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10.3389/fendo.2021.618213 | 42,325,282 | Type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) are the most frequent chronic autoimmune diseases worldwide. Several autoimmune endocrine and non-endocrine disorders tend to occur together. T1D and AITD often cluster in individuals and families, seen in the formation of autoimmune polyendocrinopathy (AP). T... | 10.1038/s41574-022-00653-y | This article is a review of autoimmune polyendocrine syndrome type 3 genetic risk loci, many of which are shared with isolated AAD and the closely clinically related autoimmune polyendocrine syndrome type 2 |
10.1073/pnas.1432869100 | 41,473,540 | The renin–angiotensin system plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. Besides angiotensin (Ang) II, other Ang peptides, such as Ang III [Ang-(2–8)], Ang IV [Ang-(3–8)], and Ang-(1–7) may also have important biological activities. Ang-(1–7) has become an angiotensin of ... | 10.1038/s41569-019-0244-8 | This study shows that angiotensin 1–7 binds to the Mas receptor |
10.1038/icb.1966.34 | 77,736,932 | Summary In McKenzie's modification of Adams' and Purves' bioassay method for thyrotrophin and long‐acting thyroid stimulator serum samples from euthyroid people may elicit significant responses. These responses have a time course which differs from those of long‐acting thyroid stimulator and thyrotrophin. Unlike long‐a... | 10.1038/s41572-020-0184-y | This is the first short report describing TSHR antibodies as long-acting thyroid stimulators. The author later injected serum from patients with GD into himself and his colleagues to show the presence of stimulating activity |
10.1530/eje-07-0450 | 125,284,396 | Introduction Autoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism. Objective To compare the effects of the common types of therapy for Graves' hyperthyroidism on TSH-receptor autoimmunity. Methods Patients with ... | 10.1038/s41572-020-0184-y | This is an important study showing that TSHR autoantibodies disappear most rapidly after surgery and quite quickly with antithyroid drugs but take a long time to fall after radioiodine therapy |
10.4049/jimmunol.1500126 | 118,496,336 | Abstract Abs that stimulate the thyrotropin receptor (TSHR), the cause of Graves’ hyperthyroidism, only develop in humans. TSHR Abs can be induced in mice by immunization, but studying pathogenesis and therapeutic intervention requires a model without immunization. Spontaneous, iodine-accelerated, thyroid autoimmunity ... | 10.1038/s41572-020-0184-y | This paper reports the first mouse model to develop spontaneous autoimmune hyperthyroidism |
10.1111/j.1365-2265.1995.tb01894.x | 62,366,605 | Summary BACKGROUND AND OBJECTIVE The original Whlckham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty‐year follow‐up survey was to determine the Incidence and natural his... | 10.1038/s41572-020-0184-y | This paper is the follow-up to the classic epidemiological study of autoimmune thyroid disease in a defined community |
10.4049/jimmunol.168.6.2789 | 99,541,755 | Abstract In this work we report a novel method to efficiently induce a murine model of Graves’ hyperthyroidism. Inbred mice of different strains were immunized by i.m. injection with adenovirus expressing thyrotropin receptor (TSHR) or β-galactosidase (1 × 1011 particles/mouse, three times at 3-wk intervals) and follow... | 10.1038/s41572-020-0184-y | This study describes the current classic approach to murine hyperthyroidism, that is, immunization with most of the TSHR ectodomain |
10.1093/poq/nfab018 | 2,328,879 | Abstract People’s activities and opinions recorded as digital traces online, especially on social media and other web-based platforms, offer increasingly informative pictures of the public. They promise to allow inferences about populations beyond the users of the platforms on which the traces are recorded, representin... | 10.1038/s41586-021-03666-1 | This paper gives a systematic overview of errors that may be introduced when analysing digital traces of human behavior |
10.1177/0049124117729703 | 39,233,177 | This article proposes a three-step methodological framework called computational grounded theory, which combines expert human knowledge and hermeneutic skills with the processing power and pattern recognition of computers, producing a more methodologically rigorous but interpretive approach to content analysis. The fir... | 10.1038/s41586-021-03666-1 | This paper proposes a methodological framework to combine expert human knowledge and hermeneutic skills with the processing power and pattern recognition of computers |
10.1126/science.1188302 | 83,477,929 | Just Breathe Design of artificial systems that mimic in vivo organs could provide a better alternative for understanding mechanisms underlying physiological responses than current cell-based models or animal tests. Huh et al. (p. 1662 ) have created a tissue-tissue interface of human-cultured epithelial cells and endot... | 10.1038/s41467-020-20052-z | This paper laid the foundation of the organ-on-a-chip research field. |
10.1093/geroni/igab046.1588 | 127,460,748 | Abstract Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully d... | 10.1038/s41576-022-00477-6 | This paper performs a multi-tissue, multispecies EWAS of differential methylation and age from more than 59 tissue types and 128 mammalian species. The identification of age-associated DMPs that are shared between tissues and mammalian species is suggestive of a universal, evolutionarily conserved ageing mechanism that... |
10.1126/sciadv.abg6082 | 59,269,760 | The notion that the germ line does not age goes back to the 19th-century ideas of August Weismann. However, being metabolically active, the germ line accumulates damage and other changes over time, i.e., it ages. For new life to begin in the same young state, the germ line must be rejuvenated in the offspring. Here, we... | 10.1038/s41576-022-00477-6 | This paper applies epigenetic clocks to track the precise changes in biological age during the early stages of prenatal development in mice and humans. The work demonstrates that there is a rejuvenation event during embryogenesis where biological age is reset to zero, which marks the beginning of organismal ageing |
