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Using a composite bioinformatics approach, the DNA:DNA:RNA triplex-forming lncRNAs HIF1α-AS1 was identified in human endothelial cells which recruits an epigenetic silencing complex to limit expression of triplex target genes.

Blocking alternative activation of p38 in tumor-infiltrating CD4⁺ T cells reduces proinflammatory cytokine production and inhibits pancreatic cancer growth in mice.

This study describes sensing of circulating cell-free DNA after stroke as the mechanism leading to recurrent ischemic events.

Here, the authors characterize the structure of the Lipooligosaccharide of the gut symbiont Akkermansia muciniphila showing unique features and TLR4 and TLR2 signaling capacity, which underscore the beneficial properties of this bacterium.

T cell memory formation is often described as occurring during the chronic phases of infection. Buchholz and colleagues use the phenomenon of ‘memory inflation’ following cytomegalovirus infection to show that a tiny subset of self-renewing T cells branch off early from the bulk population to generate memory.

Forced expression of C-X-C chemokine receptor type 6 in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer.

SARS-CoV-2-specific CD4⁺ and CD8⁺ T cell epitopes are found in both convalescent patients and virus-naive volunteers and are indicative of heterologous recognition shared with seasonal cold viruses.

Whether the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have a different role in glioblastoma progression and resistance to therapies is currently unclear. Here, the authors, by long-term tracking of individual glioma, demonstrate that both niches can partially compensate for each other and that glioma cells localized in both niches are resistant to radio- and chemotherapy.

The bone marrow is a common site of metastasis for neuroblastoma patients. Here, the authors perform single cell RNA-seq and ATAC-seq of bone marrow aspirates from 16 subjects and show conservation of tumor cell plasticity in metastases and identify tumor-to-bone marrow cell signals that trigger tumor promoting monocytes.

The processing of RNAs transcribed by RNA polymerase II requires a cap-binding complex (CBC), consisting of NCBP1 and NCBP2. Here, the authors report an alternative CBC formed by NCBP1 and a previously uncharacterized protein, NCBP3 that is critical for RNA processing under cellular stress conditions.

Hippocampal synaptic dysfunctions are an early symptom of Alzheimer’s disease. Here, the authors find adenosine A2A receptors are up-regulated in APP/PS1 model mice and that deleting or blocking receptor activity helps alleviate plasticity and memory impairments.

The function of T regulatory cells in the tissue fibrosis in chronic pancreatitis is not fully understood. Here the authors use a mouse model of chronic pancreatitis to show that Treg cells reduce IL-4 mediated chronic inflammation in the pancreas associated with M2-like macrophages in vivo.

A SARS-CoV-2-human protein contactome map uncovers an inhibitor of viral replication.

Organoid avatars of colorectal cancer and its microenvironment model immune interactions and drug efficacy.

Blockade of intrahepatic accumulation and function of platelets represents a potential approach to treat non-alcoholic steatohepatitis (NASH) and prevent subsequent progression to hepatocellular carcinoma

Structural, functional and in silico analyses of the chloroquine-resistance transporter PfCRT of Plasmodium falciparum suggest that distinct mechanistic features mediate the resistance to chloroquine and piperaquine in drug-resistant parasites.

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.

By measuring metabolic and biosynthetic activity with cell cycle progression, Litsios et el. uncover pulses in protein production rate that do not scale with cell size but drive cell cycle entry in budding yeast.

Respiratory infections occur throughout life but how this shapes the lung immune system through time is unclear. Wack and colleagues show that a previous influenza infection recruits monocytes to the lung, which then assume an alveolar macrophage-like phenotype and mediate long-term antibacterial protection.

Breast cancers have been extensively studied at the genomic and transcriptomic levels in the hope of tailoring therapeutic regimens. Here the authors generate deep coverage proteomes from several clinical breast cancer samples, and use machine learning techniques to uncover biological processes altered in specific cancer subtypes.

Chromatin is dynamically remodeled in response to DNA damage in favour of repair. Here the authors reveal how the chromatin remodeler CHD7 and chromatin binding protein 53BP1 regulate distinct DNA repair pathways.

Single-stranded DNA during DNA replication and repair in S/G2 needs protection by replication protein A (RPA). Here the authors reveal that RPA also shields inherited single-stranded DNA in G1, representing replication remnants from the previous cell cycle, to allow for post-mitotic DNA synthesis.

Primary lymphomas of the central nervous system (PCNSL) are defined as diffuse large B-cell lymphomas (DLBCL) confined to the CNS. Here, the authors complete whole genome sequencing and RNA-seq to characterize 51 PCNSLs, and find common mutations in immune pathways and upregulated TERT expression and find distinct pathway differences between DLBCL and other primary CNS lymphomas.

In a prospective, double-blind, randomized, placebo-controlled trial, supplementation with a combination of conventional and gut-targeted nicotinamide was safe and effective in ameliorating COVID-19 symptoms.

