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Down Syndrome is a common genetic cause of intellectual disability and is associated with altered fetal neurodevelopment. Here, the authors identify altered expression dynamics of lineage commitment genes and de-repression of transposable elements in DS neural progenitor cells.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries.

Analysis of ground-sourced and satellite-derived models reveals a global forest carbon potential of 226 Gt outside agricultural and urban lands, with a difference of only 12% across these modelling approaches.

Magnetic skyrmions are particle-like magnetization textures which may be manipulated in thin-film device applications. Here, the authors demonstrate the formation and control of room-temperature artificial skyrmion lattices in Co/Pd multilayers, defined by local ion irradiation and an array of magnetic vortex discs.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Here the authors describe a functional screening platform in human stem cells to identify and optimize protein-based gene editing additives that increase homologous directed recombination and have potential to improve gene therapy workflows.

There are currently two types of antiviral drugs – neutralizing antibodies and small molecule inhibitors. Here, the authors report the development of bicyclic peptides that combine the advantages of both and show their antiviral capacity against SARS-CoV-2 in vitro as well as in small animal models.

A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

Catfish represent 6.3% of all vertebrate species, and occupy a phylogenetic position close to the common ancestor of bony fish. Liu et al. present a reference genome of the channel catfish, and reveal a genomic basis for the evolutionary loss of scales in these species.

Spin-state crossovers are phenomena where, under changes in temperature or pressure, the spin-state of an ion changes. In some materials, this spin-state crossover occurs simultaneously with a metal-insulator transition, driven by a valence transition. Control over such valence, spin-state, and metal-insulator transitions has much technological appeal, but, thus far, materials displaying this have been limited to cryogenic temperatures. Here, the authors show that in strained films of (Pr1-yYy)1- xCaxCoO3-δ, these transitions can be promoted to room temperature.

The authors address spin–orbit torques and magnetization switching in MnPd₃/CoFeB hetrostructures.

Direct observation of ionic motion in buried metal/oxide interfaces and its correlation with physical properties is a challenging task. Here, the authors observe oxygen migration in a model system with controllable positive exchange bias, due to the redox-driven formation of a ferromagnetic interfacial layer.

Mechanisms allowing electrical manipulation of magnetic material possess potential applications in low power memory and sensor technologies. Here, the authors demonstrate the control of magnetic characteristics via voltage-driven migration of oxygen across a GdOx/Co interface, well into the bulk of the cobalt.

Using single-nucleus RNA sequencing data from patients with sporadic amyotrophic lateral sclerosis (ALS) cortices, the authors find that higher expression of ALS risk genes is accompanied by upregulation of stress responses in groups of extratelencephalic neurons. Analyses of glial nuclei revealed a downregulation of myelination genes in oligodendrocytes and upregulation of reactive state genes in microglia.

Klim et al. illuminate pathomechanisms of ALS using pluripotent stem cells to identify transcripts altered in human motor neurons by perturbations to ALS protein TDP-43, finding the microtubule regulator STMN2 highly sensitive to TDP-43 malfunctions.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

Integrating inventory data with machine learning models reveals the global composition of tree types—needle-leaved evergreen individuals dominate, followed by broadleaved evergreen and deciduous trees—and climate change risks.

Spin-polarized carriers could show an extra Hall component when moving through certain real-space topological spin textures. Here, He et al. report an exchange bias experienced by the topological spin textures living at the interface between a topological insulator and an adjacent antiferromagnet, suggesting a chiral spin texture is induced.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

The RNA for ALS- and frontotemporal dementia-associated C9ORF72 gene is exported from nucleus via an unknown mechanism. This study shows that reduction of nuclear export adaptor SRSF1 can alleviate neuronal cell death and nuclear export of C9ORF72 inDrosophilaand patient-derived induced motor neurons.

Heterostructures formed by the magnetic topological insulator Cr-doped (Bi,Sb)₂Te and the antiferromagnet CrSb are shown to exhibit emergent interfacial magnetic phenomena that can be tuned with the heterostructure geometry.

