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10.1126/science.aau0730 | 62,310,361 | Although we can increasingly measure transcription, chromatin, methylation, and other aspects of molecular biology at single-cell resolution, most assays survey only one aspect of cellular biology. Here we describe sci-CAR, a combinatorial indexing–based coassay that jointly profiles chromatin accessibility and mRNA (C... | 10.1038/s41576-022-00509-1 | This paper describes the first single-cell co-assay for ATAC-seq and RNA expression. |
10.1038/s41467-021-25131-3 | 134,826,623 | Abstract EpiScanpy is a toolkit for the analysis of single-cell epigenomic data, namely single-cell DNA methylation and single-cell ATAC-seq data. To address the modality specific challenges from epigenomics data, epiScanpy quantifies the epigenome using multiple feature space constructions and builds a nearest neighbo... | 10.1038/s41576-022-00509-1 | This paper describes a software package for single-cell epigenomic analysis. |
10.1093/nar/gkaa1040 | 81,448,635 | Abstract RNA–protein complexes have emerged as central players in numerous key cellular processes with significant relevance in health and disease. To further deepen our knowledge of RNA-binding proteins (RBPs), multiple proteome-wide strategies have been developed to identify RBPs in different species leading to a lar... | 10.1038/s41581-021-00497-1 | Minable tool for obtaining an insight into current knowledge on RBPs and their function |
10.1038/ncomms10127 | 124,721,138 | Abstract RNA-binding proteins (RBPs) exert a broad range of biological functions. To explore the scope of RBPs across eukaryotic evolution, we determined the in vivo RBP repertoire of the yeast Saccharomyces cerevisiae and identified 678 RBPs from yeast and additionally 729 RBPs from human hepatocytic HuH-7 cells. Comb... | 10.1038/s41581-021-00497-1 | Extensive analysis of RBPomes in several species showing the abundance of RBPs lacking a classical RNA-binding domain, so-called enigmRBPs |
10.1242/dev.046045 | 124,226,738 | The RNA-binding protein Bicaudal C is an important regulator of embryonic development in C. elegans, Drosophila and Xenopus. In mouse, bicaudal C (Bicc1) mutants are characterized by the formation of fluid-filled cysts in the kidney and by expansion of epithelial ducts in liver and pancreas. This phenotype is reminisce... | 10.1038/s41581-021-00497-1 | This work not only implicates the RBP bicaudal C in PKD but also shows its molecular function by antagonizing an miRNA known to play a role in cystogenesis |
10.1038/s41419-020-2630-x | 60,314,414 | Abstract Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and the most common cause of end-stage renal disease, for which no effective therapies are yet available. RNA-binding proteins (RBPs) play a pivotal role in epigenetic regulation; tristetraprolin (TTP) and human antigen R (HuR) ... | 10.1038/s41581-021-00497-1 | This study shows the interactions between two RBPs regarding podocyte injury in diabetic kidney disease |
10.1038/s41467-018-06557-8 | 62,580,092 | Abstract Following the realization that eukaryotic RNA-binding proteomes are substantially larger than anticipated, we must now understand their detailed composition and dynamics. Methods such as RNA interactome capture (RIC) have begun to address this need. However, limitations of RIC have been reported. Here we descr... | 10.1038/s41581-021-00497-1 | This work represents an important addition to the current toolbox for RNA-interactome capture (RIC) using LNA-modified probes and allowing for RIC from tissue |
10.1038/s41467-019-08942-3 | 104,432,507 | Abstract Recent methodological advances allowed the identification of an increasing number of RNA-binding proteins (RBPs) and their RNA-binding sites. Most of those methods rely, however, on capturing proteins associated to polyadenylated RNAs which neglects RBPs bound to non-adenylate RNA classes (tRNA, rRNA, pre-mRNA... | 10.1038/s41581-021-00497-1 | One of the three key publications implementing organic phase extraction as a central technique exploiting the unique biophysical properties of crosslinked RNA-protein complexes to enrich and isolate RNPs |
10.1126/science.1213307 | 20,613,780 | We have identified tens of thousands of short extrachromosomal circular DNAs (microDNA) in mouse tissues as well as mouse and human cell lines. These microDNAs are 200 to 400 base pairs long, are derived from unique nonrepetitive sequence, and are enriched in the 5′-untranslated regions of genes, exons, and CpG islands... | 10.1038/s41576-022-00521-5 | This landmark study reports on the presence of small circular DNA elements in human cells |
10.1126/science.1241328 | 40,298,600 | Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor... | 10.1038/s41576-022-00521-5 | This work identifies ecDNA modulation as a mechanism of resistance to targeted drug treatment |
10.1093/ve/veaa009 | 19,455,296 | Abstract Overlapping genes are commonplace in viruses and play an important role in their function and evolution. However, aside from studies on specific groups of viruses, relatively little is known about the extent and nature of gene overlap and its determinants in viruses as a whole. Here, we present an extensive ch... | 10.1038/s41576-021-00417-w | This article provides an unparalleled look into the properties of gene overlaps amongst the NCBI virus reference genome database |
10.1126/science.aay0262 | 41,668,665 | Ribosome profiling has revealed pervasive but largely uncharacterized translation outside of canonical coding sequences (CDSs). In this work, we exploit a systematic CRISPR-based screening strategy to identify hundreds of noncanonical CDSs that are essential for cellular growth and whose disruption elicits specific, ro... | 10.1038/s41576-021-00417-w | This seminal study provides robust evidence for many new overlapping genes within human genomes combining proteogenomics and CRISPR functional screens. |
10.1038/s41467-020-20841-6 | 82,328,617 | Abstract Thousands of human small and alternative open reading frames (smORFs and alt-ORFs, respectively) have recently been annotated. Many alt-ORFs are co-encoded with canonical proteins in multicistronic configurations, but few of their functions are known. Here, we report the detection of alt-RPL36, a protein co-en... | 10.1038/s41576-021-00417-w | This paper describes the discovery and biology of an alternative overlapping reading frame within the human RPL36 gene. |
