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Sleeping sickness caused by African trypanosome parasites induces a chronic, and potentially lethal, infection in humans. Here, the authors uncover a conserved protein, Q586B2, playing an important regulatory role in Trypanosomatid infection establishment.

A new targeting modality-based transcellular labeling technology called photocatalytic cell tagging enables monitoring of cell–cell interactions when combined with multiomics single-cell sequencing.

Despite decades of research, the dynamics of clathrin-coated vesicle formation is ambiguous. Here, authors use STAR microscopy to quantify the nanoscale dynamics of vesicle formation, supporting the flexible model of clathrin-mediated endocytosis.

Lab-on-a-chip systems have been widely used in microscale liquid manipulation and greatly benefit from automation. Durrer et al. show a robot-assisted acoustofluidic end effector system, comprising a robotic arm and an acoustofluidic device, that combines both robotic and microfluidic functionalities.

The transcriptional programs and chromatin accessibility changes that cause two related interneuronal subtypes to diverge from common developmental origins and acquire specialized properties are elucidated.

Conducting epigenomic studies on FFPE samples is traditionally challenging due to chromatin damage caused due to exposure to formaldehyde. Here, the authors show that an optimisation of their previous CUTAC method allows the production of high-resolution maps of regulatory elements from FFPE samples.

Intratumoural heterogeneity in high-grade serous ovarian carcinoma (HGSOC) remains to be explored. Here, the authors perform spatial transcriptomics and reveal a high degree of subclonal heterogeneity in HGSOC.

A neuron-specific activity-dependent DNA repair mechanism is identified, the impairment of which may lead to neurodevelopmental disorders, neurodegeneration and ageing.

The interaction of membrane-resident proteins plays an essential role in biological processes. Here the authors describe cellular biosensors based on chimeric receptors, as a tool to study the interaction of receptor-ligand pairs such as immune checkpoint molecules or virus attachment proteins and their receptors.

Feedback control of optically generated flows enables precise, dynamic particle assembly and complex micro-robotics.

Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a highly enriched cell surface antigen expressed in prostate cancer. Here the authors describe the design of STEAP1 directed CART cells and show their antitumor activity in preclinical models of prostate cancer, also in combination with a collagen binding domain-IL-12 fusion cytokine.

Mitchell et al. identify reduced osteoprogenitors and increased mesenchymal stromal cells in old bone marrow niche, which creates an IL1-mediated inflammatory milieu that skews myeloid differentiation and impairs haematopoietic regeneration.

The balance of stem cell maintenance, differentiation, and programmed death is critical for proper development. Here they show that SNIP1 is critical for stem cell survival and differentiation in the developing brain where it acts downstream of TGFb and NFkB and regulates PRC2 activities for governing cell fates.

CCR5 is a co-receptor for many transmitted HIV strains. Here, the authors show that biweekly injection of the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of a CCR5-tropic SHIV.

Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.

In contrast to direct-targeting monoclonal antibodies, low affinity confers agonistic monoclonal antibodies with more potency.

“Cephalopods are known for their large nervous systems, complex behaviors, and morphological innovations. Here, the authors find that soft-bodied cephalopod genomes are more rearranged than other extant molluscs and that mRNA editing patterns are associated with the nervous system and repetitive elements”.

Mature parts of the shallow megathrust beneath Costa Rica are characterized by striking corrugations that may channel fluids, according to seismic images. Nascent sections of the subduction zone plate boundary appear only weakly corrugated.

Myeloid cell recruitment during tumor inflammation depends on the VCAM-1 receptor integrin α4β1. Here the authors show that a high molecular weight form of myosin light chain kinase, MLCK210, is required for myeloid cell integrin α4β1 activation and adhesion and that MLCK210 inhibition reduces tumor growth and inflammation in preclinical cancer models.

Epigenetic therapies are known to synergize with immunotherapies through the de-repression of endogenous retroviral element (ERV)-encoded promoters. Here the authors identify treatment-induced neoantigens and validate their ability to induce T cell response and anti-tumor effects in vitro and in patient samples.

The loading of two different protein therapeutics onto extracellular vesicles can be optimized by genetically engineering the parent cells, as shown for extracellular vesicles displaying decoy receptors for two pro-inflammatory cytokines.

Integrated single-cell atlases of human fetal cerebella and MBs show potential cell populations predisposed to transformation and regulatory circuitries underlying tumour cell states and oncogenesis, highlighting hitherto unrecognized transitional progenitor intermediates predictive of disease prognosis.

Trypansome brucei infection can result in colonisation of the skin but how this impacts the skin architecture and immune response has not been fully resolved. Here the authors apply a spatially resolved single cell transcriptomics approach in a murine model of infection, and suggest a role for IL-17- producing γδ T cells in the immune response to T. brucei skin infection.

Cellular membranes have distinct lipid compositions despite intermixing, and it is unclear why plasma membrane lipids do not accumulate on endosomes. Here, the authors use the C. elegans embryo to identify lipid transfer proteins and phosphatases that are critical for endosomal lipid homeostasis.

Polycomb repressive complex 2 (PRC2) methylates H3K27 and suppresses RNA polymerase II transcription by promoting a closed chromatin. Here the authors identify the transcription factor Ybx1 as an interactor that regulates the binding of PRC2 to chromatin and H3K27 methylation to promote the genetic programs underlying neural lineages and neural progenitor self-renewal–differentiation choices.

Long noncoding RNAs (lncRNAs) regulate key steps of cell division. Here, the authors perform a comprehensive RNAi imaging screen targeting more than 2,000 human lncRNAs, and suggest a role of chromatin-associated linc00899 in regulation of cell division by suppressing the transcription of microtubule-binding protein TPPP/p25.

