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Preclinical studies indicate a synergistic effect of radiotherapy treatment (RT) and Immune checkpoint inhibitors (ICI) on tumor growth and metastasis. However, little is known about the immunomodulatory performance of different radioisotopes on the tumor microenvironment. Here, the authors employ alpha- versus beta-particle emitting radiopharmaceuticals in combination with dual ICI therapy and dissect mechanisms of in vivo immunomodulation and timing of ICI administration relative to RT, by comparing responses in immunogenic and non-immunogenic preclinical mouse models.

A year ago the WHO’s coronavirus emergency alarm was largely ignored. Why?

The latest from the hydroxychloroquine saga, as a questionable dataset threatens trust in science and forces major journals to review their processes

Global energy budgets of planets are important to understand their climate system. Here, the authors show long-term multi-instrument observations from Cassini spacecraft, which reveals dynamical imbalances of Saturn’s global energy budget.

This Perspective proposes a new framework to support the inclusion of Black, Indigenous and people of colour in conservation initiatives.

Studies of a large frost-filled basin on Pluto show that this feature altered the dwarf planet's spin axis, driving tectonic activity on its surface, and hint at the presence of a subsurface ocean. See Letters p.86, p.90, p.94 & p.97

If the activity of genetically specified neurons is silenced in a temporally precise fashion, the roles of different cell classes in neural processes can be studied. Members of the class of light-driven outward proton pumps are now shown to mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) enables near 100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light.

Sequencing the transcriptomes of more than 100 species of alga yields new channelrhodopsins with promising properties for optogenetics. A far red–shifted channelrhodopsin, Chrimson, opens up new behavioral capabilities in Drosophila, and alongside a fast yet light-sensitive blue channelrhodopsin, Chronos, enables independent excitation of two neuronal populations in brain slices.

Electrochemistry can boost processes that trap atoms inside a metal. A reactor uses these trapped atoms, combined with an ion beam, as fuel for nuclear fusion.

A monolithically integrated CMOS-compatible source is demonstrated using an optical parametric oscillator based on a silicon nitride ring resonator on silicon. Generating more than 100 wavelengths simultaneously and operating at powers below 50 mW, scientists say that it may form the basis of an on-chip high-bandwidth optical network.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

Developing rapid and affordable HPV tests is imperative for effective cervical cancer screening in resource-limited regions. Here, the authors demonstrate an advanced HPV diagnostic system that integrates CRISPR technology with digital signal processing.

A tether-less and battery-less implant allows for the recording of electroencephalograms, electromyograms and body temperature in freely moving small animals, and for closed-loop neuromodulation via optogenetics and pharmacology.

This study reveals that rising temperatures and decreased precipitation levels increase walking time for fetching drinking water in Sub-Saharan Africa. Rural areas are most affected, but community electricity access mitigates the walk time burden.

Development of the bright green and red fluorescent proteins, Clover and mRuby2, creates a fluorescence resonance energy transfer (FRET) pair with the highest Förster radius among existing ratiometric FRET pairs. Substitution of this pair for current FRET pairs in several existing sensors reliably and substantially improves sensor performance.

Phase-matched four-wave mixing can take place with high efficiency in a suitably designed silicon waveguide — this advance could allow for the implementation of dense wavelength channels for optical processing in an all-silicon photonic chip.

By exploiting the nonlinearity of on-chip silicon nanowaveguides, a parametric temporal imaging system that can compress optical waveforms in time is demonstrated, enabling generation of complex and rapidly updatable ultrafast optical waveforms.

Analysis of the whole-brain fly connectome reveals high-dimensional dynamics supported by many small independent circuits, motivating a proposal for optogenetic perturbation to efficiently learn a whole-brain causal neural dynamics model.

An analysis of the Drosophila connectome yields all cell types intrinsic to the optic lobe, and their rules of connectivity.