10.1073/pnas.1911203117 | 61,638,012 | Frameshifts in protein coding sequences are widely perceived as resulting in either nonfunctional or even deleterious protein products. Indeed, frameshifts typically lead to markedly altered protein sequences and premature stop codons. By analyzing complete proteomes from all three domains of life, we demonstrate that,... | 10.1038/s41576-021-00417-w | This article revealed that some key physicochemical properties are maintained in an altered protein sequence that is produced as a result of a +1 or –1 frameshift mutation, which therefore suggests a plausible explanation for the abundance of this overlap offset. |
10.1073/pnas.1120788109 | 45,430,738 | Bacterial genes associated with a single trait are often grouped in a contiguous unit of the genome known as a gene cluster. It is difficult to genetically manipulate many gene clusters because of complex, redundant, and integrated host regulation. We have developed a systematic approach to completely specify the genet... | 10.1038/s41576-021-00417-w | This article describes the first fully refactored complex gene cluster, which required disrupting multiple overlapping genes. |
10.1126/science.aav5477 | 38,397,547 | In synthetic biology, methods for stabilizing genetically engineered functions and confining recombinant DNA to intended hosts are necessary to cope with natural mutation accumulation and pervasive lateral gene flow. We present a generalizable strategy to preserve and constrain genetic information through the computati... | 10.1038/s41576-021-00417-w | This article outlines a powerful new method to protect a gene of interest from mutation by embedding an essential gene within it. |
10.1126/science.1168978 | 20,639,595 | Techniques for systematically monitoring protein translation have lagged far behind methods for measuring messenger RNA (mRNA) levels. Here, we present a ribosome-profiling strategy that is based on the deep sequencing of ribosome-protected mRNA fragments and enables genome-wide investigation of translation with subcod... | 10.1038/s41576-021-00417-w | This article describes the first use of Ribo-seq, which is a method to monitor translation in vivo using next-generation sequencing and has been used frequently to discover new overlapping genes. |
10.1126/science.aad0489 | 41,687,981 | Controlling supplies for DNA and RNA synthesis The mTORC1 protein kinase complex regulates anabolic metabolism and coordinates cellular signals that promote growth with availability of required precursor metabolites. Signaling through mTORC1 controls pyrimidine synthesis. Ben-Sahra et al. found that mTORC1 also functio... | 10.1038/s41568-019-0216-7 | Ben-Sahra et al. (2013), Robitaille et al. (2013) and Ben-Sahra et al. (2016) demonstrate that mTORC1 induces de novo nucleotide synthesis. Ben-Sahra et al. (2013) and Robitaille et al. (2013) reveal that CAD, the enzyme that catalyses the first three steps of the de novo pyrimidine synthesis pathway, is directly phosp... |
10.1126/science.aau3903 | 104,292,935 | Nicotinamide adenine dinucleotide phosphate (NADP + ) is essential for producing NADPH, the primary cofactor for reductive metabolism. We find that growth factor signaling through the phosphoinositide 3-kinase (PI3K)–Akt pathway induces acute synthesis of NADP + and NADPH. Akt phosphorylates NAD kinase (NADK), the sole... | 10.1038/s41568-019-0216-7 | This study demonstrates that AKT directly phosphorylates and activates NADK, which generates NADP + from NAD + |
10.1038/s41467-020-16248-y | 20,692,763 | Abstract Lipid-like nanoparticles (LNPs) have potential as non-viral delivery systems for mRNA therapies. However, repeated administrations of LNPs may lead to accumulation of delivery materials and associated toxicity. To address this challenge, we have developed biodegradable lipids which improve LNPs clearance and r... | 10.1038/s41573-021-00283-5 | This study reports the synthesis of a new lipid library that delivers mRNA using the albumin receptor |
10.4049/immunohorizons.1900029 | 58,737,309 | Abstract Accelerated blood clearance (ABC) is a phenomenon in which certain pharmaceutical agents are rapidly cleared from the blood upon second and subsequent administrations. ABC has been observed for many lipid-delivery vehicles, including liposomes and lipid nanoparticles (LNP). Previous studies have demonstrated a... | 10.1038/s41573-021-00283-5 | This study describes the potential mechanism of anti-PEG-mediated accelerated blood clearance of LNPs |
10.1073/pnas.1016912108 | 81,776,214 | The tyrosine kinase c-Met promotes the formation and malignant progression of multiple cancers. It is well known that c-Met hyperactivation increases tumorigenicity and tumor cell resistance to DNA damaging agents, properties associated with tumor-initiating stem cells. However, a link between c-Met signaling and the f... | 10.1038/s41568-018-0002-y | This study shows that MET sustains the stem cell phenotype in glioblastoma through induction of reprogramming transcription factors. |
10.2500/ajra.2014.28.4033 | 38,366,151 | Background Surgery for chronic rhinosinusitis with nasal polyps (CRSwNPs) often fails because of recurrence of disease. So far, we do not know if specific cytokine profiles are linked to recurrence after functional endoscopic sinus surgery (FESS) or can predict recurrence. In this study we investigate the cytokine prof... | 10.1038/s41572-020-00218-1 | Important paper to show how immunology impacts on the clinic of CRSwNP in terms of recurrence of disease |
10.4049/jimmunol.158.8.3902 | 139,040,886 | Abstract Nasal polyps, which often occur in association with allergic rhinitis and asthma, are characterized by a marked infiltration of eosinophils. Using a method for detecting eosinophils with DNA strand breaks, we found direct evidence for inhibition of eosinophil apoptosis in this model of tissue eosinophilia. By ... | 10.1038/s41572-020-00218-1 | This paper demonstrated that eosinophils in CRSwNP live longer than in the peripheral blood and can be killed by anti-IL-5 but not by anti-IL-3 or anti-GM-CSF; it paved the way for subsequent biologics |
