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The DNA origami vaccine platform DoriVac is shown to support multiplexed nanoparticles carrying diverse antigens against emerging infectious diseases and variants.

Ionescu, Ankol et al. show that, in ALS mouse and iPSC models, TDP-43 aggregation at NMJs stems from aberrant axonal translation, normally repressed by muscle EV-derived miR126. Loss of miR126 in ALS increases TDP-43 buildup, impairs local synthesis and triggers degeneration.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Avs proteins are bacterial anti-phage pattern recognition receptors evolutionarily related to eukaryotic NLRs. Here, Béchon et al show that a single bacterial Avs can recognize different phage proteins as a signature for infection, explaining the broad defensive range of Avs proteins.

Colorectal cancer metastasis involves dramatic plasticity and loss of PROX1-mediated repression of non-intestinal lineages.

Recent MPXV outbreaks underscore the need for better vaccines and treatments. Here, the authors isolate and structurally characterize potent antibodies interacting with A28 that they identify as a key viral surface protein essential for viral entry and that induces strong, protective antibody response in mice.

Synapses are surrounded by an extracellular matrix (ECM) of extremely long-lived proteins that is thought to only be remodeled by proteolysis and de novo synthesis. Here, the authors show an alternative molecular recycling mechanism that occurs for the key ECM protein Tenascin-R.

Klebanoff and colleagues report that survival and persistence of CAR-T and CAR-NK cells are regulated by a FAS ligand–FAS autoregulatory circuit, showing that disabling FAS signaling enhances their antitumor efficacy in preclinical models.

HCMV infection can become productive or latent. Here the authors show that variations in the number of incoming viral particles across cell types is a key factor of this decision, identifying entry efficiency as a key regulator of latency.

R2 retrotransposons are natural RNA guided gene insertion systems. Here, Edmonds et al. characterize the structure and biochemistry of an avian R2 and engineer a compact, all-RNA system to integrate DNA in mammalian cells, aiding the development of future retrotransposon-based gene editors.

A large fraction of patients with APS-1 and coeliac disease develop enamel dystrophy, characterized by the presence of autoantibodies against the enamel matrix, which are generated through the breakdown of either central (APS-1) or peripheral (coeliac) tolerance to a battery of ameloblast-sepecific proteins.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Examining human brain organoids and ex vivo neonatal murine cortical slices demonstrates that structured neuronal sequences emerge independently of sensory input, highlighting the potential of brain organoids as a model for neuronal circuit assembly.

Here, the authors characterize how different dietary components lead to functional alterations in the gut symbiont Bacteroides thetaiotaomicron, showing effects on the orientation of phase variable regions in humans, in vivo, and in vitro, and on modulating the bacterium´s proteome and immune-modulatory functionality.

Tagging and tracking the blood plasma proteome as a discovery tool reveals widespread endogenous transport of proteins into the healthy brain and the pharmacologically modifiable mechanisms by which the brain endothelium regulates this process with age.

In their study, Wang and Dagan show that 84% of antibiotic resistance genes in multidrug resistance plasmids in Escherichia, Salmonella, and Klebsiella reside within resistance islands that evolve within the framework of plasmid lineages.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

DEBIAS-M corrects technical variability in microbiome data in a manner both interpretable and suitable for machine learning. In extensive benchmarks, DEBIAS-M facilitates robust analyses that generalize across datasets.

A comprehensive spatial expression atlas of the adult human proximal small intestine reveals branched villi, immune activation at the villus tip, and a switch of migrating enterocytes from lipid droplet assembly and iron uptake at the villus bottom to chylomicron biosynthesis and iron release at the tip.

Adventitious roots are induced in various woody plants, enabling clonal propagation.

UDP-glucuronic acid is a component of the extracellular matrix. Here, the authors report biallelic variants in the gene encoding UDP-Glucose 6-Dehydrogenase (UGDH) in individuals affected by developmental epileptic encephalopathies that impair UGDH stability, oligomerization, or enzymatic activity in vitro.

Characterization of the vaginal microbiome and metabolome reveals that vaginal metabolites, including several exogenous xenobiotics, are predictive of spontaneous preterm birth.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

A multiplexed fluorescence-based assay detects seroconversion in individuals infected with SARS-CoV-2 from less than 1 µl of blood as early as the day of the first positive nasopharyngeal nucleic acid test after symptom onset.

