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10.1073/pnas.0909710107 | 38,326,015 | Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of bo... | 10.1038/s41583-019-0223-4 | The first demonstration of sleep-relevant changes in the thalamus preceeding those in the cortex at the onset of human sleep |
10.1126/science.aad5252 | 123,178,315 | Let sleeping mice remember The role of REM (rapid eye movement) sleep for memory consolidation has been discussed for a long time. Boyce et al. used optogenetics to inhibit theta oscillations in the mouse hippocampus during REM sleep (see the Perspective by Kocsis). Both object recognition memory and contextual fear me... | 10.1038/s41583-019-0223-4 | First causal demonstration of the role of septal inhibitory cells in driving REM sleep theta rhythm and their role in REM sleep-dependent contextual memory consolidation |
10.1073/pnas.0913016107 | 104,234,569 | Brain activity in sleep plays a crucial role in memory consolidation, an offline process that determines the long-term strength of memory traces. Consolidation efficacy differs across individuals, but the brain activity dynamics underlying these differences remain unknown. Here, we studied how interindividual variabili... | 10.1038/s41583-019-0223-4 | Important study of the role of inter-area coherence of network oscillations in memory consolidation during REM sleep |
10.1002/path.4456 | 83,360,032 | Abstract Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25–90%. The diagnosis of filovirus using formalin‐fixed tissues from fatal cases poses a significant challenge. The most... | 10.1038/s41572-020-0147-3 | An updated and comprehensive summary of filovirus disease autopsy data |
10.1126/scitranslmed.aaw1049 | 122,930,096 | Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group,... | 10.1038/s41572-020-0147-3 | Meta-analysis of data from individual patients with EVD highlights the difficulty in making meaningful comparisons between studies in the absence of randomization |
10.1126/science.1259657 | 103,749,897 | Evolution of Ebola virus over time The high rate of mortality in the current Ebola epidemic has made it difficult for researchers to collect samples of the virus and study its evolution. Gire et al. describe Ebola epidemiology on the basis of 99 whole-genome sequences, including samples from 78 affected individuals. Th... | 10.1038/s41572-020-0147-3 | First description of mass genomic data for EBOV during the Western African outbreak |
10.1073/pnas.1502619112 | 17,696,622 | Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1%... | 10.1038/s41572-020-0147-3 | Landmark description of the longitudinal kinetics of B cell and T cell adaptive immune responses in four acutely ill patients with EVD cared for in a US setting. Highlights robust antigen-specific immune activation (as opposed to historical presumption of mainly immune suppressive effects) and sustained immune activati... |
10.4049/jimmunol.1700827 | 82,289,530 | Abstract Zaire ebolavirus (EBOV), one of five species in the genus Ebolavirus, is the causative agent of the hemorrhagic fever disease epidemic that claimed more than 11,000 lives from 2014 to 2016 in West Africa. The combination of EBOV’s ability to disseminate broadly and rapidly within the host and its high pathogen... | 10.1038/s41572-020-0147-3 | Detailed review of the “timing is everything” host–pathogen arms race after EBOV infections in humans and non-human primates |
10.1073/pnas.1718723115 | 82,972,562 | Nearly all eukaryotic messenger RNA precursors must undergo cleavage and polyadenylation at their 3′-end for maturation. A crucial step in this process is the recognition of the AAUAAA polyadenylation signal (PAS), and the molecular mechanism of this recognition has been a long-standing problem. Here, we report the cry... | 10.1038/s41580-021-00447-6 | Cryo-EM 3D structure of CPSF directly interacting with a PAS |
10.1038/ncomms8126 | 104,351,293 | Abstract Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription and RNA processing and their impact on translation can be analysed in a single experimental setting by applying 4sU-tagging of newly transcribed RNA an... | 10.1038/s41580-021-00447-6 | First description of host genome termination defects caused by HSV-1 infection |
10.1101/gad.330167.119 | 19,476,962 | Cellular homeostasis requires transcriptional outputs to be coordinated, and many events post-transcription initiation can dictate the levels and functions of mature transcripts. To systematically identify regulators of inducible gene expression, we performed high-throughput RNAi screening of the Drosophila Metallothio... | 10.1038/s41580-021-00447-6 | Integrator promotes nascent RNA cleavage to induce PTT in Drosophila melanogaster |
10.1126/science.1193844 | 80,269,876 | Gee-Up, NEDD8 Diverse bacterial pathogens, such as Burkholderia pseudomallei and enteropathogenic Escherichia coli (EPEC), inject effector proteins into eukaryotic host cells to subvert host cell biology. Cui et al. (p. 1215 ; published online 5 August) show that certain bacterial effector proteins promoted the glutami... | 10.1038/s41589-020-0638-2 | This article reports the discovery of Gln deamidase activity for Cif family effectors. |
10.1126/science.aal1556 | 62,360,349 | Modern commercial tomato varieties are substantially less flavorful than heirloom varieties. To understand and ultimately correct this deficiency, we quantified flavor-associated chemicals in 398 modern, heirloom, and wild accessions. A subset of these accessions was evaluated in consumer panels, identifying the chemic... | 10.1038/s41576-018-0002-5 | Broadly defines the most important tomato chemicals contributing to consumer preferences and identifies QTLs impacting the contents of those chemicals in fruit. |
10.1126/science.1222218 | 123,753,812 | Modern tomato ( Solanum lycopersicum ) varieties are bred for uniform ripening ( u ) light green fruit phenotypes to facilitate harvests of evenly ripened fruit. U encodes a Golden 2-like ( GLK ) transcription factor, SlGLK2 , which determines chlorophyll accumulation and distribution in developing fruit. In tomato, tw... | 10.1038/s41576-018-0002-5 | A great example of unintended negative consequences of breeding selection on tomato fruit quality. |
10.1111/mmi.14107 | 95,617,938 | Summary Clostridioides (formerly Clostridium ) difficile produces two major toxins, TcdA and TcdB, upon entry into stationary phase. Transcription of tcdA and tcdB requires the specialized sigma factor, σ TcdR , which also directs RNA Polymerase to transcribe tcdR itself. We fused a gene for a red fluorescent protein t... | 10.1038/s41579-021-00660-2 | By fusing a red fluorescent protein gene to the tcdA promoter, this study shows that toxin production is regulated by a TcdR-dependent bistable switch |
