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10.1111/all.14489 | 20,584,908 | Abstract Background Atopic dermatitis (AD) patients are often colonized with Staphylococcus aureus, and staphylococcal biofilms have been reported on adult AD skin lesions. The commensal S epidermidis can antagonize S aureus , although its role in AD is unclear. We sought to characterize S aureus and S epidermidis colo... | 10.1038/s41579-022-00780-3 | This work presents a clinically robust and mechanistic assessment of paediatric atopic dermatitis development and progression in a US cohort. |
10.1126/scitranslmed.aay5445 | 18,433,393 | The composition of the skin microbiota varies widely among individuals when sampled at the same body site. A key question is which molecular factors determine strain-level variability within sub-ecosystems of the skin microbiota. Here, we used a genomics-guided approach to identify an antibacterial biosynthetic gene cl... | 10.1038/s41579-022-00780-3 | This study identifies a novel antimicrobial made by C. acnes in the hair follicle to facilitate inter-bacterial competition. |
10.1073/pnas.1520759113 | 62,083,783 | The role of astrocytes in neuronal function has received increasing recognition, but disagreement remains about their function at the circuit level. Here we use in vivo two-photon calcium imaging of neocortical astrocytes while monitoring the activity state of the local neuronal circuit electrophysiologically and optic... | 10.1038/s41593-018-0325-8 | In this seminal study, the authors demonstrate that astrocytic calcium transients promote the switch of the somatosensory cortical circuit to a low-frequency state, a neocortical rhythm important for sleep and memory. Noninvasive activation of astrocytes produces transient increases in extracellular glutamate, which wo... |
10.1073/pnas.1410893111 | 102,253,523 | Significance Astrocytes are well placed to modulate neural activity. However, the functions typically attributed to astrocytes are associated with a temporal dimension significantly slower than the timescale of synaptic transmission of neurons. Consequently, it has been assumed that astrocytes do not play a major role ... | 10.1038/s41593-018-0325-8 | In this study, the authors specifically induced tetanus toxin expression in astrocytes and found evidence of a reduction in cortical gamma oscillations, which was accompanied by impaired behavioral performance in the novel object recognition test |
10.1073/pnas.1605063113 | 107,226,281 | Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β 2 -adrenergic receptors (βARs) are of parti... | 10.1038/s41593-018-0325-8 | This study reports that noradrenaline signaling via β-receptors, which promotes memory consolidation, occurs in astrocytes and requires release of lactate from these cells. Lactate in turn supports the neuronal molecular changes essential for long-term memory formation |
10.1126/science.1169096 | 83,038,042 | Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium... | 10.1038/s41593-018-0325-8 | By measuring Ca 2+ dynamics in astrocytes in vivo in a mouse model of Alzheimer’s disease, this study was the first to identify a functional alteration (hyperactivity) of glial networks, in complement to the imbalances observed by others in neuronal networks |
10.1161/strokeaha.121.034947 | 135,274,740 | Despite years of basic research and pioneering clinical work, ischemic stroke remains a major public health concern. Prior STAIR (Stroke Treatment Academic Industry Roundtable) conferences identified both failures of clinical trial design and failures in preclinical assessment in developing putative ischemic stroke tre... | 10.1038/s41582-021-00605-6 | This paper provides an updated set of recommendations to improve the quality and predictability of preclinical stroke studies |
10.1111/dme.12147 | 103,036,923 | Abstract Aim To evaluate the prognosis of diabetic gastroparesis. Methods Eighty‐six patients with diabetes had measurements of gastric emptying of a mixed meal using a dual isotope test of solid and liquid meal components, mean blood glucose levels, HbA 1c , upper gastrointestinal symptoms and autonomic nerve function... | 10.1038/s41572-018-0038-z | This important article describes the natural history of diabetic gastroparesis |
10.1152/physrev.00037.2013 | 82,970,230 | Smooth muscles are complex tissues containing a variety of cells in addition to muscle cells. Interstitial cells of mesenchymal origin interact with and form electrical connectivity with smooth muscle cells in many organs, and these cells provide important regulatory functions. For example, in the gastrointestinal trac... | 10.1038/s41572-018-0038-z | This important review discusses the pacemaker cells in the GI tract |
10.1111/nmo.12893 | 26,950,600 | Abstract Background Nausea and vomiting are classic symptoms of gastroparesis. It remains unclear if characteristics of nausea and vomiting are similar in different etiologies of gastroparesis. The aims of this article were as follows: to describe characteristics of nausea and vomiting in patients with gastroparesis an... | 10.1038/s41572-018-0038-z | This paper provides an important summary of the features of idiopathic and diabetic gastroparesis observed in the NIH Gastroparesis Consortium study in United States |
10.1111/j.1365-2982.2008.01230.x | 124,943,972 | Abstract Tests of gastric, small intestinal and colonic motor function provide relevant physiological information and are useful for diagnosing and guiding the management of dysmotilities. Intraluminal pressure measurements may include concurrent measurements of transit or intraluminal pH. A consensus statement was dev... | 10.1038/s41572-018-0038-z | This consensus document discusses methods to measure gastric motor functions |
10.1152/japplphysiol.01111.2014 | 39,378,040 | The mechanisms responsible for exercise-induced reductions in baseline heart rate (HR), known as training bradycardia, remain controversial. Therefore, changes in cardiac autonomic regulation and intrinsic sinoatrial nodal (SAN) rate were evaluated using dogs randomly assigned to either a 10- to 12-wk exercise training... | 10.1038/s41569-018-0065-1 | This study is an illustrative example of the relevant work performed over the years by G. E. Billman’s group in dog models, showing the anti-arrhythmogenic and salutary effects of moderate endurance exercise training through enhanced cardiac parasympathetic regulation |