10.1002/lary.26391 | 124,475,377 | Objectives/Hypothesis Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disease process that is driven, in part, by intrinsic mucosal inflammation. Surgery plus continued medical therapy is commonly elected by medically recalcitrant, symptomatic patients. The objective was to evaluate the prevalence of nasal po... | 10.1038/s41572-020-00218-1 | This paper describes the results of surgery (recurrence of nasal polyps over 18 months) performed in university level clinics |
10.1002/lary.27815 | 41,715,726 | Objectives Nasal polyps are often characterized by type 2 inflammation and disease recurrence. We developed a new surgical technique, referred to as reboot approach , which aims to maximally remove all sinus mucosa and allow healthy re‐epithelialization from the preserved nasal mucosa. We here review type 2 endotype ch... | 10.1038/s41572-020-00218-1 | First description of the reboot technique, from rationale to technique, for severe CRSwNP |
10.1126/science.1177319 | 125,224,198 | Thalidomide Teratogenicity Target In the late 1950s and early 1960s, thalidomide was prescribed to pregnant women as a cure for morning sickness, but it was then found to have developmental defects, most obviously, stunted limbs in thousands of babies. Although its use was banned worldwide, thalidomide has since been f... | 10.1038/s41568-021-00365-x | This is the first report that the E3 ligase CRBN is a molecular target of thalidomide |
10.1126/science.1244851 | 125,069,684 | Drug With a (Re)Purpose Thalidomide, once infamous for its deleterious effects on fetal development, has re-emerged as a drug of great interest because of its beneficial immunomodulatory effects. A derivative drug called lenalidomide significantly extends the survival of patients with multiple myeloma, but the molecula... | 10.1038/s41568-021-00365-x | This is one of the first articles reporting the mechanism underlying the antitumour activity of IMiDs: binding of lenalidomide to CRBN induces degradation of IKZF1 and IKZF3 |
10.1126/science.1244917 | 83,452,688 | Drug With a (Re)Purpose Thalidomide, once infamous for its deleterious effects on fetal development, has re-emerged as a drug of great interest because of its beneficial immunomodulatory effects. A derivative drug called lenalidomide significantly extends the survival of patients with multiple myeloma, but the molecula... | 10.1038/s41568-021-00365-x | This is one of the first articles reporting the mechanism underlying the antitumour activity of IMiDs: binding of lenalidomide to CRBN induces degradation of IKZF1 and IKZF3 |
10.1126/science.aab1433 | 104,262,163 | A degrading game plan for cancer therapy Certain classes of proteins that contribute to cancer development are challenging to target therapeutically. Winter et al. devised a chemical strategy that, in principle, permits the selective degradation of any protein of interest. The strategy involves chemically attaching a l... | 10.1038/s41568-021-00365-x | This article reports the discovery of the first CRBN-recruiting PROTACs |
10.1126/science.aal3755 | 62,136,418 | An old cancer drug's degrading new look Typically, cancer drugs that help only a small number of patients in clinical trials are not pursued. This might change in a future world of precision medicine, where biomarkers will match specific drugs to the patients most likely to respond. Han et al. identified the mechanism ... | 10.1038/s41568-021-00365-x | This is one of the first articles reporting sulfonamides acting as molecular glue degraders of RBM39 via binding the E3 ligase DCAF15 |
10.1038/s41467-021-21159-7 | 41,417,274 | Abstract Over 300 BRAF missense mutations have been identified in patients, yet currently approved drugs target V600 mutants alone. Moreover, acquired resistance inevitably emerges, primarily due to RAF lesions that prevent inhibition of BRAF V600 with current treatments. Therefore, there is a need for new therapies th... | 10.1038/s41568-021-00365-x | This is one of the first articles reporting mutant-selective BRAF PROTAC degraders |
10.1073/pnas.0803670105 | 29,111,082 | Human mesenchymal stromal cells (hMSCs) were injected into the hippocampus of adult mice 1 day after transient global ischemia. The hMSCs both improved neurologic function and markedly decreased neuronal cell death of the hippocampus. Microarray assays indicated that ischemia up-regulated 586 mouse genes. The hMSCs per... | 10.1038/s41582-022-00736-4 | One of the first studies to show that intracerebral injection of MSCs modifies microglia-mediated neuroinflammation in a rodent model of a common neurological condition resulting from global cerebral ischaemia. |
10.1002/ana.21033 | 107,158,733 | Abstract Objective Intracerebroventricular or intravenous (IV) injection of neural precursor cells (NPCs) attenuates experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. Although stem cell therapy was introduced initially for cell replacement, we examine here whether NPCs possess imm... | 10.1038/s41582-022-00736-4 | This study demonstrated that NPCs suppress pro-inflammatory T cells in a model of MS. |
10.1002/jnr.21661 | 124,313,852 | Abstract Stroke, a cerebrovascular injury, is the leading cause of disability and third leading cause of death in the world. Recent reports indicate that inhibiting the inflammatory response to stroke enhances neurosurvival and limits expansion of the infarction. The immune response that is initiated in the spleen has ... | 10.1038/s41582-022-00736-4 | One of the first studies of splenic contraction and the role of the spleen in the inflammatory response after stroke. |
10.1126/science.abj6987 | 135,718,860 | Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion–base pair sequence of a huma... | 10.1038/s41576-022-00539-9 | The most recent and compete human genome sequencing assembly reveals more repetitive elements in the human genome than researchers have previously estimated, which could potentially support non-B DNA formation |
10.1038/s41467-020-15901-w | 100,995,298 | Abstract The mechanisms that underpin how insertions or deletions (indels) become fixed in DNA have primarily been ascribed to replication-related and/or double-strand break (DSB)-related processes. Here, we introduce a method to evaluate indels, orientating them relative to gene transcription. In so doing, we reveal a... | 10.1038/s41576-022-00539-9 | Using bioinformatic approaches, this study reports transcription-associated asymmetrical distribution of repetitive elements, insertions and deletions at repeats in human cancer genomes, with involvement of DNA repair pathways |
