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Enzymes in the cytidine diphosphate–ethanolamine metabolic pathway, which promotes de novo synthesis of phosphatidylethanolamine, are shown to act as post-transcriptional mediators of the differentiation of T follicular helper (T_FH) cells, by regulating the chemokine receptor CXCR5.

Boyer et al. created genetic mouse models of muscular dystrophy in which satellite cells were selectively depleted. The depletion of satellite cells at select times was protective. Myofibers no longer had plasma membrane instability leading to tissue wasting in the muscular dystrophies.

Drake and colleagues demonstrate that castration in prostate cancer models promotes IL-8 secretion and immunosuppressive myeloid-derived suppressor cell migration, and that inhibiting this axis in combination with checkpoint blockade can mitigate tumor progression.

The fusion of muscle progenitor cells to form syncytial myofibers is required for skeletal muscle development and regeneration. Here, the authors describe a novel and specific molecular regulation of muscle cell fusion driven by transforming growth factor beta (TGFβ) signaling.

IFNγ secretion by CD8⁺T cells is critical for immunotherapy efficacy. In this study, the authors show that melanoma patients can become resistant to immunotherapy by acquiring chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2.

Net gain of ~10 dB µm^–1 and sub-picosecond switching time are shown at room temperature for optical transistors using polymers in a microcavity.

Grant Stewart, Andrew Jackson, Christopher Mathew, Fowzan Alkuraya and colleagues identify a novel replication fork protein, DONSON, which is important for maintaining genome stability. Mutations in DONSON cause microcephalic dwarfism and lead to stalled replication forks and DNA damage.

The study of the pathophysiology and possible interventions for non-ST-segment elevation myocardial infarction is hindered by the lack of a reproducible pre-clinical model. Here, authors develop an ovine model to reproduce post-ischemic remodeling in non-ST myocardial infarction and reveal distinct complex sugar moieties in cellular membranes and extracellular matrix patterns in infarcted tissue.

Aß are extracellular deposits relevant in Alzheimer’s disease (AD). This study shows that Aß plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided by the microglia and unchained by reduced presenilin function, a trait of AD, in endothelial cells.

Analysis of genomic networks from 430 modern individuals across 21 Pacific island populations reveals the human settlement history of Polynesia.

To characterize molecular changes during cell type transitions, the authors develop a method to simultaneously measure protein expression and thermal stability changes. They apply this approach to study differences between human pluripotent stem cells, their progenies, parental and allogeneic cells.

Global warming and ocean acidification impact coral ecosystems. Here, the authors show higher skeletal porosity and reduced bulk density at lower pH in corals living along a natural pH gradient in the Mediterranean, which may contribute to reduce population density and increase damage susceptibility.

Current preclinical models to investigate human HR + breast cancer progression and response to immunotherapy in vivo are limited. Here, the authors demonstrate that mammary tumours driven by a synthetic progestin combined with an oral carcinogen recapitulate several immunobiological features of human HR + breast cancers.

Excessive glucose production by the liver contributes to poor blood glucose control in type 2 diabetes. Here the authors report that the liver kinase B1 (Lkb1) suppresses amino acid driven postprandial glucose production in the liver through the aminotransferase Agxt.

In this study, the authors show that that oncogenic hijacking of PRC1 sensitizes genomically stable Ewing sarcoma cells for PLK1 inhibition alone or in synergy with a microtubule-destabilizing drug via induction of cytokinesis defects, rendering PRC1 a promising, broadly applicable predictive biomarker

AMPK regulates cellular energy balance using its γ subunit as an energy sensor of cellular AMP and ADP to ATP ratios. Here, the authors show that γ2 AMPK activation lowers heart rate by reducing the activity of pacemaker cells, whereas loss of γ2 AMPK increases heart rate and prevents the adaptive bradycardia of endurance training in mice.

The supramammillary region (SuM) regulates arousal that reinforces and energizes behavioral interaction with the environment. Here the authors investigate how SuM neurons interact with medial septal neurons and ventral tegmental dopamine neurons to regulate motivation for environmental interaction.

Multiple molecular profiling methods are required to study urothelial non-muscle-invasive bladder cancer (NMIBC) due to its heterogeneity. Here the authors integrate multi-omics data of 834 NMIBC patients, identifying a molecular subgroup associated with multiple alterations and worse outcomes.

Dysfunction of the trabecular meshwork (TM) is the chief cause of elevated intraocular pressure, the major risk factor of glaucoma. Here, the authors identify the transcription factor, GLIS1, as a critical regulator of TM maintenance and intraocular pressure, and as a glaucoma risk gene.

CRISPR–Cas9 mutagenesis screenings reveal that targeting REGNASE-1 leads to improved therapeutic efficacy of CD8⁺ T cells against mouse models of cancer, and identify BATF as a key target of REGNASE-1.

Lung samples collected soon after death from COVID-19 are used to provide a single-cell atlas of SARS-CoV-2 infection and the ensuing molecular changes.

Immunological stressors are linked to the transformation of preleukemic B cells to B-cell acute lymphoblastic leukemia. Here the authors show a dysregulation of innate immune signaling in preleukemic precursor B cells and link to the development of B-cell acute lymphoblastic leukemia in a murine model.

Multiomic profiling of several cohorts of patients treated with immune checkpoint blockade highlights the presence and potential role of B cells and tertiary lymphoid structures in promoting therapy response.

Senescence of hematopoietic progenitor cells, enforced by the BRAF^V600E mutation, underlies the development of Langerhans cell histiocytosis and could be a new target for drug development and therapy of this disease in patients.