10.1152/japplphysiol.00175.2012 | 7,415,402 | The risk of sudden cardiac death is increased following myocardial infarction. Exercise training reduces arrhythmia susceptibility, but the mechanism is unknown. We used a canine model of sudden cardiac death (healed infarction, with ventricular tachyarrhythmias induced by an exercise plus ischemia test, VF+); we previ... | 10.1038/s41569-018-0065-1 | This preclinical study finds that exercise training could prevent ischaemia-induced ventricular fibrillation owing to a combination of beneficial effects on cellular electrophysiology and calcium handling |
10.1152/japplphysiol.00004.2011 | 36,012,006 | The ability of exercise to protect the heart against ischemia-reperfusion (I/R) injury is well known in both human epidemiological studies and experimental animal models. In this review article, we describe what is currently known about the ability of exercise to precondition the heart against infarction. Just 1 day of... | 10.1038/s41569-018-0065-1 | This detailed review discusses how exercise training evokes sustainable protection against cardiac ischaemia–reperfusion injury through several mechanisms, such as improved oxidant buffering capacity, decreased cellular and/or mitochondrial calcium overload, and preservation of bioenergetics |
10.1152/ajpendo.00074.2003 | 20,668,973 | The purpose of the present study was to test the hypothesis that a transient increase in plasma IL-6 induces an anti-inflammatory environment in humans. Therefore, young healthy volunteers received a low dose of recombinant human (rh)IL-6 or saline for 3 h. Plasma IL-6 levels during rhIL-6 infusion were ∼140 pg/ml, cor... | 10.1038/s41569-018-0065-1 | This study is an example of work by B. K. Pedersen’s group representing a paradigm shift regarding the role of IL-6; when released from working muscles, this molecule can have anti-inflammatory rather than pro-inflammatory effects |
10.1152/ajpendo.00326.2011 | 41,717,248 | Regular physical activity protects against several types of diseases. This may involve altered secretion of signaling proteins from skeletal muscle. Our aim was to identify the most abundantly secreted proteins in cultures of human skeletal muscle cells and to monitor their expression in muscles of strength-training in... | 10.1038/s41569-018-0065-1 | In this study, the authors show that muscle strength training increases the levels of several secretory muscle proteins in humans, many of which are candidate myokines |
10.1126/scitranslmed.aaw2888 | 62,148,576 | Most vaccines for diseases in low- and middle-income countries fail to be developed because of weak or absent market incentives. Conquering diseases such as tuberculosis, HIV, malaria, and Ebola, as well as illnesses caused by multidrug-resistant pathogens, requires considerable investment and a new sustainable model o... | 10.1038/s41586-019-1656-7 | The authors demonstrate how promising and much needed vaccines for global health fail to reach full development because of inadequate financial incentives, and propose mechanisms to overcome this problem |
10.1098/rstb.2014.0138 | 6,351,315 | The reason for holding a meeting to discuss biological challenges to vaccines is simple: not all vaccines work equally well in all settings. This special issue reviews the performance of vaccines in challenging environments, summarizes current thinking on the reasons why vaccines underperform and considers what approac... | 10.1038/s41586-019-1656-7 | This article introduces a series of papers presented at a scientific meeting held at the Royal Society in London in 2015 that address the wide range of biological reasons for the variability in vaccine efficacy, such as age, sex, environment, genetics and co-infections |
10.1038/s41467-020-14371-4 | 60,482,832 | Abstract Most mono- and co-culture bioprocess applications rely on large-scale suspension fermentation technologies that are not easily portable, reusable, or suitable for on-demand production. Here, we describe a hydrogel system for harnessing the bioactivity of embedded microbes for on-demand small molecule and pepti... | 10.1038/s41467-021-21740-0 | A stress-resilient platform for on-demand bioproduction of compounds from diverse microbial hosts via encapsulation in functionalized pluronic hydrogels |
10.1073/pnas.1618307114 | 84,562,029 | Living systems, such as bacteria, yeasts, and mammalian cells, can be genetically programmed with synthetic circuits that execute sensing, computing, memory, and response functions. Integrating these functional living components into materials and devices will provide powerful tools for scientific research and enable n... | 10.1038/s41467-021-21740-0 | Stretchable, robust living materials containing engineered bacteria for broad applications as wearable devices |
10.1126/science.aas9315 | 18,958,387 | Using bugs in the gut to detect blood Bacteria are environmentally resilient and can be engineered to sense various biomolecules. Mimee et al. combined biosensor bacteria with a miniaturized wireless readout capsule to produce a minimally invasive device capable of in vivo biosensing in harsh, difficult-to-access envir... | 10.1038/s41467-021-21740-0 | An ingestible device for in situ gastrointestinal health monitoring with broad applications in disease detection and management |
10.1038/s41467-019-09722-9 | 62,228,689 | Abstract Cell-free transcription–translation systems have great potential for biosensing, yet the range of detectable chemicals is limited. Here we provide a workflow to expand the range of molecules detectable by cell-free biosensors through combining synthetic metabolic cascades with transcription factor-based networ... | 10.1038/s41467-021-21740-0 | A modular method coupling synthetic metabolic cascades with transcription factor-based sensing to expand the range of products detectable by cell-free biosensing systems |
10.1038/ncomms15028 | 103,713,437 | Abstract Bacteria can be genetically engineered to kill specific pathogens or inhibit their virulence. We previously developed a synthetic genetic system that allows a laboratory strain of Escherichia coli to sense and kill Pseudomonas aeruginosa in vitro . Here, we generate a modified version of the system, including ... | 10.1038/s41467-021-21740-0 | Demonstration of prophylactic and therapeutic activities of engineered bacteria against gut infections, highlighting their potential as a therapeutic strategy |
10.1093/jlb/lsz007 | 19,691,990 | Abstract Recent advances in technology have significantly improved the accuracy of genetic testing and analysis, and substantially reduced its cost, resulting in a dramatic increase in the amount of genetic information generated, analysed, shared, and stored by diverse individuals and entities. Given the diversity of a... | 10.1038/s41576-022-00455-y | This work provides a comprehensive overview of the legal landscape surrounding genetic privacy in the United States. |