10.1177/1535370220918329 | 55,423,915 | It has been noted for quite some time that DNA methylation levels decline with age. The significance of this change remained unknown until it became possible to measure methylation status of specific sites on the DNA. It was observed that while the methylation of some sites does indeed decrease with age, that of others... | 10.1038/s41576-022-00477-6 | This perspective piece proposes a mechanistic understanding of the biological phenomenon underpinning the epigenetic clock |
10.1038/s41467-018-03073-7 | 60,048,649 | Abstract Circadian rhythmicity governs a remarkable array of fundamental biological functions and is mediated by cyclical transcriptomic and proteomic activities. Epigenetic factors are also involved in this circadian machinery; however, despite extensive efforts, detection and characterization of circadian cytosine mo... | 10.1038/s41576-022-00477-6 | This paper demonstrates that CpGs in liver and lung tissues in mice exhibit circadian oscillations, which precede age-related changes in DNAm. The work also shows that the amplitudes of oscillating CpGs are highly correlated with linear age-dependent DNAm changes |
10.1111/jnc.13037 | 124,901,726 | Abstract The clinical symptoms of Alzheimer disease ( AD ) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been... | 10.1038/s41583-019-0132-6 | This paper contains the first report of mTORC1 activation and consequent markers of insulin resistance and inhibition of autophagy in brains of subjects with aMCI, consistent with the notion that mTORC1 activation occurs well before dementia in the progression of AD and reflects glucose dysmetabolism early in the disea... |
10.1042/bj20151227 | 82,890,263 | Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted ... | 10.1038/s41583-019-0132-6 | This article provides a very good account of the mechanisms and consequences of oxidative protein damage |
10.1126/science.abj4008 | 132,949,598 | Regulation of cytokine production in stimulated T cells can be disrupted in autoimmunity, immunodeficiencies, and cancer. Systematic discovery of stimulation-dependent cytokine regulators requires both loss-of-function and gain-of-function studies, which have been challenging in primary human cells. We now report genom... | 10.1038/s41577-022-00802-4 | This study conducted comprehensive bulk and single-cell CRISPR screens in primary human T cells for regulators of cytokine production |
10.1126/science.aat5030 | 38,435,608 | During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8 + T cells by Batf3- dependent CD8α + /XCR1 + classical dendritic cells (cDC1s). We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain–containing protei... | 10.1038/s41577-022-00802-4 | This study reports an intercellular CRISPR screening platform through a DC–T cell co-culture that enables identification of novel regulators of antigen cross-presentation |
10.1038/s41467-019-09656-2 | 104,224,981 | Abstract Therapies that target the function of immune cells have significant clinical efficacy in diseases such as cancer and autoimmunity. Although functional genomics has accelerated therapeutic target discovery in cancer, its use in primary immune cells is limited because vector delivery is inefficient and can pertu... | 10.1038/s41577-022-00802-4 | This study developed a novel tool for in vivo CRISPR screening (CHIME) using bone marrow cells from Cas9-expressing mice to identify regulators of immune cell homeostasis |
10.1126/science.abg5784 | 134,645,935 | Defining tumor cell immune evasion Mouse models used to study cancer often lack a full immune system, allowing implantation of human tumors into the mice. By contrast, naturally evolving tumors must contend with a fully functional immune system and its destruction of some of the cells (see the Perspective by Ho and Woo... | 10.1038/s41577-022-00802-4 | This study conducted in vivo CRISPR screening in multiple tissue-derived tumour cell lines with or without adaptive immune pressure, showing that cancer is largely driven by tumour immune evasion |
10.1111/febs.14263 | 124,119,246 | Host‐defense peptides (HDPs) feature evolution‐tested potency against life‐threatening pathogens. While piscidin 1 (p1) and piscidin 3 (p3) are homologous and potent fish HDPs, only p1 is strongly membranolytic. Here, we hypothesize that another mechanism imparts p3 strong potency. We demonstrate that the N‐termini of ... | 10.1038/s41579-021-00585-w | This study identifies the host defence peptide piscidin 3 as more active than piscidin 1 in the host milieu as nuclease exposure improves its biofilm-directed effects |
10.1038/s41598-018-19669-4 | 123,446,609 | Abstract Biofilms represent a multicellular growth state of bacteria that are intrinsically resistant to conventional antibiotics. It was recently shown that a synthetic immunomodulatory cationic peptide, 1018 (VRLIVAVRIWRR-NH 2 ), exhibits broad-spectrum antibiofilm activity but the sequence determinants of antibiofil... | 10.1038/s41579-021-00585-w | This study describes a method for screening peptide libraries for antibiofilm activity and developing quantitative structure–activity relationship models for further optimization of screened peptides |
10.1126/sciadv.abc1828 | 80,127,603 | Chronic suppurative otitis media (CSOM) is a neglected pediatric disease affecting 330 million worldwide for which no new drugs have been introduced for over a decade. We developed a mouse model with utility in preclinical drug evaluation and antimicrobial discovery. Our model used immune-competent mice, tympanic membr... | 10.1038/s41579-021-00585-w | This study describes a clinically relevant model of chronic suppurative otitis media (ear infection) and shows the importance of monitoring for recurrent infection when determining therapeutic efficacy |
10.1126/science.aal3573 | 123,199,486 | Synergy between copper and zinc oxide on a catalyst surface facilitates methanol synthesis via CO 2 hydrogenation. | 10.1038/s41570-021-00289-y | This article focuses on the elucidation of the active sites for CH 3 OH synthesis from CO 2 using traditional Cu/ZnO catalysts |
10.1083/jcb.201711042 | 102,010,101 | Tight junctions (TJs) are essential cell adhesion structures that act as a barrier to separate the internal milieu from the external environment in multicellular organisms. Although their major constituents have been identified, it is unknown how the formation of TJs is regulated. TJ formation depends on the preceding ... | 10.1038/s41580-020-00298-7 | This study finds that cholesterol is enriched at tight junction membranes and, surprisingly, that the lipid compositional bias is not regulated by the tight junction but by the neighbouring adherens junction |
