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The molecular mechanisms underlying merlin-intact meningioma growth remain to be explored. Here, the authors show that merlin activates Wnt signalling and tumour growth through its dephosphorylation on serine 13 attenuating the inhibitory interactions with β-catenin.

Wolf et al. examine the impact of maternal risk factors on gestational duration mediated by changes in cervical length during pregnancy. Their study finds that previous preterm birth, pre-pregnancy BMI, parity, and previous abortion have unique influences on preterm birth risk through linear changes in the cervix.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

METTL3-dependent RNA N⁶-methyladenosine (m⁶A) deposition can lead to DNA demethylation. The m⁶A reader FXR1 recruits DNA 5-methylcytosine dioxygenase TET1 to chromatin, which is linked to chromatin accessibility and gene transcription.

PCNA is essential for DNA replication and cellular proliferation. Here, the authors reveal that PCNA ubiquitination protects stalled replication forks from DNA2-mediated degradation via regulation of Okazaki fragment maturation and chromatin assembly.

In patient with glioblastoma, a major cause of resistance to chemotherapy and radiotherapy is the high degree to intratumoral heterogeneity and cell plasticity. Here, the authors demonstrate that chemoradiation induces the reprograming of glioblastoma cells into an invasive and vessel co-opting state, termed VC-Resist, capable of promoting resistance to therapy.

Drug addiction is a chronic disorder and many sufferers experience relapses even after a period of successful abstinence. Here, the authors reveal a subset of neurons in the rat infralimbic cortex that suppresses relapse into cocaine or alcohol use by responding to drug-omission cues.

Use of the consensus protein design method facilitated the generation of stable engineered mammalian odorant receptors to gain insight into the molecular properties of odorant–receptor interactions.

GPR84 is an important GPCR regulating macrophage function. Here, the authors show the pro-phagocytic function of the GPR84-Gi signaling axis in native macrophages and determine a cryo-EM structure of the GPR84-Gi complex with a synthetic agonist.

Combining antibiotics remains a promising approach to treat patients and to prevent the emergence of antimicrobial resistance

It is unclear why neuronal activity induced methylation changes are limited to specific loci in the genome. Here, authors show that the DNA demethylation enzyme, TET1, gains its specificity via the interaction with EGR1, a sequence specific DNA binding protein.

ApoE4 is a risk factor for Alzheimer’s disease and vascular dementia. We report that in ApoE4 mice perivascular macrophages are the sole source and effectors of the ApoE4 mediating the neurovascular dysfunction, enhanced white matter damage and cognitive impairment.

A risk score based on a 34-gene signature for outcome prediction in meningioma was developed and validated in large multi-institutional cohorts and showed better performance in discriminating postoperative menignioma outcomes compared with existing meningioma classification systems.

Stereotactic ablative radiotherapy (SABR) is standard-of-care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC), however the risk of systemic recurrences remains high. Here the authors report the results of a phase I study testing the addition of atezolizumab (anti-PD-L1) to SABR in high risk, medically inoperable, early-stage, NSCLC.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

CSF MTBR-tau243 is more related to tau tangles and clinical cognitive impairment in Alzheimer’s disease than phospho-tau biomarkers, which are more related to amyloid plaques.

The combination of neoadjuvant nivolumab, ipilimumab and chemotherapy showed promising efficacy in patients with resectable non-small cell lung cancer, with higher tumor immune cell infiltration and tertiary lymphoid structures after treatment compared with neoadjuvant nivolumab plus chemotherapy.

Serosurveillance studies show a heterogenous mix of the Indian population with immunity to COVID-19 due to vaccination or natural infection. Here, the authors enrol subjects representative of the general population, to assess whether pre-existing antibodies are further boosted by a single dose of an inactivated SARS-CoV-2 vaccines, BBV152.

Monoclonal antibodies are highly effective therapeutics that can be delivered as proteins or encoded DNA or mRNA. Here the authors develop lipid nanoparticle-formulated nucleoside-modified mRNA encoding an HIV-1 neutralizing antibody and see sustained and protective antibody levels in treated mice.

