source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1073/pnas.1221526110 | 83,277,901 | Angiogenesis is a complex morphogenetic process whereby endothelial cells from existing vessels invade as multicellular sprouts to form new vessels. Here, we have engineered a unique organotypic model of angiogenic sprouting and neovessel formation that originates from preformed artificial vessels fully encapsulated wi... | 10.1038/s41568-018-0104-6 | This paper describes how angiogenic sprouting can be replicated in a microfluidic device and how this model enables the investigation of the effects of angiogenic inhibitors on sprouting morphogenesis |
10.1073/pnas.1417115112 | 62,263,786 | A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasatio... | 10.1038/s41568-018-0104-6 | This study develops a vascularized microfluidic assay to study breast cancer extravasation into different organ microenvironments |
10.1038/srep31589 | 62,262,015 | Abstract There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro . This “organs-on-chips” approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized micro... | 10.1038/s41568-018-0104-6 | This study uses a microfluidic platform with vascularized microtumours to reveal that dual target angiogenesis inhibitors are more effective to regress the vasculature than single target inhibitors |
10.1073/pnas.0806173105 | 20,753,714 | Topical application of phorbol myristate acetate (PMA) elicits intense local inflammation that facilitates outgrowth of premalignant lesions in skin after carcinogen exposure. The inflammatory response to PMA treatment activates immune stimulatory mechanisms. However, we show here that PMA exposure also induces plasmac... | 10.1038/s41568-019-0106-z | This genetic study of IDO establishes its key contributions to formation of a pathogenic inflammatory milieu that is critical for malignant development |
10.1158/0008-5472.can-15-1456 | 102,893,496 | Abstract Cytosolic DNA sensing is an important process during the innate immune response that activates the stimulator of interferon genes (STING) adaptor and induces IFN-I. STING incites spontaneous immunity during immunogenic tumor growth and accordingly, STING agonists induce regression of therapy-resistant tumors. ... | 10.1038/s41568-019-0106-z | This study shows that STING promotes growth of poorly immunogenic tumours by stimulating DCs in TDLNs to express IDO |
10.1158/1078-0432.ccr-05-1966 | 18,937,515 | Abstract PURPOSE: The pathologic interactions between tumor and host immune cells within the tumor microenvironment create an immunosuppressive network that promotes tumor growth and protects the tumor from immune attack. In this study, we examined the contribution of the immunomodulatory enzyme indoleamine 2,3-dioxyge... | 10.1038/s41568-019-0106-z | This is one of the earliest studies to establish that high IDO activity in human tumours tends to associate with a poor prognosis |
10.1182/blood-2006-06-031856 | 123,160,117 | Abstract l-arginine (l-Arg) plays a central role in several biologic systems including the regulation of T-cell function. l-Arg depletion by myeloid-derived suppressor cells producing arginase I is seen in patients with cancer inducing T-cell anergy. We studied how l-Arg starvation could regulate T-cell–cycle progressi... | 10.1038/s41568-019-0106-z | This study links Arg catabolism to blocking T cell entry into cell cycle via a GCN2-dependent mechanism |
10.1084/jem.20130066 | 107,183,919 | The cytotoxic T lymphocyte antigen-4 (CTLA-4)–blocking antibody ipilimumab results in durable responses in metastatic melanoma, though therapeutic benefit has been limited to a fraction of patients. This calls for identification of resistance mechanisms and development of combinatorial strategies. Here, we examine the ... | 10.1038/s41568-019-0106-z | This study suggests that IDO blockade can empower immune checkpoint therapy |
10.1158/0008-5472.can-17-2995 | 82,625,626 | Abstract Host immunity influences the impact of radiotherapy (RT) in cancer, but mechanistic connections remain obscure. In this study, we investigated the relationship of indoleamine 2,3-dioxygenase (IDO) systemic activity on clinical outcomes in RT-treated non–small cell lung cancer (NSCLC). IDO-mediated production o... | 10.1038/s41568-019-0106-z | This study reveals strong correlations between high systemic IDO activity in patients with lung cancer (NSCLC) and poor survival prospects after radiochemotherapy |
10.1155/2016/1851865 | 17,432,634 | The archaeal ancestor scenario (AAS) for the origin of eukaryotes implies the emergence of a new kind of organism from the fusion of ancestral archaeal and bacterial cells. Equipped with this “chimeric” molecular arsenal, the resulting cell would gradually accumulate unique genes and develop the complex molecular machi... | 10.1038/s41576-019-0105-7 | The sources of eukaryotic protein superfold families are analysed and arguments are presented for three cellular domains, in contrast to Zaremba-Niedzwiedzka et al. (2017) |
10.1126/science.aaj1849 | 101,315,564 | Origin of DNA compaction As a repeating unit in eukaryotic chromatin, a nucleosome wraps DNA in superhelical turns around a histone octamer. Mattiroli et al. present the crystal structure of an archaeal histone-DNA complex in which the histone-mediated DNA geometry is exactly the same as that in the nucleosome. Compari... | 10.1038/s41576-019-0105-7 | This paper shows that archaeal histones can form extended polymers that wrap DNA and affect gene regulation |
10.1126/science.aam9702 | 122,341,339 | Packaging without nucleosomes The fundamental compaction of DNA in chromosomes is thought to start with the wrapping of DNA around nucleosomes, but is nucleosome wrapping required for the condensation of mitotic chromosomes? Shintomi et al. combined Xenopus egg extracts and mouse sperm nuclei and found that chromosome-... | 10.1038/s41576-019-0105-7 | The authors show that condensins and topoisomerase II can form chromosome axes without nucleosomes, but nucleosomes are needed for full condensation and to prevent fragility |
