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10.1126/science.1192033 | 123,005,725 | Nanoprobes of Cell Potential Direct electrical measurements of cell potentials usually face design compromises. Microelectrodes probe within the cytosol of cells but have a minimum size (hundreds of nanometers in width) for obtaining useful signals. Nanoscale field effect transistors (FETs) can have an active probe siz... | 10.1038/s41578-018-0062-3 | This paper is the first to describe the design of Si-based 3D flexible electronics that can penetrate the cell and enable robust intracellular recordings of single cell action potentials |
10.1126/science.aas9315 | 18,958,387 | Using bugs in the gut to detect blood Bacteria are environmentally resilient and can be engineered to sense various biomolecules. Mimee et al. combined biosensor bacteria with a miniaturized wireless readout capsule to produce a minimally invasive device capable of in vivo biosensing in harsh, difficult-to-access envir... | 10.1038/s41578-018-0062-3 | This study describes the first prototype of an ingestible optoelectronic device for remote sensing of the gastrointestinal microenvironment by detecting and transmitting engineered bacterial bioluminescence signals to report local bleeding and biomolecular dynamics |
10.1038/ncomms14049 | 83,408,094 | Abstract Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3′ mRNA counting of tens of thousands of single cells per sample. Cell encapsulation, of up to 8 samples at a time, takes place in ∼6 min, with ∼50% c... | 10.1038/s41588-022-01162-4 | This paper reports the process of single-cell RNA sequencing by 10X genomics. |
10.1002/art.37753 | 45,562,939 | Abstract Objective To determine genome‐wide methylation profiles of bone from patients with hip osteoarthritis (OA) and those with osteoporotic (OP) hip fractures. Methods Trabecular bone pieces were obtained from the central part of the femoral head of 27 patients with hip fractures and 26 patients with hip OA. DNA wa... | 10.1038/s41574-019-0282-7 | The first epigenome-wide association study of human bone detected 241 differentially methylated CpG sites in femoral head trabecular bone specimens between 27 patients with osteoporotic hip fractures and 26 patients with hip osteoarthritis |
10.1002/jbmr.2018 | 4,854,990 | ABSTRACT Osteoporosis is related to the alteration of specific circulating metabolites. However, previous studies on only a few metabolites inadequately explain the pathogenesis of this complex syndrome. To date, no study has related the metabolome to bone mineral density (BMD), which would provide an overview of metab... | 10.1038/s41574-019-0282-7 | The first metabolomics study of osteoporosis in humans compared high and low BMD groups and reported four distinguishing metabolites: lactate, acetone, acetate and glutamine |
10.1126/science.aaf1098 | 41,740,064 | Training immune cells to remember Classical immunological memory, carried out by T and B lymphocytes, ensures that we feel the ill effects of many pathogens only once. Netea et al. review how cells of the innate immune system, which lack the antigen specificity, clonality, and longevity of T cell and B cells, have some... | 10.1038/s41577-019-0263-z | This Review outlines the properties of trained immunity, and the similarities to and differences from adaptive immunity |
10.1126/science.1254803 | 102,257,728 | After an infection, pathogen-specific tissue-resident memory T cells (T RM cells) persist in nonlymphoid tissues to provide rapid control upon reinfection, and vaccination strategies that create T RM cell pools at sites of pathogen entry are therefore attractive. However, it is not well understood how T RM cells provid... | 10.1038/s41577-019-0263-z | Together with Schenkel et al. (2014), this study reports how CD8 + tissue-resident memory T cells activate an alarm function in a tissue, providing protection from an unrelated pathogen |
10.1126/science.1247606 | 123,208,453 | How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) a... | 10.1038/s41577-019-0263-z | This study illustrates how diet can shift barrier tissues between type 17 and type 2 immunity based on the state of tissue-resident ILCs |
10.1126/science.1257530 | 41,049,235 | CD8 tissue-resident memory T (T RM ) cells provide efficient local control of viral infection, but the role of CD4 T RM is less clear. Here, by using parabiotic mice, we show that a preexisting pool of CD4 T RM cells in the genital mucosa was required for full protection from a lethal herpes simplex virus 2 (HSV-2) inf... | 10.1038/s41577-019-0263-z | This study identifies how macrophages and tissue-resident memory CD4 + T cells cooperate to form stable clusters in tissues |
10.1126/science.aaf2403 | 62,604,497 | Analysis of the pattern of proteins or messengerRNAs (mRNAs) in histological tissue sections is a cornerstone in biomedical research and diagnostics. This typically involves the visualization of a few proteins or expressed genes at a time. We have devised a strategy, which we call “spatial transcriptomics,” that allows... | 10.1038/s41576-022-00515-3 | The first publication to introduce the concept of spatial indexing with subsequent transcriptome readout using NGS |
10.1126/science.abb9536 | 38,309,923 | Spatial patterns of gene expression manifest at scales ranging from local (e.g., cell-cell interactions) to global (e.g., body axis patterning). However, current spatial transcriptomics methods either average local contexts or are restricted to limited fields of view. Here, we introduce sci-Space, which retains single-... | 10.1038/s41576-022-00515-3 | This publication describes a spatial method using combinatorial indexing to combine spatial indexing with subsequent single-cell sequencing |