10.1038/s41467-019-13878-9 | 41,676,447 | Abstract Alternative DNA structure-forming sequences can stimulate mutagenesis and are enriched at mutation hotspots in human cancer genomes, implicating them in disease etiology. However, the mechanisms involved are not well characterized. Here, we discover that Z-DNA is mutagenic in yeast as well as human cells, and ... | 10.1038/s41576-022-00539-9 | This study reports that the MMR protein complex MSH2–MSH3 binds to Z-DNA and recruits the NER nuclease ERCC1–XPF to the site, resulting in structure-specific cleavage and DSBs at Z-DNA regardless of DNA replication status |
10.1038/s41557-021-00736-9 | 123,155,057 | Abstract DNA–protein interactions regulate critical biological processes. Identifying proteins that bind to specific, functional genomic loci is essential to understand the underlying regulatory mechanisms on a molecular level. Here we describe a co-binding-mediated protein profiling (CMPP) strategy to investigate the ... | 10.1038/s41576-022-00539-9 | Hundreds of putative G4 DNA binding proteins from various functional classes are identified using G4-ligand probes crosslinked to G4 binding proteins in situ in living cells, suggesting complex and active DNA structure-related metabolism in vivo |
10.1101/gr.270082.120 | 135,447,771 | DNA topology and alternative DNA structures are implicated in regulating diverse biological processes. Although biomechanical properties of these structures have been studied extensively in vitro, characterization in vivo , particularly in multicellular organisms, is limited. We devised new methods to map DNA supercoil... | 10.1038/s41576-022-00539-9 | DNA supercoiling regions and non-B DNA structures in the genome of C. elegans embryos are mapped and found to co-localize at functional regions in the genome, such as transcription start sites |
10.1038/s41467-019-11104-0 | 125,297,522 | Abstract Genome-wide studies of DNA replication origins revealed that origins preferentially associate with an Origin G-rich Repeated Element (OGRE), potentially forming G-quadruplexes (G4). Here, we functionally address their requirements for DNA replication initiation in a series of independent approaches. Deletion o... | 10.1038/s41576-022-00539-9 | G4 DNA-forming sequences in the OGRE are required for the activity of several types of replication origin; adding G4 DNA-stabilizing ligands affects origin activities accordingly, suggesting a role for G4 DNA in replication regulation |
10.1073/pnas.2013080118 | 19,293,728 | Nearly 50 hereditary diseases result from the inheritance of abnormally long repetitive DNA microsatellites. While it was originally believed that the size of inherited repeats is the key factor in disease development, it has become clear that somatic instability of these repeats throughout an individual’s lifetime str... | 10.1038/s41576-022-00539-9 | This study finds that MMR proteins are involved in generating DBSs at long GAA(100) repeats that can form H-DNA in non-dividing cells, resulting in large-scale deletions, including the repeat and adjacent regions, and mediated by error-prone non-homologous end-joining or gene conversions via ectopic homologous recombin... |
10.1038/ncomms12465 | 101,647,060 | Abstract Studies in knockout mice provide evidence that MSH2–MSH3 and the BER machinery promote trinucleotide repeat (TNR) expansion, yet how these two different repair pathways cause the mutation is unknown. Here we report the first molecular crosstalk mechanism, in which MSH2–MSH3 is used as a component of the BER ma... | 10.1038/s41576-022-00539-9 | The MMR protein complex MSH2–MSH3 is found to crosstalk with the BER machinery, stimulating the synthesis activity of DNA Polβ through triplet repeats and facilitating the formation of flap structures, which leads to repeat expansions |
10.1126/science.aan1425 | 104,305,658 | Evolution generates a remarkable breadth of living forms, but many traits evolve repeatedly, by mechanisms that are still poorly understood. A classic example of repeated evolution is the loss of pelvic hindfins in stickleback fish ( Gasterosteus aculeatus ). Repeated pelvic loss maps to recurrent deletions of a pelvic... | 10.1038/s41576-022-00539-9 | Structure-specific DSBs and large deletions caused by a Z-DNA-forming GT repeat in the Pel gene from marine stickleback fish populations have important roles in the evolutionary loss of pelvic hindfins in freshwater sticklebacks, suggesting that non-B DNA structure-induced genetic instability has contributed to evoluti... |
10.1126/science.aav4837 | 83,382,136 | Grid cells with their rigid hexagonal firing fields are thought to provide an invariant metric to the hippocampal cognitive map, yet environmental geometrical features have recently been shown to distort the grid structure. Given that the hippocampal role goes beyond space, we tested the influence of nonspatial informa... | 10.1038/s41583-021-00479-z | Using a memory-guided cheeseboard maze, this study finds that individuals fields of MEC grid cells can shift towards reward locations through learning, indicating that grid cells are more dynamically modulated by task demands than previously appreciated (see also Butler et al. (2019)) |
10.1097/gme.0000000000000714 | 41,122,525 | Abstract Objective: The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk. Methods: Prospective cohort... | 10.1038/s41574-022-00708-0 | Women with a shorter reproductive lifespan (<30 years) have a 37% higher risk of T2DM than women with a normal reproductive lifespan (36–40 years) |
10.1097/gme.0000000000001033 | 58,822,972 | Abstract Objective: Vasomotor symptoms (VMS), encompassing hot flashes and night sweats, may be associated with diabetes, but evidence is limited. We sought to estimate these associations. Methods: Among 150,007 postmenopausal Women's Health Initiative participants from 1993 to 2014, we prospectively examined associati... | 10.1038/s41574-022-00708-0 | The risk of T2DM is higher in women with severe vasomotor symptoms than in women without severe vasomotor symptoms |