10.1038/s41467-021-23878-3 | 19,510,819 | Abstract C. difficile is a major cause of antibiotic-associated gastrointestinal infections. Two C. difficile exotoxins (TcdA and TcdB) are major virulence factors associated with these infections, and chondroitin sulfate proteoglycan 4 (CSPG4) is a potential receptor for TcdB, but its pathophysiological relevance and ... | 10.1038/s41579-021-00660-2 | In addition to describing a structure of the TcdB–CSPG4 complex, this study reveals how bezlotoxumab blocks CSPG4 binding by an allosteric mechanism and demonstrates the efficacy of a CSPG4-mimicking decoy in preventing toxicity |
10.1126/science.aar1999 | 103,227,145 | Toxic hijack of a cell signaling pathway The pathogen Clostridium difficile colonizes the human colon when the normal microbiota is disrupted, often after antibiotic treatment. It is a leading cause of hospital-acquired diarrhea, especially among elderly patients. Chen et al. describe a 2.5-Å-resolution crystal structu... | 10.1038/s41579-021-00660-2 | The crystal structure of the FZD2 cysteine-rich domain bound to the TcdB delivery domain reveals the presence of palmitoleic acid within the binding interface |
10.1073/pnas.1915255117 | 20,693,728 | Gastrointestinal infections often induce epithelial damage that must be repaired for optimal gut function. While intestinal stem cells are critical for this regeneration process [R. C. van der Wath, B. S. Gardiner, A. W. Burgess, D. W. Smith, PLoS One 8, e73204 (2013); S. Kozar et al. , Cell Stem Cell 13, 626–633 (2013... | 10.1038/s41579-021-00660-2 | This study shows that epidemic ribotype 027 strains promote stem cell dysfunction in a manner that is independent of FZD1/2/7 binding |
10.1038/s41467-020-14306-z | 122,926,601 | Abstract Large Clostridial Toxins (LCTs) are a family of six homologous protein toxins that are implicated in severe disease. LCTs infiltrate host cells using a translocation domain (LCT-T) that contains both cell-surface receptor binding sites and a membrane translocation apparatus. Despite much effort, LCT translocat... | 10.1038/s41579-021-00660-2 | A genomics analysis uncovers 1,104 homologues of the LCT translocase region and demonstrates that a distant homologue from Serratia marcescens acts as a pH-dependent translocase |
10.1126/scitranslmed.aax4905 | 122,944,317 | Antibiotic-resistant Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the colon and is responsible for more than 29,000 deaths in the United States each year. Hence, C. difficile infection (CDI) poses an urgent threat to public health. Antibody-mediated neutralization of TcdA and TcdB tox... | 10.1038/s41579-021-00660-2 | Saccharomyces boulardii engineered to secrete a single tetraspecific antibody to TcdA and TcdB is effective against primary and recurrent CDI in both prophylactic and therapeutic models of disease |
10.1073/pnas.1916965117 | 103,085,989 | Intestinal bile acids are known to modulate the germination and growth of Clostridioides difficile . Here we describe a role for intestinal bile acids in directly binding and neutralizing TcdB toxin, the primary determinant of C. difficile disease. We show that individual primary and secondary bile acids reversibly bin... | 10.1038/s41579-021-00660-2 | This study suggests that, in addition to modulating spore germination and bacterial viability, intestinal bile acids may modulate virulence by directly binding and inactivating TcdB |
10.1371/journal.ppat.1009181 | 42,556,588 | Clostridioides difficile is the major worldwide cause of antibiotic-associated gastrointestinal infection. A pathogenicity locus (PaLoc) encoding one or two homologous toxins, toxin A (TcdA) and toxin B (TcdB), is essential for C . difficile pathogenicity. However, toxin sequence variation poses major challenges for th... | 10.1038/s41579-021-00660-2 | The tcdA and tcdB genes clustered into 7 (A1–A7) and 12 (B1–B12) distinct subtypes and this forms the basis for a new toxin-based subtyping that can be accessed through an open online database (DiffBase) |
10.1126/science.aao2189 | 62,488,940 | Curving bones On larger length scales, bone is known to have a hierarchical structure in which small crystals of calcium phosphates arrange themselves around helices of collagen. These make up larger structures, such as the osteons found in compact bone. However, at smaller lengths, does the hierarchical structure pers... | 10.1038/s41570-020-00242-5 | This study describes mineral collagen assembly in bone and its hierarchical mineral structure on the nanoscale |
10.1038/s41467-018-04319-0 | 20,260,712 | Abstract A major goal in materials science is to develop bioinspired functional materials based on the precise control of molecular building blocks across length scales. Here we report a protein-mediated mineralization process that takes advantage of disorder–order interplay using elastin-like recombinamers to program ... | 10.1038/s41570-020-00242-5 | This work uses elastin-like recombinamer membranes to template the formation of minerals that closely resemble the hierarchical structure of enamel over multiple length scales |
10.1002/mabi.200700089 | 29,148,592 | Abstract DNA is a versatile building material for nanoconstruction because of its remarkable molecular‐recognition capability and well‐predicted duplex conformation. A number of DNA motifs have been engineered, which can assemble into well‐defined nanostructures in Mg 2+ ‐containing buffer solution. XRD studies reveal ... | 10.1038/s41570-020-00242-5 | This study highlights the guided formation of CaCO 3 using DNA nanostructures as templates |
10.1002/ange.201700148 | 61,411,009 | Abstract We demonstrate for the first time that hydronium ions can be reversibly stored in an electrode of crystalline 3,4,9,10‐perylenetetracarboxylic dianhydride (PTCDA). PTCDA exhibits a capacity of 85 mAh g −1 at 1 A g −1 after an initial conditioning process. Ex situ X‐ray diffraction revealed reversible and signi... | 10.1038/s41578-020-00241-4 | This report is the first on the storage of H 3 O + ions in an organic electrode |
10.1002/ange.201909324 | 60,209,755 | Abstract Plating battery electrodes typically deliver higher specific capacity values than insertion or conversion electrodes because the ion charge carriers represent the sole electrode active mass, and a host electrode is unnecessary. However, reversible plating electrodes are rare for electronically insulating nonme... | 10.1038/s41578-020-00241-4 | This paper reports large-scale storage based on anionic and cationic deposition processes |