10.1126/science.aaa6090 | 104,392,664 | Multiplexed RNA imaging in single cells The basis of cellular function is where and when proteins are expressed and in what quantities. Single-molecule fluorescence in situ hybridization (smFISH) experiments quantify the copy number and location of mRNA molecules; however, the numbers of RNA species that can be simulta... | 10.1038/s41576-022-00515-3 | This study introduces MERFISH and demonstrates that multiplexed FISH-based methods could multiplex hundreds to a thousand genes with high detection efficiency |
10.1073/pnas.1912459116 | 103,715,196 | The expression profiles and spatial distributions of RNAs regulate many cellular functions. Image-based transcriptomic approaches provide powerful means to measure both expression and spatial information of RNAs in individual cells within their native environment. Among these approaches, multiplexed error-robust fluore... | 10.1038/s41576-022-00515-3 | Together with Eng et al., this paper shows that multiplexed FISH-based methods can be used to profile ~10,000 genes. |
10.1126/science.aat5691 | 83,509,105 | Retrieving high-content gene-expression information while retaining three-dimensional (3D) positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. We developed and applied a technology for 3D intact-tissue RNA sequencing, ... | 10.1038/s41576-022-00515-3 | This reference introduces starMAP and the use of SNAIL probes to generate RCPs without cDNA synthesis |
10.1126/science.aax2656 | 20,832,452 | Methods for highly multiplexed RNA imaging are limited in spatial resolution and thus in their ability to localize transcripts to nanoscale and subcellular compartments. We adapt expansion microscopy, which physically expands biological specimens, for long-read untargeted and targeted in situ RNA sequencing. We applied... | 10.1038/s41576-022-00515-3 | This study uses expansion microscopy to improve the efficiency and resolution of targeted and untargeted in situ sequencing with the technique ExSeq |
10.1126/science.1250212 | 41,741,358 | Transcripts Visualized in Situ Despite advances, current methods for single-cell sequencing are unable to resolve transcript location within the cell, so Lee et al. (p. 1360 , published online 27 February) developed a method of fluorescent in situ RNA sequencing (FISSEQ) that works in vivo to show messenger RNA localiz... | 10.1038/s41576-022-00515-3 | This reference introduces FISSEQ, an untargeted in situ sequencing method |
10.1126/science.aau5324 | 104,305,054 | The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei—including the molecular identity, spatial organization, and function of distinct cell types—is poorly understood. Here, we developed an imaging-based in situ cell-type identification... | 10.1038/s41576-022-00515-3 | This study illustrates the potential for image-based transcriptomic methods to profile large tissue areas and numbers of cells by profiling 1.1 million cells |
10.1126/science.aar7042 | 41,529,389 | Making multiplexed subcellular protein maps Being able to visualize protein localizations within cells and tissues by means of immuno-fluorescence microscopy has been key to developments in cell biology and beyond. Gut et al. present a high-throughput method that achieves the detection of more than 40 different protein... | 10.1038/s41576-022-00515-3 | This reference presents a highly multiplexed use of indirect IF (4i) to study subcellular organization, demonstrating that 40 proteins can be visualized in the same cells |
10.1126/science.abg7216 | 136,366,684 | Spatial omics emerged as a new frontier of biological and biomedical research. Here, we present spatial-CUT&Tag for spatially resolved genome-wide profiling of histone modifications by combining in situ CUT&Tag chemistry, microfluidic deterministic barcoding, and next-generation sequencing. Spatially resolved c... | 10.1038/s41576-022-00515-3 | This paper introduces the concept of spatial epigenomic profiling using spatial indexing of histone modifications using microfluidics |
10.1126/science.aaw9886 | 20,575,666 | The Hippo signaling pathway and its two downstream effectors, the YAP and TAZ transcriptional coactivators, are drivers of tumor growth in experimental models. Studying mouse models, we show that YAP and TAZ can also exert a tumor-suppressive function. We found that normal hepatocytes surrounding liver tumors displayed... | 10.1038/s41580-022-00538-y | This article describes how liver hepatocytes compete with cancer cells and restrain tumour expansion due to relative differences in Hippo pathway signalling. Also see Liu et al. ( J. Cell Sci , 2019) for elegant work on how heterogeneity in Hippo signalling between subpopulations of cancer cells results in the active e... |
10.1038/s41598-019-51607-w | 123,890,478 | Abstract In high-latitude marine environments, primary producers and their consumers show seasonal peaks of abundance in response to annual light cycle, water column stability and nutrient availability. Predatory species have adapted to this pattern by synchronising life-history events such as reproduction with prey av... | 10.1038/s41558-022-01354-0 | This paper demonstrates the effect of trophic mismatch on marine ecosystems due to warm temperatures |
10.1038/s41467-021-25699-w | 134,721,303 | Abstract The future response of marine ecosystem diversity to continued anthropogenic forcing is poorly constrained. Phytoplankton are a diverse set of organisms that form the base of the marine ecosystem. Currently, ocean biogeochemistry and ecosystem models used for climate change projections typically include only 2... | 10.1038/s41558-022-01354-0 | This paper investigates future potential changes in phytoplankton community diversity |
10.1158/2159-8290.cd-18-1020 | 62,289,637 | Abstract Despite recent advances in the use of immunotherapy, only a minority of patients with small cell lung cancer (SCLC) respond to immune checkpoint blockade (ICB). Here, we show that targeting the DNA damage response (DDR) proteins PARP and checkpoint kinase 1 (CHK1) significantly increased protein and surface ex... | 10.1038/s41572-020-00235-0 | This paper defined a mechanism of combinatorial synergy between targeting DNA damage repair and immune checkpoints |