10.1093/eurheartj/ehz913 | 124,231,192 | Abstract Aims To investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age. Methods and results All Danish residents aged 40–89 years without a history major adverse cardiovascular events, inclu... | 10.1038/s41574-022-00708-0 | Despite higher absolute rates of cardiovascular disease in men, women have higher relative rates of cardiovascular disease associated with diabetes mellitus than men |
10.1210/clinem/dgab042 | 35,338,568 | Abstract Context This mini-review provides an overview of menopausal hormone therapy (HT) and cardiovascular disease (CVD) risk, with a focus on the role of hormone formulation, dose, and route of delivery. Methods This summary is based on authors’ knowledge in the field of menopausal HT and supplemented by a PubMed se... | 10.1038/s41574-022-00708-0 | Transdermal oestrogens pose a lower risk of venous thromboembolism than oral oestrogens and micronized progesterone does not oppose the beneficial effects of oestrogens on cardiovascular risk factors |
10.7554/elife.55729 | 41,097,318 | Axons of dopaminergic neurons innervate the striatum where they contribute to movement and reinforcement learning. Past work has shown that striatal GABA tonically inhibits dopamine release, but whether GABA-A receptors directly modulate transmission or act indirectly through circuit elements is unresolved. Here, we us... | 10.1038/s41583-022-00561-0 | This study elegantly demonstrates presynaptic mechanisms by which ionotropic GABA A receptors and nAChRs regulate DA release in the striatum |
10.1177/1087057115618608 | 60,013,177 | Protein-based, fluorescent biosensors power basic research on cell signaling in health and disease, but their use in automated laboratories is limited. We have now created two live-cell assays, one for diacyl glycerol and another for cAMP, that are robust (Z′ > 0.7) and easily deployed on standard fluorescence plate... | 10.1038/s41583-022-00561-0 | This article describes the development of fluorescent biosensors for the signalling molecules DAG and cAMP |
10.1126/scitranslmed.aaa5447 | 104,211,232 | Nanoparticle-functionalized T cells actively transport a cytotoxic drug to systemic sites of lymphoma dissemination, enhancing the efficacy of antitumor chemotherapy. | 10.1038/s41467-018-03705-y | Harnessed the inherent ability of T-cells to traffic throughout the lymphatic system to deliver therapeutics to disseminated tumors. This work might impact our way to treat disseminated tumors |
10.3390/microorganisms9020386 | 83,063,381 | Autoinducer 2 (AI-2) is a ubiquitous metabolite but, instead of acting as a “universal signal,” relatively few phenotypes have been associated with it, and many scientists believe AI-2 is often a metabolic byproduct rather than a signal. Here, the aim is to present evidence that AI-2 influences both biofilm formation a... | 10.1038/s41564-022-01294-7 | A comprehensive review of the roles of AI-2 in E. coli. |
10.1126/science.aaf7671 | 62,155,590 | Accumulating impacts Anthropogenic climate change is now in full swing, our global average temperature already having increased by 1°C from preindustrial levels. Many studies have documented individual impacts of the changing climate that are particular to species or regions, but individual impacts are accumulating and... | 10.1038/s41558-019-0526-5 | A comprehensive review showing that over 80% of ecological processes considered in terrestrial, marine, and freshwater ecosystems as well as human systems have evidence of observed impact from climate change |
10.1126/science.aai9214 | 62,591,643 | Consequences of shifting species distributions Climate change is causing geographical redistribution of plant and animal species globally. These distributional shifts are leading to new ecosystems and ecological communities, changes that will affect human society. Pecl et al. review these current and future impacts and... | 10.1038/s41558-019-0526-5 | A comprehensive review showing that impacts of species redistribution extends from nature to society |
10.1126/science.aat2360 | 20,819,648 | Policy must anticipate conflict over geographic shifts | 10.1038/s41558-019-0526-5 | A paper highlighting the complexity of future governance of marine ecosystems under climate change |
10.1111/brv.12344 | 104,392,870 | ABSTRACT Climate change is driving a pervasive global redistribution of the planet's species. Species redistribution poses new questions for the study of ecosystems, conservation science and human societies that require a coordinated and integrated approach. Here we review recent progress, key gaps and strategic direct... | 10.1038/s41558-019-0526-5 | A comprehensive review on complex management scenarios when considering species redistribution |
10.1084/jem.20020781 | 123,411,467 | Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children. Administration of a formalin inactivated vaccine against RSV to children in the 1960s resulted in increased morbidity and mortality in vaccine recipients who subsequently contracted RSV. This incid... | 10.1038/s41579-019-0149-x | This manuscript demonstrates that vaccine-enhanced disease is mediated by immune complexes |
10.1126/science.1234914 | 20,408,209 | Building Better Vaccines Vaccines are one of the most effective tools to protect against infectious diseases. Unfortunately, vaccines for diseases with the highest global health burdens, such as HIV, malaria, and tuberculosis, are not yet available. Koff et al. (p. 1064 ) review the latest advances in vaccine developme... | 10.1038/s41579-019-0149-x | This work provides the first 3D structure of the prefusion conformation of RSV F and defines a major antigenic site recognized by prefusion-specific antibodies |
10.1073/pnas.1309070110 | 85,508,618 | Human respiratory syncytial virus is a human pathogen that causes severe infection of the respiratory tract. Current information about the structure of the virus and its interaction with host cells is limited. We carried out an electron cryotomographic characterization of cell culture-grown human respiratory syncytial ... | 10.1038/s41579-019-0149-x | This manuscript reveals the organization and morphology of RSV virions by cryo-electron tomography |
10.1073/pnas.94.25.13961 | 123,920,361 | A live, cold-passaged ( cp ) candidate vaccine virus, designated respiratory syncytial virus (RSV) B1 cp -52/2B5 ( cp -52), replicated efficiently in Vero cells, but was found to be overattenuated for RSV-seronegative infants and children. Sequence analysis of reverse-transcription–PCR-amplified fragments of this mutan... | 10.1038/s41579-019-0149-x | This work demonstrates that infectious RSV requires only the F protein on its surface |