How histone modifications crosstalk with DNA methylation to regulate epigenomic patterning and genome stability in mammals remains elusive. Here, the authors show that DNA methyltransferase DNMT1 is a reader for histone H4K20 trimethylation via its BAH1 domain, which leads to optimal maintenance of DNA methylation at repetitive LINE-1 elements.

In early mouse embryos, PRC1-mediated H2AK119ub1 deposition precedes H3K27me3. Deficiency in variant PRC1 reduces H2AK119ub1 and leads to gene-selective loss of H3K27me3 in oocytes, which is inherited by embryos.

Depletion of BRD4 reduces the chromatin occupancy of NIPBL, resulting in aberrant genome folding. Loss of BRD4 impedes neural crest differentiation, which can be rescued by depletion of WAPL.

A nanomedicine encapsulating a docetaxel prodrug, and conjugated to an antibody specific for the receptor EphA2, provides enhanced antitumour activity in multiple tumour-xenografted mice, and has minimal toxicity in rats and dogs.

Chronic intestinal inflammatory diseases including ulcerative colitis and Crohn’s disease display extensive heterogeneity in the immunopathology, disease manifestation and response to treatment. Here the authors apply single cell transcriptomic and spatial molecular imaging, and characterise macrophage and neutrophils in samples from patients with inflammatory bowel diseases.

Suppression of transcription in S-phase is crucial to prevent genome instability. Zhang et al demonstrate that increase of H4K20me1 due to loss of Kmt5b cause genome instability in muscle stem cells, resulting in stem cell senescence but rhabdomyosarcoma formation when p53 is inactivated.

During cell division, it is currently unclear how kinetochores transit from lateral microtubule attachment to durable association to dynamic microtubule plus ends. Here, using in vitro reconstitution and computer modeling, the authors provide biophysical mechanism for microtubule end-conversion driven by two kinetochore components, CENP-E and Ndc80 complex

Novel experiences in mice lead to opposing effects on inhibition of Fos-activated hippocampal CA1 pyramidal neurons by parvalbumin- and cholecystokinin-expressing interneurons, revealing the roles of FOS and SCG2 in neural plasticity and consolidation of memories.

The transcriptional regulation of murine spermatogenesis is not well understood. Here, the authors use single-cell and bulk RNA-Sequencing of juvenile and adult mice to characterise somatic and germ cell development, and chromatin profile the X chromosome to show that spermatid-specific genes are repressed by H3K9me3 during meiosis.

Platelet-neutrophil aggregates are a hallmark of thromboinflamation. Here, the authors use cargo-free particles to block platelet-neutrophil aggregates’ vascular wall adhesion, which could become an effective thromboinflammation therapy, regardless of disease cause.

Small colony variants of Staphylococcus aureus induce glycolysis and necroptosis in host cells, which impairs trained immunity and host protection from subsequent S. aureus infection.

Ph⁺ and Ph-like B-ALL remain poor prognosis leukemias. VAV3, a guanine nucleotide exchange factor, is activated and overexpressed in these leukemias. Here the authors reveal that leukemic VAV3 is predominantly nuclear. Nuclear VAV3, through its guanine nucleotide exchange factor and its effector nuclear RAC2, controls the repressive transcriptional activity of the polycomb repression complex-1 via nuclear AKT/PHLPP2 regulated BMI1.

Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelination during development and remyelination in mice.

A subset of oestrogen-sensitive neurons integrate melanocortin and oestrogen signalling to rebalance energy allocation in female mice leading to reduced sedentary behaviour and decreasing obesity in oestrogen-depleted female mice

Tet-mediated DNA demethylation is intimately involved in reguatling embryonic development. Here the authors characterise DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice and provide evidence that Tet-mediated DNA demethylation plays a role in regulating chromatin organization during early heart development.

Microrobotics offers great potential for precise drug delivery as medication can be released in the bloodstream only where it is needed. But the dynamic environment of the bloodstream is a challenge for navigation. An approach presented by Ahmed and colleagues combines magnetic and acoustic fields to allow swarms of particles to swim against a current.

Ring ATPase translocases that operate on disordered substrates adopt lockwasher architectures and use a hand-over-hand mechanism. By challenging the dsDNA packaging motor of bacteriophage ϕ29 with hybrid and dsRNA, the authors propose that the motor cycles between planar and lock-washer structures.

The search for DNA homology is vital to recombinational DNA repair and occurs by intersegment contact sampling wherein the three-dimensional conformational state of the double-stranded DNA target and the length of the homologous RecA–single-stranded DNA filament have important roles.

Sustained cardiac function depends on circadian REV-ERBs. Here, Dierickx et al. show that circadian nuclear receptors REV-ERBα and β are indispensable to establish the transcriptional program that controls cardiac metabolism and NAD⁺ production. Deregulation of REV-ERBs leads to dilated cardiomyopathy and premature death.

The mitochondrial transcription factor TFAM is a multifunctional DNA-binding protein essential for transcriptional regulation and mitochondrial DNA organization. Here, Ngo et al.present two novel crystal structures that provide additional mechanistic insight into how TFAM performs its diverse functions.

Osteoclasts induce chemotaxis of osteoblasts during bone remodelling, but maintain spatial segregation. Here the authors show that osteoclasts repel osteoblasts via contact inhibition of locomotion mediated by Semaphorin-Plexin signalling and develop an optogenetic tool for Plexin-B1 to show how this signalling axis induces cell repolarization.

Janus colloids with an attractive patch on the surface are model systems to explore structure formation but experimental realizations of such particles are rare. Here, the authors report a scalable method to precisely vary the Janus balance over a wide range and observe the formation of various structures including fibers, bilayers, and nonequilibrium rings catalyzed by substrate binding.