10.1084/jem.20070657 | 103,780,449 | Hypertension promotes atherosclerosis and is a major source of morbidity and mortality. We show that mice lacking T and B cells (RAG-1−/− mice) have blunted hypertension and do not develop abnormalities of vascular function during angiotensin II infusion or desoxycorticosterone acetate (DOCA)–salt. Adoptive transfer of... | 10.1038/s41577-019-0160-5 | This paradigm-shifting paper reports on research that reignited the study of immunity and inflammation in hypertension with a demonstration that mice lacking B cells and T cells have reduced hypertensive responses |
10.1152/ajpregu.00373.2009 | 125,127,912 | Activation of the immune system by ANG II contributes to the pathogenesis of hypertension, and pharmacological suppression of lymphocyte responses can ameliorate hypertensive end-organ damage. Therefore, to examine the mechanisms through which lymphocytes mediate blood pressure elevation, we studied ANG II-dependent hy... | 10.1038/s41577-019-0160-5 | This important report shows that immunodeficient SCID mice lacking B cells and T cells are protected from hypertension |
10.1152/ajpregu.00304.2012 | 103,780,793 | Hypertension and renal damage in Dahl SS rats are associated with increased infiltrating immune cells in the kidney. To examine the role of infiltrating immune cells in this disease process, a zinc finger nuclease targeting bases 672–706 of recombination-activating gene 1 (Rag1) was injected into the pronucleus of Dahl... | 10.1038/s41577-019-0160-5 | This study is the first to show that immunodeficiency in rats prevents salt-sensitive hypertension |
10.1161/hypertensionaha.114.04147 | 83,279,004 | Recent studies have emphasized a role of adaptive immunity, and particularly T cells, in the genesis of hypertension. We sought to determine the T-cell subtypes that contribute to hypertension and renal inflammation in angiotensin II–induced hypertension. Using T-cell receptor spectratyping to examine T-cell receptor u... | 10.1038/s41577-019-0160-5 | This study implicates oligoclonal CD8 + T cells as the main T cell subset involved in promoting hypertension |
10.1161/hypertensionaha.109.145094 | 83,272,223 | We have shown previously that T cells are required for the full development of angiotensin II–induced hypertension. However, the specific subsets of T cells that are important in this process are unknown. T helper 17 cells represent a novel subset that produces the proinflammatory cytokine interleukin 17 (IL-17). We fo... | 10.1038/s41577-019-0160-5 | This study introduces IL-17 as a contributing factor in experimental hypertension |
10.1161/hypertensionaha.115.05779 | 101,801,933 | Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection again... | 10.1038/s41577-019-0160-5 | This study is the first to show that B cells are required for the development of experimental hypertension |
10.1161/circulationaha.109.930446 | 83,281,260 | Background— The pathogenesis of hypertension remains poorly understood, and treatment is often unsuccessful. Recent evidence suggests that the adaptive immune response plays an important role in this disease. Various hypertensive stimuli cause T-cell activation and infiltration into target organs such as the vessel and... | 10.1038/s41577-019-0160-5 | This paradigm-shifting study shows that T cell activation in hypertension requires the costimulatory CD80/CD86–CD28 axis, which thereby implicates the involvement of classical antigen presentation |
10.1161/hypertensionaha.114.03512 | 80,723,355 | Female spontaneously hypertensive rats (SHR) have more regulatory T cells (Tregs) in their kidneys than males. The goal of this study was to determine the impact of blood pressure (BP) on the renal immune profile. We hypothesize that increases in BP promote a proinflammatory renal T cell and cytokine profile in SHR, al... | 10.1038/s41577-019-0160-5 | This study shows that there are sex differences in T reg cell populations during hypertension |
10.1161/hypertensionaha.110.162941 | 62,137,715 | Angiotensin (Ang) II induces hypertension by mechanisms mediated in part by adaptive immunity and T effector lymphocytes. T regulatory lymphocytes (Tregs) suppress T effector lymphocytes. We questioned whether Treg adoptive transfer would blunt Ang II–induced hypertension and vascular injury. Ten- to 12-week–old male C... | 10.1038/s41577-019-0160-5 | This study shows that injection of T reg cells can prevent the development of experimental hypertension |
10.1042/cs20110523 | 17,605,657 | Activation of TLRs (Toll-like receptors) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of CVDs (cardio-vascular diseases). Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism... | 10.1038/s41577-019-0160-5 | This study implicates the innate immune response in the development of hypertension |
10.1161/hypertensionaha.115.05315 | 62,606,617 | Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blo... | 10.1038/s41577-019-0160-5 | This early study shows links between the gut microbiome and hypertension |
10.1161/circulationaha.116.024545 | 103,783,793 | Background: Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiova... | 10.1038/s41577-019-0160-5 | This study shows that diet-induced modulation of the gut microbiome regulates experimental hypertension |
10.1111/bph.13230 | 122,960,946 | Background and Purpose Inflammasomes are multimeric complexes that facilitate caspase‐1‐mediated processing of the pro‐inflammatory cytokines IL ‐1β and IL ‐18. Clinical hypertension is associated with renal inflammation and elevated circulating levels of IL ‐1β and IL ‐18. Therefore, we investigated whether hypertensi... | 10.1038/s41577-019-0160-5 | This study implicates the NLRP3 inflammasome in the development of experimental hypertension |
10.1152/ajprenal.00517.2012 | 81,026,553 | Hypertension affects one-third of the adult population of the world. The causes of hypertension are incompletely understood, but relative impairment of sodium excretion is central to its pathogenesis. Immune cell infiltration in the kidney is a constant finding in hypertension that in association with local angiotensin... | 10.1038/s41577-019-0160-5 | This study implicates HSP70 as an antigenic stimulus that activates the immune system during experimental hypertension |