10.1002/adma.201907802 | 61,268,746 | Abstract Nonmetallic ammonium (NH 4 + ) ions are applied as charge carriers for aqueous batteries, where hexagonal MoO 3 is initially investigated as an anode candidate for NH 4 + storage. From experimental and first‐principle calculated results, the battery chemistry proceeds with reversible building–breaking behavior... | 10.1038/s41578-020-00241-4 | This paper shows that stable NH 4 + storage based on hydrogen bonds is achieved by rationally selecting electrode materials |
10.1083/jcb.201904113 | 103,738,395 | The intraluminal vesicles (ILVs) of endosomes mediate the delivery of activated signaling receptors and other proteins to lysosomes for degradation, but they also modulate intercellular communication when secreted as exosomes. The formation of ILVs requires four complexes, ESCRT-0, -I, -II, and -III, with ESCRT-0, -I, ... | 10.1038/s41580-023-00576-0 | This work demonstrates that expression of an activated ALIX mutant is sufficient to recruit ESCRT-III to endosomes and drive the formation of tetraspanin-containing small EVs |
10.1073/pnas.1713433114 | 81,459,885 | The cytoplasmic tyrosine kinase SRC controls cell growth, proliferation, adhesion, and motility. The current view is that SRC acts primarily downstream of cell-surface receptors to control intracellular signaling cascades. Here we reveal that SRC functions in cell-to-cell communication by controlling the biogenesis and... | 10.1038/s41580-023-00576-0 | This work demonstrates that SRC regulates the syndecan–syntenin–ALIX pathway of exosome biogenesis by phosphorylating syndecan 1 and syntenin |
10.1126/science.1153124 | 62,251,830 | Intraluminal vesicles of multivesicular endosomes are either sorted for cargo degradation into lysosomes or secreted as exosomes into the extracellular milieu. The mechanisms underlying the sorting of membrane into the different populations of intraluminal vesicles are unknown. Here, we find that cargo is segregated in... | 10.1038/s41580-023-00576-0 | This work reveals a ceramide-dependent but ESCRT-independent pathway that produces exosomes containing proteolipid protein |
10.1038/s41467-017-00767-2 | 59,054,961 | Abstract ARMMs (arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles) are extracellular vesicles that bud directly at the plasma membrane; however, little is known about the molecular composition and physiological function of these vesicles. Here we report that ARMMs contain active NOTCH receptors and m... | 10.1038/s41580-023-00576-0 | Together with Nabhan et al. (2012), these studies define a class of ARRDC1-dependent ectosomes termed ‘ARRMs’ that form through ESCRT and E3 ubiquitin ligase activity at the plasma membrane |
10.1083/jcb.200902147 | 81,414,270 | For decades, enterocyte brush border microvilli have been viewed as passive cytoskeletal scaffolds that serve to increase apical membrane surface area. However, recent studies revealed that in the in vitro context of isolated brush borders, myosin-1a (myo1a) powers the sliding of microvillar membrane along core actin b... | 10.1038/s41580-023-00576-0 | This work identifies ectosomes forming at the tips of microvilli in intestinal enterocytes |
10.1080/20013078.2020.1764192 | 122,719,878 | ABSTRACT Extracellular vesicles (EVs) are membrane‐enclosed particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. Protein S ‐acylation, frequently called palmitoylation, has been proposed as a post‐translational mechanism that modulates the dynamic... | 10.1038/s41580-023-00576-0 | This is the first global palmitoyl-proteomic analysis to identify proteins enriched in large and small EVs |
10.1084/jem.20182313 | 38,926,435 | Emerging evidence suggests that extracellular vesicle (EV)–containing miRNAs mediate intercellular communications in response to noxious stimuli. It remains unclear how a cell selectively sorts the cellular miRNAs into EVs. We report that caveolin-1 (cav-1) is essential for sorting of selected miRNAs into microvesicles... | 10.1038/s41580-023-00576-0 | This work demonstrates that oxidative stress promotes phosphorylation of caveolin 1 to induce O -GlcNAcylation of its binding partner hnRNPA2B1 and downstream sorting of miRNAs into large EVs |
10.1083/jcb.201912074 | 123,400,897 | Cells respond to inflammatory disease states by releasing exosomes containing highly specific protein and RNA cargos, but how inflammation alters cargo specificity and secretion of exosomes is unknown. We show that increases in exosome secretion induced by either viral infection or LPS/ATP exposure result from inflamma... | 10.1038/s41580-023-00576-0 | This work demonstrates that the RNA-binding protein FMRP binds to HRS and promotes the exosomal secretion of miRNAs containing an AAUGC consensus sequence in response to inflammasome activation |
10.1038/ncomms15287 | 20,831,527 | Abstract Emerging evidence is revealing that exosomes contribute to many aspects of physiology and disease through intercellular communication. However, the biological roles of exosome secretion in exosome-secreting cells have remained largely unexplored. Here we show that exosome secretion plays a crucial role in main... | 10.1038/s41580-023-00576-0 | This work localizes DNA inside MVBs and demonstrates that ALIX and RAB27A reduce levels of cytoplasmic nuclear DNA, suggesting that DNA is expelled from the cell via exosomes |
10.3390/jcm8071027 | 20,798,863 | Exosomes—small membrane vesicles secreted by both normal and malignant cells upon fusion of endosomal multivesicular bodies (MVBs) with the plasma membrane—play an important role in cell-to-cell communication. During the last decade, several reports have highlighted the involvement of these nanovesicles in many aspects... | 10.1038/s41580-023-00576-0 | This work reveals a feed-forward mechanism to propagate leptin signalling by EVs to recipient cells |
10.1126/science.1252553 | 103,699,282 | Improving Reactions at Interfaces Alloying precious metals such as platinum with more abundant transition metals, such as iron and nickel, can both improve their catalytic reactivity and lower catalyst cost. Chen et al. (p. 495 ) explored using coatings of iron oxide–hydroxide layers on supported platinum nanoparticles... | 10.1038/s41565-020-00799-8 | Demonstrates the concept of using inverse structures — depositing common support materials on precious metals — to develop a stable and active catalyst for CO oxidation based on PtFeNi alloy nanocrystals |
