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Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Pathological neural communication drives the spread of the epileptic network and contributes to memory impairment in focal epilepsy. The authors show that closed-loop electrical stimulation in rodents can prevent this interaction and preserve long-term memory.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Neurodegenerative diseases are linked to changes in the immune system and inflammation. Here, the authors studied immune cells from healthy individuals and neurodegenerative diseases and identified sex-specific disease-associated changes.

Natural physical and biological systems change in regions of temperature increase. Such changes have occurred on all continents and in most oceans since at least 1970. This paper presents statistical evidence that these changes cannot be explained by natural climate variations alone, and concludes that anthropogenic climate change is affecting physical and biological systems globally and on some continents.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

Tailored to provide diabetes management recommendations from large training and validation datasets, an artificial intelligence system integrating language and computer vision capabilities is shown to improve self-management of patients in a prospective implementation study.

Ding and colleagues use bulk, single-cell and single-nucleus multi-omics together with spatial transcriptomics and multiplex imaging of clinical tumor samples to characterize gene expression and chromatin accessibility of breast cancer lineages.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Single-cell sequencing approaches need to balance sensitivity, throughput and experimental complexity. Here the authors combine droplet-based microfluidics and combinatorial indexing to develop OAK, a versatile method for ultra-high throughput single-cell multiomic profiling.

Foldamers are small molecules or oligomers that can adopt secondary and tertiary structures due to noncovalent interactions. Here, the authors show that an amphiphilic foldamer can adopt a hollow truncated octahedron crystal structure comprising of 48 individual foldamer units.

Vinuesa et al. identify patients with systemic autoimmunity and a TNIP1 variant that result in dysregulated B cell function. Mice with the orthologous Tnip1 mutation develop spontaneous autoimmunity associated with impaired mitophagy and autophagic silencing of proteins downstream of Toll-like receptor 7 signaling.

UK Biobank moement tracking data show increased performance as compared to symptoms and genetic and lifestyle factors in identifying prodromal Parkinson’s disease in the general population.

In a phase 2, randomized clinical trial in patients with severe hypertriglyceridemia, pegozafermin, a long-acting analog of human fibroblast growth factor 21, was safe and met the primary endpoint of the trial for reducing serum triglyceride levels.

SEAMLESSM4T is a single machine translation tool that supports speech-to-speech translation, speech-to-text translation, text-to-speech translation, text-to-text translation and automatic speech recognition between up to 100 languages.

Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

A genomic, transcriptomic and epigenomic analysis of chronic lymphocytic leukemia identifies genetic drivers and molecular subtypes associated with clinical outcomes.

The R package barcodetrackR facilitates the analysis and visualization of clonal tracking data, and it includes a graphical user interface to allow researchers without programming experience to utilize various quantitative tools.

CRISPR is a microbial RNA-based immune system protecting against viral and plasmid invasions. The CRISPR system is thought to rely on cleavage of a precursor RNA transcript by Cas endonucleases, but not all species possessing CRISPR-type immunity encode Cas proteins. This study now describes an alternative pathway in Streptococcus pyogenes that employs trans-encoded small RNA that directs the processing of precursor RNA into crRNAs through endogenous RNase III and the CRISPR-associated Csn1 protein.

Successful engraftment of human hematopoietic stem cells during gene therapy requires myeloablative conditioning of the recipient, at the expense of toxicity. Authors show here that a single-dose of anti-CD117 antibody-drug conjugate achieves similar engraftment results as traditional multi-dose busulfan conditioning but preserves fertility in a non-human primate model.

Despite the rapid progress and interest in brain-machine interfaces that restore motor function, the performance of prosthetic fingers and limbs has yet to mimic native function. Here, the authors demonstrate that shallow-layer neural network decoders outperform and enable higher velocity finger movements than the current linear decoding standard.

Patients with stage 4 or unresectable stage 3 melanoma refractory to first-line anti-programmed death protein 1 (PD-1) or anti-programmed cell death 1 ligand 1 have longer progression-free survival when treated with a combination of anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) and anti-PD-1 versus anti-CTLA-4 alone.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

Enterotoxigenic Bacteroides fragilis, a bacterium from the intestinal flora, may promote colon tumor formation through a pathway that involves Stat3 expression and T helper type 17 immune responses.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

This study uses epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for neurons dissected from different regions projecting to different targets across the whole mouse brain.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Adipocyte tissue macrophages (ATM) are recruited and activated in obesity. The authors show that adipocytes release lactate as a signal of inflammation and that this metabolite can enhance obesity associated inflammation through stimulation of ATM by direct binding with PHD2.

LKB1 is frequently mutated in lung squamous cell carcinomas. Here, the authors show that sole LKB1 depletion is sufficient to drive the development of this cancer, where downstream defective MKK7-JNK1/2 signalling activates the ∆Np63/p63 pathway to induce subsequent epithelial cells transformation and tumour progression.

Cancer-associated fibroblasts (CAFs) are the main component of the stroma in pancreatic cancer, but their tissue of origin remains to be defined. Here the authors perform lineage tracing and single cell RNA sequencing in mice and suggest the splanchnic mesenchyme as the tissue of origin for CAFs.

Liu and colleagues find differential effects of microglial apoE isoforms on brain function and microglial responses. ApoE3 enhances microglial responses, promoting brain function and reducing amyloid deposition and associated neurotoxicity, while the Alzheimer’s disease-associated apoE4 results in lipid droplet accumulation and impaired microglial responses, which are critical for limiting the development of amyloid pathology.

Cancers of the same tissue type are characterized with different molecular features depending on anatomical ___location. Here, the authors show that proximal and distal colon stem cells have distinct transcriptional programs mediated by the transcription factor CDX2, with differential roles in colon cancers based on anatomical ___location.

Here, a draft sequence of the giant panda genome is assembled using next-generation sequencing technology alone. Genome analysis reveals a low divergence rate in comparison with dog and human genomes and insights into panda-specific traits; for example, the giant panda's bamboo diet may be more dependent on its gut microbiome than its own genetic composition.

mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.

The transcription process of DNA is highly complex and while short DNA sequence motifs recognized by transcription factors are well known, less is known about the context in the DNA sequence that determines whether a transcription factor will actually bind its motif. Zheng and colleagues present a method that uses convolutional neural networks to identify sequence features that help predict whether transcribing proteins can bind to their target sequences in DNA.

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.

Patient-derived xenografts provide a resource for basic and translational cancer research. Here, the authors generate multiple pediatric high-grade glioma xenografts, use omics technologies to show that they are representative of primary tumours and use them to assess therapeutic response.