10.1038/ncomms12958 | 123,147,744 | Abstract The structure and dynamics of promoter chromatin have a profound effect on the expression levels of genes. Yet, the contribution of DNA sequence, histone post-translational modifications, histone variant usage and other factors in shaping the architecture of chromatin, and the mechanisms by which this architec... | 10.1038/s41576-019-0105-7 | Optical tweezers are used to show that H2A.Z nucleosomes have a lower breaking force than H2A nucleosomes and that positioning of H2A.Z nucleosomes relative to the TSS can lead to distinct regulation strategies |
10.1126/science.aaa3761 | 125,270,712 | Deformation powers the nucleosome slide In eukaryotes, DNA is packed onto nucleosomes. For transcription factors and other proteins to gain access to DNA, nucleosomes must be moved out of the way, or “remodeled”—but not disassembled. Nucleosomes are composed of histone protein octamers, the cores of which have generall... | 10.1038/s41576-019-0105-7 | Deformation of the histone octamer is shown to be required for remodelling activity of the SNF2h remodeller but not INO80, and it reduces nucleosome eviction by RSC. The authors propose that altered nucleosome conformations may be relevant in other processes such as eviction by pioneer factors |
10.1073/pnas.1905057117 | 125,225,984 | Many proteins are refractory to targeting because they lack small-molecule binding pockets. An alternative to drugging these proteins directly is to target the messenger (m)RNA that encodes them, thereby reducing protein levels. We describe such an approach for the difficult-to-target protein α-synuclein encoded by the... | 10.1038/s41573-022-00521-4 | Describes the design of a small molecule that inhibits the translation of the undruggable, intrinsically disordered protein α-synuclein by targeting its mRNA |
10.1038/s41467-019-09493-3 | 41,532,903 | Abstract Riboswitches are naturally occurring RNA aptamers that regulate gene expression by binding to specific small molecules. Riboswitches control the expression of essential bacterial genes and are important models for RNA-small molecule recognition. Here, we report the discovery of a class of synthetic small molec... | 10.1038/s41573-022-00521-4 | An example of how structural studies can enhance the understanding of ligand binding and function, in the context of PreQ1 riboswitch |
10.1073/pnas.2012217117 | 83,070,596 | RNAs have important functions that are dictated by their structure. Indeed, small molecules that interact with RNA structures can perturb function, serving as chemical probes and lead medicines. Here we describe the development of a fragment-based approach to discover and optimize bioactive small molecules targeting RN... | 10.1038/s41573-022-00521-4 | The first application of fully functionalized fragments to the discovery of RNA ligands |
10.1126/sciadv.abl6096 | 130,183,168 | Small-molecule targeting of RNA stem loops in 5′-end of SARS-CoV-2 reveals novel RNA targets for viral inhibition. | 10.1038/s41573-022-00521-4 | Identification of small molecules that inhibit SARS-CoV-2 viral replication by interacting with the 5′UTR of the viral mRNA |
10.1126/science.aau0964 | 125,066,628 | Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within the tissue parenchyma remain poorly defined. Here we studied IMs ... | 10.1038/s41590-022-01217-y | This paper demonstrates that LYVE1 + MHCII − interstitial macrophages are pro-reparative in a model of bleomycin-induced lung damage |
10.1126/science.1229963 | 41,621,469 | DNA Sensing Is a (c)GAS DNA is normally localized to the nucleus, and so its cytoplasmic localization sends off alarm bells to the immune system because it indicates that a virus may have entered. But how does the immune system actually detect the DNA (see the Perspective by O'Neill )? Sun et al. (p. 786 , published on... | 10.1038/s41577-021-00524-z | Together with reference 7, this study identifies cGAS as a cytosolic DNA sensor inducing type I interferon signalling by producing the second messenger cGAMP |
10.1038/s41467-017-00833-9 | 80,134,165 | Abstract Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon binding double-stranded DNA, cyclic GMP-AMP synthase synthesizes a cyclic dinucleotide that initiates an inflammatory cellular response. Mouse... | 10.1038/s41577-021-00524-z | This study identifies the first class of small-molecule inhibitors of cGAS |
10.1126/science.1189138 | 20,488,839 | The continued growth of human populations and of per capita consumption have resulted in unsustainable exploitation of Earth’s biological diversity, exacerbated by climate change, ocean acidification, and other anthropogenic environmental impacts. We argue that effective conservation of biodiversity is essential for hu... | 10.1038/s41564-022-01151-7 | A review article that presents the services and benefits of biodiversity to society |
10.1073/pnas.1516684112 | 62,568,810 | Soil bacteria and fungi play key roles in the functioning of terrestrial ecosystems, yet our understanding of their responses to climate change lags significantly behind that of other organisms. This gap in our understanding is particularly true for drylands, which occupy ∼41% of Earth´s surface, because no global, sys... | 10.1038/s41564-022-01151-7 | This paper reports on the decline of microbial diversity driven by aridity |
10.1126/science.aao1710 | 62,066,160 | SNF'ing out antitumor immunity Immune checkpoint inhibitors induce durable tumor regressions in some, but not all, cancer patients. Understanding the mechanisms that determine tumor sensitivity to these drugs could potentially expand the number of patients who benefit (see the Perspective by Ghorani and Quezada). Pan e... | 10.1038/s41568-022-00442-9 | Together with Manguso et al. (2017) and Patel et al. (2017), this paper describes CRISPR screens that identify tumour-intrinsic mechanisms of resistance to immunotherapy using in vitro co-culture of melanoma cells and tumour-specific T cells |
10.1126/science.aan3706 | 104,442,622 | Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced ... | 10.1038/s41568-022-00442-9 | Together with Gopalakrishnan et al. (2018) and Matson et al. (2018), this paper demonstrates how the diversity and composition of gut microbiome can influence the response to ICIs in melanoma and epithelial tumours. The papers also present mouse models for faecal microbiota transplant |