10.1126/science.aah4321 | 20,823,822 | Low-temperature CO removal Carbon monoxide deactivates fuel cell catalysts, so it must be removed from H 2 generated from hydrocarbons on site. Yao et al. developed a catalyst composed of layered gold clusters on molybdenum carbide (MoC) nanoparticles to convert CO through its reaction with water into H 2 and CO 2 at t... | 10.1038/s41565-020-00799-8 | Exploit interfacial effects to create layered gold clusters on molybedenum carbide, evidencing high performance in the low-temperature water-gas shift reaction |
10.1002/anie.201902136 | 61,676,664 | Abstract Controlling the structure sensitivity of catalyzed reactions over metals is central to developing atom‐efficient chemical processes. Approaching the minimum ensemble size, the properties enter a non‐scalable regime in which each atom counts. Almost all trends in this ultra‐small frontier derive from surface sc... | 10.1038/s41565-020-00799-8 | Evidences the critical effect of nuclearity and critically discusses the challenges associated with discriminating between atomically-dispersed species |
10.1073/pnas.1714511115 | 83,321,845 | Phenological responses to climate change (e.g., earlier leaf-out or egg hatch date) are now well documented and clearly linked to rising temperatures in recent decades. Such shifts in the phenologies of interacting species may lead to shifts in their synchrony, with cascading community and ecosystem consequences. To da... | 10.1038/s41558-020-0752-x | Shows that the relative timing of interacting species across many types of interactions and taxonomic groups has changed substantially in recent decades |
10.1098/rstb.2007.2207 | 62,597,138 | In highly seasonal environments, offspring production by vertebrates is timed to coincide with the annual peak of resource availability. For herbivores, this resource peak is represented by the annual onset and progression of the plant growth season. As plant phenology advances in response to climatic warming, there is... | 10.1038/s41558-020-0752-x | Demonstrates the ecological consequences of trophic mismatch for a migratory herbivore and its host plant community due to climate change |
10.1111/oik.01909 | 107,380,926 | The timing of biological events (phenology) is an important aspect of both a species’ life cycle and how it interacts with other species and its environment. Patterns of phenological change have been given much scientific attention, particularly recently in relation to climate change. For pairs of interacting species, ... | 10.1038/s41558-020-0752-x | Reviews theoretical work related to Cushing’s hypothesis and proposes that phenological mismatch is not necessarily an expected outcome based on evolutionary theory |
10.1111/1365-2656.12554 | 62,016,743 | Summary Climate change may cause phenological asynchrony between trophic levels, which can lead to mismatched reproduction in animals. Although indirect effects of mismatch on fitness are well described, direct effects on parental prey choice are not. Moreover, direct effects of prey variation on offspring condition th... | 10.1038/s41558-020-0752-x | Provides a strong test of the Cushing hypothesis by testing many confounding factors and key assumptions, thus showing that this hypothesis is relevant to a bird-caterpillar interaction |
10.1098/rstb.2010.0144 | 61,333,348 | Climate change alters phenological relations between interacting species. We might expect the historical baseline, or starting-point, for such effects to be precise synchrony between the season at which a consumer most requires food and the time when its resources are most available. We synthesize evidence that synchro... | 10.1038/s41558-020-0752-x | Proposes that before climate change the fitness of some consumers may not have been at its maximum (i.e. asynchrony baseline) and that phenological mismatch due to climate change should not necessarily be the null hypothesis |
10.1126/science.1157174 | 103,735,641 | Rapid climate change has been implicated as a cause of evolution in poorly adapted populations. However, phenotypic plasticity provides the potential for organisms to respond rapidly and effectively to environmental change. Using a 47-year population study of the great tit ( Parus major ) in the United Kingdom, we show... | 10.1038/s41558-020-0752-x | Demonstrates that in this population of the great tit ( Parus major ) birds’ laying dates have remained synchronized with the timing of caterpillar emergence through phenotypic plasticity. |
10.1146/annurev-biochem-081420-102432 | 107,179,783 | Microbial natural products have provided an important source of therapeutic leads and motivated research and innovation in diverse scientific disciplines. In recent years, it has become evident that bacteria harbor a large, hidden reservoir of potential natural products in the form of silent or cryptic biosynthetic gen... | 10.1038/s41587-022-01563-0 | This review article summarizes methods for eliciting production of silent BGCs. |
10.1073/pnas.1501124112 | 122,485,445 | In molecular evolutionary analyses, short DNA sequences are used to infer phylogenetic relationships among species. Here we apply this principle to the study of bacterial biosynthesis, enabling the targeted isolation of previously unidentified natural products directly from complex metagenomes. Our approach uses short ... | 10.1038/s41587-022-01563-0 | This paper demonstrates how metagenomic BGCs are identified and mined. |
10.1063/1.4899186 | 125,313,924 | We report on the design, verification and performance of MuMax3, an open-source GPU-accelerated micromagnetic simulation program. This software solves the time- and space dependent magnetization evolution in nano- to micro scale magnets using a finite-difference discretization. Its high performance and low memory requi... | 10.1038/s41467-021-26711-z | See also Donahue, M. J. & Porter, D. G. Interagency Report NISTIR 6376 (National Institute of Standards and Technology, Gaithersburg, MD, Sept 1999) |
10.1002/anie.201700966 | 123,285,833 | Abstract To quantify and characterize the potentially toxic protein aggregates associated with neurodegenerative diseases, a high‐throughput assay based on measuring the extent of aggregate‐induced Ca 2+ entry into individual lipid vesicles has been developed. This approach was implemented by tethering vesicles contain... | 10.1038/s41570-021-00254-9 | This article reports a high-throughput oligomer quantification assay based on the measurement of Ca 2+ entry into individual lipid vesicles |