The potential of tissue engineering to deliver clinical advances hinges on a connected ecosystem that includes academics, funding agencies, entrepreneurs, investors, the pharmaceutical industry and regulatory bodies. Open dialog on goals and risks across these stakeholders is key to implementing bioengineered tissue models in drug development and tissue therapies.

Zhao et al. show that ASTE1 is a downstream effector of the shieldin complex, which cleaves the 3′ overhang of DNA double-strand breaks to promote shieldin-dependent non-homologous end-joining.

Mitochondrial biogenesis and maintenance relies on protein import from the cytosol. Here, authors show that import failure impacts organelle structure and dynamics. They also identify a rescue mechanism involving intercellular mitochondrial transfer.

By subjecting chlorophyte lipid extracts to pyrolysis, the authors demonstrate that the lipid biomarkers 24-isopropylcholestane and 24-n-propylcholestane can be generated from algal C₂₉ sterol in experiments simulating diagenetic processes, thereby undermining their status as sponge biomarkers.

Accelerated bisulfite sequencing detects 5-methylcytosine in low-input DNA and RNA samples

SKP2 is an oncogenic E3-ubiquitin ligase. Here the authors show that SKP2 is epigenetically regulated by the muscle lineage transcription factor MYOD, supports tumorigenesis in the Fusion Negative (FN) subtype of rhabdomyosarcoma (RMS) and impairs differentiation promoting degradation of p57^Kip2.

Dysfunction of the lymphatic system leads to secondary lymphedema and results in degradation of quality of life. Here, the authors show that delivery of nucleoside-modified Vascular Endothelial Growth Factor C (VEGFC) mRNA, encapsulated in lipid nanoparticles, induces organ-specific lymphatic growth and reverses experimental lymphedema.

The low photoluminescence of monolayer transition metal disulfides remains a challenge for their optoelectronic application. Here the authors present an effective and green method to enhance the photoluminescence of monolayer MoS₂ and WS₂, and a detailed mechanistic picture of the treatments.

FOXM1 is a known transcription factor which promotes cell proliferation in cancer cells. Here, the authors show that FOXM1 is required for the maintenance of quiescence and self-renewal of leukemia stem cells in MLL-AF9-rearranged acute myeloid leukemia patient and mouse models.

Here, Andrade et al. assess the memory B cell (MBC) and antibody response to Zika virus (ZIKV) in individuals with and without prior dengue virus (DENV) infection and find that ZIKV infection elicits a robust and specific MBC response that is only modestly affected by the number of prior DENV infections.

One cause of relapse in cancer patients treated with chimeric antigen receptor (CAR) T cells is the loss of CAR-targeted antigens, which is particularly common in multiple myeloma (MM). Here the authors engineer a CAR recognizing two common MM-associated antigens and demonstrate its superiority to single-antigen CARs in a mouse model of MM.

STIM1 is a calcium sensor that is essential for functional lymphocyte responses. Gwack and colleagues demonstrate a calcium-independent role for STIM1 in macrophages that regulates their production of type I interferons.

G protein-coupled receptors are a major class of drug targets. Here, the authors develop a method whereby their biophysical and functional properties can be altered through directed evolution in mammalian cells, leading to variants exhibiting features such as high stability and expression, or increased allosteric coupling.

US universities have made public commitments to recruit and retain faculty of colour. Analysis of three federal datasets shows that at current rates diversity in US faculty will never reach racial parity. Yet, colleges and universities could achieve parity by 2050 by diversifying their faculty at 3.5 times the current pace.

We consider the shift from broad, population-level medicine to ultra-precise, individualized medicine using emerging therapeutic constructs, AI, deep phenotyping, and individual-centered trials to optimize health across diverse individual genetic and physiological profiles.

Single-cell proteomic profiling of circulating CAR T cells in patients treated with CD19-CAR shows that CD4⁺Helios⁺ CAR T cells on day 7 after infusion are associated with progressive disease and less severe neurotoxicity.

The female reproductive tract constitutes the ovary, fallopian tubes, uterus, and cervix, but it is challenging to engineer this systemin vitro. Here, the authors develop a microfluidic device (EVATAR) with reproductive tract and peripheral tissues to replicate hormone release of a 28-day menstrual cycle.

Bulk and single cell measurements are integrated to identify phenotype-associated subpopulations of cells.