10.1161/circresaha.110.217299 | 20,640,511 | Rationale : We have previously found that T lymphocytes are essential for development of angiotensin II–induced hypertension; however, the mechanisms responsible for T-cell activation in hypertension remain undefined. Objective : We sought to study the roles of the CNS and pressure elevation in T-cell activation and va... | 10.1038/s41577-019-0160-5 | This study shows the importance of centrally mediated blood pressure responses in the peripheral inflammation associated with hypertension. It is also the first study to show that blood pressure is a primary determinant of peripheral inflammation |
10.1084/jem.192.7.1027 | 104,401,357 | PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 ... | 10.1038/s41573-022-00493-5 | This article reports that PDL1 could interact with PD1 to inhibit T cell activity |
10.1126/scitranslmed.3003689 | 62,668,510 | Activated tumor-infiltrating lymphocytes may induce B7-H1 on melanocytes, which suggests adaptive resistance to antitumor immunity. | 10.1038/s41573-022-00493-5 | This paper provides the first pathological data of TIME classification in human cancer and staining of PDL1 as a biomarker |
10.1261/rna.029405.111 | 125,230,777 | Human mitochondrial long noncoding RNAs (lncRNAs) have not been described to date. By analysis of deep-sequencing data we have identified three lncRNAs generated from the mitochondrial genome and confirmed their expression by Northern blotting and strand-specific qRT–PCR. We show that the abundance of these lncRNAs is ... | 10.1038/s41576-022-00480-x | The study was the first to report the existence of mitochondrial long non-coding RNAs and their potential roles in gene expression. |
10.1126/science.aaa1193 | 125,099,511 | The highly divergent ribosomes of human mitochondria (mitoribosomes) synthesize 13 essential proteins of oxidative phosphorylation complexes. We have determined the structure of the intact mitoribosome to 3.5 angstrom resolution by means of single-particle electron cryogenic microscopy. It reveals 80 extensively interc... | 10.1038/s41576-022-00480-x | The 2015 papers by Greber et al. and Amunts et al. were the first to report the cryoEM structure of the mammalian mitochondrial ribosome, identifying new and unexpected features of organelle translation. |
10.1038/s41594-021-00637-y | 128,869,563 | Abstract Human mitochondrial transcripts contain messenger and ribosomal RNAs flanked by transfer RNAs (tRNAs), which are excised by mitochondrial RNase (mtRNase) P and Z to liberate all RNA species. In contrast to nuclear or bacterial RNase P, mtRNase P is not a ribozyme but comprises three protein subunits that carry... | 10.1038/s41576-022-00480-x | This paper reports the complete atomic structure of the mitochondrial RNase P complex revealed by cryoEM. |
10.1038/s41467-020-18068-6 | 104,170,193 | Abstract Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits of the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. Th... | 10.1038/s41576-022-00480-x | The Article provides the most comprehensive account to date of mitochondrial tRNA modifications, validated by mass spectrometry. |
10.1126/science.1241488 | 20,808,763 | Toward Titanium Carbide Batteries Many batteries and capacitors make use of lithium intercalation as a means of storing and transporting charge. Lithium is commonly used because it offers the best energy density, but also because there are difficulties in storing larger cations without disrupting the crystal structure ... | 10.1038/s41570-022-00384-8 | This article highlights the broad electrochemical tolerance of MXenes for a variety of cations |
10.1126/sciadv.aat0491 | 62,114,069 | Nanoindentation experiments show that Ti 3 C 2 T x MXenes have a higher elastic modulus than other solution-processed 2D materials. | 10.1038/s41570-022-00384-8 | This paper reports the elastic properties of the MXene monolayer and bilayer |
10.1126/science.abf1581 | 41,469,401 | A decade after the first report, the family of two-dimensional (2D) carbides and nitrides (MXenes) includes structures with three, five, seven, or nine layers of atoms in an ordered or solid solution form. Dozens of MXene compositions have been produced, resulting in MXenes with mixed surface terminations. MXenes have ... | 10.1038/s41570-022-00384-8 | A comprehensive review of the extensive applications of MXenes in the past decade |
10.1126/science.289.5480.739 | 41,560,733 | Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural features, including a bundle of seven transmembrane α helices connected by six loops of varying lengths. We determined the struc... | 10.1038/s41594-019-0252-8 | Ref. 26 provided the first crystal structure of a GPCR |
10.1126/science.1150577 | 62,564,996 | Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human β 2 -adrenergic receptor–T4 lysozyme fusion protein bound to the partial inverse agoni... | 10.1038/s41594-019-0252-8 | Refs. 27–29 provided the first crystal structures of non-opsin GPCRs |
10.1073/pnas.1809548115 | 125,270,468 | Cell death and inflammation are intimately linked during Yersinia infection. Pathogenic Yersinia inhibits the MAP kinase TGFβ-activated kinase 1 (TAK1) via the effector YopJ, thereby silencing cytokine expression while activating caspase-8–mediated cell death. Here, using Yersinia pseudotuberculosis in corroboration wi... | 10.1038/s41577-019-0228-2 | Together with Chen et al. (2019) and Orning et al. (2018), this paper reports a new pathway in which caspase 8 controls GSDMD cleavage and activation upon treatment with triggers of extrinsic apoptosis |