10.1002/ana.25513 | 45,474,322 | Objective Oligomeric forms of amyloid β protein (oAβ) are believed to be principally responsible for neurotoxicity in Alzheimer disease (AD), but it is not known whether anti‐Aβ antibodies are capable of lowering oAβ levels in humans. Methods We developed an ultrasensitive immunoassay and used it to measure oAβ in cere... | 10.1038/s41570-021-00254-9 | This paper demonstrates the use of an Erenna immunoassay to show target engagement of an antibody to amyloid-β aggregation in clinical trials |
10.1038/s41467-020-16728-1 | 62,597,805 | Abstract The chemical and structural properties of biomolecules determine their interactions, and thus their functions, in a wide variety of biochemical processes. Innovative imaging methods have been developed to characterise biomolecular structures down to the angstrom level. However, acquiring vibrational absorption... | 10.1038/s41570-021-00254-9 | The combination of atomic force microscopy with infrared spectroscopy enables one to structurally characterize single molecules |
10.1126/science.aar5839 | 123,009,758 | The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify t... | 10.1038/s41570-021-00254-9 | This work introduces the use of interferometric scattering microscopy for single-molecule detection |
10.1186/s40478-020-0887-z | 41,087,418 | Abstract Multiple neurodegenerative diseases are characterized by aggregation of tau molecules. Adult humans express six isoforms of tau that contain either 3 or 4 microtubule binding repeats (3R or 4R tau). Different diseases involve preferential aggregation of 3R (e.g Pick disease), 4R (e.g. progressive supranuclear ... | 10.1038/s41570-021-00254-9 | This work illustrates the use of real-time quaking-induced conversion (RT-QuIC), a seed amplification assay, to discriminate different tauopathies |
10.1002/chem.201100316 | 107,331,115 | Abstract Chemical and thermal stabilities of isotypic metal–organic frameworks (MOFs) like Al‐BDC (Al‐benzenedicarboxylate called MIL‐53‐Al), Cr‐BDC (MIL‐53‐Cr) and V‐BDC (MIL‐47‐V), after purification to remove uncoordinated organic linkers, have been compared to understand the effect of the central metal ions on the ... | 10.1038/s41578-019-0140-1 | Study showing that the trend in chemical stability for a family of isostructural carboxylate frameworks is in line with the kinetics of metal–ligand exchange but contrasts with the trend in metal–oxygen bond strength |
10.1126/science.aam8743 | 104,437,888 | Solar heat helps harvest humidity Atmospheric humidity and droplets constitute a huge freshwater resource, especially at the low relative humidity (RH) levels typical of arid environments. Water can be adsorbed by microporous materials such as zeolites, but often, making these materials release the water requires too m... | 10.1038/s41578-019-0140-1 | The first report of a device with a MOF (MOF-801) that captures H 2 O from the atmosphere and can be regenerated using low-grade heat from natural sunlight |
10.1126/science.203.4379.433 | 3,725,388 | A hole was drilled through the Ross Ice Shelf 450 kilometers from the barrier. Scientific sampling through this hole revealed a sparse population of crustaceans, fish, and microbial biomass. The seabed consists of mid-Miocene glaciomarine mud. Geothermal heat flow is average. Oceanographic data indicate an active circu... | 10.1038/s41561-023-01130-5 | An article that describes the first ice shelf borehole, which drilled through the Ross Ice Shelf 450 km from the open ocean in 1977; the authors found refreezing at the ice base and, surprisingly, macrofauna at the sea floor. |
10.1038/s41467-022-29892-3 | 129,730,576 | Abstract The “marine ice-sheet instability” hypothesis continues to be used to interpret the observed mass loss from the Antarctic and Greenland ice sheets. This hypothesis has been developed for conditions that do not account for feedbacks between ice sheets and environmental conditions. However, snow accumulation and... | 10.1038/s41561-023-01130-5 | This work emphasizes a lack of general stability conditions for marine ice sheets, and demonstrates the importance of assessing regionally unique ice, ocean, and seafloor feedbacks. |
10.1083/jcb.201207189 | 18,458,787 | Telomeres in cells that use the recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length. We therefore investigated whether ALT telomeres contain structural abnormalities that contribute to ALT activity. Here we used next genera... | 10.1038/s41568-022-00490-1 | This study shows that telomere variant repeats become interspersed throughout ALT-positive telomeres, thereby disrupting shelterin binding |
10.1038/s41598-019-55537-5 | 103,227,460 | Abstract Cancer cells maintain their telomeres by either re-activating telomerase or adopting the homologous recombination (HR)-based Alternative Lengthening of Telomere (ALT) pathway. Among the many prominent features of ALT cells, C-circles (CC) formation is considered to be the most specific and quantifiable biomark... | 10.1038/s41568-022-00490-1 | Along with Lu et al 61 and Silva et al 63 , this study demonstrates the role of the FANCM–BTR complex in alleviating replication stress at ALT-positive telomeres and provides the first evidence for the FANCM–BTR interaction as a novel drug target |
10.15252/embj.201796889 | 84,560,774 | Abstract Alternative lengthening of telomeres (ALT) is a telomere lengthening pathway that predominates in aggressive tumors of mesenchymal origin; however, the underlying mechanism of telomere synthesis is not fully understood. Here, we show that the BLM–TOP3A–RMI (BTR) dissolvase complex is required for ALT‐mediated ... | 10.1038/s41568-022-00490-1 | This study demonstrates that BLM and SLX4 have opposing functions at ALT-positive telomeres, with BLM promoting telomere extension and SLX4 counteracting telomere extension by inducing telomere exchange events |
10.1242/jcs.222349 | 79,449,181 | Cancers that utilize the Alternative Lengthening of Telomeres (ALT) mechanism for telomere maintenance are often difficult to treat and have a poor prognosis. They are also commonly deficient for expression of ATRX protein, a repressor of ALT activity, and a component of PML nuclear bodies (PML NBs) which are required ... | 10.1038/s41568-022-00490-1 | This paper identifies a mutant version of HSV1 that can be used to selectively induce lysis in ALT-positive cancer cells |