10.1073/pnas.1115941109 | 101,191,508 | Human respiratory syncytial virus (hRSV) is the most important viral agent of pediatric respiratory infections worldwide. The only specific treatment available today is a humanized monoclonal antibody (Palivizumab) directed against the F glycoprotein, administered prophylactically to children at very high risk of sever... | 10.1038/s41579-019-0149-x | This study provides the first evidence for the existence of prefusion F-specific antibodies and their dominant contribution to the RSV-neutralizing activity of human sera |
10.1126/science.1243283 | 103,739,115 | Designer Vaccine Respiratory syncytial virus (RSV) is one of the last remaining childhood diseases without an approved vaccine. Using a structure-based approach, McLellan et al. (p. 592 ) designed over 150 fusion glycoprotein variants, assessed their antibody reactivity, determined crystal structures of stabilized vari... | 10.1038/s41579-019-0149-x | This manuscript reports the first structure-based design of a prefusion F vaccine antigen and demonstrates its superior immunogenicity to postfusion F antigens |
10.3390/v10080446 | 103,447,488 | Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in young children. With repeat infections throughout life, it can also cause substantial disease in the elderly and in adults with compromised cardiac, pulmonary and immune systems. RSV is a pleomorphic enveloped RNA virus i... | 10.1038/s41579-019-0149-x | This work conclusively demonstrates that RSV is a filamentous virus upon budding from infected cells |
10.1073/pnas.0509996103 | 83,280,969 | The host restriction factor TRIM5α mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5α variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction ... | 10.1038/s41579-019-0225-2 | This study reports TRIM5 binding to assembled HIV-1 CA–nucleocaspid protein tubes, which are functional and structural mimics of the HIV-1 capsid. The ‘fate of capsid’ assay is used to show accelerated disassembly of the HIV-1 capsid under restricting conditions |
10.1126/science.aah4972 | 19,105,970 | Structural insights into capsid flexibility Viral capsids are protein structures that enclose the genetic material of viruses. Previous structural studies of the HIV-1 capsid have relied on recombinant, cross-linked, or mutant capsid proteins. Mattei et al. now report subnanometer-resolution cryo–electron tomography st... | 10.1038/s41579-019-0225-2 | The studies by Ganser et al. and Mattei et al. act as bookends for a large body of work describing the architecture of retroviral capsids |
10.1073/pnas.1402448111 | 61,251,175 | Significance Retroviral infection of cells can be blocked by the action of the postentry restriction factors. The Trim5α and Fv1 factors do so by targeting the capsid that surrounds the viral core. The nature of the interaction of these factors with the viral assembly is unclear. We show that these factors form antipar... | 10.1038/s41579-019-0225-2 | The studies by Kar et al., Langelier et al., Sanchez et al. and Goldstone et al. establish that TRIM5 coiled-coil domains form elongated antiparallel dimers |
10.1073/pnas.1013426108 | 81,379,864 | TRIM5α proteins are restriction factors that protect mammalian cells from retroviral infections by binding incoming viral capsids, accelerating their dissociation, and preventing reverse transcription of the viral genome. Individual TRIM5 isoforms can often protect cells against a broad range of retroviruses, as exempl... | 10.1038/s41579-019-0225-2 | This study demonstrates that purified TRIM5α assembles into a hexagonal lattice that matches the symmetry and spacing of retroviral capsid lattices. The HIV-1 capsid lattice is shown to act as a template for assembly of TRIM5α in vitro |
10.1038/ncomms10714 | 18,538,510 | Abstract The host cell factor cyclophilin A (CypA) interacts directly with the HIV-1 capsid and regulates viral infectivity. Although the crystal structure of CypA in complex with the N-terminal domain of the HIV-1 capsid protein (CA) has been known for nearly two decades, how CypA interacts with the viral capsid and m... | 10.1038/s41579-019-0225-2 | The studies by Vajdos et al., Yoo et al., Price et al. (2009), Caines et al. and Liu et al. establish the structural and biochemical principles that govern binding of CypA to retroviral capsids |
10.1073/pnas.0510483103 | 81,504,702 | The primate TRIM5α proteins have recently been defined as cellular restriction factors, preventing primate infection by retroviruses from different species. For instance, rhesus TRIM5α (rhTRIM5α) restricts infection by HIV-1. Virtually all TRIM5α proteins block the early replication of retroviruses by preventing the ac... | 10.1038/s41579-019-0225-2 | This study demonstrates that inhibition of the proteasome can relieve the TRIM5-mediated block to reverse transcription, even though virus infectivity is not restored |
10.1038/s41467-021-24332-0 | 80,792,014 | Abstract Non-centrosomal microtubule arrays serve crucial functions in cells, yet the mechanisms of their generation are poorly understood. During budding of the epithelial tubes of the salivary glands in the Drosophila embryo, we previously demonstrated that the activity of pulsatile apical-medial actomyosin depends o... | 10.1038/s41580-022-00473-y | This paper shows how a microtubule array formed by severing and minus-end stabilization affects tissue morphogenesis. |
10.1083/jcb.201601099 | 107,324,399 | Differentiation induces the formation of noncentrosomal microtubule arrays in diverse tissues. The formation of these arrays requires loss of microtubule-organizing activity (MTOC) at the centrosome, but the mechanisms regulating this transition remain largely unexplored. Here, we use the robust loss of centrosomal MTO... | 10.1038/s41580-022-00473-y | This paper provides important insights into switching from a centrosomal to a non-centrosomal microtubule array during cell differentiation and into the role of γ-TuRC-associated proteins in this process. |