10.1055/s-0038-1634025 | 17,245,819 | Summary Objectives: Current genomic privacy technologies assume the identity of genomic sequence data is protected if personal information, such as demographics, are obscured, removed, or encrypted. While demographic features can directly compromise an individual’s identity, recent research demonstrates such protection... | 10.1038/s41576-022-00455-y | This pioneering work shows the use of data perturbation for genomic data privacy. |
10.29012/jpc.v5i1.629 | 59,202,486 | Traditional statistical methods for confidentiality protection of statistical databases do not scale well to deal with GWAS databases especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, i... | 10.1038/s41576-022-00455-y | This is the first study to use differential privacy for privacy-preserving GWAS data sharing. |
10.1101/gr.207464.116 | 59,355,136 | Genomics data introduce a substantial computational burden as well as data privacy and ownership issues. Data sets generated by high-throughput sequencing platforms require immense amounts of computational resources to align to reference genomes and to call and annotate genomic variants. This problem is even more prono... | 10.1038/s41576-022-00455-y | This work shows the use of blockchain technologies for privacy-preserving personal genomic data sharing. |
10.1093/bioinformatics/btx568 | 39,841,488 | Abstract Motivation Rapid and low cost sequencing of genomes enabled widespread use of genomic data in research studies and personalized customer applications, where genomic data is shared in public databases. Although the identities of the participants are anonymized in these databases, sensitive information about ind... | 10.1038/s41576-022-00455-y | This study optimizes SNP masking while mitigating kinship privacy risks stemming from familial searches. |
10.1038/s41564-019-0510-x | 20,264,647 | Abstract Bacteriophages from the Inoviridae family (inoviruses) are characterized by their unique morphology, genome content and infection cycle. One of the most striking features of inoviruses is their ability to establish a chronic infection whereby the viral genome resides within the cell in either an exclusively ep... | 10.1038/s41579-019-0311-5 | This study uses a machine learning approach to identify 10,295 previously uncharacterized inoviruses from microbial genomes and metagenomes |
10.1038/ncomms12524 | 60,455,641 | Abstract In single-stranded ribonucleic acid (RNA) viruses, virus capsid assembly and genome packaging are intertwined processes. Using cryo-electron microscopy and single particle analysis we determined the asymmetric virion structure of bacteriophage MS2, which includes 178 copies of the coat protein, a single copy o... | 10.1038/s41579-019-0311-5 | This article reports the ability of RNA phages to adopt defined conformations that can be involved in genome packaging and virion assembly |
10.1073/pnas.1303047110 | 60,314,138 | It has been proposed that viruses can be divided into a small number of structure-based viral lineages. One of these lineages is exemplified by bacterial virus Hong Kong 97 (HK97), which represents the head-tailed dsDNA bacteriophages. Seemingly similar viruses also infect archaea. Here we demonstrate using genomic ana... | 10.1038/s41579-019-0311-5 | This article focuses on the MCP HK97 fold and its conservation at the structural level between tailed phages and archaeal and eukaryotic viruses |
10.1073/pnas.1601060113 | 83,452,456 | The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a dee... | 10.1038/s41579-019-0311-5 | This study identifies 44 phage groups in the gut microbiota, nine of which are shared across more than one-half of individuals and are proposed to be part of a healthy gut phageome |
10.1038/ncomms15892 | 26,993,492 | Abstract Microbes drive ecosystems under constraints imposed by viruses. However, a lack of virus genome information hinders our ability to answer fundamental, biological questions concerning microbial communities. Here we apply single-virus genomics (SVGs) to assess whether portions of marine viral communities are mis... | 10.1038/s41579-019-0311-5 | This study uses single-virus genomics to identify the most widespread phages in the ocean, which were previously overlooked in metagenomics projects because of their high microdiversity |
10.1523/jneurosci.3842-04.2005 | 38,298,294 | Sleep disturbances in neurological disorders have a devastating impact on patient and carer alike. However, their pathological origin is unknown. Here we show that patients with Huntington's disease (HD) have disrupted night-day activity patterns. This disruption was mirrored in a transgenic model of HD (R6/2 mice) in ... | 10.1038/s41582-021-00577-7 | This study revealed disruption of circadian rhythms throughout the course of HD, in animal models and individuals affected by the disease. |
10.1126/science.1180962 | 103,690,015 | Sleep and Alzheimer's Disease Accumulation of amyloid-β (Aβ) in the brain is thought to be the initiating event in the pathogenesis of Alzheimer's disease (AD). Aβ is a peptide secreted in a soluble monomeric form predominantly by neurons and its aggregation into toxic forms is concentration dependent. Synaptic activit... | 10.1038/s41582-021-00577-7 | This study demonstrated influences of the sleep–wake cycles and orexin system on Aβ dynamics. |
10.1038/s41598-020-68199-5 | 62,522,017 | Abstract Circadian disruption resulting from exposure to irregular light–dark patterns and sleep deprivation has been associated with beta amyloid peptide (Aβ) aggregation, which is a major event in Alzheimer’s disease (AD) pathology. We exposed 5XFAD mice and littermate controls to dim-light vs. bright-light photophas... | 10.1038/s41582-021-00577-7 | This study showed that increasing light levels might reduce amyloid load in an AD transgenic mouse model. |
10.1073/pnas.1421533112 | 20,626,279 | Before the Syrian uprising that began in 2011, the greater Fertile Crescent experienced the most severe drought in the instrumental record. For Syria, a country marked by poor governance and unsustainable agricultural and environmental policies, the drought had a catalytic effect, contributing to political unrest. We s... | 10.1038/s41558-018-0299-2 | Analyses recent drought episodes in Syria and neighbouring countries and suggests a link to economic and political instability |