Immunology is in an unprecedented era of exciting exploration, made possible by powerful new tools and technologies. To capitalize on this progress and translate discovery to meaningful impact, a parallel culture of ‘evidence-based immunology’ must be developed.

Akt signaling has been implicated in a number of diseases, but its role in brain disorders is less clear. Here, the authors report that CTMP, an endogenous inhibitor of Akt, is critical in the neurodegeneration that is associated with stroke. Blockade of CTMP in a stroke model rescues hippocampal neurons.

Inhibition of Bcl-2 and Bcl-x_L by ABT-737 is known to enhance tumor cell death. Here the authors find that it is actually protective against neuronal death in an animal model of ischemia via blockade of Bcl-x_L–induced mitochondrial channel activity. These findings point to Bcl-x_L as a potential therapeutic target.

The glycopeptide antibiotic-related compounds complestatin and corbomycin function by binding to peptidoglycan and blocking the action of autolysins—peptidoglycan hydrolase enzymes that remodel the cell wall during growth.

In this study, the authors show that they can induce the direct conversion of fibroblasts into nociceptor neurons via the expression of only five key transcription factors. They further confirm that these induced neurons are bona fide nociceptors by demonstrating that their expression profiles resemble that of their endogenous counterparts and show that they are responsive to common nociceptor agonists.

Mutations in the Wnt co-receptor, LRP5, lead to skeletal diseases in humans. Matthew Warman and his colleagues have now developed mutant mice with tissue-specific alterations of Lrp5 expression and found that these mice phenocopy the human skeletal diseases. They also found that Lrp5 acts locally to affect bone homeostasis. Their data suggest that increasing LRP5 signaling in mature bone cells may be a strategy to treat osteoporosis.

This study shows that most known mediators of immunity, such as TLR2, MyD88, T cells or B cells, and neutrophils and monocytes, are dispensable for pain produced by Staphylococcus aureus infection; instead, bacterial products, such as N-formylated peptides and α-haemolysin, induce pain by directly activating nociceptor neurons, which in turn modulate inflammation.

Inactivating the CLP1 RNA kinase in mice leads to a progressive loss of motor neurons, through a mechanism related to the accumulation of a novel set of small RNA fragments derived from aberrant processing of tyrosine pre-transfer RNA.

During embryogenesis, the cytoplasmic protein Myomarker (MYMK) mediates muscle fibre formation by fusion of myoblasts. Here, the authors identify autosomal recessive mutations in MYMK that cause Carey-Fineman-Ziter syndrome in humans, and model the disease variants in zebrafish.

Fast and reliable entanglement distribution in quantum networks requires multiplexing to enhance rates and distillation to compensate the loss in fidelity. Classical communication latency associated with both swapping and distillation protocols is a significant hurdle, which the authors address by proposing a class of quasi-local entanglement distribution policies for multiplexed repeater chains.

Human embryonic stem cells (hESCs) are shown to have high 26S/30S proteasome activity owing to increased expression of the 19S proteasome subunit PSMD11; FOXO4 regulates proteasome activity in hESCs by modulating PSMD11 expression, and the high proteasome activity decreases after induced differentiation.

Yuen et al. developed a cloud-based database with 5,205 whole genomes from families with autism spectrum disorder (ASD). They identified 18 new candidate ASD-risk genes and approximately 100 risk genes and copy-number loci, which account for 11% of the cases. They also found that individuals bearing mutations in ASD-risk genes had lower adaptive ability.

Stimulating the intrinsic growth capacity of neurons and providing growth-supportive substrate and chemoattraction can allow axon regrowth across anatomically complete spinal cord injuries in adult rodents.

A spatially explicit global map of tree symbioses with nitrogen-fixing bacteria and mycorrhizal fungi reveals that climate variables are the primary drivers of the distribution of different types of symbiosis.

Autism is a highly heritable neurodevelopmental disorder, and yet few specific susceptibility genes have been identified to date. A linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms is now described in a common set of 1,031 multiplex autism families. The linkage regions identified provide targets for rare variation screening whereas the discovery of a single novel association, SEMA5A, demonstrates the action of common variants.