10.1126/science.aan2556 | 45,486,040 | Making the right catch Tension reveals cryptic vinculin-binding sites on α-catenin and talin at cadherin-based cell-cell and integrin-based cell-matrix adhesions, respectively. The enrichment of vinculin at cellular adhesions is thus an indicator of load-induced reinforcement of the cytoskeletal linkage. Huang et al. u... | 10.1038/s41580-020-00298-7 | This study uses the state-of-the-art optical tweezer to show that vinculin exhibits catch bond behaviour towards F-actin |
10.1073/pnas.0811350106 | 59,520,461 | The cadherin family of Ca 2+ -dependent cell adhesion proteins are critical for the morphogenesis and functional organization of tissues in multicellular organisms, but the molecular interactions between cadherins that are at the core of cell–cell adhesion are a matter of considerable debate. A widely-accepted model is... | 10.1038/s41580-020-00298-7 | This paper finds that the X-dimer conformation forms catch bonds in the presence of calcium, whereas the strand–swap dimer forms slip bonds, effectively allowing E-cadherin to increase affinity above the weak trans interaction observed in solution |
10.1083/jcb.201406135 | 59,109,502 | Cell–cell contact formation is a dynamic process requiring the coordination of cadherin-based cell–cell adhesion and integrin-based cell migration. A genome-wide RNA interference screen for proteins required specifically for cadherin-dependent cell–cell adhesion identified an Elmo–Dock complex. This was unexpected as E... | 10.1038/s41580-020-00298-7 | This study uses genome-wide RNAi screening to find that the ELMO–DOCK complex promotes formation of cadherin-based cell–cell contacts by locally regulating actin assembly |
10.1126/science.1234781 | 102,574,380 | To Fuse or Not to Fuse? Cell-cell fusion is poorly understood, although we know that in the nematode, Caenorhabditis elegans , it involves cell-surface fusogens and in the fly, Drosophila , the actin cytoskeleton plays a role. Shilagardi et al. (p. 359 ) reconstituted a high-efficiency, inducible cell-fusion culture sy... | 10.1038/s41580-020-00298-7 | This work demonstrates that the fusogenic interface consists of two main adhesion proteins, Sns and Duf, that organize actin into podosome-like protrusive structures and thin sheaths of actin beneath the membrane, respectively |
10.1126/science.aad9964 | 125,065,878 | Phase separation organizes signaling In T cell receptors, signaling molecules reorganize into tiny phase-separated droplets—like oil in water. Su et al. used an in vitro system with artificial membranes and 12 components of the T cell receptor signaling system to closely monitor the role of these molecular clusters (se... | 10.1038/s41580-020-00298-7 | This paper shows that purified, phosphorylated LAT of T cells can form a phase-separated cluster in the presence of GRB2 and SOS1, which promotes the MAPK signalling cascade in cells |
10.1126/science.aau5721 | 38,216,459 | The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) is a key Ras activator that is autoinhibited in the cytosol and activates upon membrane recruitment. Autoinhibition release involves structural rearrangements of the protein at the membrane and thus introduces a delay between initial recruitment and ac... | 10.1038/s41580-020-00298-7 | This paper shows that the GEF domain of SOS requires long activation times (~50 s), and a biomolecular condensate, such as that formed between LAT–GRB2–SOS in 2D, extends the dwell times of SOS to release its autoinhibition and allow the protein to achieve full activation of its GEF activity for RAS — a necessary step ... |
10.1126/science.1226132 | 83,125,454 | Forced Asymmetry in Cp The cyclopentadienyl (Cp) ligand—a pentagon of carbons—is a common feature in transition metal catalysts, but chiral variants of the structure have rarely been applied to asymmetric reactions. Two studies now demonstrate distinct approaches to rendering a Cp-derived rhodium catalyst enantioselect... | 10.1038/s41586-022-04456-z | Demonstration that transition metal complexes embedded in protein hosts can work in synergy with amino acid side chains to accelerate a challenging C–H activation process |
10.1126/science.aat8474 | 122,907,200 | Multielectron redox reactions often require multicofactor metalloenzymes to facilitate coupled electron and proton movement, but it is challenging to design artificial enzymes to catalyze these important reactions, owing to their structural and functional complexity. We report a designed heteronuclear heme-[4Fe-4S] cof... | 10.1038/s41586-022-04456-z | This study shows how the introduction of new functional elements into metalloproteins can generate artificial enzymes for challenging chemical tranformations that have thus far eluded synthetic catalysts |
10.1126/science.aau3744 | 104,288,854 | Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biog... | 10.1038/s41586-022-04456-z | This study uses a combination of design and evolution to transform a designed zinc-binding peptide into a globular metalloenzyme that accelerates ester hydrolysis with high efficiency |
10.1126/science.1190239 | 123,029,715 | Biocatalytic Boost Enzymes tend to direct reactions toward specific products much more selectively than synthetic catalysts. Unfortunately, this selectivity has evolved for cellular purposes and may not promote the sorts of reactions chemists are seeking to enhance (see the Perspective by Lutz ). Siegel et al. (p. 309 ... | 10.1038/s41586-022-04456-z | Computational design and experimental characterization of enzymes catalysing a bimolecular Diels–Alder reaction, an important carbon–carbon bond-forming process |
10.1126/science.abj8754 | 83,474,088 | DeepMind presented remarkably accurate predictions at the recent CASP14 protein structure prediction assessment conference. We explored network architectures incorporating related ideas and obtained the best performance with a three-track network in which information at the 1D sequence level, the 2D distance map level,... | 10.1038/s41586-022-04456-z | Development of RoseTTAFold, a freely available deep learning programme for fast and accurate prediction of protein structure |