10.1126/science.1257216 | 102,352,447 | Cancer's alternative means to an end To stay alive and proliferating, tumor cells must maintain their telomeres: the DNA sequences at the ends of chromosomes. The majority accomplish this by activating the enzyme telomerase. However, certain tumor types favor a different mechanism called alternative lengthening of telo... | 10.1038/s41568-022-00490-1 | This paper shows the potential efficacy of ATR inhibitors on ALT-associated cells and has led to the progression of these agents into clinical trials for patients with ALT-positive cancers |
10.1093/nar/gkac113 | 128,265,838 | Abstract Alternative lengthening of telomeres (ALT) occurs in ∼10% of cancer entities. However, little is known about the heterogeneity of ALT activity since robust ALT detection assays with high-throughput in situ readouts are lacking. Here, we introduce ALT-FISH, a method to quantitate ALT activity in single cells fr... | 10.1038/s41568-022-00490-1 | Along with Claude et al 292 , this study documents a new method to accurately identify ALT-positive cells using native telomere-FISH |
10.1083/jcb.201804201 | 20,766,556 | The basolateral protein Scribble (Scrib), a member of the LAP protein family, is essential for epithelial apicobasal polarity (ABP) in Drosophila. However, a conserved function for this protein in mammals is unclear. Here we show that the crucial role for Scrib in ABP has remained obscure due to the compensatory functi... | 10.1038/s41580-022-00465-y | This paper shows that single knockouts of mammalian Scribble orthologues have no effect on apical–basal polarity in a colon cell line, whereas simultaneous knockouts of three orthologues disrupt polarity, demonstrating that they are functionally redundant |
10.1083/jcb.201903031 | 75,815,303 | Mechanisms coupling the atypical PKC (aPKC) kinase activity to its subcellular localization are essential for cell polarization. Unlike other members of the PKC family, aPKC has no well-defined plasma membrane (PM) or calcium binding domains, leading to the assumption that its subcellular localization relies exclusivel... | 10.1038/s41580-022-00465-y | This work shows that the PS domain of aPKC binds to lipids in the plasma membrane once it is exposed by Par-6 binding |
10.1038/s41467-020-16135-6 | 20,355,101 | Abstract The evolutionarily conserved Par3/Par6/aPKC complex regulates the polarity establishment of diverse cell types and distinct polarity-driven functions. However, how the Par complex is concentrated beneath the membrane to initiate cell polarization remains unclear. Here we show that the Par complex exhibits cell... | 10.1038/s41580-022-00465-y | This work shows that Bazooka/Par-3 forms phase-separated condensates and that this is enhanced by Par-6, but inhibited by aPKC phosphorylation of Bazooka |
10.1242/dev.186593 | 28,054,019 | Apical-basal polarity underpins the formation of epithelial barriers that are critical for metazoan physiology. Although apical-basal polarity is long known to require the basolateral determinants Lethal Giant Larvae (Lgl), Discs Large (Dlg) and Scribble (Scrib), mechanistic understanding of their function is limited. ... | 10.1038/s41580-022-00465-y | This work shows that Lgl is not part of the Scribble complex but requires Dlg to protect it from aPKC phosphorylation |
10.1083/jcb.202009116 | 109,195,195 | Cdc42-GTP is required for apical domain formation in epithelial cells, where it recruits and activates the Par-6–aPKC polarity complex, but how the activity of Cdc42 itself is restricted apically is unclear. We used sequence analysis and 3D structural modeling to determine which Drosophila GTPase-activating proteins (G... | 10.1038/s41580-022-00465-y | This work demonstrates that RhoGAP19D is recruited to the lateral membrane by Cadherin adhesion complexes where it inactivates Cdc42, thereby coupling cell–cell adhesion to the apical restriction of Cdc42 activity |
10.1073/pnas.1520638113 | 82,133,152 | Polarized epithelial cells exhibit a characteristic array of microtubules that are oriented along the apicobasal axis of the cells. The minus-ends of these microtubules face apically, and the plus-ends face toward the basal side. The mechanisms underlying this epithelial-specific microtubule assembly remain unresolved,... | 10.1038/s41580-022-00465-y | This paper shows that CAMSAP3 is required to anchor microtubule minus ends to the apical cortex of Caco-2 cells |
10.1038/ncomms12426 | 40,496,690 | Abstract Coordinated polarization of epithelial cells is a key step during morphogenesis that leads to the formation of an apical lumen. Rab11 and its interacting protein FIP5 are necessary for the targeting of apical endosomes to the midbody and apical membrane initiation site (AMIS) during lumenogenesis. However, the... | 10.1038/s41580-022-00465-y | This work shows that the tight junction protein cingulin tethers FIP5 vesicles at the AMIS through its interactions with midbody microtubules |
10.1038/s41467-021-24993-x | 127,556,636 | Abstract Polarized epithelial cells can organize into complex structures with a characteristic central lumen. Lumen formation requires that cells coordinately orient their polarity axis so that the basolateral domain is on the outside and apical domain inside epithelial structures. Here we show that the transmembrane a... | 10.1038/s41580-022-00465-y | This work shows that the transmembrane aminopeptidase CD13 acts upstream of RAB11A and RAB35 to both initiate the internalization of apical proteins from the basal membrane and localize RAB35 at the AMIS to enable apical vesicle docking |
10.1534/genetics.108.093351 | 80,874,243 | Abstract We model selection at a locus affecting a quantitative trait (QTL) in the presence of genetic variance due to other loci. The dynamics at the QTL are related to the initial genotypic value and to the background genetic variance of the trait, assuming that background genetic values are normally distributed, und... | 10.1038/s41576-020-0250-z | This study is one of the first to investigate whether genomic sweep signatures are also possible for polygenic adaptation |
10.1534/genetics.116.196972 | 41,508,366 | Abstract Although many studies have shown that a population initially well adapted to its environment can evolve rapidly when conditions suddenly change, the... Although a number of studies have shown that natural and laboratory populations initially well adapted to their environment can evolve rapidly when conditions ... | 10.1038/s41576-020-0250-z | This paper provides analytical approaches to describe cases of sweep signatures for large-effect alleles and small allele shifts for small-effect loci during polygenic adaptation |