The innate immune response in epithelial cells after SARS-CoV-2 infection is not fully understood. Here the authors use human air-liquid interface culture and show single cell transcription changes and delayed type I Interferon responses after SARS-CoV-2 infection compared with other respiratory viruses.

Inhibition of YBX1, a downstream target of the Janus kinase JAK2, sensitizes myeloproliferative neoplasm cells to JAK and could provide a means to eradicate such cells in human haematopoietic cancers.

The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS).  Here the authors find that DNA methylation at HLA-DRB1 gene mediates the effect of DRB1*15:01 and of a protective HLA variant on HLA-DRB1 expression and the risk of MS.

The microbiota of the rhizosphere (roots) and phyllosphere (leaves) of healthy plants consist of taxonomically structured bacterial communities; here the majority of species representing the main bacterial phyla from these two organs were isolated and genomes of about 400 representative bacteria were sequenced; the resources of cultured bacteria, corresponding genomes and a gnotobiotic plant system enabled an examination of the taxonomic overlap and functional specialization between the rhizosphere and phyllosphere bacterial microbiota.

Sequencing and deep analysis of mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project reveal widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent, and the analyses point to putative causal variants for dozens of disease-associated loci.

Primary cilia are key sensory organelles whose dysfunction leads to ciliopathy disorders such as Bardet-Biedl syndrome (BBS). Here they identify a role for Bbs1 in lipid homeostasis of photoreceptor outer segments in zebrafish, which may contribute to vision loss in patients with Bardet-Biedl syndrome.

By combining experimental models with prospective clinical studies, the authors show that spinal cord injury causes a rapid reduction in cardiac function that precedes structural changes, and that the loss of descending sympathetic control is the major cause of reduced cardiac function following spinal cord injury.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Zhang et al. show that bone marrow fatty acid metabolism fuels expanded leukocyte production after myocardial infarction and, based on mouse, pig and human data, suggest that lipolysis in marrow adipocytes provides fatty acids to hematopoietic stem cells.

Brown fat is a thermogenically active organ that burns energy instead of storing it and has been the focus of intense research recently in the hopes of harnessing this activity to combat obesity. Sven Enerbäck and his colleagues now show that human neonates possess a classical form of this type of fat, suggesting hope that its expansion in adults may indeed be an avenue of therapy to treat obesity.

In this placebo-controlled trial, 10/13 malaria naïve subjects immunized with a simplified regimen of chemoattenuated P. falciparum sporozoites, PfSPZ-CVac, show sterile protection from heterologous malaria challenge. Immunization was well tolerated and induced high levels of anti-PfCSP antibodies.

Mast cells within the tumor microenvironment have controversial roles. Here, the authors show, using genetic mouse models, that in gastric cancer, mast cells at the periphery of the tumors are activated via cancer cell produced-IL33 and promote tumorigenesis by recruiting macrophages within the tumors.

Integrin β7-dependent Glp1r^high natural gut intraepithelial T lymphocytes that reside in the small intestine modulate dietary metabolism in mice by restricting the bioavailability of GLP-1.

Social encounters are associated with varying degrees of stress. The authors show that modulation of stress system components in the medial amygdala alters preference for familiar vs. novel conspecifics. Inhibition of the relevant circuit in a group of familiar mice kept under semi-natural conditions increased pro-social behavior.

Nanoparticles can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo.

The lipid kinase phosphatidylinositol-4-OH kinase (PI(4)K) is identified as a target of the imidazopyrazines, a new antimalarial compound class that can inhibit several Plasmodium species at each stage of the parasite life cycle; the imidazopyrazines exert their inhibitory action by interacting with the ATP-binding pocket of PI(4)K.

Hypothalamic melanocortin neurons control energy homoeostasis by modulating appetite. Here, the authors reveal a role for the transcription factor Tbx3 as a regulator of the peptidergic identity and function of immature and mature mouse melanocortin neurons.

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.

Magnetic resonance imaging of swollen tendons suggests that the elasticity and stress relaxation of extracellular matrix depend on electrostatic repulsions between proteoglycans rather than on hydration-associated changes.

Studies on interferon-driven brain pathology have so far been hampered by the lack of appropriate animal models. Here the authors characterize RNASET2-deficient mice and show that neuroinflammation and brain atrophy are IFNAR1-dependent.

Eilers and colleagues report that Aurora-A suppresses transcription–replication conflicts in MYCN-driven neuroblastoma, a vulnerability that can be targeted with a combination of Aurora-A and ATR kinase inhibitors.

The mechanosensitive ion channel PIEZO1 senses shear stress induced by collagen-fibre sliding in tendons, regulates their stiffness and influences jumping performance.

The WAVE regulatory complex activates Arp2/3 at the cell cortex and in membrane protrusions to generate persistent cell migration. Here authors show that PPP2R1A, a scaffold subunit of protein phosphatase 2, associates with an alternative form of the WAVE complex where WAVE, the subunit that activates Arp2/3, is replaced by NHSL1.