10.1126/science.aam9335 | 82,996,400 | How microtubules organize in embryos Cell functions ranging from cell division to morphogenesis rely on microtubules, with microtubule-organizing centers serving as anchoring sites for their outgrowth. Although the centrosome organizes the microtubule cytoskeleton in most animal cells, this organelle is absent in early... | 10.1038/s41580-022-00473-y | This paper shows how the cytokinetic bridge is transformed into an MTOC during early mammalian development. |
10.1126/sciadv.aaz4344 | 103,583,842 | Neuronal activities depend heavily on microtubules, which shape neuronal processes and transport myriad molecules within them. Although constantly remodeled through growth and shrinkage events, neuronal microtubules must be sufficiently stable to maintain nervous system wiring. This stability is somehow maintained by v... | 10.1038/s41580-022-00473-y | This study demonstrates that the protein responsible for strong stabilization of neuronal microtubules localizes to microtubule lumen and induces their deformation |
10.1083/jcb.201907154 | 83,321,373 | Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid ce... | 10.1038/s41580-022-00473-y | This study provides convincing support for the concept that one of the functions of the microtubule network is to preserve the integrity of highly branched cells during cell migration in complex environments. |
10.1126/science.aaf0659 | 18,090,077 | A close-up view of cardiac cell mechanics Heart cells contain a very well-organized array of cytoskeletal elements, including actin and microtubules that help them to perform their mechanical functions. Robison et al. used an advanced imaging approach to study the inner workings of mouse cardiac myocytes in real time. ... | 10.1038/s41580-022-00473-y | This paper demonstrates that specific interactions between microtubules and intermediate filaments contribute to the mechanics of heart cell contraction. |
10.1073/pnas.85.21.8335 | 62,166,947 | We have analyzed the polarity orientation of microtubules in the axons and dendrites of cultured rat hippocampal neurons. As previously reported of axons from other neurons, microtubules in these axons are uniform with respect to polarity; (+)-ends are directed away from the cell body toward the growth cone. In sharp c... | 10.1038/s41580-022-00473-y | This paper demonstrates that the microtubule array in dendrites from cultured neurons has mixed polarity. |
10.1083/jcb.202010039 | 100,504,608 | Microtubules play a major role in intracellular trafficking of vesicles in endocrine cells. Detailed knowledge of microtubule organization and their relation to other cell constituents is crucial for understanding cell function. However, their role in insulin transport and secretion is under debate. Here, we use FIB-SE... | 10.1038/s41580-022-00473-y | This study uses electron microscopy to visualize the complete microtubule cytoskeleton and membrane organelles in entire β cells. |
10.1038/s41586-020-2012-7 | 62,665,780 | Abstract Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report t... | 10.1038/s41579-021-00652-2 | This is one of the first studies to discover viruses related to SARS-CoV-2 in wild Rhinolophus spp. bats in China |
10.1038/s41467-020-17687-3 | 62,201,083 | Abstract Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. Here we use a Bayesian statistical fra... | 10.1038/s41579-021-00652-2 | Using 5 years of surveillance data on coronaviruses in bats in China, the authors show that host switching is common in bat coronaviruses, particularly in Rhinolophus spp |
10.1126/science.abe5901 | 104,344,682 | Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-... | 10.1038/s41579-021-00652-2 | The study provides evidence of spillback of SARS-CoV-2 into mink populations, rapid and widespread transmission, and seeding of mink-associated genetic variants back into humans |
10.1242/dev.113001 | 20,701,406 | Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be ... | 10.1038/s41576-018-0051-9 | This work shows the capacity of mouse PSCs to recapitulate, in 3D, complex gastrulation-like processes that resemble those occurring in the early embryo |
10.1126/science.1160930 | 58,599,143 | Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor–binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies d... | 10.1038/s41576-021-00447-4 | This report establishes a framework for studying gene regulatory evolution using reproductive hybrids that has now been extended to composite cell lines |
10.1073/pnas.1005484107 | 125,310,327 | Photosynthetic antenna complexes capture and concentrate solar radiation by transferring the excitation to the reaction center that stores energy from the photon in chemical bonds. This process occurs with near-perfect quantum efficiency. Recent experiments at cryogenic temperatures have revealed that coherent energy t... | 10.1038/s41570-019-0109-z | Temperature dependence of the coherence signal is observed and shows persistence of the signal on the timescale of energy transfer, even at physiological temperature |
10.1073/pnas.1702261114 | 125,106,271 | During the first steps of photosynthesis, the energy of impinging solar photons is transformed into electronic excitation energy of the light-harvesting biomolecular complexes. The subsequent energy transfer to the reaction center is commonly rationalized in terms of excitons moving on a grid of biomolecular chromophor... | 10.1038/s41570-019-0109-z | Coherences assigned to vibrational ground-state signals due to the absence of signals within the excited-state absorption portion of the signal |
10.1073/pnas.1211157110 | 19,008,103 | The delocalized, anticorrelated component of pigment vibrations can drive nonadiabatic electronic energy transfer in photosynthetic light-harvesting antennas. In femtosecond experiments, this energy transfer mechanism leads to excitation of delocalized, anticorrelated vibrational wavepackets on the ground electronic st... | 10.1038/s41570-019-0109-z | Quantum beating signals assigned to Raman-like signals on the ground state but dependent on vibronic couplings in the excited-state manifold relevant to energy transfer |
10.1063/1.3002335 | 20,815,564 | Energy transfer within photosynthetic systems can display quantum effects such as delocalized excitonic transport. Recently, direct evidence of long-lived coherence has been experimentally demonstrated for the dynamics of the Fenna–Matthews–Olson (FMO) protein complex [Engel et al., Nature (London) 446, 782 (2007)]. Ho... | 10.1038/s41570-019-0109-z | Environmentally assisted quantum transport mechanism shows an optimal dephasing regime near where FMO dephasing is observed |