10.1146/annurev-genom-083115-022316 | 41,600,773 | Many traits of interest are highly heritable and genetically complex, meaning that much of the variation they exhibit arises from differences at numerous loci in the genome. Complex traits and their evolution have been studied for more than a century, but only in the last decade have genome-wide association studies (GW... | 10.1038/s41576-020-0250-z | This comprehensive review discusses the connection between GWAS and polygenic adaptation |
10.1126/science.aag0776 | 125,088,765 | Identifying genes under recent selection Evolutionary analyses aim to identify recent genetic changes that are likely to have been subject to selection. Field et al. present a method to identify such changes, the singleton density score, which they applied to over 3000 human genomes. Over the past ∼100 generations (200... | 10.1038/s41576-020-0250-z | This paper introduces the singleton density score to detect polygenic adaptation |
10.1126/science.aaf7812 | 104,335,287 | When confronted with an adaptive challenge, such as extreme temperature, closely related species frequently evolve similar phenotypes using the same genes. Although such repeated evolution is thought to be less likely in highly polygenic traits and distantly related species, this has not been tested at the genome scale... | 10.1038/s41576-020-0250-z | This paper is an empirical demonstration of convergent local adaptation between two distantly related tree species confronted with the same adaptive challenge |
10.1534/genetics.119.302662 | 103,773,581 | Abstract Predictions about the effect of natural selection on patterns of linked neutral variation are largely based on models involving the rapid fixation of unconditionally beneficial mutations. However, when phenotypes adapt to a new optimum trait value, the strength of selection on individual mutations decreases as... | 10.1038/s41576-020-0250-z | This study presents a comprehensive simulation of polygenic adaptation of a single additive trait |
10.1101/792952 | 80,957,430 | Abstract Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on th... | 10.1038/s41576-020-0250-z | This paper presents an analytical description of the adaptation process for a highly polygenic trait |
10.1534/genetics.118.301018 | 83,279,182 | Abstract Adaptive introgression is common in nature and can be driven by selection acting on multiple, linked genes. We explore the effects of polygenic selection on introgression under the infinitesimal model with linkage. This model assumes that the introgressing block has an effectively infinite number of loci, each... | 10.1038/s41576-020-0250-z | This paper models adaptation for the infinitesimal model with linkage and finds that this can lead to large frequency changes |
10.1534/genetics.115.182550 | 41,510,672 | Abstract How predictable is the genetic basis of phenotypic adaptation? Answering this question begins by estimating the repeatability of adaptation at the genetic level. Here, we provide a comprehensive estimate of the repeatability of the genetic basis of adaptive phenotypic evolution in a natural system. We used qua... | 10.1038/s41576-020-0250-z | This paper presents an innovative approach using QTL mapping to explore redundancy |
10.1126/science.1107239 | 29,202,099 | Major phenotypic changes evolve in parallel in nature by molecular mechanisms that are largely unknown. Here, we use positional cloning methods to identify the major chromosome locus controlling armor plate patterning in wild threespine sticklebacks. Mapping, sequencing, and transgenic studies show that the Ectodysplas... | 10.1038/s41576-020-0250-z | This classic study shows that the same allele is independently selected in many river populations of sticklebacks |
10.1038/s41467-021-21089-4 | 62,587,101 | Abstract Multivalent protein-protein and protein-RNA interactions are the drivers of biological phase separation. Biomolecular condensates typically contain a dense network of multiple proteins and RNAs, and their competing molecular interactions play key roles in regulating the condensate composition and structure. Em... | 10.1038/s41586-022-05138-6 | A ternary system of protein and RNA is used to show that the wetting morphologies of the resulting biphasic condensates depend strongly on component stoichiometry and intermolecular interaction hierarchy. |
10.1038/s41567-022-01537-8 | 135,838,103 | Abstract Many membraneless organelles are liquid-like domains that form inside the active, viscoelastic environment of living cells through phase separation. To investigate the potential coupling of phase separation with the cytoskeleton, we quantify the structural correlations of membraneless organelles (stress granul... | 10.1038/s41586-022-05138-6 | Tubulin subunits and microtubules adhere to condensate interfaces in a manner consistent with a Pickering model that accounts for the finite interfacial thickness. |
10.1073/pnas.2024109118 | 128,269,409 | Seeds of dicotyledonous plants store proteins in dedicated membrane-bounded organelles called protein storage vacuoles (PSVs). Formed during seed development through morphological and functional reconfiguration of lytic vacuoles in embryos [M. Feeney et al. , Plant Physiol. 177, 241–254 (2018)], PSVs undergo division d... | 10.1038/s41586-022-05138-6 | Wetting of phase-separated droplets on plant vacuolar membranes can lead to membrane budding or the formation of membrane nanotubes depending on the contact angle and the membrane spontaneous curvature. |
10.1038/s41567-021-01285-1 | 104,018,771 | Abstract Interactions between liquids and surfaces generate forces 1,2 that are crucial for many processes in biology, physics and engineering, including the motion of insects on the surface of water 3 , modulation of the material properties of spider silk 4 and self-assembly of microstructures 5 . Recent studies have ... | 10.1038/s41586-022-05138-6 | The condensed transcription factor FoxA1 wets DNA and regulates its tension by allowing slack DNA to spool into FoxA1 droplets. |
10.1073/pnas.2109967118 | 133,519,422 | Significance Membraneless organelles are assemblies of highly concentrated biomolecules that condense through liquid–liquid phase separation. One major question in the field is how proteins assemble into multilayered condensates. Understanding mechanisms of formation of these systems is important for understanding the ... | 10.1038/s41586-022-05138-6 | Amphiphilic surfactant-like proteins regulate the size and multiphasic wetting morphologies of condensates in a concentration-dependent and sequence-dependent manner. |