10.1126/science.aar7607 | 104,292,192 | Pyroptosis is a lytic form of cell death that is induced by inflammatory caspases upon activation of the canonical or noncanonical inflammasome pathways. These caspases cleave gasdermin D (GSDMD) to generate an N-terminal GSDMD fragment, which executes pyroptosis by forming membrane pores. We found that calcium influx ... | 10.1038/s41577-019-0228-2 | This article shows that calcium influx through GSDMD pores can activate the ESCRT machinery to initiate repair of the damaged membranes |
10.1126/science.aat4191 | 104,252,647 | The dielectric constant ε of interfacial water has been predicted to be smaller than that of bulk water (ε ≈ 80) because the rotational freedom of water dipoles is expected to decrease near surfaces, yet experimental evidence is lacking. We report local capacitance measurements for water confined between two atomically... | 10.1038/s41570-022-00418-1 | Validated predictions of significant dielectric constant decrease for interfacial water relative to bulk value |
10.1126/sciadv.aaz9708 | 102,300,340 | Knowledge of the occurrences of water films on minerals is critical for global biogeochemical and atmospheric processes, including element cycling and ice nucleation. The underlying mechanisms controlling water film growth are, however, misunderstood. Using infrared nanospectroscopy, amplitude-modulated atomic force mi... | 10.1038/s41570-022-00418-1 | These nanospectroscopy observations of anisotropic water film development on mineral surface highlighted the controlling roles that defect sites may have, especially in a dynamically reactive interfacial environment. |
10.1093/brain/awaa332 | 125,215,710 | Abstract In the phase 3 EPOCH trial (Clinicaltrials.gov; NCT01739348), treatment with the BACE inhibitor verubecestat failed to improve cognition in patients with mild-to-moderate Alzheimer’s disease, but was associated with reduced hippocampal volume after 78 weeks as assessed by MRI. The aims of the present explorato... | 10.1038/s41582-018-0116-6 | Presented at the 11th Clinical Trials on Alzheimer’s Disease Barcelona, Spain |
10.1182/blood-2007-06-095299 | 119,514,370 | Abstract Spontaneous somatic reversions of inherited mutations are poorly understood phenomena that are thought to occur uncommonly in a variety of genetic disorders. When molecularly characterized, revertant cells have rarely exhibited more than one revertant genotype per patient. We analyzed individual allospecific T... | 10.1038/s41576-019-0139-x | These authors report up to 34 different SGR events in a single patient with Wiskott–Aldrich syndrome, demonstrating that distinct somatic mutations can accumulate in different clones from the same individual |
10.1126/science.288.5466.669 | 83,484,463 | Severe combined immunodeficiency–X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the γc cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which particip... | 10.1038/s41576-019-0139-x | This study reports successful gene therapy of SCID X1 based on the selective advantage provided by wild-type gene integration, which mimics natural revertants |
10.1126/science.1070104 | 122,683,466 | Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)–deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloabl... | 10.1038/s41576-019-0139-x | This study reports successful gene therapy of ADA SCID, based on the selective advantage provided by wild-type gene integration, which mimics natural revertants |
10.1182/blood-2005-03-0936 | 79,415,588 | Abstract Omenn syndrome (OS) is a rare primary immunodeficiency characterized by the presence of activated/oligoclonal T cells, eosinophilia, and the absence of circulating B cells. OS patients carry leaky mutations of recombination activating genes (RAG1 or RAG2) resulting in partial V(D)J recombination activity, wher... | 10.1038/s41576-019-0139-x | This study demonstrates that SGR can lead to deleterious consequences by generating pathogenic T lymphocytes and by causing Omenn syndrome |
10.1111/liv.12988 | 4,605,743 | Abstract In the past decade our understanding of idiosyncratic drug induced liver injury ( IDILI ) and the contribution of genetic susceptibility and the adaptive immune system to the pathogenesis of this disease process has grown tremendously. One of the characteristics of IDILI is that it occurs rarely and only in a ... | 10.1038/s41572-019-0105-0 | A description of various factors that contribute to pathogenesis of idiosyncratic DILI, highlighting the participation of genetic susceptibility due to HLA variants and the potential importance of immune tolerance |
10.1111/cts.12629 | 41,482,267 | The drug‐induced liver injury (DILI)‐sim Initiative is a public‐private partnership involving scientists from industry, academia, and the US Food and Drug Administration (FDA). The Initiative uses quantitative systems toxicology (QST) to build and refine a model ( DILI sym) capable of understanding and predicting liver... | 10.1038/s41572-019-0105-0 | This is a review of a 15 year public–private partnership that has been using quantitative systems toxicology approaches to understand and predict the likelihood that a new drug candidate will cause DILI. The review focuses on specific advances in mechanistic understanding that have evolved from this consortium |
10.1126/science.aan4737 | 81,576,745 | Consecutive attosecond pulses reveal the dynamics of excitons ensuing from core-electron excitation in silica. | 10.1038/s41578-022-00530-0 | This work presents the capability of attosecond transient absorption spectroscopy to directly probe core excitons and characterize their transient properties |
10.1073/pnas.1707602114 | 82,478,437 | Coulomb correlations can manifest in exotic properties in solids, but how these properties can be accessed and ultimately manipulated in real time is not well understood. The insulator-to-metal phase transition in vanadium dioxide (VO 2 ) is a canonical example of such correlations. Here, few-femtosecond extreme UV tra... | 10.1038/s41578-022-00530-0 | This work uncovers a record speed for the photoinduced metal-to-insulator transition in a correlated transition metal oxide, VO 2 |