10.1126/science.abf3363 | 104,250,517 | Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the ... | 10.1038/s41568-022-00442-9 | Together with Baruch et al. (2021), this paper demonstrates clinical benefits to patients with melanoma of faecal microbiota transplantation to overcome ICI resistance |
10.1111/j.1532-5415.2009.02670.x | 100,644,467 | OBJECTIVES: To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical fa... | 10.1038/s41581-020-0266-9 | A study linking lower kidney function with cognitive impairment in older patients with CKD |
10.1126/science.1190287 | 104,341,626 | Antidepressant Action of Ketamine In contrast to the weeks or months of treatment required for standard antidepressant medication, ketamine administration produces an antidepressant response within 4 to 6 hours in depressed patients. What lies behind the rapid actions of ketamine? Li et al. (p. 959 ; see the Perspectiv... | 10.1038/s41583-021-00540-x | This study is among the first to demonstrate the relationship between ketamine’s ability to modulate neuroplasticity, especially through effects on the mTOR pathways and BDNF, and the drug’s antidepressant-like properties |
10.3389/fnbeh.2022.845491 | 127,191,709 | Major depressive disorder (MDD) is amongst the most devastating psychiatric conditions affecting several millions of people worldwide every year. Despite the importance of this disease and its impact on modern societies, still very little is known about the etiological mechanisms. Treatment strategies have stagnated ov... | 10.1038/s41583-021-00540-x | This work presents comprehensive genetic profiling that reveals marked sexual dimorphism at the transcriptional level in depressed humans and stressed mice, highlighting the importance of studying sex-specific treatments for depression |
10.1126/science.1229223 | 83,375,820 | Allostery Across DNA Proteins, such as transcription factors and RNA polymerase, bind close to each other on DNA and their function is coordinated. Kim et al. (p. 816 ; see the Perspective by Crothers ) report single-molecule experiments that show that the DNA binding affinity of a protein is significantly altered by a... | 10.1038/s41477-022-01220-z | This paper reports that the DNA-binding affinity of a protein can be altered by a second DNA-bound protein nearby. |
10.1002/ana.26067 | 83,309,528 | Objective Blood tests to monitor disease activity, attack severity, or treatment impact in neuromyelitis optica spectrum disorder (NMOSD) have not been developed. This study investigated the relationship between serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity and assessed the impact of in... | 10.1038/s41582-021-00616-3 | This study leveraged blood samples from a large multicentre cohort of participants with neuromyelitis optica spectrum disorder and described in detail the dynamics of blood GFAP levels following inflammatory-mediated astrocyte injury |
10.1083/jcb.201202012 | 19,971,550 | The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins—myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans—do not display retinal degeneration. We found here that, in macaque photoreceptor cells, all USH1 proteins colocalize... | 10.1038/s41586-018-0076-4 | Example of the limitations of mice as a disease model. |
10.1038/s41536-019-0079-2 | 58,811,346 | Abstract The lymphatic vasculature mediates essential physiological functions including fluid homeostasis, lipid and hormone transport, and immune cell trafficking. Recent studies have suggested that promoting lymphangiogenesis enhances cardiac repair following injury, but it is unknown whether lymphangiogenesis is req... | 10.1038/s41569-020-00489-x | Together with Gancz et al. (2019) and Harrison et al. (2019), this study shows that cardiac lymphatics are required for complete heart regeneration in adult zebrafish after cryosection injury |
10.1101/gad.1588407 | 41,683,527 | The origin of the mammalian lymphatic vasculature has been debated for more than 100 years. Whether lymphatic endothelial cells have a single or dual, venous or mesenchymal origin remains controversial. To resolve this debate, we performed Cre/loxP -based lineage-tracing studies using mouse strains expressing Cre recom... | 10.1038/s41569-020-00489-x | This study identified the venous origin of the lymphatic vasculature |
10.1073/pnas.1406508111 | 83,485,928 | Significance This study addresses a fundamentally important and widely debated issue in the field of inflammation, which is why inflammation can be simultaneously deleterious after injury and yet is essential for tissue repair. Recently, an important new paradigm has emerged in the macrophage field: Organs are replete ... | 10.1038/s41569-020-00489-x | This study shows that neonatal hearts expand a population of embryonic-derived cardiac resident macrophages after MI, in contrast to adult hearts, which replace this population with monocyte-derived macrophages |
10.1126/science.1200708 | 104,406,757 | The heart in a newborn mouse can rebuild itself after injury, but this regenerative capacity is lost within a few days. | 10.1038/s41569-020-00489-x | This study was the first to demonstrate the cardiac regenerative window in neonatal mice, and the studies by Wang et al. ( Cells , 2020) and Ye et al. (2018) demonstrate the cardiac regenerative window in rats and pigs, respectively |
10.1073/pnas.0906426106 | 123,865,561 | Increases in arousal and activity in anticipation of a meal, termed “food anticipatory activity” (FAA), depend on circadian food-entrainable oscillators (FEOs), whose locations and output signals have long been sought. It is known that ghrelin is secreted in anticipation of a regularly scheduled mealtime. We show here ... | 10.1038/s41575-020-00401-5 | This study demonstrates that ghrelin can modulate food-anticipatory activity and might act as an FEO |
10.1073/pnas.0808180106 | 20,849,944 | There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined ... | 10.1038/s41575-020-00401-5 | This study showed that misalignment between the behavioural rhythm (feeding–fasting and sleep–wake cycles) and the endogenous circadian rhythm decreased leptin, increased glucose despite increased insulin, inverted the daily cortisol rhythm, increased mean arterial pressure and reduced sleep efficiency |