10.1542/peds.2017-1198 | 59,199,366 | Poor families without health insurance present unique challenges for pediatricians who want to do what is best for the children who are their patients. Families are often willing to make tremendous sacrifices to pay for recommended and needed medical care. Physicians may have to decide whether, or how strongly to, reco... | 10.1038/s41581-020-00338-7 | Case illustration of ethical dilemmas facing health care practitioners when treating children with kidney failure in low-income settings |
10.1111/nep.13135 | 107,377,694 | Summary at a Glance This review focused on the complexities of adolescent nephrology in an African setting. This review will provide meaningful information in the field of the transition medicine all over the world. | 10.1038/s41581-020-00338-7 | This article highlights the challenges of managing adolescents with kidney disease |
10.1126/science.aan2255 | 125,120,507 | Replacing platinum in air-fed fuel cells Replacing expensive and scarce platinum catalysts in polymer electrolyte membrane fuel cells for the oxygen reduction reaction (ORR) with ones based on non-noble metals would speed up the adoption of hydrogen fuel vehicles. Most of the candidate replacement catalysts that have s... | 10.1038/s41467-021-25911-x | State of the art power densities at 80 °C for PGM-free catalysts and important insights in the active site of Fe–N–C catalysts |
10.1128/iai.67.10.5455-5462.1999 | 18,840,400 | ABSTRACT The complete nucleotide sequence and organization of the enteropathogenic Escherichia coli (EPEC) adherence factor (EAF) plasmid of EPEC strain B171 (O111:NM) were determined. The EAF plasmid encodes two known virulence-related operons, the bfp operon, which is composed of genes necessary for biosynthesis of b... | 10.1038/s41579-018-0031-2 | In this paper, Tobe and colleagues analyse the structure of pB171 from EPEC E. coli B171 |
10.1126/science.aaf7501 | 28,040,115 | Plasmid copy number promotes plague The virulence of the plague bacterium, Yersinia pestis , is encoded on a plasmid. Normally, the bacterium only tolerates one copy of the plasmid, which provides the molecular machinery for injecting toxins into host cells. Wang et al. have found that Y. pestis can only be pathogenic ... | 10.1038/s41579-018-0031-2 | This paper reveals that plasmid copy number and then virulence are shaped by host signals, such as the ambient temperature. The molecular mechanisms underlying this phenomenon are not known. |
10.1038/srep09374 | 122,937,069 | Abstract Toxin-antitoxin (TA) modules contribute to the generation of non-growing cells in response to stress. These modules abound in bacterial pathogens although the bases for this profusion remain largely unknown. Using the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as a model, here we ... | 10.1038/s41579-018-0031-2 | This paper reveals potential functions for plasmid toxin–antitoxin systems that are not concerned with plasmid maintenance. |
10.1126/science.aaf4238 | 125,066,968 | INTRODUCTION Embryonic development and tissue homeostasis depend on cooperation between specialized cell types. Resident macrophages are professional phagocytes that survey their surroundings; eliminate unfit cells, microorganisms, and metabolic waste; and produce a large range of bioactive molecules and growth factors... | 10.1038/s41577-023-00848-y | This paper describes a macrophage developmental atlas, showing that pMacs are the main progenitors of early tissue-resident macrophages. |
10.1126/science.1219179 | 125,128,054 | Macrophages and dendritic cells (DCs) are key components of cellular immunity and are thought to originate and renew from hematopoietic stem cells (HSCs). However, some macrophages develop in the embryo before the appearance of definitive HSCs. We thus reinvestigated macrophage development. We found that the transcript... | 10.1038/s41577-023-00848-y | This paper shows that several tissue-resident macrophage populations are derived from fetal progenitors. |
10.1084/jem.20131199 | 20,689,403 | Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the ... | 10.1038/s41577-023-00848-y | This paper shows that alveolar macrophages are long-lived and contribute to lung function. |
10.1084/jem.20120340 | 42,529,213 | Langerhans cells (LCs) are the dendritic cells (DCs) of the epidermis, forming one of the first hematopoietic lines of defense against skin pathogens. In contrast to other DCs, LCs arise from hematopoietic precursors that seed the skin before birth. However, the origin of these embryonic precursors remains unclear. Usi... | 10.1038/s41577-023-00848-y | This study demonstrates that epidermal Langerhans cells are derived from fetal monocytes undergoing a stepwise differentiation and colonizing the developing epidermis shortly before birth. |
10.1038/s41467-017-02492-2 | 41,161,531 | Abstract Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal. However, the route and characteristics of YS macrophage trafficking during embryogenesis are incompletely understood. Here we show the early migration... | 10.1038/s41577-023-00848-y | This study shows that yolk sac erythromyeloid progenitors migrate to the mouse embryo in a defined embryonic time window via the developing vasculature. |
10.1126/science.abk2432 | 136,137,471 | For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae , that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250... | 10.1038/s41577-023-00848-y | This study represents the results of the Fly Cell Atlas consortium to provide a complex single cell transcriptomic atlas of adult Drosophila melanogaster . |
10.1146/annurev-cellbio-092910-154008 | 18,499,393 | T cells are the key mediators in cell-mediated immunity. Their development and maturation involve a complex variety of interactions with nonlymphoid cell products and receptors. Highly specialized to defend against bacterial and viral infections, T cells also mediate immune surveillance against tumor cells and react to... | 10.1038/s41590-022-01323-x | A Review article that discusses the role of Notch1 signaling in T cell development and leukemogenesis. |
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