10.1038/s41467-020-16480-6 | 60,729,845 | Abstract Recent progress in high power ultrafast short-wave and mid-wave infrared lasers has enabled gas-phase high harmonic generation (HHG) in the water window and beyond, as well as the demonstration of HHG in condensed matter. In this Perspective, we discuss the recent advancements and future trends in generating a... | 10.1038/s41578-022-00530-0 | This review of attosecond science provides further reading on how solid-state high-harmonic generation along with attosecond transient absorption spectroscopy can push the limits of time resolution in ultrafast spectroscopy |
10.1126/science.aan4368 | 62,285,057 | An atlas for drug interactions Kinase inhibitors are an important class of drugs that block certain enzymes involved in diseases such as cancer and inflammatory disorders. There are hundreds of kinases within the human body, so knowing the kinase “target” of each drug is essential for developing successful treatment st... | 10.1038/s41573-020-0063-y | This study reports a comprehensive list of targets for 243 clinical kinase inhibitors through chemical proteome profiling in four cell lines |
10.1126/science.1233606 | 125,210,538 | The efficacy of therapeutics is dependent on a drug binding to its cognate target. Optimization of target engagement by drugs in cells is often challenging, because drug binding cannot be monitored inside cells. We have developed a method for evaluating drug binding to target proteins in cells and tissue samples. This ... | 10.1038/s41573-020-0063-y | This seminal study describes the development and application of cellular thermal shift assay (CETSA) for evaluating target engagement by a drug in intact cells |
10.1126/science.1255784 | 41,667,229 | The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles delineated more than 50 t... | 10.1038/s41573-020-0063-y | This study builds on the CETSA assay by incorporating TMT and quantitative mass spectrometry for proteome-wide analysis of on- and off-target drug effects |
10.1038/ncomms11416 | 80,635,034 | Abstract Cell lysis is an inevitable step in classical mass spectrometry–based strategies to analyse protein complexes. Complementary lysis conditions, in situ cross-linking strategies and proximal labelling techniques are currently used to reduce lysis effects on the protein complex. We have developed Virotrap, a vira... | 10.1038/s41573-020-0063-y | This study describes a novel approach for identifying membrane–protein interactions and small-molecule binders by trapping them within viral-like particles (Virotrap) |
10.1111/gcb.12551 | 103,861,017 | Abstract Bottom–up estimates from long‐term field experiments and modelling are the most commonly used approaches to estimate the carbon (C) sequestration potential of the agricultural sector. However, when data are required at European level, important margins of uncertainty still exist due to the representativeness o... | 10.1038/s41558-022-01321-9 | Quantifies the carbon storage potential of six major practices at the European scale |
10.1111/gcb.14815 | 62,277,021 | Abstract There is growing international interest in better managing soils to increase soil organic carbon (SOC) content to contribute to climate change mitigation, to enhance resilience to climate change and to underpin food security, through initiatives such as international ‘4p1000’ initiative and the FAO's Global as... | 10.1038/s41558-022-01321-9 | Review of the scientific and technical challenges of soil monitoring |
10.1038/ncomms8247 | 26,753,131 | Abstract Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases ( n =152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations wit... | 10.1038/s41582-021-00541-5 | GWAS in corticobasal degeneration that links CBD and PSP on the basis of common risk variants |
10.1073/pnas.1301175110 | 20,363,650 | Filamentous inclusions made of hyperphosphorylated tau are characteristic of numerous human neurodegenerative diseases, including Alzheimer’s disease, tangle-only dementia, Pick disease, argyrophilic grain disease (AGD), progressive supranuclear palsy, and corticobasal degeneration. In Alzheimer’s disease and AGD, it h... | 10.1038/s41582-021-00541-5 | An important study that supports the hypothesis that tau spreading is the mechanism underlying progression, using human brain homogenates |
10.1093/brain/awm104 | 17,598,905 | Abstract Clinical syndromes associated with progressive supranuclear palsy-tau pathology now include progressive supranuclear palsy-parkinsonism (PSP-P), in addition to classic Richardson's syndrome (RS) and pure akinesia with gait freezing (PAGF). Although pathological heterogeneity of progressive supranuclear palsy (... | 10.1038/s41582-021-00541-5 | One of the first studies to show that differences in the underlying distribution and burden of tau pathology explain different PSP phenotypes |
10.1002/mds.26054 | 125,046,181 | Abstract The phenotypic variability of progressive supranuclear palsy (PSP) may account for its frequent misdiagnosis, in particular in early stages of the disease. However, large multicenter studies to define the frequency and natural history of PSP phenotypes are missing. In a cohort of 100 autopsy‐confirmed patients... | 10.1038/s41582-021-00541-5 | One of the largest clinicopathological studies in PSP that identified more phentoypes than previously described |
10.1002/mds.24968 | 83,342,593 | Abstract Conventional magnetic resonance imaging (cMRI) is often used to aid the diagnosis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), but its ability to predict the histopathological diagnosis has not been systematically studied. cMRI from 48 neuropathologically confirmed cases, includin... | 10.1038/s41582-021-00541-5 | One of very few studies of MRI in definite PSP and MSA |
