Search

The study of human microglia function in health and disease is limited by the availability of sound models. Here, the authors develop a method to generate functional microglia in human cortical organoids and investigate the role of human microglia during amyloid beta1-42- induced inflammation.

BRCA1-mediated resolution of R-loops has previously been described. Here the authors reveal a functional association of BRCA1 with TERRA RNA at telomeres, which develops in an R-loop-, and a cell cycle-dependent manner.

The intratumoural injection of recombinantly expressed cytokines bound tightly to the common vaccine adjuvant aluminium hydroxide leads to weeks-long retention of the cytokines in the tumours with minimal side effects, as shown in multiple syngeneic mouse models.

CRISPR-mediated gene knockout and activation are used to identify molecules in cancer cells and macrophages that regulate antibody-dependent cancer cell phagocytosis.

Necroptosis is a form of cell death characterized by membrane rupture via MLKL oligomerization, although mechanistic details remain unclear. Here, the authors show that MLKL ubiquitylation of K219 facilitates high-order membrane assembly and subsequent rupture, promoting cytotoxicity.

Whipworms are large parasites causing chronic disease in humans and other mammals. Here, the authors show how larvae create tunnels inside the gut lining and reveal the early host response to infection via Isg15 in mice and murine caecaloids.

Cell-type-specific chromatin accessibility QTL during neurogenesis allow fine mapping of causal variants and more complete underlying of regulatory mechanisms underlying noncoding loci associated with gene expression and neuropsychiatric disorders.

Clinical benefit or intestinal toxicity resulting from combined immune checkpoint blockade in patients with melanoma associates with prevalent commensal bacteria and can be decoupled by IL-1R inhibition.

The serotonergic raphe nuclei modulate neuronal function typically over minutes or hours. The authors report that raphe nuclei affect odor responses in output neurons of the olfactory bulb at sub-second time scales. These effects are mediated through multiple neurotransmitters and are distinct depending on the type of output neuron.

During renal fibrosis epithelial cells undergo a partial epithelial-to-mesenchymal transition that can be targeted to reverse established disease.

SAUCIE, a deep learning platform to analyze single-cell data across samples and platforms, allows information to be obtained from the internal layers of the network, which provides additional mechanistic understanding that can be used to further tune data analysis.

A BAH module in BAHCC1 recognizes H3K27me3 and is involved in gene silencing. BAHCC1 is highly expressed in acute leukemia cells and contributes to their proliferation.

Of 12 serology assays tested, four detect antibodies in more than 80% of patients with COVID-19.

RNA-sequencing analysis of cells in the human cortex enabled identification of diverse cell types, revealing well-conserved architecture and homologous cell types as well as extensive differences when compared with datasets covering the analogous region of the mouse brain.

The genomic profile and early transmission dynamics of the Omicron strain of SARS-CoV-2.

The 501Y.V2 variant of SARS-CoV-2 in South Africa became dominant over other variants within weeks of its emergence, suggesting that this variant is linked to increased transmissibility or immune escape.

An almost-complete, sequence-verified collection of Arabidopsis thaliana root stele transcription factors is reported. The authors use it in the enhanced yeast-one hybrid (eY1H) assay to map gene regulatory interactions in the plant. Also in this issue, Reece-Hoyes et al. describe the eY1H pipeline.

A novel poly(ADP-ribose)-binding zinc finger (PBZ) motif is identified. This motif is found in several eukaryotic checkpoint and DNA repair proteins, such as CHFR and APLF. Mutations in the PBZ of CHFR affect its function in checkpoint regulation, suggesting that both the poly (ADP-ribosyl)ation of proteins, and the interaction of this modification with other factors, is important for the DNA damage response.

By coupling a high-power, high-repetition-rate near-infrared frequency comb to a femtosecond optical cavity, a frequency comb operating in the extreme-ultraviolet spectral range has been produced, by high harmonic generation, and provides high-resolution spectroscopy in this spectral region.

Aging is associated with various changes in the brain, including transcription alteration. Here, Bradshaw and colleagues describe the transcriptome of aged human cortical microglia, and show age-related gene expression as related to neurodegeneration.

Presynaptic activity in photoreceptor cones regulates connectivity of retinal neurons. Yoshimatsu et al.investigate the development of ultraviolet (UV) and blue cone inputs onto horizontal cells, and demonstrate that UV inputs regulate synaptogenesis with blue cones via an activity-dependent sensory drive.

The pannexin 1 channel on the plasma membrane of apoptotic cells mediates the release of find-me molecular signals to attract phagocytic cells for clearance of the apoptotic cells; here the quinolone antibiotic trovafloxacin is identified as a direct inhibitor of pannexin 1, which results in dysregulated fragmentation of apoptotic cells and may partly explain quinolone toxicity.