10.1038/ncomms13090 | 62,449,345 | Abstract A significant obstacle in training predictive cell models is the lack of integrated data sources. We develop semi-supervised normalization pipelines and perform experimental characterization (growth, transcriptional, proteome) to create Ecomics, a consistent, quality-controlled multi-omics compendium for Esche... | 10.1038/s41580-019-0108-4 | This study shows how cellular behaviour can be computationally predicted by mathematical modelling combined with omics integration |
10.1073/pnas.1512503112 | 18,395,205 | T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulat... | 10.1038/s41588-022-01107-x | This paper introduces a method for the efficient generation of gene knockouts in primary human T cells using Cas9 ribonucleoproteins. |
10.1126/science.226.4681.1432 | 15,744,325 | Nuclear tracks have been identified in interplanetary dust particles (IDP's) collected from the stratosphere. The presence of tracks unambiguously confirms the extraterrestrial nature of IDP's, and the high track densities (10 10 to 10 11 per square centimeter) suggest an exposure age of approximately 10 4 years within... | 10.1038/s41550-022-01662-7 | This paper reports the detection of tracks in IDPs using TEM methods |
10.1111/maps.13732 | 134,853,051 | Abstract Transmission electron microscope (TEM) imaging techniques combined with focused ion beam sample preparation were used to calibrate the solar energetic particle track production rate in lunar samples. Track density measurements by TEM as a function of depth were obtained from lunar rock 64455 that has a well‐co... | 10.1038/s41550-022-01662-7 | This paper reports the track production rate calibration used to determine IDP exposure ages |
10.1126/science.1241328 | 40,298,600 | Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor... | 10.1038/s41588-022-01183-z | This paper demonstrates that glioblastoma cells can reversibly modulate their EGFR oncogene copy number to develop resistance to treatment, because the oncogene was amplified on ecDNA. |
10.1126/science.aaf9011 | 41,609,411 | A substantial fraction of mutations in human cancer are attributable to random errors occurring during DNA replication. | 10.1038/s41568-019-0143-7 | In this paper, the authors correlate the frequency of stem cell divisions with cancer incidence and conclude that up to two-thirds of mutations are caused by DNA replication errors |
10.1126/scitranslmed.aar7223 | 42,563,554 | Selective mislocalization of E2F7 in head and neck cancers drives anthracycline resistance and can be reversed. | 10.1038/s41568-019-0143-7 | This study shows that E2F7 is frequently excluded from the nucleus in multiple cancer types, and in head and neck cancer, this localization pattern decreases the effectiveness of chemotherapy |
10.1126/science.aan5780 | 62,154,069 | Integrating glucose and fat Consuming too much glucose makes you fat, but it is unclear how this conversion is mediated by the body. Glycolysis links to gene transcription via the essential coenzyme nicotinamide adenine dinucleotide in its oxidized state (NAD + ). Ryu et al. found that compartmentalized NAD + synthesis... | 10.1038/s41589-020-0517-x | This paper details the subcellular compartmentalization of NAD + synthesis and how these nuclear and cytoplasmic NAD + pools regulate adipogenic transcriptional programs |
10.1073/pnas.1802901115 | 42,592,441 | Histone posttranslational modifications (PTMs) regulate chromatin dynamics, DNA accessibility, and transcription to expand the genetic code. Many of these PTMs are produced through cellular metabolism to offer both feedback and feedforward regulation. Herein we describe the existence of Lys and Arg modifications on his... | 10.1038/s41589-020-0517-x | This paper and ref. 53 characterize glycation as an abundant histone PTM modulated by glycolytic activity and regulated by the enzymes GLO-1 and DJ-1. |
10.1038/s41467-019-09192-z | 81,582,296 | Abstract Cellular proteins continuously undergo non-enzymatic covalent modifications (NECMs) that accumulate under normal physiological conditions and are stimulated by changes in the cellular microenvironment. Glycation, the hallmark of diabetes, is a prevalent NECM associated with an array of pathologies. Histone pro... | 10.1038/s41589-020-0517-x | This paper and ref. 24 characterize glycation as an abundant histone PTM modulated by glycolytic activity and regulated by the enzymes GLO-1 and DJ-1 |
10.1038/s41467-018-05749-6 | 103,682,666 | Abstract Various types of structures self-organised by animals exist in nature, such as bird flocks and insect swarms, which stem from the local communications of vast numbers of limited individuals. Through the designing of algorithms and wireless communication, robotic systems can emulate some complex swarm structure... | 10.1038/s41586-021-03453-y | This article demonstrates how paramagnetic nanoparticles self-organize in a microswarm that can pass obstacles and how its locomotion can be controlled by applying oscillating magnetic fields |
10.1002/adfm.201905911 | 39,482,405 | Abstract DNA nanotechnology is developed for decades to construct dynamic responsive systems in optics, quantum electronics, and therapeutics. While DNA nanotechnology is a powerful tool in nanomaterials, it is rare to see successful applications of DNA molecules in the macroscopic regime of material sciences. Here, a ... | 10.1038/s41586-021-03453-y | This article shows impressively how to translate nanometre-scale DNA self-assembly into macroscopic movements of soft materials, an encouraging achievement for soft robotics |
10.1002/adma.201801114 | 83,029,968 | Abstract Robots that can move, feel, and respond like organisms will bring revolutionary impact to today's technologies. Soft robots with organism‐like adaptive bodies have shown great potential in vast robot–human and robot–environment applications. Developing skin‐like sensory devices allows them to naturally sense a... | 10.1038/s41586-021-03453-y | This work presents soft robots driven by self-generated electricity via the triboelectric effect, which can sense and embrace close objects |
10.1126/science.aat2975 | 104,305,771 | Self-healing materials are notable for their ability to recover from physical or chemical damage. We report that commodity copolymers, such as poly(methyl methacrylate)/n-butyl acrylate [p(MMA/nBA)] and their derivatives, can self-heal upon mechanical damage. This behavior occurs in a narrow compositional range for cop... | 10.1038/s41586-021-03453-y | A remarkable example for an advanced soft material with self-healing capabilities |