10.1126/science.abg7071 | 134,740,439 | A Pickering-stabilized intracellular emulsion Pickering emulsions, droplet suspensions stabilized by solid particles, were discovered more than 100 years ago and are well studied in foods, oils, cosmetics, and pharmaceuticals. The particles adsorb to the droplet interface and prevent the emulsion from coarsening. Folkm... | 10.1038/s41586-022-05138-6 | MEG-3 assemblies adhere to the interface of P granules and slow their coarsening through a Pickering effect, thereby stabilizing the emulsion of P granules. |
10.1158/1538-7445.am2016-2696 | 102,265,462 | Abstract CNS-primitive neuroectodermal tumors (CNS PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Histological diagnosis is complicated by morphological heterogeneity and divergent differentiation. Recent studies ... | 10.1038/s41568-019-0169-x | This paper uses molecular classification methods to show that the majority of what was previously termed CNS-PNETs are, in fact, other known tumour entities, and also identified four novel tumour classes with distinct features |
10.1126/science.3175621 | 81,448,601 | Retinoblastoma (RB) is a malignant tumor of developing retina that arises when abnormalities resulting in loss of function affect both alleles of the gene at the retinoblastoma locus (RB1) on chromosome 13q. The majority of RB tumors do not show gross alterations in a 4.7-kb fragment (4.7R), which is a candidate RB1 ge... | 10.1038/s41568-019-0169-x | This paper presents the first identification of somatic and germline mutations in the RB1 gene as a defining feature of retinoblastoma |
10.1200/jco.2016.66.6552 | 104,425,010 | Purpose Recurrent glioblastoma multiforme (GBM) is incurable with current therapies. Biallelic mismatch repair deficiency (bMMRD) is a highly penetrant childhood cancer syndrome often resulting in GBM characterized by a high mutational burden. Evidence suggests that high mutation and neoantigen loads are associated wit... | 10.1038/s41568-019-0169-x | This study reports durable responses of recurrent paediatric glioblastoma with biallelic mismatch repair deficiency to immune checkpoint inhibition |
10.4049/jimmunol.1301966 | 41,467,734 | Abstract Despite increasing evidence that antitumor immune control exists in the pediatric brain, these findings have yet to be exploited successfully in the clinic. A barrier to development of immunotherapeutic strategies in pediatric brain tumors is that the immunophenotype of these tumors’ microenvironment has not b... | 10.1038/s41568-019-0169-x | This paper is one of the first to systematically characterize the frequency and phenotype of infiltrating immune cells in the most common paediatric brain tumour types |
10.1126/science.aaw4153 | 60,834,281 | Cancer treatment decisions are increasingly based on the genomic profile of the patient’s tumor, a strategy called “precision oncology.” Over the past few years, a growing number of clinical trials and case reports have provided evidence that precision oncology is an effective approach for at least some children with c... | 10.1038/s41568-019-0169-x | A comprehensive overview of different approaches to precision medicine clinical trial design and associated challenges |
10.1111/nan.12598 | 82,253,859 | DNA methylation‐based machine learning algorithms represent powerful diagnostic tools that are currently emerging for several fields of tumour classification. For various reasons, paediatric brain tumours have been the main driving forces behind this rapid development and brain tumour classification tools are likely fu... | 10.1038/s41568-019-0169-x | This paper describes a comprehensive molecular classification using DNA methylation patterns across a wide variety of human brain tumours |
10.1158/1535-7163.mct-09-0952 | 64,149,400 | Abstract Rapamycin demonstrated broad-spectrum tumor growth inhibition activity against the in vivo panels of childhood tumors used in the Pediatric Preclinical Testing Program (PPTP). Here we have evaluated rapamycin combined with agents used frequently in the treatment of childhood malignancies. Rapamycin was tested ... | 10.1038/s41568-019-0169-x | This study describes a systematic approach to in vivo combination testing using paediatric preclinical models |
10.1158/1078-0432.ccr-18-0455 | 20,402,642 | Abstract Purpose: Despite promising clinical activity, T-cell–engaging therapies including T-cell bispecific antibodies (TCB) are associated with severe side effects requiring the use of step-up-dosing (SUD) regimens to mitigate safety. Here, we present a next-generation CD20-targeting TCB (CD20-TCB) with significantly... | 10.1038/s41568-019-0169-x | This paper describes methods for in vivo testing of T cell-engaging immuno-oncology agents that can be applied to paediatric preclinical testing |
10.1161/circulationaha.111.034793 | 20,364,325 | Background— Targeted therapies to stabilize the clinical manifestations and prolong pregnancy in preeclampsia do not exist. Soluble fms-like tyrosine kinase 1 (sFlt-1), an alternatively spliced variant of the vascular endothelial growth factor receptor 1, induces a preeclampsia-like phenotype in experimental models and... | 10.1038/s41581-019-0119-6 | This proof-of-concept clinical study demonstrates that removal of sFLT1 was associated with improvement of pre-eclamptic signs and extension of pregnancy |
10.1681/asn.2016070806 | 17,299,198 | The effect of clinically recovered AKI (r-AKI) on future pregnancy outcomes is unknown. We retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General Hospital to assess whether a previous episode of r-AKI associated with subsequent adverse maternal and fetal outcomes, includi... | 10.1038/s41581-019-0119-6 | This paper reports that a prior history of acute kidney injury is a major risk factor for pre-eclampsia |
10.3171/foc.2001.10.2.8 | 41,454,914 | The DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents. MGMT activity is controlled by a promoter; methylation of the promoter silences the gene in cancer, and the cells no longer produce MGMT. We examined gliomas to determine whether methylation of ... | 10.1038/s41576-018-0074-2 | In this study, the authors describe for first time the connection between CpG methylation at the MGMT promoter and response to therapy in glioblastomas. It is one of the first reports on the use of CpG methylation in pharmacoepigenetics |
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