10.1126/science.1222794 | 83,550,382 | Predictions of Genetic Disease Many genome-wide association studies (GWAS) have identified loci and variants associated with disease, but the ability to predict disease on the basis of these genetic variants remains small. Maurano et al. (p. 1190 ; see the Perspective by Schadt and Chang ; see the cover) characterize t... | 10.1038/s41594-022-00896-3 | This study provides evidence of the enrichment of GWAS variants in enhancers with tissue- and developmental-specific chromatin accessibility |
10.1126/science.1160631 | 38,304,971 | Some developmentally important genes can be regulated via two enhancers, one located nearby and the other, a "shadow" enhancer, 10 to 20 kilobases away. | 10.1038/s41594-022-00896-3 | This study demonstrates that developmental genes can be regulated by multiple enhancers, which may provide robustness to enhancer deregulation |
10.1126/science.abj5117 | 132,878,268 | Associations between genetic variation and traits are often in noncoding regions with strong linkage disequilibrium (LD), where a single causal variant is assumed to underlie the association. We applied a massively parallel reporter assay (MPRA) to functionally evaluate genetic variants in high, local LD for independen... | 10.1038/s41594-022-00896-3 | This study systematically assesses the effect of genetic variants on regulatory activity by massive parallel reporter assays leading to the identification of causal variants |
10.1073/pnas.112212199 | 81,876,328 | Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutan... | 10.1038/s41594-022-00896-3 | This study links mutations of an enhancer to dysregulation of the SHH gene resulting in polydactyly |
10.1038/s41467-019-13056-x | 20,879,477 | Abstract Single-cell transcriptomics yields ever growing data sets containing RNA expression levels for thousands of genes from up to millions of cells. Common data analysis pipelines include a dimensionality reduction step for visualising the data in two dimensions, most frequently performed using t-distributed stocha... | 10.1038/s41580-021-00407-0 | This article provides a discussion and tips for using t -SNE as a dimensionality reduction technique on single-cell transcriptomics data |
10.1038/s42256-021-00307-0 | 83,487,993 | Abstract Machine learning methods offer great promise for fast and accurate detection and prognostication of coronavirus disease 2019 (COVID-19) from standard-of-care chest radiographs (CXR) and chest computed tomography (CT) images. Many articles have been published in 2020 describing new machine learning-based models... | 10.1038/s41580-021-00407-0 | This study assesses 62 machine learning studies that analyse medical images for COVID-19 and none is found to be of clinical use, indicating the difficulties of training a useful model |
10.1210/jc.2016-2587 | 80,240,329 | Abstract Context: A substantial proportion of athyreotic levothyroxine (LT4)-treated patients experience hypothyroid-like symptoms. During LT4 replacement, levels of the active hormone triiodothyronine (T3) strictly depend on type 2-deiodinase (D2)-mediated activation of LT4. The Thr92Ala polymorphism and the 258 G/A i... | 10.1038/s41574-019-0218-2 | This study is the first to show, using an alternative method to the classic deiodinase enzymatic assay, that DIO2 Thr92Ala reduces DIO2 activity |
10.2337/diabetes.51.3.880 | 40,702,646 | Thyroid hormone action is an important determinant of energy and glucose metabolism. T4 metabolism is regulated by the deiodinases of which type 2 is expressed in humans in skeletal muscle and brown adipose tissue, where its transcription is stimulated by the β-3 adrenergic pathway. We performed molecular scanning of t... | 10.1038/s41574-019-0218-2 | This work is the first to identify the DIO2 Thr92Ala polymorphism |
10.1210/jc.2008-1301 | 61,474,013 | Abstract Introduction: Animal studies suggest that up to 80% of intracellular T3 in the brain is derived from circulating T4 by local deiodination. We hypothesized that in patients on T4 common variants in the deiodinase genes might influence baseline psychological well-being and any improvement on combined T4/T3 witho... | 10.1038/s41574-019-0218-2 | This is the first paper to demonstrate the potential benefit of the combined levothyroxine and liothyronine treatment |
10.1126/sciimmunol.add5446 | 127,180,580 | SARS-CoV-2 Omicron sub-variants have generated a world-wide health crisis due to resistance to most approved SARS-CoV-2 neutralizing antibodies and evasion of vaccination-induced antibodies. To manage Omicron sub-variants and prepare for potential new variants, additional means of isolating broad and potent humanized S... | 10.1038/s41577-022-00784-3 | This work demonstrates a class 3 mAb, SP1-77, potently neutralizing SARS-CoV-2 by blocking membrane fusion |
10.1126/science.abj3321 | 131,190,414 | Targeting a range of betacoranaviruses In the past 20 years, three highly pathogenic β-coronaviruses have crossed from animals to humans, including the most recent: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A spike protein that decorates these viruses has an S1 domain that binds host cell receptors ... | 10.1038/s41577-022-00784-3 | This study is the first to identify SH-targeting nAbs that can inhibit all beta-CoV subgenera and reduce viral burden in hamsters infected with SARS-CoV-2 |
10.1126/science.abq3773 | 128,017,827 | The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region... | 10.1038/s41577-022-00784-3 | This study is the first to identify FP-targeting nAbs that show broad neutralizing activity against a range of coronaviruses, including Omicron sublineages of SARS-CoV-2 |
10.1038/s41422-022-00612-2 | 127,842,459 | Abstract The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines. Here, we discovered a new STING agonist, CF501, and found that CF501-adjuvanted RBD-Fc vaccine (CF501/RBD-Fc) elicited significantly stronger neutralizing... | 10.1038/s41577-022-00784-3 | This is the first report about the development of a pan-sarbecovirus vaccine based on a novel adjuvant |