10.1126/scirobotics.aaw6060 | 125,189,448 | Despite the growing interest in soft robotics, little attention has been paid to the development of soft matter computational mechanisms. Embedding computation directly into soft materials is not only necessary for the next generation of fully soft robots but also for smart materials to move beyond stimulus-response re... | 10.1038/s41586-021-03453-y | The authors propose a computational system integrated into a soft material, which, inspired by biological systems, tranfers information via a fluid perfusing through the system |
10.1126/sciadv.1700160 | 20,683,702 | An on-chip photonic device mimics the function of synaptic connections between neurons. | 10.1038/s41586-021-03453-y | This article shows an artificial synapse consisting of a photonic waveguide and a phase-change material, which paves the way for on-chip neuromorphic computing |
10.1073/pnas.1501064112 | 62,245,484 | The first stages of productive bacteriophage infections of bacterial host cells require efficient adsorption to the cell surface followed by ejection of phage DNA into the host cytoplasm. To achieve this goal, a phage virion must undergo significant structural remodeling. For phage T4, the most obvious change is the co... | 10.1038/s41579-018-0070-8 | This study analyses cryo-electron microscopic images of phage T4 at different stages of infection to reveal that, contrary to common descriptions, most long tail fibres are folded back against the virion before infection |
10.1073/pnas.1607966113 | 114,228,479 | Contractile phage tails are powerful cell puncturing nanomachines that have been co-opted by bacteria for self-defense against both bacteria and eukaryotic cells. The tail of phage T4 has long served as the paradigm for understanding contractile tail-like systems despite its greater complexity compared with other contr... | 10.1038/s41579-018-0070-8 | This study defines the assembly pathway of the phage Mu baseplate and demonstrates that Mu-like, simple baseplates are conserved in prophages and are the most likely evolutionary precursors of contractile, tail-derived bacterial apparatuses, such as the T6SS |
10.1107/s1399004714002685 | 104,389,884 | Attachment of phages to host cells, followed by phage DNA ejection, represents the first stage of viral infection of bacteria. Salmonella phage P22 has been extensively studied, serving as an experimental model for bacterial infection by phages. P22 engages bacteria by binding to the sugar moiety of lipopolysaccharides... | 10.1038/s41579-018-0070-8 | This study resolves the crystal structure of the phage P22 tail spike by making a single amino-acid exchange in the linker sequence between the particle binding domain and the receptor binding domain of the protein. It also suggests a role of the linker in signal transmission from the distal tip of the tail spike to th... |
10.1146/annurev-virology-101416-041632 | 39,250,475 | Many dsDNA bacterial viruses (bacteriophages/phages) have long tail structures that serve as organelles for DNA delivery to host targets. These structures, particularly those of Myoviridae and Siphoviridae phages, have an evolutionary relationship with other cellular biological entities that share the common function o... | 10.1038/s41579-018-0070-8 | This review provides a comprehensive overview of the function, structure and engineering of antibacterial tailocins that are released by cell lysis |
10.1128/aem.00141-08 | 101,110,901 | ABSTRACT R-type pyocins are high-molecular-weight bacteriocins that resemble bacteriophage tail structures and are produced by some Pseudomonas aeruginosa strains. R-type pyocins kill by dissipating the bacterial membrane potential after binding. The high-potency, single-hit bactericidal kinetics of R-type pyocins sugg... | 10.1038/s41579-018-0070-8 | This innovative paper describes how the host range of R-type pyocins can be reprogrammed by replacing parts of the tail fibres between phages with different host ranges |
10.1126/science.abg2533 | 60,837,422 | Transmission electron microscopes use electrons with wavelengths of a few picometers, potentially capable of imaging individual atoms in solids at a resolution ultimately set by the intrinsic size of an atom. However, owing to lens aberrations and multiple scattering of electrons in the sample, the image resolution is ... | 10.1038/s41592-022-01587-z | This paper reports one of the highest resolutions obtained by EM to date, sub-0.5 Å, using STEM methods. |
10.1038/s41467-020-16531-y | 81,831,132 | Abstract Porous metal-organic frameworks (MOFs) have shown wide applications in catalysis, gas storage and separation due to their highly tunable porosity, connectivity and local structures. However, the electron-beam sensitivity of MOFs makes it difficult to achieve the atomic imaging of their bulk and local structure... | 10.1038/s41592-022-01587-z | This article demonstrates atomic resolution on a beam-sensitive metal–organic framework using the iDPC-STEM technique at cryo-compatible doses of 40 e– Å–2. |
10.1093/oso/9780198844402.001.0001 | 80,520,486 | Programmable Integrated Photonics (PIP) is a new paradigm that aims at designing common integrated optical hardware configurations, which by suitable programming can implement a variety of functionalities that, in turn, can be exploited as basic operations in many application fields. Programmability enables by means of... | 10.1038/s41586-020-2764-0 | The first book on the subject of programmable photonics gives a detailed overview of the fundamental principles, architectures and potential applications |
10.1515/nanoph-2017-0077 | 32,014,793 | Abstract Integrated optical signal processors have been identified as a powerful engine for optical processing of microwave signals. They enable wideband and stable signal processing operations on miniaturized chips with ultimate control precision. As a promising application, such processors enables photonic implementa... | 10.1038/s41586-020-2764-0 | A comprehensive overview of the various ways in which a programmable photonic circuit can be used to process microwave signals, and on how this type of circuit is transitioning from custom ASPICs to generic programmable PICs |
