch and learns. The setup combines behavior, electrophysiology, and imaging, offering insights into naturalistic sensory and decision-making processes.

A comparison of the repertoire of SARS-CoV-2-specific epitopes targeted by T cells induced by vaccination or natural infection reveals that T cells predominantly target non-spike epitopes in convalescent individuals, while there is a broader spike-specific CD8⁺ T-cell response in vaccinees. Despite differences in T-cell response, the targeted T-cell epitopes were conserved between the wild-type and Omicron variants in both groups.

Glucose uptake in astrocytes is thought to rely on GLUT1. Here, the authors show that adult mice tolerate astrocyte-specific GLUT1 deletion, which increases astrocytic glucose metabolism and confers neuroprotection in a model of stroke.

The carbonylation of alkenes is tremendously important industrial process, but many substrates are highly challenging. Here the authors report a highly active catalytic system for the alkoxycarbonylation of alkenes that is also general across the range of alkene substitution patterns.

Hydrogen borrowing is an attractive method for C-N bond formation - avoiding multiple alkylation products and reducing waste - but often is carried out with noble metals. Here the authors show that a manganese catalyst allows the selective N-alkylation of amines with alcohols.

Neuromorphic software and hardware solutions vary widely, challenging interoperability and reproducibility. Here, authors establish a representation for neuromorphic computations in continuous time and demonstrate support across 11 platforms.

Synthesis of fluorinated organic molecules is of high interest for agrochemistry and pharmaceutics, but efficient and general reagents for introducing -CF₂- groups are lacking. Here, the authors report the synthesis of 3,3-difluoropropen-1-yl ammonium salts as stable and scalable gem-difluoromethylation reagents, which react with a range of nucleophiles under mild conditions and high regioselectivity.

Synthetic methods aiming at minimizing reaction steps while increasing molecular complexity are highly sought after by organic chemists. Here, the authors report two cascade procedures combining nucleophilic substitution, palladium-catalyzed Heck and C–H activation reactions for the synthesis of spiro-fused heterocycles.

N-methylated amines display high biological activity in living organisms. Here, the authors show the convenient synthesis of a wide range of biologically relevant N-methylamines via reduction of nitrobenzenes using a recyclable iron catalyst and paraformaldehyde without additional hydrogen pressure.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

Here, Bachmann et al. provide data on long-term dynamics of the HIV-1 reservoir in 1,057 individuals on suppressive antiretroviral therapy and show that in 26.6% of individuals the reservoir increases. Viral blips and low-level viremia are significantly associated with a slower reservoir decay.

Simultaneous PET-MRI measurements provide fundamental insights into the modulation of neural networks mediated by nicotinic acetylcholine receptors in human obesity as a putative biological mechanism for future weight loss interventions.

The HIV reservoir is a major hurdle for a cure of HIV, but the factors determining its size and dynamics remain unclear. Here the authors show in a large cohort of 610 HIV-1 infected individuals, who are on suppressive ART for a median of 5.4 years, that viral genetic factors contribute substantially to the HIV-1 reservoir size.

Vaccines induce beneficial immunity for COVID-19, but immune waning prompts boosting vaccination. Here, the authors show that a third, boosting dose of COVID-19 mRNA vaccine induces transient CD8 + T effector cell response while conserving the CD8 memory T cell pool, thereby permitting reactivation of spike-specific CD8 + T cells upon breakthrough infection or 4th vaccination.

Amyloid fibril structures can display polymorphism. Here the authors reveal the cryo-EM structures of several different fibril morphologies of a peptide derived from an amyloidogenic immunoglobulin light chain and present a mathematical analysis of physical factors that influence fibril polymorphism.

Dataset integration is common practice to overcome limitations in statistically underpowered omics datasets. Here the authors present “HarmonizR”, a tool for missing data tolerant experimental variance reduction in large, integrated but independently generated datasets without data imputation, adjustable for individual dataset modalities, correction algorithm, and user preferences.

Here, the authors present and characterise a collection of human gut bacteria including novel taxa associated with health conditions and a large diversity of plasmids. All isolates, their genomes and metadata are publicly available, facilitating research by others (www.hibc.rwth-aachen.de).

Medulloblastomas (MBs) are highly heterogeneous paediatric brain tumours that remain challenging to treat. Here, the authors integrate proteomics, epigenomics, transcriptomics and post-translational modification analyses to find molecular subgroups and potential therapeutic targets in MB tumours.

This study reports adhibin, a synthetic carbazole that suppresses the migratory and adhesive properties of cancer cells by a mechanism of targeted RhoGAP class-IX myosin inhibition and selective RhoGTPase interference, both translating into migrastatic activity, opening other perspectives in cancer therapy and basic research.

Cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNA ribonucleoprotein complexes bound to the transcription–export complex reveal how mRNAs are packaged and recognized for nuclear export.

Researchers use phase-change materials to demonstrate an integrated optical memory with 13.4 pJ switching energy.