10.1136/bmjsem-2019-000596 | 125,328,745 | Background Physical activity recommendations state that for the same energy expenditure, moderate-to-vigorous physical activities (MVPAs) produce similar health benefits. However, few epidemiological studies have tested this hypothesis. Design We examined whether, compared with moderate, vigorous activity was associate... | 10.1038/s41591-022-02101-w | This pooled analysis of 11 population cohorts found that questionnaire-measured long bouts (>15 continuous minutes) of vigorous intensity activity were associated with larger reductions in mortality risk than activities of moderate intensity. |
10.1007/s40279-020-01368-8 | 28,213,775 | Abstract Recently revised public health guidelines acknowledge the health benefits of regular intermittent bouts of vigorous intensity incidental physical activity done as part of daily living, such as carrying shopping bags, walking uphill, and stair climbing. Despite this recognition and the advantages such lifestyle... | 10.1038/s41591-022-02101-w | This paper presented a framework for future VILPA research comprising the development of: (1) an empirical definition of VILPA; (2) device-based methods to measure VILPA; (3) approaches to explore the short- and long-term dose–response effects of VILPA; and (4) scalable and acceptable behavioral VILPA-promoting interve... |
10.1038/s41591-021-01433-3 | 122,995,056 | Abstract Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients—247 home-isolated and 65 hospitalized—comprising 82% ... | 10.1038/s41591-022-01838-8 | This paper describes the post-COVID illness trajectory in community (non-hospitalized) patients in Norway |
10.1111/jgs.14533 | 80,540,200 | Objectives To determine the relationship between clinically diagnosed catheter‐associated urinary tract infection ( CAUTI ) and standardized criteria and to assess microorganism‐level differences in symptom burden in a cohort of catheterized nursing home ( NH ) residents. Design Post hoc analysis of a prospective longi... | 10.1038/s41579-020-0324-0 | In this study, the authors demonstrate the molecular basis for synergy among members of polymicrobial communities during colonization of urinary catheters in the health-care setting |
10.1073/pnas.1611665114 | 60,377,849 | Sterile (noninfected) inflammation underlies the pathogenesis of many widespread diseases, such as allergies and autoimmune diseases. The evolutionarily conserved innate immune system is considered to play a key role in tissue injury recognition and the subsequent development of sterile inflammation; however, the under... | 10.1038/s41577-018-0004-8 | This manuscript exemplifies how recognition of DAMPs by C-type lectins can trigger inappropriate responses that promote allergic inflammation. |
10.1126/science.1258867 | 20,881,266 | Immune cells, including natural killer (NK) cells, recognize transformed cells and eliminate them in a process termed immunosurveillance. It is thought that tumor cells evade immunosurveillance by shedding membrane ligands that bind to the NKG2D-activating receptor on NK cells and/or T cells, and desensitize these cell... | 10.1038/s41577-018-0004-8 | This is the first report showing that an NKG2D ligand, ULBP1, shed from cancerous cells can activate, rather than repress, the protective functions of NK cells. |
10.1126/science.1225829 | 20,844,166 | Ditching Invading DNA Bacteria and archaea protect themselves from invasive foreign nucleic acids through an RNA-mediated adaptive immune system called CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated (Cas). Jinek et al. (p. 816 , published online 28 June; see the Perspective by Brou... | 10.1038/s41580-019-0186-3 | This work introduces the Cre– loxP -based Polylox system for inducible recombination of DNA barcodes in mice, which is used to study haematopoiesis |
10.1126/science.aat9804 | 103,639,831 | In vivo barcoding using nuclease-induced mutations is a powerful approach for recording biological information, including developmental lineages; however, its application in mammalian systems has been limited. We present in vivo barcoding in the mouse with multiple homing guide RNAs that each generate hundreds of mutan... | 10.1038/s41580-019-0186-3 | This study reports the generation of a mouse line (MARC1) for prospective genetic lineage tracing using CRISPR–Cas9, which is used to build lineage trees of early embryogenesis |
10.1017/s1047951109990837 | 19,230,311 | Abstract Aims We investigated the prevalence, type, and course of congenital cardiac defects and systemic hypertension in our patients with Williams-Beuren-Beuren syndrome. Methods and results We reviewed the clinical records of all patients with Williams-Beuren syndrome examined between 1981 and 2006. We identified 15... | 10.1038/s41572-021-00276-z | This paper reports the cardiovascular outcomes from a large number of individuals with WS over a range of 0.5–25 years (average 6 years) of age. |
10.1111/pan.12967 | 107,380,241 | Summary Background Children with elastin arteriopathy ( EA ), the majority of whom have Williams–Beuren syndrome, are at high risk for sudden death. Case reports suggest that the risk of perioperative cardiac arrest and death is high, but none have reported the frequency or risk factors for morbidity and mortality in a... | 10.1038/s41572-021-00276-z | This is the largest study ( n = 48) that discusses risks associated with anaesthesia in individuals with WS. |
10.1002/ajmg.a.30012 | 20,089,198 | Abstract Williams–Beuren syndrome (WBS) is a genetic disorder characterized by a distinctive facial gestalt, mental retardation, mild growth deficiency, and cardiovascular disease. The occurrence of sudden death in the WBS is known from several case reports, but information about the risk of sudden death as derived fro... | 10.1038/s41572-021-00276-z | 127A This is the first study to demonstrate an elevated relative risk of sudden cardiovascular death in individuals with WS. |
10.1002/mgg3.695 | 17,072,184 | Abstract Background Williams syndrome (WBS) is a genetic multisystem disorder. The main symptom is borderline (intelligence quotient, IQ 70–79) or abnormally low intelligence (IQ < 70). According to earlier studies young individuals with WBS demonstrate generally a slightly higher verbal IQ (VIQ) compared to perform... | 10.1038/s41572-021-00276-z | These authors provide long-term follow-up information on some of the oldest adults with WS reported to date and document difficulties across numerous medical and functional domains. |