Here, Brotherton and colleagues sequence 39 mitochondrial genomes from ancient human remains. They track population changes across Central Europe and find that the foundations of the European mitochondrial DNA pool were formed during the Neolithic rather than the post-glacial period.

Gottlieb and colleagues show that stearoyl-CoA desaturase promotes metabolic adaptation of acute lymphoblastic leukemia cells to the central nervous system microenvironment, revealing a potential site-specific metabolic vulnerability of this disease.

The TRPV1 ion channel is a heat-sensing receptor that is also activated by vanilloid compounds, but the molecular underpinnings of thermosensing have remained elusive. Here authors use in solution NMR on the isolated human TRPV1 S1-S4 domain and show that this domain undergoes a non-denaturing temperature-dependent transition with a high thermosensitivity.

Wilms tumour is a rare renal neoplasm that primarily affects children but the genomic changes responsible for its development are currently largely unknown. In this study, the authors identify somatic mutations of the MLLT1gene that are potentially involved in the aetiology of a subset of Wilms tumours.

Glycosylphosphatidylinositol (GPI) anchors are found on many cell surface proteins but their biosynthesis is not fully understood. Here, the authors identify genes involved in GPI galactosylation and reveal functional connections between GPI processing, glycosphingolipid biosynthesis and ER-associated degradation.

Prior stressful experience affects subsequent behavior even in different situations. Daviu et al. demonstrate that CRH^PVN neurons encode stress controllability and contribute to shifts between active and passive innate defensive strategies.

The epigenetic landscape of esophageal squamous cell carcinoma (ESCC) at genome-wide high resolution is incompletely studied. Here, the authors performed an integrated multi-omics analysis of ESCC and non-tumor tissues to define the genome-wide methylome landscape and epigenetic alterations to uncover oncogenic drivers of ESCC.

VirtualFlow, an open-source drug discovery platform, enables the efficient preparation and virtual screening of ultra-large ligand libraries to identify molecules that bind with high affinity to target proteins.

Temozolomide therapy seems to lead to mismatch repair deficiency and hypermutation in gliomas, but not to an increase in response to immunotherapy.

Radisky and colleagues show that, in contrast to its pro-tumorigenic properties, the MYC oncogene is also able to inhibit metastasis by suppressing cell migration and invasiveness. Mechanistically, they show that MYC transcriptionally represses the integrin αv and β3 subunits, which are needed for efficient cell motility and invasion.

Magdalena Götz, Stephen Robertson and colleagues show that biallelic mutations in DCHS1 and FAT4 cause a multisystem disorder that includes periventricular neuronal heterotopia. They further show that reducing expression of Dchs1 and Fat4 in mouse embryonic neuroepithelium causes an increase in progenitor cell numbers and reduced neuronal differentiation, resulting in heterotopic accumulation of cells below the neuronal layers in the neocortex.

Growing evidence suggests that environmental rather than genetic factors are major contributors to asthma development. Here the authors show that high intake of dietary fibre by pregnant mice increases resistance of their progeny to the development of allergic airways disease.

Men that carrierBRCA2germline mutations are at risk of developing prostate cancer. Here, the authors analyse the genomes of prostate cancer from these individuals and demonstrate increased genomic instability in comparison to sporadic prostate cancer.

Malignant pleural effusion (MPE) is a lethal condition associated with various cancers. Here, the authors show that cancer cells withKRASmutations promote MPE by recruiting myeloid cells via CCL2 signalling and that pharmaceutical targeting of KRAS results in reduced MPE incidence and volume in mouse models.

Josef Prchal and colleagues identify a mutation in EGLN1 associated with adaptation to high altitude in Tibetan individuals. Their functional studies suggest a mechanism acting to reduce the erythropoietic response to hypoxia.

Flexible fear-related responses may be advantageous in adolescence. Here the authors use microprisms to image prefrontal cortical spine maturation across development and report that plasticity in adolescent fear extinction responses is associated with dynamic reorganization in the amygdalahippocampal-PFC circuit.

Genomic analyses of localized, non-indolent prostate cancer identify recurrent aberrations that can predict relapse, and also highlight differences between early prostate cancer and metastatic, castration-resistant disease.

Naive pluripotent embryonic stem cells (ESCs) and embryonic germ cells (EGCs) have distinct developmental origins. Genome-wide expression and global DNA-methylation analyses now reveal that ESCs and ESGs are highly similar at the transcriptome level and, contrary to previous assumptions, are both characterized by DNA hypomethylation. Also, global methylation levels in both ESCs and EGCs are directly responsive to culture conditions.

Oculopharyngeal muscular dystrophy is caused by trinucleotide repeat expansions in thePABPN1gene. Here the authors use AAV-based gene therapy to knockdown the mutant gene and replace it with a wild-type allele, and show effectiveness in mice and in patient cells.

Lung alveoli are lined by two types of alveolar epithelial cells, squamous alveolar type (AT) 1 cells that mediate gas exchange and cuboidal AT2 cells that secrete surfactant to prevent alveolar collapse during breathing; here alveolar markers, genetic lineage tracing and clonal analysis are used in mice to identify alveolar progenitor and stem cells in vivo, and to map their locations and potential during lung development, maintenance and cancer.

Humans tend to attend to specific visual features rather than particular locations in space. In this study, Warren et al. use brain imaging and computational modelling to show that the same well-studied processes associated with spatial attention can also explain selective attention in non-spatial domains.