10.1038/lsa.2017.110 | 18,863,698 | Abstract Propagation of light beams through scattering or multimode systems may lead to the randomization of the spatial coherence of the light. Although information is not lost, its recovery requires a coherent interferometric reconstruction of the original signals, which have been scrambled into the modes of the scat... | 10.1038/s41586-020-2764-0 | Early demonstration of a forward-only programmable mesh used to unmix different modes in a waveguide, implementing integrated transparent detectors that measure the light intensity in the waveguide without inducing additional optical loss |
10.1038/s41467-017-00714-1 | 60,826,200 | Abstract Integrated photonics changes the scaling laws of information and communication systems offering architectural choices that combine photonics with electronics to optimize performance, power, footprint, and cost. Application-specific photonic integrated circuits, where particular circuits/chips are designed to o... | 10.1038/s41586-020-2764-0 | The first experimental demonstration of a recirculating waveguide mesh with seven unit cells that can be programmed to perform more than a hundred different functions |
10.1186/1471-2407-12-421 | 20,793,353 | Abstract Background Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour p... | 10.1038/s41568-020-00299-w | This early work shows that hypoxia, at least partly via the transcription factor hypoxia-inducible factor 1α, increases sEV secretion by breast cancer cells, identifying extracellular stress as a regulator of sEV abundance |
10.1038/s41467-019-13316-w | 123,295,667 | Abstract There are disease-causing biohazards in the blood that cannot be treated with modern medicines. Here we show that an intelligently designed safe biomaterial can precisely identify, tow and dump a targeted biohazard from the blood into the small intestine. Positively charged mesoporous silica nanoparticles (MSN... | 10.1038/s41568-020-00299-w | In this article, the capacity of selectively ablating cancer-derived EVs by charged mesoporous silica nanoparticles functionalized with EGFR-targeting aptamers is demonstrated in animal models and blood of patients with lung cancer |
10.1038/s41467-019-12321-3 | 20,764,830 | Abstract Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. Moreover, CAR-T cells ... | 10.1038/s41568-020-00299-w | This work in preclinical models shows that EVs derived from CAR T cells contain CAR and have similar anticancer efficacies to CAR T cells but cannot be inhibited by PD1 |
10.1523/jneurosci.4249-08.2009 | 41,749,420 | After brain damage such as stroke, topographically organized sensory and motor cortical representations remap onto adjacent surviving tissues. It is conceivable that cortical remapping is accomplished by changes in the temporal precision of sensory processing and regional connectivity in the cortex. To understand how t... | 10.1038/s41583-020-00396-7 | This study reports reorganization of limb representations in the motor cortex following stroke |
10.1523/jneurosci.4295-06.2007 | 123,179,587 | Recovery of function after stroke is thought to be dependent on the reorganization of adjacent, surviving areas of the brain. Macroscopic imaging studies (functional magnetic resonance imaging, optical imaging) have shown that peri-infarct regions adopt new functional roles to compensate for damage caused by stroke. To... | 10.1038/s41583-020-00396-7 | This study provides evidence for dendritic spine turnover after stroke |
10.1177/1545968315624783 | 59,048,399 | Background and objective. Prior studies have suggested that after stroke there is a time-limited period of increased responsiveness to training as a result of heightened plasticity—a sensitive period thought to be induced by ischemia itself. Using a mouse model, we have previously shown that most training-associated re... | 10.1038/s41583-020-00396-7 | This study provides evidence for the existence of a sensitive period after stroke |
10.1038/s41467-017-01090-6 | 79,841,890 | Abstract Current neuromodulatory strategies to enhance motor recovery after stroke often target large brain areas non-specifically and without sufficient understanding of their interaction with internal repair mechanisms. Here we developed a novel therapeutic approach by specifically activating corticospinal circuitry ... | 10.1038/s41583-020-00396-7 | This study shows that optogenetic silencing of corticospinal neurons that have sprouted new connections after stroke impairs motor function that was regained |
10.1038/s41467-018-04445-9 | 82,262,976 | Abstract Treatments that stimulate neuronal excitability enhance motor performance after stroke. cAMP-response-element binding protein (CREB) is a transcription factor that plays a key role in neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool of motor neurons enhances motor recove... | 10.1038/s41583-020-00396-7 | This study shows that overexpression of CREB improves motor function, presumably through neuronal allocation |
10.1126/science.aaw4325 | 20,648,182 | In 1904, Richard Semon introduced the term “engram” to describe the neural substrate for storing memories. An experience, Semon proposed, activates a subset of cells that undergo off-line, persistent chemical and/or physical changes to become an engram. Subsequent reactivation of this engram induces memory retrieval. A... | 10.1038/s41583-020-00396-7 | This paper is a thorough review of memory engrams during normal learning |
10.1177/1545968315604400 | 121,818,554 | Novel molecular, cellular, and pharmacological therapies to stimulate repair of sensorimotor circuits after stroke are entering clinical trials. Compared with acute neuroprotection and thrombolysis studies, clinical trials for repair in subacute and chronic hemiplegic participants have a different time course for deliv... | 10.1038/s41583-020-00396-7 | This report presents discussions on the design of neural repair trials in stroke research |
10.1038/srep35230 | 89,951,866 | Abstract The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cell... | 10.1038/s41575-018-0033-6 | This is an overview of imaging techniques to monitor HCC in mice |
10.1126/science.3865369 | 62,209,804 | In an attempt to establish a model of the healthy carrier state in hepatitis B virus (HBV) infections, transgenic mice expressing HBV genes were produced. Fertilized one-cell eggs were microinjected with subgenomic fragments of HBV DNA containing the coding regions for the HBV surface antigen (HBsAg) and pre-S and X an... | 10.1038/s41575-018-0033-6 | This is the first design and description of a mouse model to study hepatitis B infection |