10.1002/ajmg.a.20496 | 61,455,950 | Abstract Most individuals with Williams syndrome (WS) have a 1.6 Mb deletion in chromosome 7q11.23 that encompasses the elastin ( ELN ) gene, while most families with autosomal dominant supravalvar aortic stenosis (SVAS) have point mutations in ELN . The overlap of the clinical phenotypes of the two conditions (cardiov... | 10.1038/s41572-021-00276-z | 123A This paper demonstrates the roles of the deletion of centromeric and telomeric portions of the WSCR in the WS neurocognitive profile. |
10.1161/circresaha.119.315348 | 103,305,967 | Rationale: Elastin is an important ECM (extracellular matrix) protein in large and small arteries. Vascular smooth muscle cells (SMCs) produce the layered elastic laminae found in elastic arteries but synthesize little elastin in muscular arteries. However, muscular arteries have a well-defined internal elastic lamina ... | 10.1038/s41572-021-00276-z | This paper dissects the role of endothelial and smooth muscle cells in the elastin-insufficiency phenotype and is the first mouse model to show neointima formation in an elastin mutant. |
10.1161/atvbaha.117.309079 | 18,485,333 | Objective— Williams syndrome is characterized by obstructive aortopathy attributable to heterozygous loss of ELN , the gene encoding elastin. Lesions are thought to result primarily from excessive smooth muscle cell (SMC) proliferation and consequent medial expansion, although an initially smaller caliber and increased... | 10.1038/s41572-021-00276-z | This paper posits that elastin insufficiency impacts the circumferential growth of developing arteries. |
10.1542/peds.2019-3761 | 82,932,675 | This set of recommendations is designed to assist the pediatrician in caring for children with Williams syndrome (WS) who were diagnosed by using clinical features and with chromosome 7 microdeletion confirmed by fluorescence in situ hybridization, chromosome microarray, or multiplex ligation-dependent probe amplificat... | 10.1038/s41572-021-00276-z | These are the most recent US general health-care recommendations for children with WS. |
10.1002/ajmg.a.30400 | 123,772,126 | Abstract To address the natural history of Williams syndrome (WS), we performed multisystem assessments on 20 adults with WS over 30 years of age and documented a high frequency of problems in multiple organ systems. The most striking and consistent findings were: abnormal body habitus; mild–moderate high frequency sen... | 10.1038/s41572-021-00276-z | This article presents multisystem assessments on adults with WS, emphasizing the major medical conditions in adults with WS, and provides recommendations for monitoring guidelines. |
10.1002/ajmg.b.30344 | 61,455,979 | Abstract The prevalence of a range of DSM‐IV psychiatric disorders in a sample of 119 4–16‐year‐old children with Williams syndrome (WS) was assessed using a structured diagnostic interview with their parents. Most children (80.7%) met criteria for at least one DSM‐IV diagnosis. The most prevalent diagnoses were Attent... | 10.1038/s41572-021-00276-z | 141B Clinical diagnostic interview of children and teens with WS that demonstrated a high frequency of ADHD and an increasing frequency of generalized anxiety disorder with age. |
10.1126/science.288.5469.1251 | 26,798,212 | The lungs of cystic fibrosis (CF) patients are chronically infected for years by one or a few lineages of Pseudomonas aeruginosa. These bacterial populations adapt to the highly compartmentalized and anatomically deteriorating lung environment of CF patients, as well as to the challenges of the immune defenses and anti... | 10.1038/s41579-020-00477-5 | This paper is the first to describe the high prevalence of hyper-mutator strains of P. aeruginosa in CF lung samples |
10.1038/s41467-018-05944-5 | 61,805,064 | Abstract Life-long bacterial infections in cystic fibrosis (CF) airways constitute an excellent model both for persistent infections and for microbial adaptive evolution in complex dynamic environments. Using high-resolution transcriptomics applied on CF sputum, we profile transcriptional phenotypes of Pseudomonas aeru... | 10.1038/s41579-020-00477-5 | This metatranscriptomic investigation of P. aeruginosa representing global gene expression in the CF lung shows that the expression profile reflects the lung environment with only minor influence from the bacterial genotype |
10.1038/s41467-019-08504-7 | 20,642,636 | Abstract Persistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host via simultaneous adaptation of multiple traits, which can obscure evolutionary trends and complicate infection management. Accordingly, here we screen 8 infection-relevant phenotypes of 443 lo... | 10.1038/s41579-020-00477-5 | This comprehensive phenotypic analysis of a collection of longitudinal P. aeruginosa isolates from several patients with CF with early-stage infections shows both diversity generation and convergence of specific traits |
10.1038/s41579-019-0196-3 | 20,813,085 | Abstract Increasing concerns about the rising rates of antibiotic therapy failure and advances in single-cell analyses have inspired a surge of research into antibiotic persistence. Bacterial persister cells represent a subpopulation of cells that can survive intensive antibiotic treatment without being resistant. Seve... | 10.1038/s41579-020-00477-5 | This review of the literature describes the phenomenon of persisters — surviving subpopulations of bacteria treated with antibiotics — and clarifies the biology and experimental conditions for monitoring persister development in bacterial populations |
10.1126/science.aaw1219 | 20,831,748 | Spatial positions of cells in tissues strongly influence function, yet a high-throughput, genome-wide readout of gene expression with cellular resolution is lacking. We developed Slide-seq, a method for transferring RNA from tissue sections onto a surface covered in DNA-barcoded beads with known positions, allowing the... | 10.1038/s41592-022-01576-2 | Slide-seq is a high-resolution sequencing-based spatial transcriptomics technology using spatially indexed measurement beads. |
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/s41592-022-01576-2 | MERFISH is an imaging-based spatial transcriptomics technology that profiles gene expression at subcellular resolution. |