In this Technical Report, Chuong and colleagues introduce Jaws, an archaeon-derived, photoactivatable chloride pump that responds to red light. Owing to its efficiency in absorbing red photons and its large photocurrent, Jaws can be transcranially activated deep in the brain and thus allows noninvasive optogenetic silencing.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Single-cell immunoblotting previously separated proteins on a polyacrylamide slab in the xy direction and was limited by throughput and sample consumption. Here the authors adapt the system to separate proteins in the z direction, allowing for closer spacing of sample wells and improved sample consumption.

Unlike most processive motor proteins, the stepping motion of cytoplasmic dynein’s two linked motor domains is not precisely coordinated. Cleary et al.show that the ATPase activity of just one head is required for processive movement, and that tension on the linker gates the release of the motor from microtubules.

Two signals identified in short gamma-ray bursts from archival Burst and Transient Source Experiment data show kilohertz quasiperiodic oscillations, implying the ringing of a hypermassive neutron star before collapsing to a black hole.

Combining fluorescence correlation spectroscopy and ultrafast spectroscopy, the sample-averaged dynamics of defects are studied with single-particle sensitivity in two-dimensional hexagonal boron nitride heterogeneous emitters.

Rett syndrome (RTT) is caused by mutations in MeCP2. This study describes a new line of knock-in mutant mice that mimics a MeCP2 mutation found in individuals with RTT and recapitulates RTT-like phenotypes, including motor and cognitive impairments. These MeCP2 knock-in mice also have age-dependent abnormalities in audiogenic event-related neuronal information processing.

Structured light is shown to be robust against unitary perturbations.

Label-free surface-enhanced Raman spectroscopy is an emergent method for the detection and discrimination of biological analytes. Here, the authors describe SERS sensors with arrayed mildly-selective surface chemistries to give a fingerprint based on different interactions for analysing biological samples.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

The formation of kidney stones is governed by the same principles as other stone systems. These ‘diagenetic phase transitions’ that create human kidney stones reflect the environment within the kidney during stone formation and could, therefore, improve understanding of urolithiasis and enable future treatment development. In this wide-ranging and unique Review, the authors explain how kidney stone formation parallels that of other stone systems such as stony corals, travertine in Roman aqueducts, stalactites and agates, and describe how the new field of GeoBioMed could be harnessed to improve patient care.

Two distinct and opposing models for clathrin-mediated endocytosis have been inferred from EM and structural biology data. Here the authors develop an optical method to directly visualize membrane-bending dynamics and show that coat assembly accommodates membrane bending during or after the assembly of the clathrin lattice, which is not predicted by either model.

Measurement of in vivo neuronal activity with single neuron and single action potential resolution is important for studying neuronal function. Delivery of a FRET-based fluorescent Ca²⁺ indicator protein using adeno-associated virus results in high expression levels allowing in vivo detection of single action potentials at low firing rates. Griesbeck et al., also in this issue, describe the use of a similar sensor for recording neuronal activity in vivo.

The Carnot efficiency and the power output of thermoelectric power generation increase with temperature but current thermoelectrics are characterized up to 1,500 K. Here, Li et al. develop reduced graphene oxide films that can convert heat up to 3,000 K with high power factors, opening the door for novel applications.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

The ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 induces an immune response in rhesus macaques and leads to reduced SARS-CoV-2 viral loads in respiratory tissues and an absence of pneumonia, but not to a reduction in nasal virus shedding, compared with unvaccinated animals.

GNF-2 is a recently discovered, selective allosteric Bcr–Abl inhibitor. Solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry are now used to show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. The results show that the combination of allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.

A single-cell Western (scWestern) blotting technique allows quantitative measurements of up to 11 protein targets from ~2,000 individual cells in under 4 hours, expanding single-cell heterogeneity studies to the proteome.

Joseph Testa, Michele Carbone and colleagues report that germline mutations in BAP1 predispose to malignant mesothelioma and uveal melanoma. They further hypothesize that mesothelioma predominates in BAP1 mutation carriers following exposure to asbestos.

Tighter patent rules could raise drug costs in poor countries.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.