10.1002/jgrc.20078 | 59,388,112 | Sea level in the Mediterranean Sea over the period 1993–2011 is studied on the basis of altimetry, temperature, and salinity data and gravity measurements from Gravity Recovery and Climate Experiment (GRACE) (2002–2010). An observed increase in sea level corresponds to a linear sea level trend of 3.0 ± 0.5 mm/yr domina... | 10.1038/s41558-018-0299-2 | Demonstrates the relative contribution of multiple forcings to Mediterranean sea-level changes for the period 1993–2011 |
10.1029/2009gb003594 | 83,287,040 | The aim of this study is to produce future scenarios on the river inputs of water and nutrients (nitrate and phosphate) into the Mediterranean and Black Sea. They are based on the four contrasting scenarios that were developed by the Millenium Ecosystem Assessment (MEA) for the years 2030 and 2050 and implemented in a ... | 10.1038/s41558-018-0299-2 | Comprehensive study of hydrological and water quality changes for Mediterranean catchments in the past and for projected future conditions |
10.1126/science.aah5015 | 107,401,469 | A warming limit for the Mediterranean basin Pollen cores from sediments provide rich detail on the history of vegetation and climate in the Mediterranean during the Holocene (the most recent ~10,000 years). Guiot and Cramer used this information as a baseline against which to compare predictions of future climate and v... | 10.1038/s41558-018-0299-2 | Using a process-based ecosystem model fitted to pollen-based vegetation reconstructions, this study demonstrates that only a 1.5 °C global climate trajectory allows Mediterranean land ecosystems to remain in the variability range of the past 10,000 years |
10.1046/j.1461-0248.2003.00439.x | 123,577,255 | Abstract The north‐western Mediterranean Sea's high biodiversity originates from a mixture of temperate and subtropical species. Large‐scale warming has been detected through northward range shifts of ‘warm‐water’ species, and mass‐mortality events for ‘cold‐water’ invertebrates. Marine caves are affected in a more sub... | 10.1038/s41558-018-0299-2 | One of the earliest studies demonstrating impacts of climate fluctuations on northwest Mediterranean marine biota |
10.1038/srep34162 | 81,114,811 | Abstract Mediterranean ecosystems support important processes and functions that bring direct benefits to human society. Yet, marine ecosystem services are usually overlooked due to the challenges in identifying and quantifying them. This paper proposes the application of several biophysical and ecosystem modelling app... | 10.1038/s41558-018-0299-2 | One of the earliest comprehensive assessments of ecosystem service provisioning changes in the Mediterranean Sea |
10.1093/plcell/koab099 | 107,320,846 | Abstract Clustered regularly interspaced short palindromic repeat (CRISPR)-associated systems have revolutionized genome engineering by facilitating a wide range of targeted DNA perturbations. These systems have resulted in the development of powerful new screens to test gene functions at the genomic scale. While there... | 10.1038/s41477-023-01388-y | A review article presenting the general concepts, tools, and workflows for establishing CRISPR screens in plants. |
10.1038/s41467-020-15084-4 | 122,823,002 | Abstract Vertebrates exhibit specific requirements for replicative H3 and non-replicative H3.3 variants during development. To disentangle whether this involves distinct modes of deposition or unique functions once incorporated into chromatin, we combined studies in Xenopus early development with chromatin assays. Here... | 10.1038/s41580-020-0262-8 | This work demonstrates a critical developmental role for H3.3 Ser31, identifies interacting proteins that may depend on this amino acid, and together with Martire et al. (2019) links its phosphorylation to histone acetylation |
10.1101/2019.12.18.880716 | 15,229,644 | ABSTRACT The packaging of DNA into nucleosomes represents a challenge for transcription. Nucleosome disruption and histone eviction enables RNA Polymerase II progression through DNA, a process that compromises chromatin integrity and the maintenance of epigenetic information. Here, we used the imaging SNAP-tag system t... | 10.1038/s41580-020-0262-8 | This study demonstrates the flexibility of histone variant chaperone complexes and downstream functional consequences for maintenance of chromatin states |
10.1101/gad.2045111 | 121,947,927 | In higher eukaryotes, the centromere is epigenetically specified by the histone H3 variant Centromere Protein-A (CENP-A). Deposition of CENP-A to the centromere requires histone chaperone HJURP (Holliday junction recognition protein). The crystal structure of an HJURP–CENP-A–histone H4 complex shows that HJURP binds a ... | 10.1038/s41580-020-0262-8 | This work together with Ricketts et al. (2015) and Liu et al. (2012) demonstrates the convergence of modes of H3 variant–chaperone structural interactions in the absence of sequence conservation |
10.1126/science.aan4965 | 41,665,565 | A multifactorial strategy establishes and maintains repressive chromatin marks in plants in response to environmental signals. | 10.1038/s41580-020-0262-8 | This work shows that H3.3-enriched genes protect against heterochromatization during DNA replication in plants by inhibiting (through specific H3.3 Thr31) the methyltransferases ATXR5 and ATXR6 |
10.1126/scitranslmed.aal3973 | 104,089,772 | The mode of action of new antimicrobial compounds can be predicted from changes in metabolome profiles in Mycobacterium . | 10.1038/s41589-022-01040-4 | Combination of high-throughput metabolic profiling of chemical libraries and limited proteolysis reveal the modes of action of new antituberculosis compounds |
10.1038/s41598-019-39387-9 | 82,450,781 | Abstract Identification of novel antibiotics remains a major challenge for drug discovery. The present study explores use of phenotypic readouts beyond classical antibacterial growth inhibition adopting a combined multiparametric high content screening and genomic approach. Deployment of the semi-automated bacterial ph... | 10.1038/s41589-022-01040-4 | This study comprehensively demonstrates the power of combining multiparametric highcontent screening and genomic approaches, beyond classical susceptibility screening, to guide lead compound selection and their functional annotation |