Organellar transport is carefully regulated, and endolysosome localized ARL8 is important for kinesin recruitment and anterograde movement. Here, the authors show that RUFY3 and RUFY4 promote retrograde transport of endolysosomes by mediating interaction of ARL8 with dynein-dynactin.

The chemokine CXCL10 is associated with pathogenesis of cerebral malaria in Plasmodium falciparum infection. Here the authors show that P. falciparum produces extracellular vesicles laden with RNAs that are taken up by monocytes resulting in a RIG-I and HUR-1 mediated mechanism of inhibition of CXCL10 protein translation.

How cells adapt to glucose starvation is still elusive. Here, Levy et al. show that the mTOR substrate 4EBP1 protects human, mouse, and yeast cells from glucose starvation and is exploited by cancer cells to promote tumorigenesis.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Microglia in the aging hippocampus accumulate lipid droplets, and are functionally impaired and inflamed. Lipid droplet formation in microglia is regulated by genes linked to neurodegeneration such as progranulin.

This study presents a new T cell therapy targeting spinal cord injury, providing a potential new approach for injured CNS.

A randomized crossover trial showed that transition to a Western diet resulted in pro-inflammatory changes, whereas transition to an African heritage diet rich in fruits and vegetables, legumes and fermented products led to opposite effects.

GTPases are master regulators at the trans-Golgi network (TGN). Here, authors report that ARMH3 (C10orf76) is an ARL5 effector, and that a SYS1-ARFRP1-ARL5-ARMH3-PI4KB axis promotes PI4P synthesis, GOLPH3 recruitment, and glycan modifications at the TGN.

Protein imaging is multiplexed using combinatorial staining and deep learning decompression.

CAPPSID relies on an engineered S. typhimurium to act as a synthetic ‘capsid’ to transcribe and deliver viral RNA inside cancer cells, launching a virus that can directly lyse surrounding cells.

A genetic screen that expresses single guide RNA libraries targeting host genes in the human cytomegalovirus genome enables identification of host factors and provides insights into their roles during the viral replication cycle.

The authors identified a sub-clade of NPF transporters that orchestrates GA12 long-distance shoot-to-root translocation. Once in the phloem unloading zone, ABA and GA are loaded into pericycle vacuoles and then slowly released to induce endodermal suberin formation in the maturation zone.

Fgf17 in young CSF boosts oligodendrocyte progenitor cell proliferation and differentiation in the aged hippocampus, improving memory function.

Proteasomal degradation of cellular proteins generate defence peptides constitutively and in response to bacterial infection. Such peptides might provide a source of natural antibiotics that could lead to biotechnology applications and therapeutic interventions.

A ‘mouse atlas’, comprising single-cell transcriptomic data from more than 100,000 cells from 20 organs and tissues, has been created as a resource for cell biology.

The role neurochemistry plays in encoding newly-acquired motor skills remains unclear. Here, the authors use multimodal imaging to show that early inhibitory and excitatory changes promote overnight behavioral, structural, and connectivity-related gains.

Brain organoids replicate cellular organization found in the developing human brain. Here, the authors utilize microelectronics to map activity in brain organoids and assemble functional circuits that mirror complexity found in brain networks in vivo.

The origin of photosynthetic eukaryotes requires two major endosymbiosis events. Organelle acquisitions impose an increase in reactive oxygen species production, as well as the expansion of redox-sensitive proteasome in photosynthetic eukaryotes.

Retinal pigment epithelial cells are identified as a local source of insulin in the retina, which is stimulated by phagocytosis of photoreceptor outer segments and starvation and has the potential to influence retinal physiology and disease.

Activating mutations in Interleukin-7 receptor alpha (IL7Ra) have been reported in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) but its role in leukaemogenesis is not clear. Here, the authors show that activation of IL7Ra in primary human hematopoietic progenitors initiates preleukaemia and cooperates with CDKN2A silencing to develop BCP-ALL.

Here, the authors show in human iPSC-derived motor neurons from ALS patients and a TDP-43 mouse model that axonal TDP-43 forms G3BP1 positive RNP condensates, which sequester mRNA of nuclear encoded mitochondrial proteins and decrease local protein synthesis in motor neuron axons and neuromuscular junctions.

Plasmodium falciparum secretes extracellular vesicles (EVs) while growing inside red blood cells (RBCs). Here the authors show that these EVs contain assembled and functional 20S proteasome complexes that remodel the cytoskeleton of naïve human RBCs, priming the RBCs for parasite invasion.