10.1002/path.2913 | 41,559,747 | Abstract Somatic mutations in isocitrate dehydrogenase 1 ( IDH1 ) and IDH2 occur in gliomas and acute myeloid leukaemia (AML). Since patients with multiple enchondromas have occasionally been reported to have these conditions, we hypothesized that the same mutations would occur in cartilaginous neoplasms. Approximately... | 10.1038/s41568-020-0288-4 | This paper presents the first description of IDH1 and IDH2 mutations in chondrosarcoma |
10.1126/science.aac7272 | 62,408,194 | An oncohistone deranges inhibitory chromatin Missense mutations (that change one amino acid for another) in histone H3 can produce a so-called oncohistone and are found in a number of pediatric cancers. For example, the lysine-36–to-methionine (K36M) mutation is seen in almost all chondroblastomas. Lu et al. show that ... | 10.1038/s41568-020-0288-4 | This study provides a mechanistic explanation of how mesenchymal tumour-associated histone mutations broadly affect the chromatin landscape and mesenchymal differentiation |
10.1073/pnas.1303800110 | 83,176,773 | Inactivation of the switch/sucrose nonfermentable complex component SMARCB1 is extremely prevalent in pediatric malignant rhabdoid tumors (MRTs) or atypical teratoid rhabdoid tumors. This alteration is hypothesized to confer oncogenic dependency on EZH2 in these cancers. We report the discovery of a potent, selective, ... | 10.1038/s41568-020-0288-4 | This paper demonstrates that small-molecule inhibition of the catalytic subunit of PRC2 inhibits the growth of preclinical models of SWI/SNF complex-altered sarcoma, providing a scientific rationale for subsequent clinical trials with tazemetostat |
10.1093/jnci/djx285 | 122,991,068 | Abstract Cancer- and treatment-related cognitive changes have been a focus of increasing research since the early 1980s, with meta-analyses demonstrating poorer performance in cancer patients in cognitive domains including executive functions, processing speed, and memory. To facilitate collaborative efforts, in 2011 t... | 10.1038/s41582-021-00617-2 | Recommendations for MRI sequences to facilitate increased use of neuroimaging in studies on cancer and cognition. |
10.1200/jco.2011.37.0189 | 101,948,502 | Purpose Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the imp... | 10.1038/s41582-021-00617-2 | One of the few studies on very late cognitive effects of chemotherapy. |
10.1002/pon.3163 | 62,314,330 | Abstract Objective The purpose of this study was to determine if cognition progressively worsens with cumulative chemotherapy exposure. We reasoned that the demonstration of such a ‘dose–response’ relationship would help to establish whether cognitive changes are caused by neurotoxic effects of chemotherapy or whether ... | 10.1038/s41582-021-00617-2 | The first and only study that evaluated cognition after each course of chemotherapy. |
10.1002/pon.1133 | 80,903,200 | Abstract Adjuvant chemotherapy can produce mild cognitive decline among breast cancer survivors which adversely effects function and quality of life. However, no treatment to date has been proposed or developed for this problem despite large numbers of cancer patients who report post‐treatment memory dysfunction. This ... | 10.1038/s41582-021-00617-2 | The first investigation into behavioural interventions for cognitive problems after chemotherapy. |
10.1001/jama.2021.3224 | 62,433,900 | Importance The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. Objective To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for we... | 10.1038/s41573-021-00337-8 | This article shows the effects of continuous versus withdrawing treatment with semaglutide 2.4 mg in people with overweight and obesity |
10.1126/science.1141634 | 62,604,389 | Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetesâsusceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that pred... | 10.1038/s41573-021-00337-8 | This article discovers that genetic variation in the FTO gene is associated with obesity |
10.1126/scitranslmed.3007218 | 123,917,763 | Compared to best-in-class GLP-1 mono-agonists, unimolecular co-agonists of GLP-1 and GIP with optimized pharmacokinetics enhance glycemic and metabolic benefits in mammals. | 10.1038/s41573-021-00337-8 | This article shows that unimolecular GLP1/GIP co-agonism corrects obesity and glucose intolerance in obese rodents and non-human primates |
10.2337/dbi21-0004 | 84,369,395 | Gastric inhibitory peptide (GIP) is best known for its role as an incretin hormone in control of blood glucose concentrations. As a classic satiation signal, however, the literature illustrates a mixed picture of GIP involvement with an at best weak anorectic response profile being reported for GIP receptor (GIPR) sign... | 10.1038/s41573-021-00337-8 | This article shows that GIP attenuates GLP1-mediated effects on emesis in rodents and shrews |
10.1351/pac197951040709 | 103,565,063 | Abstract | 10.1038/s41579-021-00636-2 | This review details how a particular group of bacterial membrane lipids gave rise to a ubiquitous and abundant class of chemical fossils |
10.1146/annurev-earth-050212-123958 | 103,565,501 | Our ability to read the molecular fossil record has advanced significantly in the past decade. Improvements in biomarker sampling and quantification methods, expansion of molecular sequence databases, and the application of genetic and cellular biological tools to problems in biomarker research have enabled much of thi... | 10.1038/s41579-021-00636-2 | This paper details our changing understanding on the role of 2-methylhopanoids in bacteria, and how this change impacts our interpretation of the related molecular fossil. It provides a case study on the importance of knowing what a biomarker biologically does in a microbe, not just its presence or absence |
10.1111/j.1462-2920.2007.01331.x | 60,622,588 | Summary Hopanoids are ubiquitous isoprenoid lipids found in modern biota, in recent sediments and in low‐maturity sedimentary rocks. Because these lipids primarily are derived from bacteria, they are used as proxies to help decipher geobiological communities. To date, much of the information about sources of hopanoids ... | 10.1038/s41579-021-00636-2 | This paper is the first example of using a biomarker biosynthesis gene, the squalene–hopene cyclase gene necessary for hopanoid production, to demonstrate the potential diversity of biomarker producers in environmental metagenomic data sets |