10.17504/protocols.io.6qpvr3xozvmk/v1 | 151,425,274 | This document outlines the 10X Genomics Visium Protocol used for normal lung and colon tissues for SCENT at Duke University. | 10.1038/s41592-022-01576-2 | Visium is a commercially available sequencing-based spatial transcriptomics technology for fixed tissue. |
10.1002/cpt.1820 | 59,816,026 | Atorvastatin (ATV) is frequently prescribed and generally well tolerated, but can lead to myotoxicity, especially at higher doses. A genome‐wide association study of circulating levels of ATV, 2‐hydroxy (2‐OH) ATV, ATV lactone (ATV L), and 2‐OH ATV L was performed in 590 patients who had been hospitalized with a non‐ST... | 10.1038/s41569-021-00549-w | A GWAS showing strong associations between rs4149056 and both circulating atorvastatin levels and muscle-related adverse effects in patients who had been hospitalized with a non-ST-segment elevation ACS and treated with atorvastatin |
10.1126/science.1218198 | 20,705,223 | Genetic exchange is common among bacteria, but its effect on population diversity during ecological differentiation remains controversial. A fundamental question is whether advantageous mutations lead to selection of clonal genomes or, as in sexual eukaryotes, sweep through populations on their own. Here, we show that ... | 10.1038/s41579-020-0368-1 | Demonstrates that gene-specific selective sweeps followed by gradually decreasing gene flow can lead to ecologically differentiated conspecific subpopulations |
10.1126/science.aar4120 | 123,169,683 | Maps of defense arsenals in microbial genomes To survive the attack of foreign invaders such as viruses and plasmids, bacteria and archaea fight back with immune systems that are usually clustered in “defense islands” in their genomes. Doron et al. took advantage of this property to map microbial defense systems system... | 10.1038/s41586-019-1894-8 | This study describes the identification of numerous new anti-phage systems in defence islands |
10.1126/science.aal2130 | 104,147,420 | Phages build themselves a wall The compartmentalization of DNA replication away from other cytoplasmic events is a key feature of the cell nucleus. Chaikeeratisak et al. studied the replication of the very large Pseudomonas bacteriophage 201φ2-1 by using fluorescence microscopy and cryo–electron tomography. They found ... | 10.1038/s41586-019-1894-8 | This study describes how jumbophages can produce nucleus-like protein shells inside a bacterium for phage replication |
10.1146/annurev-biochem-061516-044952 | 123,174,566 | Metabolites are the small biological molecules involved in energy conversion and biosynthesis. Studying metabolism is inherently challenging due to metabolites’ reactivity, structural diversity, and broad concentration range. Herein, we review the common pitfalls encountered in metabolomics and provide concrete guideli... | 10.1038/s41592-021-01197-1 | A useful and comprehensive review highlighting the pitfalls encountered in metabolomics and providing guidelines for accurate metabolite measurements |
10.1038/s41467-019-09550-x | 20,697,932 | Abstract Large-scale metabolite annotation is a challenge in liquid chromatogram-mass spectrometry (LC-MS)-based untargeted metabolomics. Here, we develop a metabolic reaction network (MRN)-based recursive algorithm (MetDNA) that expands metabolite annotations without the need for a comprehensive standard spectral libr... | 10.1038/s41592-021-01197-1 | This represents an important example of a tool using a metabolic reaction network that expands metabolite annotations without the need for a comprehensive standard spectral library |
10.1111/tpj.14649 | 103,725,088 | Summary Roots, tubers, and bananas (RTB) are vital staples for food security in the world's poorest nations. A major constraint to current RTB breeding programmes is limited knowledge on the available diversity due to lack of efficient germplasm characterization and structure. In recent years large‐scale efforts have b... | 10.1038/s41592-021-01197-1 | Recent exemplary documentation of a metabolomics experiment that evaluated metabolite levels in crop species, providing not only an extensive database but moreover an excellent example of how to correctly investigate understudied species |
10.1038/s41467-021-22997-1 | 100,733,120 | Abstract Hair cells detect sound, head position or water movements when their mechanosensory hair bundle is deflected. Each hair bundle has an asymmetric architecture that restricts stimulus detection to a single axis. Coordinated hair cell orientations within sensory epithelia further tune stimulus detection at the or... | 10.1038/s41591-023-02218-6 | An article identifying GPR156 as a critical regulator of stereocilia orientation. |
10.1042/bj20030407 | 83,363,700 | The IL (interleukin)-6-type cytokines IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functi... | 10.1038/s41577-018-0066-7 | This article provides a comprehensive overview of the signal transduction mechanisms employed by the IL-6 cytokine family |
10.1146/annurev-immunol-032414-112134 | 29,336,503 | Interleukin-27 (IL-27) is a cytokine with strikingly diverse influences on the immune response. Although it was initially linked with the development of Th1 responses, it is now recognized as a potent antagonist of different classes of inflammation through its ability to directly modify CD4 + and CD8 + T cell effector ... | 10.1038/s41577-018-0066-7 | This is an excellent commentary on the biological properties of IL-27 |
10.4049/jimmunol.171.6.3202 | 39,792,422 | Abstract Studies in IL-6-deficient (IL-6−/−) mice highlight that IL-6 contributes to arthritis progression. However, the molecular mechanism controlling its activity in vivo remains unclear. Using an experimental arthritis model in IL-6−/− mice, we have established a critical role for the soluble IL-6R in joint inflamm... | 10.1038/s41577-018-0066-7 | This study provides an early example of the importance of cytokine trans -signalling in chronic inflammatory disease |
10.1083/jcb.111.3.1009 | 26,855,399 | We have tested the functional capacity of different beta tubulin isoforms in vivo by expressing beta 3-tubulin either in place of or in addition to beta 2-tubulin in the male germ line of Drosophila melanogaster. The testes-specific isoform, beta 2, is conserved relative to major metazoan beta tubulins, while the devel... | 10.1038/s41580-020-0214-3 | This study is the first to directly demonstrate functional singularity of tubulin isotypes |