10.1128/mbio.02627-19 | 80,510,010 | Multidrug combination therapy is an important strategy for treating tuberculosis, the world’s deadliest bacterial infection. Long treatment durations and growing rates of drug resistance have created an urgent need for new approaches to prioritize effective drug regimens. Hence, we developed a computational model calle... | 10.1038/s41589-022-01040-4 | The authors used a machine learning approach to screen in silico more than 1 million potential drug combinations using Mycobacterium tuberculosis transcriptomic profiles of individual drug effects, resulting mechanistic insights on drug–drug interactions |
10.21203/rs.3.rs-1414437/v1 | 128,708,487 | Abstract Cognitive decline is a common pathological outcome during aging, with an ill-defined cellular or molecular basis. Among the cellular changes observed with age are alterations to neuronal plasticity, changes in the glial compartment and the decline of the neurogenic niche. In the recent years, the concept of in... | 10.1038/s41590-022-01209-y | This preprint suggests potential extension of the beneficial effects of brain-specific IL-2 delivery to the context of cognitive decline during normal aging |
10.1128/jb.186.21.7312-7326.2004 | 61,723,512 | ABSTRACT The processes associated with early events in biofilm formation have become a major research focus over the past several years. Events associated with dispersion of cells from late stage biofilms have, however, received little attention. We demonstrate here that dispersal of Pseudomonas aeruginosa PAO1 from bi... | 10.1038/s41579-020-0385-0 | This seminal study shows that dispersal of P. aeruginosa from biofilms can be induced by the addition of simple carbon sources, and that dispersed cells adopt a specific phenotype |
10.1128/jb.00575-19 | 45,493,601 | Pseudomonas aeruginosa forms multicellular aggregates or biofilms encased in a matrix. We show for the first time here that dispersion by P. aeruginosa requires the endogenous expression of pelA and pslG , leading to the degradation of both Pel and Psl polysaccharides, with PslG-induced dispersion being CdrA dependent.... | 10.1038/s41579-020-0385-0 | This study suggests matrix degradation to induce dispersion is a multistep process |
10.1128/aac.00234-19 | 105,357,160 | Pseudomonas aeruginosa is an opportunistic, nosocomial bacterial pathogen that forms persistent infections due to the formation of protective communities, known as biofilms. Once the biofilm is formed, the bacteria embedded within it are recalcitrant to antimicrobial treatment and host immune defenses. | 10.1038/s41579-020-0385-0 | This study demonstrates that biofilm disassembly, induced by the exogenous addition of a matrix-degrading protein, PslG, has a positive outcome in the treatment of biofilm-related infections |
10.1128/aac.48.7.2633-2636.2004 | 122,571,036 | ABSTRACT The gram-positive bacterium Staphylococcus epidermidis is the most common cause of infections associated with catheters and other indwelling medical devices. S. epidermidis produces an extracellular slime that enables it to form adherent biofilms on plastic surfaces. We found that a biofilm-releasing enzyme pr... | 10.1038/s41579-020-0385-0 | This study features the characterization of one of the first biofilm-releasing enzymes produced by the resident biofilm bacteria to induce biofilm disassembly |
10.1128/mbio.01338-18 | 103,714,873 | ABSTRACT Candida albicans surface-attached biofilms such as those formed on intravenous catheters with direct access to the bloodstream often serve as a nidus for continuous release of cells capable of initiating new infectious foci. We previously reported that cells dispersed from a biofilm are yeast cells that origin... | 10.1038/s41579-020-0385-0 | This seminal study shows that dispersal of P. aeruginosa from biofilms can be induced by the addition of simple carbon sources and that dispersed cells adopt a specific phenotype |
10.1038/s41598-018-29121-2 | 19,495,153 | Abstract Chronic infections are often associated with the presence of a biofilm, a community of microorganisms coexisting within a protective matrix of extracellular polymeric substance. Living within a biofilm can make resident microbes significantly more tolerant to antibiotics in comparison to planktonic, free-float... | 10.1038/s41579-020-0385-0 | This study shows that P. aeruginosa biofilm cells dispersed from mouse chronic wound infections by glycoside hydrolases can cause fatal sepsis unless antibiotics are given in conjunction |
10.1128/jb.187.1.382-387.2005 | 103,376,828 | ABSTRACT Polymeric β-1,6- N -acetyl- d -glucosamine (poly-β-1,6-GlcNAc) has been implicated as an Escherichia coli and Staphylococcus epidermidis biofilm adhesin, the formation of which requires the pgaABCD and icaABCD loci, respectively. Enzymatic hydrolysis of poly-β-1,6-GlcNAc, demonstrated for the first time by chr... | 10.1038/s41579-020-0385-0 | This study demonstrates for the first time that enzymatic hydrolysis of PGA disrupts biofilm formation by strains harbouring pgaABCD homologues, including Yersinia pestis and P. fluorescens |
10.1073/pnas.1207832109 | 18,844,451 | Dispersion enables biofilm bacteria to transit from the biofilm to the planktonic growth state and to spawn novel communities in new locales. Although the chemotaxis protein BdlA plays a role in the dispersion of Pseudomonas aeruginosa biofilms in response to environmental cues, little is known about regulation of BdlA... | 10.1038/s41579-020-0385-0 | This study demonstrates the post-translational modification of BdlA in response to dispersion cue sensing |
10.1128/jb.00779-06 | 83,116,254 | ABSTRACT Bacterial biofilms at times undergo regulated and coordinated dispersal events where sessile biofilm cells convert to free-swimming, planktonic bacteria. In the opportunistic pathogen Pseudomonas aeruginosa , we previously observed that dispersal occurs concurrently with three interrelated processes within mat... | 10.1038/s41579-020-0385-0 | This seminal study shows that dispersal of P. aeruginosa from biofilms can be induced by the addition of NO and that combined exposure to both NO and antimicrobial agents greatly enhanced the efficacy of antimicrobial compounds in the removal of established P. aeruginosa biofilms |
10.1126/science.1135926 | 29,300,727 | A number of brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. We found that smokers with brain damage involving the insula, a region implicated in conscious urges, were more likely than smokers with brain damage not... | 10.1038/s41591-022-01864-6 | The first study to link lesion locations to remission of smoking addiction |