Systemic AL amyloidosis is caused by misfolding of immunoglobulin light chains (LCs) but how post-translational modifications (PTMs) of LCs influence amyloid formation is not well understood. Here, the authors present the cryo-EM structure of an AL amyloid fibril derived from the heart tissue of a patient that is partially pyroglutamylated, N-glycosylated and contains an intramolecular disulfide bond. Based on their structure and biochemical experiments the authors conclude that the mutational changes, disulfide bond and glycosylation determine the fibril protein fold and that glycosylation protects the fibril core from proteolytic degradation.

Continuous-variable QKD protocols are usually easier to implement than discrete-variables ones, but their security analyses are less developed. Here, the authors propose and demonstrate in the lab a CVQKD protocol that can generate composable keys secure against collective attacks.

While the role of effective population size (N_e) in explaining variation in genetic diversity has received much attention, the role of spontaneous mutation rate is largely ignored. Here, Xu et al. show that giant duckweed has a high N_e yet low genetic diversity, likely due to its low mutation rate.

A microfluidic approach allows spatiotemporal control of morphogen distribution in human pluripotent stem cell cultures. This approach recapitulates early developmental processes such as localized signaling and symmetry-breaking events.

Measurements on a chiral magnet show that non-symmorphic symmetries enforce topological crossings exactly at the Fermi level in certain materials; these crossings can be controlled by an applied magnetic field.

Azacitidine (AZA) treatment is used for patients with myelodysplasias that cannot undergo bone marrow transplantation; however, AZA treatment is only partially effective. Here the authors show synergy of AZA with compounds inhibiting the chromatin regulators CBP and p300, which is mediated by the RNA-dependent functions of AZA affecting protein translation.

Solvent dynamics are an often overlooked component in enzymatic activity. Terahertz spectroscopy, X-ray absorption analysis and molecular dynamics simulations show that solvent movement is tightly correlated with formation of a productive enzyme–substrate complex, but not an enzyme–inhibitor complex, in a metalloprotease, indicating that solvent motions may assist catalysis.

Exploring benign and green methodologies for the synthesis of functionalized nitriles continues to attract the interest of academic and industrial chemists. Here, the authors efficiently synthesize various aryl, heterocyclic, allylic, and aliphatic nitriles from alcohols in water under very mild conditions using zeolitic imidazolate frameworks derived Fe₁-N-C catalysts.

Human-driven landscape change may alter disease transmission among insect pollinators. Here, the authors show that species traits, flower-rich habitat and floral resource overlap with honeybees explain load and prevalence of viruses in wild bees and hoverflies co-occurring with honeybees.

Point defects in solids have potential applications in quantum technologies, but the mechanisms underlying different defects’ performance are not fully established. Nagy et al. show how the wavefunction symmetry of silicon vacancies in SiC leads to promising optical and spin coherence properties.

The exciton–phonon coupling (EXPC) affects the opto-electronic properties of atomically thin semiconductors. Here, the authors develop two-dimensional micro-spectroscopy to determine the EXPC of monolayer MoSe₂.

The radiation emission rate from gravity-related wave function collapse is calculated and the results of a dedicated experiment at the Gran Sasso laboratory are reported, ruling out the natural parameter-free version of the Diósi–Penrose model.

Invasive pulmonary aspergillosis is a life-threatening fungal lung disease devoid of specific rapid diagnosis and with limited therapeutic options. Here, the authors show how state-of-the-art imaging approaches can enable specific diagnosis and therapy monitoring of this infection.

Cryo-EM photosystem I structure reveals adaptation mechanisms to extreme high light in Chlorella ohadii.

Paediatric high-grade gliomas with MYCN amplification (HGG-MYCN) are rare and highly aggressive. Here, the authors generate a mouse model for HGG-MYCN that can recapitulate the histological and molecular profiles of the human tumours, and perform high-throughput drug screening to identify potential treatment options.

The first operation of the European X-ray free-electron laser facility accelerator based on superconducting technology is reported. The maximum electron energy is 17.5 GeV. A laser average power of 6 W is achieved at a photon energy of 9.3 keV.

The kinase RIPK3 initiates necroptosis, which has been reported to promote inflammation in various pathological conditions. Here, the authors show that genetic ablation of Ripk3results in adipocyte apoptosis and white adipose tissue inflammation in obese mice, which promotes glucose intolerance.

Plasma extracellular vesicles contain quantifiable amounts of TDP-43 and full-length tau, allowing the accurate assessment of pathology in frontotemporal dementia, frontotemporal dementia spectrum disorders and amyotrophic lateral sclerosis.

Marked ecosystem changes in the Baltic Sea have been recorded in the sediments, but the reasons are not fully understood. Now an integrated study of high-resolution sediment records (of the past 1,000 years) in combination with an ecosystem modelling approach reveals that surface temperature changes strongly influence deepwater oxygenation.