10.1038/s41586-021-03362-0 | 62,591,231 | Abstract Hepatocellular carcinoma (HCC) can have viral or non-viral causes 1–5 . Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need 6,7 . Here we report the ... | 10.1038/s41568-021-00383-9 | This paper supports stratifying patients with HCC according to their underlying aetiology, before using immunotherapy as a main or adjuvant treatment |
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/s41576-021-00370-8 | This article is an exemplary application of integrating multiplexed ISH with scRNA-seq to reveal the spatial organization and circuitry of neuronal subpopulations pertinent to social behaviours at a single-cell resolution |
10.1126/science.aad0501 | 104,265,171 | Single-cell expression profiles of melanoma Tumors harbor multiple cell types that are thought to play a role in the development of resistance to drug treatments. Tirosh et al. used single-cell sequencing to investigate the distribution of these differing genetic profiles within melanomas. Many cells harbored heterogen... | 10.1038/s41576-021-00370-8 | This study exemplifies how scRNA-seq can be wielded to characterize single cells beyond the cell subtype |
10.1093/nar/gkab043 | 20,695,475 | Abstract Spatially resolved gene expression profiles are key to understand tissue organization and function. However, spatial transcriptomics (ST) profiling techniques lack single-cell resolution and require a combination with single-cell RNA sequencing (scRNA-seq) information to deconvolute the spatially indexed datas... | 10.1038/s41576-021-00370-8 | This article presents SPOTlight, to date the only deconvolution technique published in a peer-reviewed journal that is tailored towards deconvolving spatial barcoding capture spots through regression. The article also presents a comprehensive strategy for benchmarking emerging deconvolution methods |
10.1038/s42003-020-01247-y | 104,304,446 | Abstract The field of spatial transcriptomics is rapidly expanding, and with it the repertoire of available technologies. However, several of the transcriptome-wide spatial assays do not operate on a single cell level, but rather produce data comprised of contributions from a – potentially heterogeneous – mixture of ce... | 10.1038/s41576-021-00370-8 | This report presents stereoscope, an effective approach for deconvolving spatial barcoding capture spots through probabilistic modelling and one of the few spatial barcoding deconvolution strategies published in a peer-reviewed journal to date |
10.1038/s41467-020-15968-5 | 125,306,283 | Abstract Single-cell RNA sequencing (scRNA-seq) provides details for individual cells; however, crucial spatial information is often lost. We present SpaOTsc, a method relying on structured optimal transport to recover spatial properties of scRNA-seq data by utilizing spatial measurements of a relatively small number o... | 10.1038/s41576-021-00370-8 | This report presents SpaOTsc, one of the few peer-reviewed methods that formally integrate spatial and scRNA-seq data into an algorithm to decode intercellular communication in tissues. SpaOTsc predicts the maximum signalling range for ligand–receptor pairs through a spatial transcriptomic analysis of each ligand–recep... |
10.1093/nar/gkz934 | 73,905,652 | Abstract Spatially resolved transcriptomic techniques allow the characterization of spatial organization of cells in tissues, which revolutionize the studies of tissue function and disease pathology. New strategies for detecting spatial gene expression patterns are emerging, and spatially resolved transcriptomic data a... | 10.1038/s41576-021-00370-8 | This article is one of the first publications describing a database directly geared towards aggregating spatial transcriptomic data |
10.1126/science.aag0804 | 83,508,710 | The current model for industrial chemical manufacturing employs large-scale megafacilities that benefit from economies of unit scale. However, this strategy faces environmental, geographical, political, and economic challenges associated with energy and manufacturing demands. We review how exploiting biological process... | 10.1038/s41560-018-0197-x | This review compares the biomanufacturing and chemical process in regard to economies of unit number, investment scale and financial risk, and proposes that biomanufacturing could play an important role in conversion of single-carbon feedstocks to chemicals and biofuels with rapid adaptation to new and changing markets |
10.1126/science.aad3317 | 125,081,095 | Using light in the darkness Solid-state devices can efficiently capture solar energy to produce chemicals and fuels from carbon dioxide. Yet biology has already developed a high-specificity, low-cost system to do just that through photosynthesis. Sakimoto et al. developed a biological-inorganic hybrid that combines the... | 10.1038/s41560-018-0197-x | A biological–inorganic hybrid, combining inorganic semiconductors and non-photosynthetic bacterium, was developed for highly efficient light harvesting and CO 2 fixation toward acetate production. |
10.2337/dc13-2656 | 81,395,559 | OBJECTIVE We compared South Asians with four other racial/ethnic groups in the U.S. to determine whether sociodemographic, lifestyle, or metabolic factors could explain the higher diabetes prevalence and whether insulin resistance and β-cell dysfunction occurred at younger ages and/or lower adiposity levels compared wi... | 10.1038/s41574-022-00669-4 | An important study conducted in the USA comparing diabetes mellitus prevalence, insulin secretion and insulin resistance across ethnicities |
10.1136/bmjdrc-2020-001988 | 79,583,845 | Introduction South Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels. Research design and methods We used prospective cohort data to estimate age-sp... | 10.1038/s41574-022-00669-4 | An interesting comparison of T2DM incidence, BMI, insulin secretion and insulin resistance in south Asian people living in India and Pakistan compared with the Pima Indian people in the USA |
10.2337/dc05-2179 | 62,350,855 | Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are intermediate states in glucose metabolism that exist between normal glucose tolerance and overt diabetes. Epidemiological studies demonstrate that the two categories describe distinct populations with only partial overlap, suggesting that different... | 10.1038/s41574-022-00669-4 | An informative discussion of the distinct metabolic features of impaired fasting glucose and impaired glucose tolerance |