10.1002/ana.25285 | 115,128,061 | Brain damage can occasionally result in paradoxical functional benefit, which could help identify therapeutic targets for neuromodulation. However, these beneficial lesions are rare and lesions in multiple different brain locations can improve the same symptom. Using a technique called lesion network mapping, we show t... | 10.1038/s41591-022-01864-6 | A proof-of-concept study of network-based localization of treatment targets based on brain lesions that resulted in improvement of pre-existing symptoms. |
10.1002/art.1780341221 | 19,827,042 | Abstract The prevalence of antibodies to hepatitis C virus (HCVAb) was investigated in 52 unselected patients with mixed cryoglobulinemia and in 84 patients with other systemic immunologic diseases. HCVAb were detected by an enzyme‐linked immunosorbent assay, and their specificity was evaluated by a recombinant‐based i... | 10.1038/s41572-018-0009-4 | This study pioneers the notion that viral agents (including HCV) have a role in the pathogenesis of mixed cryoglobulinaemia patients |
10.1002/art.1780290907 | 41,727,536 | Abstract The incidence and nature of cryoglobulins, as well as their correlation with the clinical and serologic picture of Sjögren's syndrome (SS), were studied in the sera of 30 consecutive primary SS patients. Sera from 29 patients with systemic lupus erythematosus, 58 patients with rheumatoid arthritis, and 125 hea... | 10.1038/s41572-018-0009-4 | This study suggests that primary Sjögren syndrome expresses, in addition to polyclonal B cell hyper-reactivity, a monoclonal process in the absence of lymphoid neoplasia; it showed that the extraglandular manifestations of the syndrome may be due to an immune-complex-mediated pathology |
10.1111/j.1365-2141.1994.tb05036.x | 80,935,595 | Summary. Hepatitis C virus (HCV), which is both a hepatotropic and a lymphotropic virus, has been proposed as a possible causative agent of mixed cryoglobulinaemia. This ‘benign’ lymphoproliferative disorder can switch over to a malignant B‐cell non‐Hodgkin's lymphoma (NHL). Therefore HCV infection has been investigate... | 10.1038/s41572-018-0009-4 | This study provides the first insight about the crosslink between haematological malignancies, mainly B cell lymphomas, and HCV infection |
10.1002/hep.28753 | 124,358,816 | Hepatitis C virus (HCV)‐associated mixed cryoglobulinemia (MC) vasculitis commonly regresses upon virus eradication, but conventional therapy with pegylated interferon and ribavirin yields approximately 40% sustained virologic responses (SVR). We prospectively evaluated the efficacy and safety of sofosbuvir‐based direc... | 10.1038/s41572-018-0009-4 | Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for HCV-associated patients with mixed cryoglobulinaemia |
10.1016/j.jalz.2016.09.014 | 42,629,583 | Abstract The last decade has seen a substantial increase in research focused on the identification of blood‐based biomarkers that have utility in Alzheimer's disease (AD). Blood‐based biomarkers have significant advantages of being time‐ and cost‐efficient as well as reduced invasiveness and increased patient acceptanc... | 10.1038/s41582-018-0079-7 | This article provides a comprehensive review of the recent literature on blood-based biomarkers in AD and proposes a novel collaborative paradigm for advancing the field from discovery to the clinic |
10.1016/j.jalz.2012.05.2116 | 99,047,934 | Abstract The aim of this perspective article is to stimulate radical shifts in thinking and foster further discussion on the effective discovery, development, validation, and qualification process of biological markers derived from all available technical modalities that meet the complex conceptual and pathophysiologic... | 10.1038/s41582-018-0079-7 | This article is a milestone in the discovery, development, validation and qualification processes of biological markers for AD |
10.14283/jpad.2016.112 | 132,873,734 | During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer’s disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is t... | 10.1038/s41582-018-0079-7 | This pivotal article introduces the concept of precision medicine in AD |
10.3233/jad-179932 | 20,518,121 | The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as... | 10.1038/s41582-018-0079-7 | This paper highlights the development of the precision neurology paradigm in AD and the growing importance of the APMI movement |
10.1016/j.jalz.2014.08.099 | 19,758,665 | Abstract The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood‐based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal flu... | 10.1038/s41582-018-0079-7 | This article provides a summary of selected pre-analytical methodologies used in several international AD cohort studies and presents advanced guidelines and protocols for pre-analytical methods |
10.1126/science.1240636 | 41,581,092 | Diurnal Immunology Like most organ systems in the body, several components of the immune system appear to be regulated in a diurnal manner. However, the cell populations affected, the underlying molecular mechanisms controlling these processes, and the functional consequences of such regulation are poorly understood. N... | 10.1038/s41577-018-0008-4 | This paper shows that oscillations in the number of inflammatory monocytes in tissues are driven by the myeloid cell clock. |
10.1073/pnas.1106750109 | 62,276,434 | Diurnal variation in inflammatory and immune function is evident in the physiology and pathology of humans and animals, but molecular mechanisms and mediating cell types that provide this gating remain unknown. By screening cytokine responses in mice to endotoxin challenge at different times of day, we reveal that the ... | 10.1038/s41577-018-0008-4 | This article presents the first demonstration that synthetic ligands targeting a circadian clock protein modify inflammatory responses. |
10.1084/jem.20160723 | 17,325,900 | Various aspects of the immune system display circadian rhythms. Although lymphocyte trafficking has been suggested to show diurnal variations, the mechanisms and influences on immune responses are unclear. Here, we show in mice that inputs from adrenergic nerves contribute to the diurnal variation of lymphocyte recircu... | 10.1038/s41577-018-0008-4 | This study shows how adrenergic tone modulates lymphocyte trafficking rhythms and humoral immune responses through β2-adrenergic receptors expressed by lymphocytes. |
10.1182/blood-2017-04-778779 | 103,231,763 | Key Points Human circulating leukocytes in humanized mice reproduce similar circadian oscillations as seen in humans. A novel molecular clock network exhibiting opposite effects on regulating human and mouse leukocyte circadian rhythm is discovered. | 10.1038/s41577-018-0008-4 | This is a very interesting report of cell-intrinsic phase encoding of leukocytes, driven by opposite effects of p38MAPK–MK2 signalling upon HIF1α induction and CXCR4 expression. |