10.1126/science.aaf0659 | 18,090,077 | A close-up view of cardiac cell mechanics Heart cells contain a very well-organized array of cytoskeletal elements, including actin and microtubules that help them to perform their mechanical functions. Robison et al. used an advanced imaging approach to study the inner workings of mouse cardiac myocytes in real time. ... | 10.1038/s41580-020-0214-3 | This study shows for the first time how microtubules buckle at high frequency in contracting heart muscle cells and how this behaviour is dependent on tubulin detyrosination |
10.1083/jcb.200512058 | 82,130,877 | Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes the addition of a C-terminal tyrosine residue to α-tubulin in the tubulin tyrosination cycle, is involved in tumor progression and has a vital role in neuronal organization. We show that in mammalian fibroblasts, cytoplasmic linker protein (CLIP) 170 and other mi... | 10.1038/s41580-020-0214-3 | This study identifies tubulin tyrosination as an essential factor for the microtubule plus end localization of CAP-Gly proteins |
10.1126/science.aaa5175 | 62,377,138 | Chromosomes: Let me be your guide The correct alignment of chromosomes at the center of the mitotic spindle—the metaphase plate—before cell division is one of the key mechanisms for the maintenance of genomic stability. But is there anything special about the microtubules of the spindle that helps this process? Barisic... | 10.1038/s41580-020-0214-3 | This study is the first to directly reveal a function of a tubulin PTM during cell division |
10.1038/s41467-018-03909-2 | 29,313,775 | Abstract Within cells, motor and non-motor microtubule-associated proteins (MAPs) simultaneously converge on the microtubule. How the binding activities of non-motor MAPs are coordinated and how they contribute to the balance and distribution of motor transport is unknown. Here, we examine the relationship between MAP7... | 10.1038/s41580-020-0214-3 | This study describes how different MAPs can have differential effects on the behaviour of a given motor protein on microtubules |
10.1126/science.aao5676 | 62,378,431 | Tubulin is subjected to a number of posttranslational modifications to generate heterogeneous microtubules. The modifications include removal and ligation of the C-terminal tyrosine of ⍺-tubulin. The enzymes responsible for detyrosination, an activity first observed 40 years ago, have remained elusive. We applied a gen... | 10.1038/s41580-020-0214-3 | This study co-discovers, together with Aillaud et al. (2017), the identity of tubulin detyrosinases as vasohibin-family proteins |
10.1126/science.1113010 | 60,048,694 | Polyglutamylation of tubulin has been implicated in several functions of microtubules, but the identification of the responsible enzyme(s) has been challenging. We found that the neuronal tubulin polyglutamylase is a protein complex containing a tubulin tyrosine ligase–like (TTLL) protein, TTLL1. TTLL1 is a member of a... | 10.1038/s41580-020-0214-3 | This study reports the discovery of tubulin glutamylases as TTL-like proteins |
10.1083/jcb.102.3.1118 | 101,815,985 | The C-terminus of alpha-tubulin undergoes a reversible posttranslational tyrosination/detyrosination. The distributions of the tyrosinated (Tyr) and nontyrosinated (Glu) species during mitosis of cultured cells have been investigated by immunofluorescence using antibodies directed against the C-terminus of either Tyr o... | 10.1038/s41580-020-0214-3 | This is the first study demonstrating the differential distribution of tyrosinated versus detyrosinated tubulin on different microtubules of the mitotic spindle |
10.1126/science.aan0092 | 124,023,058 | How selfish genes get their way At the core of Mendelian genetics is the concept that gametes are equally likely to carry either of the two parental copies of a gene. Selfish genetic elements can cheat, however, by subverting Mendelian segregation to increase their representation in the gametes. Akera et al. show how t... | 10.1038/s41580-020-0214-3 | Akera et al. demonstrate how asymmetric distribution of tyrosination in meiotic spindles drives non-Mendelian chromosome segregation in mouse oocytes. This study links tubulin PTMs to meiotic drive |
10.3389/fphar.2021.768015 | 133,211,266 | Understanding snake venom proteomes is becoming increasingly important to understand snake venom biology, evolution and especially clinical effects of venoms and approaches to antivenom development. To explore the current state of snake venom proteomics and transcriptomics we investigated venom proteomic methods, assoc... | 10.1038/s41570-022-00393-7 | A review of the proteomic methods used to separate and quantify snake venom toxins, comparing their merits and limitations |
10.1111/j.1742-4658.2011.08115.x | 83,042,230 | Snake venoms are cocktails of enzymes and non‐enzymatic proteins used for both the immobilization and digestion of prey. The most common snake venom enzymes include acetylcholinesterases, l ‐amino acid oxidases, serine proteinases, metalloproteinases and phospholipases A 2 . Higher catalytic efficiency, thermal stabili... | 10.1038/s41570-022-00393-7 | A paper focusing on the structure and reaction mechanisms of the most prominent snake venom enzymatic toxins |
10.1002/wcms.1281 | 20,410,551 | Quantum mechanics/molecular mechanics ( QM / MM ) methods offer a very appealing option for the computational study of enzymatic reaction mechanisms, by separating the problem into two parts that can be treated with different computational methods. Hence, in a QM / MM formalism, the part of the system in which catalysi... | 10.1038/s41570-022-00393-7 | A review of the computational methods being used to elucidate the snake venom enzymatic reactivity |
10.3390/toxins12040255 | 37,920,484 | For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and bl... | 10.1038/s41570-022-00393-7 | This review describes the application of snake venoms to treat cancer and infection by antibiotic-resistant microorganisms |
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