10.1136/bmj.m997 | 20,633,536 | Abstract Objective To assess the prevalence of diabetes and its risk factors. Design Population based, cross sectional study. Setting 31 provinces in mainland China with nationally representative cross sectional data from 2015 to 2017. Participants 75 880 participants aged 18 and older—a nationally representative sampl... | 10.1038/s41574-022-00669-4 | A national study of the prevalence of diabetes mellitus in China |
10.1152/physrev.00042.2009 | 125,224,992 | Islet amyloid polypeptide (IAPP, or amylin) is one of the major secretory products of β-cells of the pancreatic islets of Langerhans. It is a regulatory peptide with putative function both locally in the islets, where it inhibits insulin and glucagon secretion, and at distant targets. It has binding sites in the brain,... | 10.1038/s41574-022-00669-4 | A highly informative review of the potential role of islet amyloid deposition in T2DM pathogenesis |
10.1136/bmjdrc-2020-001506 | 83,463,199 | Introduction Type 2 diabetes is characterized by considerable heterogeneity in its etiopathogenesis and clinical presentation. We aimed to identify clusters of type 2 diabetes in Asian Indians and to look at the clinical implications and outcomes of this clustering. Research design and methods From a network of 50 diab... | 10.1038/s41574-022-00669-4 | This study is the first to investigate the subgroups of diabetes mellitus in India |
10.1210/clinem/dgaa524 | 100,129,706 | Abstract Context This study applied the Swedish novel data-driven classification in Chinese newly diagnosed diabetic patients and validated its adoptability. Objective This study aimed to validate the practicality of the Swedish diabetes regrouping scheme in Chinese adults with newly diagnosed diabetes. Design Patients... | 10.1038/s41574-022-00669-4 | A large and informative analysis of the subgroups of diabetes mellitus in China |
10.1111/jdi.13262 | 75,261,989 | Abstract Aims/Introduction There are substantial differences in genes, diet, culture and environment between the northern and southern Chinese populations, which might influence treatment strategy and screening policy. We studied the differences in type 2 diabetes and diabetic complications between northern and souther... | 10.1038/s41574-022-00669-4 | An interesting study demonstrating the heterogeneity of T2DM outcomes within China |
10.1002/dmrr.3158 | 104,224,310 | Summary The prevalence of diabetes in China has increased rapidly from 0.67% in 1980 to 10.4% in 2013, with the aging of the population and westernization of lifestyle. Since its foundation in 1991, the Chinese Diabetes Society (CDS) has been dedicated to improving academic exchange and the academic level of diabetes r... | 10.1038/s41574-022-00669-4 | An article that summarizes the standard approaches to the pharmacological management of T2DM recommended in China |
10.1126/science.abe2218 | 59,292,353 | We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of c... | 10.1038/s41477-022-01204-z | This paper reports the function of condensin II in determining 3D chromatin architecture. |
10.1038/s41467-020-19621-z | 107,167,112 | Abstract The nuclear lamina plays an important role in the regulation of chromatin organization and gene positioning in animals. CROWDED NUCLEI (CRWN) is a strong candidate for the plant nuclear lamina protein in Arabidopsis thaliana but its biological function was largely unknown. Here, we show that CRWNs localize at ... | 10.1038/s41477-022-01204-z | This paper reports the subnuclear localization of a plant lamina protein, CROWDED NUCLEI, and its function in gene positioning. |
10.1101/gad.314856.118 | 29,113,296 | Circular RNAs (circRNAs) are generated from many protein-coding genes. Most accumulate in the cytoplasm, but how circRNA localization or nuclear export is controlled remains unclear. Using RNAi screening, we found that depletion of the Drosophila DExH/D-box helicase Hel25E results in nuclear accumulation of long (>8... | 10.1038/s41576-019-0158-7 | This study provides the first data on how circRNAs are exported from the nucleus to the cytoplasm |
10.1073/pnas.1402218111 | 81,312,447 | Significance The family with sequence similarity 20, member C (Fam20C) is a secretory pathway-specific kinase that phosphorylates secreted proteins on Ser-x-Glu/pSer motifs. Mutations in human FAM20C cause a devastating childhood disorder known as Raine syndrome. Some patients with FAM20C mutations as well as Fam20C KO... | 10.1038/s41580-020-00294-x | This paper is the first demonstration of cross-talk between extracellular protein phosphorylation and O-glycosylation |
10.1073/pnas.1804005115 | 103,499,429 | The Notch-signaling pathway is normally activated by Notch–ligand interactions. A recent structural analysis suggested that a novel O -linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands. This serine occurs between conserved cysteines 3 and ... | 10.1038/s41580-020-00294-x | This paper describes the identification and differential functions of POGLUT isoenzymes in glycosylation of NOTCH EGF-like repeats and their regulation of NOTCH functions |
10.1073/pnas.1613165114 | 41,130,310 | Thrombospondin type 1 repeats (TSRs) occur in diverse proteins involved in adhesion and signaling. The two extracellular TSRs of the netrin receptor UNC5A contain WxxWxxWxxC motifs that can be C- mannosylated on all tryptophans. A single C -mannosyltransferase (dumpy-19, DPY-19), modifying the first two tryptophans, oc... | 10.1038/s41580-020-00294-x | This paper describes the DPY19L isoenzymes directing C-mannosylation and identifies distinct differences in their substrate preferences |
10.4049/jimmunol.1402099 | 83,299,210 | Abstract There has been increasing recognition of the importance of cellular metabolism and metabolic substrates for the function and differentiation of immune cells. In this study, for the first time to our knowledge, we investigate the metabolic requirements for production of IFN-γ by freshly isolated NK cells. Prima... | 10.1038/s41577-019-0139-2 | This study shows that acute activation of mouse NK cells does not result in changes in NK cell metabolism and reveals differential requirements for metabolic pathways for the function of cytokine-stimulated versus receptor-stimulated NK cells |
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