The correct folding of proteins often requires the intervention molecular chaperones, which can occur co-translationally. Here the authors identify elements of yeast Ssb (Hsp70) that mediate ribosomal binding, and suggest a mechanism that directs efficient interaction of Ssb with the nascent chain.

Karin Tuschl, Philippa Mills and colleagues report mutations in the manganese (Mn) transporter gene SLC39A14in childhood-onset parkinsonism-dystonia. Using functional recapitulation, the authors also show that slc39A14 loss-of-function in zebrafish can lead to Mn dysregulation and locomotor impairment.

Smoking tobacco is known to alter DNA methylation. Here, the authors show that hypomethylation of smoke-related genes is associated with future increase in lung cancer risk.

This study has developed the first small molecule NEDD8-activating enzyme (NAE) inhibitor, which induces cancer cell death and exerts anti-tumour activity in preclinical mouse models. This work establishes NAE as an anti-cancer target and may lead to new anti-cancer therapeutics.

Human pluripotent stem cell derived neurons have the potential for cell replacement therapy for brain injury and disease but problems on transplantation need to be overcome. Here, the authors use a microtopographic scaffold to graft neurons into both hippocampal organoids and the mouse brain striatum.

By sampling a two-dimensional diffraction pattern on a spherical detector, three-dimensional structure determination of single molecules should be possible from a single measurement.

A 'mechanically induced catalytic amplification reaction' reads out receptor-mediated forces in cells.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

The costimulatory T-cell receptor 4-1BB is an immuno-oncology target. Here the authors present the ligand bound 4-1BB receptor crystal structure in addition to the structures of 4-1BB bound with two therapeutic antibodies and verify the antibody binding sites by mutational analysis, which is of interest for further 4-1BB therapeutics development.

A multi-omics study on a biotechnologically relevant soil bacterium reveals remodeling of key metabolic nodes maintains high yield of cofactors to satisfy cofactor requirements for the catabolism of lignin-derived aromatics.

A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.

The role that the striatum plays in tracking the association between actions and combinations of rewarding and aversive outcomes remains unclear. Here, by using both calcium imaging in mice and reinforcement learning models, the authors find that individual striatal neurons can encode associations between actions and multiple, sometimes conflicting, outcomes.

Camargo and colleagues employed an RNAi screen to identify LKB1 as an upstream regulator of the Hippo pathway. They show that LKB1 regulates SCRIB localization through the MARK kinase, leading to regulation of the activity of YAP through MST1/2 kinases.

Land plants lack the cytoplasmic dynein motor in fungi and animals that shows processive minus-end-directed motility on microtubules. Here the authors demonstrate that land plants have evolved novel processive minus-end-directed kinesin-14 motors that likely compensate for the absence of dynein.

Boyd et al. monitored the effects of patient-derived acute myeloid leukaemia (AML) cells on human HSPCs in vivo and found that AML impairs bone marrow adipocyte differentiation, and this in turn impedes healthy endogenous haematopoiesis.

Evf2 is a polyadenylated, noncoding RNA that is transcribed from the intergenic region of Dlx5 and Dlx6, which are genes for homeodomain transcriptional factors. The authors now show that the loss of Evf2 in mice results in a substantial reduction of GABAergic interneurons via interference with Dlx5/6 expression.

The spliceosome removes introns from precursor messenger RNAs to produce mature mRNAs. Here the authors report a U6 snRNP crystal structure that provides insight on how the 3′ phosphate of U6 snRNA is recognized by the Lsm2–8 complex and how the U6 snRNP proteins sequester and protect the active site RNA until it is assembled into the spliceosome.

Cross-neutralization assays of early variants and the 501Y.V2 variant of SARS-CoV-2 show that plasma from individuals infected with 501Y.V2 effectively neutralizes all variants, indicating that a vaccine that targets 501Y.V2 may also be effective against other SARS-CoV-2 variants.

Sensitive detection of individual RNA and DNA molecules is achieved by exponentially amplifying the fluorescence signal.

Overgrowth of cellular microtubules (MTs) is associated with a range of disease processes. Cellular and biophysical reconstitution experiments reveal that estradiol transforms dynamic, growing MTs into paused, non-growing MTs.

jYCaMP1, a yellow variant of the calcium indicator jGCaMP7, enables fast multicolor two-photon imaging at excitation wavelengths above 1,000 nm for use with popular ytterbium-doped fiber and modelocked semiconductor lasers.

Chiral active systems are composed of spinning constituent particles that self-organize into complex structures through hydrodynamic interactions. The authors develop methods to control these self-organized structures by introducing additional chemical interactions between spinning particles.