10.1038/s41467-017-02111-0 | 18,493,880 | Abstract The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multi... | 10.1038/s41577-018-0008-4 | This report shows the importance of appropriate immune cell crosstalk in an EAE model, as disruption of the myeloid clock increases T H 1 and T H 17 cell responses in the central nervous system. |
10.1126/science.aan0677 | 39,246,408 | Light, fat, and commensals The gut microbiota facilitates energy harvest from food and transfers it into fat storage. Working in mice, Wang et al. found that an epithelial cell circadian transcription factor, NFIL3, is involved in regulating body composition through lipid uptake. Flagellin and lipopolysaccharide produc... | 10.1038/s41577-018-0008-4 | Along with previous work from the same authors (reference 58), this study links the clock protein REV-ERBα with rhythmic expression of NFIL3, a critical regulator of both T H 17 cell differentiation and enterocyte lipid metabolism. |
10.1073/pnas.1408886111 | 125,315,029 | Significance We generated high-resolution multiorgan expression data showing that nearly half of all genes in the mouse genome oscillate with circadian rhythm somewhere in the body. Such widespread transcriptional oscillations have not been previously reported in mammals. Applying pathway analysis, we observed new cloc... | 10.1038/s41577-018-0008-4 | This article presents a comprehensive analysis of oscillating genes and non-coding RNAs in murine organs, highlighting the relationships between rhythmic genes, disease-associated genes and current drug targets. |
10.1126/science.aay5967 | 20,851,886 | Chimeric antigen receptor (CAR)–T cells have shown efficacy in patients with B cell malignancies. Yet, their application for solid tumors has challenges that include limited cancer-specific targets and nonpersistence of adoptively transferred CAR-T cells. Here, we introduce the developmentally regulated tight junction ... | 10.1038/s41565-020-00822-y | In this paper, a lipid nanomaterial-based mRNA vaccine (CARVac) was designed to enhance CAR T-cell expansion in vivo. |
10.1038/s41467-020-14425-7 | 60,442,934 | Abstract The failure of immunotherapies in immune-excluded tumor (IET) is largely ascribed to the void of intratumoral cytotoxic T cells (CTLs). The major obstacles are the excessive stroma, defective vasculatures and the deficiency of signals recruiting CTLs. Here we report a dual-mechanism based CTLs infiltration enh... | 10.1038/s41565-020-00822-y | This study developed a core–shell calcium phosphate liposome nanomaterial to enhance CTL infiltration in an immune-excluded tumour. |
10.1126/science.aav8692 | 134,025,518 | A boost for CAR–T cells Chimeric antigen receptor (CAR)–T cell immunotherapy has been highly successful for treating certain blood cancers. Yet this approach has been a challenge for solid tumors, in part because it is difficult to target functional engineered T cells to the tumor site. Ma et al. designed a vaccine str... | 10.1038/s41565-020-00822-y | In this study, amphiphile CAR T ligands that can preferentially be anchored to the dendritic cell surface to boost in vivo CAR T-cell expansion were developed |
10.1002/adma.201900192 | 41,681,956 | Abstract Chimeric antigen receptor (CAR)‐redirected T lymphocytes (CAR T cells) show modest therapeutic efficacy in solid tumors. The desmoplastic structure of the tumor and the immunosuppressive tumor microenvironment usually account for the reduced efficacy of CAR T cells in solid tumors. Mild hyperthermia of the tum... | 10.1038/s41565-020-00822-y | This study developed a photothermal agent-encapsulated PLGA nanomaterial to disrupt tumour ECM to enhance CAR T-cell penetration in solid tumour. |
10.1002/hep.28459 | 82,444,183 | Potent immunosuppressive drugs have significantly improved early patient survival after liver transplantation (LT). However, long‐term results remain unsatisfactory because of adverse events that are largely associated with lifelong immunosuppression. To solve this problem, different strategies have been undertaken to ... | 10.1038/s41575-020-0334-4 | This study is the first showing evidence that T reg cell-enriched cell therapy is efficient in inducing tolerance in adult living-donor liver transplant recipients early after the liver transplantation |
10.1182/blood-2008-05-159921 | 41,455,949 | Abstract The liver has been generally considered an organ prone to tolerance induction and maintenance. However, whether and how the unique liver microenvironment contributes to tolerance maintenance is largely unknown. Here, we used liver fibroblastic stromal cells to mimic the liver microenvironment and found that li... | 10.1038/s41575-020-0334-4 | This paper presents evidence that the liver microenvironment can programme progenitors to differentiate into regulatory dendritic cells in situ and that these cells contribute to the maintenance of liver tolerance |
10.1038/s41467-018-06318-7 | 62,216,524 | Abstract The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We prov... | 10.1038/s41575-020-0334-4 | This paper presents single-cell resolution of the characteristics of liver-resident cells, providing a map of the human hepatic immune microenvironment |
10.4049/jimmunol.1102460 | 2,676,102 | Abstract Hepatic stellate cells (HSCs) may play an important role in hepatic immune regulation by producing numerous cytokines/chemokines and expressing Ag-presenting and T cell coregulatory molecules. Due to disruption of the endothelial barrier during cold-ischemic storage and reperfusion of liver grafts, HSCs can in... | 10.1038/s41575-020-0334-4 | This paper presents data suggesting that endotoxin-stimulated HSCs might serve as important immune regulators in liver transplantation by inducing selective expansion of tolerance-promoting T reg cells and reducing inflammation and alloimmunity |
10.1073/pnas.1406674111 | 41,420,683 | Significance The liver possesses unique immunological properties, with the capability of inducing tolerance upon transplantation, yet is also the target of immune-mediated damage in chronic viral hepatitis. To investigate the basis of these dichotomous outcomes, we manipulated several determinants capable of influencin... | 10.1038/s41575-020-0334-4 | This study reveals a hierarchy of factors that determine the fate of CD8 + T cells during hepatic immune responses and provides an explanation for different immune outcomes under various immune-mediated liver pathological conditions |