10.1073/pnas.2101276118 | 135,515,151 | Significance Steroids are one of three major lipid components of the eukaryotic cellular membrane, along with glycerophospolipids and sphingolipids. Steroids have critical roles in eukaryotic endocytosis and thus may have been structural prerequisites for the endocytic acquisition of mitochondria during eukaryogenesis.... | 10.1038/s41579-021-00636-2 | This recent study uses a phylogenetic approach to assess the evolutionary history of sterol biosynthesis and the potential impact of bacterial sterol biosynthesis on the rise of eukaryotes |
10.1073/pnas.74.11.5088 | 83,525,241 | A phylogenetic analysis based upon ribosomal RNA sequence characterization reveals that living systems represent one of three aboriginal lines of descent: ( i ) the eubacteria, comprising all typical bacteria; ( ii ) the archaebacteria, containing methanogenic bacteria; and ( iii ) the urkaryotes, now represented in th... | 10.1038/s41579-021-00636-2 | This classic study shows how ribosomal RNA sequences reveal that all life follows one of three lines of descent from a common ancestor |
10.1210/en.2013-1974 | 61,468,025 | Osteoblastogenesis is the process by which mesenchymal stem cells differentiate into osteoblasts that synthesize collagen and mineralize matrix. The pace and magnitude of this process are determined by multiple genetic and environmental factors. Two inbred strains of mice, C3H/HeJ and C57BL/6J, exhibit differences in p... | 10.1038/s41574-019-0246-y | This study tracks the changes in oxygen consumption and glycolytic metabolism that occur during osteoblast differentiation in vitro |
10.1073/pnas.1707876115 | 82,693,510 | Sclerostin has traditionally been thought of as a local inhibitor of bone acquisition that antagonizes the profound osteoanabolic capacity of activated Wnt/β-catenin signaling, but serum sclerostin levels in humans exhibit a correlation with impairments in several metabolic parameters. These data, together with the inc... | 10.1038/s41574-019-0246-y | This work suggests that sclerostin acts outside the skeleton to influence adipose tissue physiology |
10.1126/science.aba2894 | 18,956,926 | The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement bel... | 10.1038/s41580-022-00480-z | This article, together with concurrently published work by Venturini et al. (ref.127) , demonstrates how physical confinement that compresses the nucleus triggers increased cell cortical contractility via recruitment of cPLA2 to the stretched nuclear membranes |
10.1126/science.aad7297 | 41,474,627 | Repairing tears in the nuclear envelope The nuclear envelope segregates genomic DNA from the cytoplasm and regulates protein trafficking between the cytosol and the nucleus. Maintaining nuclear envelope integrity during interphase is considered crucial. However, Raab et al. and Denais et al. show that migrating immune ... | 10.1038/s41580-022-00480-z | Together with the work by Raab et al. (ref. 75) , this is the first report of migration-induced nuclear envelope rupture and DNA damage, while also identifying a role of ESCRT proteins in interphase nuclear envelope resealing |
10.1126/science.1240104 | 38,253,167 | Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elastic... | 10.1038/s41580-022-00480-z | Detailed proteomic analysis linking higher levels of lamins A/C (and collagen) to cells residing in stiff tissues, suggesting a mechano-adaptive role of lamin A/C expression |
10.1083/jcb.201210152 | 62,136,716 | Cell migration through 3D tissue depends on a physicochemical balance between cell deformability and physical tissue constraints. Migration rates are further governed by the capacity to degrade ECM by proteolytic enzymes, particularly matrix metalloproteinases (MMPs), and integrin- and actomyosin-mediated mechanocoupli... | 10.1038/s41580-022-00480-z | This study demonstrates that nuclear deformability presents a rate-limiting factor in the ability of cells to migrate through constrictions smaller than ~10% of the undeformed nuclear cross-section |
10.1126/science.aba2644 | 103,677,977 | The physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within tissues remains largely unknown. Here, using a zebrafish model, we show that the nucleus, the b... | 10.1038/s41580-022-00480-z | As presented in work by Lomakin et al. (ref. 17) , it was shown that the nuclear envelope provides a gauge of cell deformation and activates a mechanotransduction pathway that controls actomyosin contractility via mechanically induced recruitment of cPLA2 to the INM |
10.1038/s41467-021-24849-4 | 130,830,512 | Abstract Mutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3–4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LIN... | 10.1038/s41580-022-00480-z | First report showing that LINC complex disruption can improve disease progression in a laminopathy mouse model of dilated cardiomyopathy |
10.1083/jcb.201308029 | 41,473,300 | Cell migration through solid tissue often involves large contortions of the nucleus, but biological significance is largely unclear. The nucleoskeletal protein lamin-A varies both within and between cell types and was shown here to contribute to cell sorting and survival in migration through constraining micropores. La... | 10.1038/s41580-022-00480-z | Study demonstrating that increased nuclear deformability caused by reduced lamin A/C expression enhances cell migration through confined environments but renders cells more susceptible to mechanically induced damage and cell death |
10.1083/jcb.200509124 | 104,114,883 | The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmi... | 10.1038/s41580-022-00480-z | First description of the LINC complex and its role in connecting the cytoskeleton and nuclear interior |
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