10.4049/jimmunol.158.10.4654 | 139,041,730 | Abstract MHC-mismatched liver grafts are accepted spontaneously between many mouse strains. The underlying mechanism(s) is unclear. In the B10 (H2(b)) to C3H (H2(k)) strain combination used in this study, donor T cells within the liver were rapidly replaced within 2 to 4 days of transplantation with those of the recipi... | 10.1038/s41575-020-0334-4 | This paper presents observations suggesting that deletion of graft-infiltrating cytotoxic T cells might be responsible for spontaneous liver allograft acceptance in the mouse |
10.1002/hep.29529 | 82,119,554 | Although a key role of cross‐dressing has been established in immunity to viral infection and more recently in the instigation of transplant rejection, its role in tolerance is unclear. We investigated the role of intragraft dendritic cells (DCs) and cross‐dressing in mouse major histocompatibility complex (MHC)‐mismat... | 10.1038/s41575-020-0334-4 | This study is the first demonstration that cross-dressing (acquisition of intact donor MHC antigen) of host dendritic cells has an important role in experimental organ transplant tolerance |
10.1017/cbo9781107415324 | 83,558,975 | This latest Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) will again form the standard scientific reference for all those concerned with climate change and its consequences, including students and researchers in environmental science, meteorology, climatology, biology, ecology and atmo... | 10.1038/s41586-018-0173-4 | The latest comprehensive assessment of the state and future of the climate system, based on observations and Earth system models |
10.1126/science.1222821 | 107,159,900 | Changing environments and resource demands present challenges to Antarctic conservation. | 10.1038/s41586-018-0173-4 | This horizon-scanning assessment provides an inclusive examination of current and future conservation challenges for Antarctica and the Southern Ocean. |
10.1126/science.aah3443 | 104,261,785 | Emissions inevitably approach zero with a “carbon law” | 10.1038/s41586-018-0173-4 | This paper presents a roadmap to decarbonisation consistent with achieving the goals of the Paris Agreement, highlighting the necessity for fossil fuel emissions to peak by 2020. |
10.1126/science.1256117 | 19,030,465 | Decadal trends in the properties of seawater adjacent to Antarctica are poorly known, and the mechanisms responsible for such changes are uncertain. Antarctic ice sheet mass loss is largely driven by ice shelf basal melt, which is influenced by ocean-ice interactions and has been correlated with Antarctic Continental S... | 10.1038/s41586-018-0173-4 | This paper summarises changes observed in the Southern Ocean in recent decades, showing that continental shelf waters have warmed in the Amundsen Sea and driven thinning of ice shelves and retreat of grounding lines in this sector. |
10.1126/science.1249055 | 83,462,565 | Antarctic Collapse The West Antarctic Ice Sheet (WAIS) is particularly vulnerable to ocean warming-induced collapse. The Thwaites Glacier of West Antarctica is one of the largest WAIS regional contributors to sea level rise, and has been considered to be potentially unstable for many years. Joughin et al. (p. 735 ) use... | 10.1038/s41586-018-0173-4 | Ice sheet model simulations suggest that unstable retreat of the Thwaites Glacier, the largest drainage of the West Antarctic Ice Sheet, is already underway, although the timing of full collapse is uncertain. |
10.1126/science.aaa0940 | 20,759,744 | Disappearing faster around the edges The floating ice shelves around Antarctica, which buttress ice streams from the continent and slow their discharge into the sea, are thinning at faster rates. Paolo et al. present satellite data showing that ice shelves in many regions around the edge of the continent are losing mas... | 10.1038/s41586-018-0173-4 | A multi-mission record (1994 to 2012) of ice-shelf surface height from satellite radar altimetry showed accelerated loss of volume of Antarctica’s ice shelves, with early small increases in East Antarctica due to accumulation, and substantial losses in West Antarctica, where some ice shelves thinned by up to 18% in the... |
10.1126/science.aah4119 | 44,128,338 | The burden of proof is being turned upside down | 10.1038/s41586-018-0173-4 | Here, an evidence-based argument is laid out for why the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) faces a critical window of opportunity to remain a global leader in resource management. |
10.1111/gcb.12794 | 29,337,209 | Abstract A quantitative assessment of observed and projected environmental changes in the Southern Ocean ( SO ) with a potential impact on the marine ecosystem shows: (i) large proportions of the SO are and will be affected by one or more climate change processes; areas projected to be affected in the future are larger... | 10.1038/s41586-018-0173-4 | An integrated assessment of how environmental change drivers will act in concert to affect Southern Ocean benthic, pelagic and sea-ice species and ecosystems. |
10.1039/c6mb00678g | 31,366,792 | Small-molecule marine natural products are identified to selectively recognize and stabilize the DNA-binding conformation of FOXO1, an oncogenic transcription factor. | 10.1038/s41573-020-0088-2 | This study reports the discovery of small-molecule compounds capable of stabilizing the DNA-bound conformation of FOXO1 |
10.1038/s41388-019-1044-7 | 104,150,979 | Abstract The transcription factor FOXO3 has been associated in different tumor entities with hallmarks of cancer, including metastasis, tumor angiogenesis, maintenance of tumor-initiating stem cells, and drug resistance. In neuroblastoma (NB), we recently demonstrated that nuclear FOXO3 promotes tumor angiogenesis in v... | 10.1038/s41573-020-0088-2 | This paper reports a drug-repurposing approach to identify compounds that bind to the FOXO3 DNA-binding domain and inhibit the transcriptional activity of FOXO3 |
10.1073/pnas.0801030105 | 38,256,693 | Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents. Increasing evidence from animal models suggests that the insulin/IGF-1 signaling (IIS) pathway is an important, evolutionarily conserved biological pathway that influences aging and longevity... | 10.1038/s41573-020-0088-2 | This paper is the first report of a polymorphism in the FOXO3 gene associated with human longevity |
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