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.1305275110 | 27,964,529 | Significance We determined the transcriptional program that is rapidly provoked to counteract heat-induced stress and uncovered the broad range of molecular mechanisms that maintain cellular homeostasis under hostile conditions. Because transcriptional responses are directed in the complex chromatin environment that un... | 10.1038/s41576-018-0001-6 | This study maps HSF1 and HSF2 target loci in freely cycling and mitotic human cells, demonstrating how HSF2 marks genes for post-mitotic transcription whereas HSF1 is largely excluded from the dividing chromatin. |
10.1126/science.1162228 | 41,536,477 | RNA polymerases are highly regulated molecular machines. We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and map... | 10.1038/s41576-018-0001-6 | This report describes the development of global run-on sequencing methodology and the identification of divergent transcription from genes. |
10.1126/science.1229386 | 83,341,971 | Pressing Pause The pausing of RNA polymerase II (Pol II) near promoters is an important and distinct regulatory step in the process of transcribing DNA into RNA. Although protein factors and DNA elements involved in pausing have been identified, the post-initiation events that lead to pausing are poorly understood. Kwa... | 10.1038/s41576-018-0001-6 | In this study, the authors refine global run-on sequencing to nucleotide resolution and identify mechanisms that coordinate initiation and pausing. |
10.1073/pnas.1711120114 | 82,999,001 | Transcription is a highly regulated process, and stress-induced changes in gene transcription have been shown to play a major role in stress responses and adaptation. Genome-wide studies reveal prevalent transcription beyond known protein-coding gene loci, generating a variety of RNA classes, most of unknown function. ... | 10.1038/s41576-018-0001-6 | This paper describes global read-through transcription upon osmotic, oxidative or heat stress. |
10.4049/jimmunol.169.7.3883 | 103,274,712 | Abstract The role of LL-37, a human cationic antimicrobial peptide, in the immune system is not yet clearly understood. It is a widely expressed peptide that can be up-regulated during an immune response. In this report, we demonstrate that LL-37 is a potent antisepsis agent with the ability to inhibit macrophage stimu... | 10.1038/s41573-019-0058-8 | One of the first studies to demonstrate the immunomodulatory properties of CHDP LL-37 and discuss immunomodulation as being critical to the antimicrobial functions of the peptide |
10.1136/thoraxjnl-2017-210739 | 109,428,277 | Background Exacerbation in asthma is associated with decreased expression of specific host defence peptides (HDPs) in the lungs. We examined the effects of a synthetic derivative of HDP, innate defence regulator (IDR) peptide IDR-1002, in house dust mite (HDM)-challenged murine model of asthma, in interleukin (IL)-33-c... | 10.1038/s41573-019-0058-8 | The first study to demonstrate the therapeutic potential of an IDR peptide in allergen-challenged airway inflammation in the context of asthma |
10.1073/pnas.1101130108 | 103,231,125 | Natural antimicrobial peptides (AMPs) provide prototypes for the design of unconventional antimicrobial agents. Existing bulk assays measure AMP activity but do not provide details of the growth-halting mechanism. We use fluorescence microscopy to directly observe the attack of the human antimicrobial peptide LL-37 on ... | 10.1038/s41573-019-0058-8 | The real-time attack on E. coli by the cathelicidin LL-37 is visualized for the first time |
10.1111/j.1432-1033.1996.0325z.x | 38,431,645 | The peptide FA‐LL‐37, previously termed FALL‐39, was originally predicted from an ORF of a cDNA clone isolated from a human bone marrow library. This peptide was synthesized and found to have antibacterial activity. We have now characterized and sequenced the complete gene for FA‐LL‐37, termed FALL39. It is a compact g... | 10.1038/s41573-019-0058-8 | A seminal study which defines post-translational processing of cathelin precursor propeptide to the mature CHDP LL-37 |
10.1126/scitranslmed.3003515 | 111,047,485 | Anti-inflammatory drugs based on host defense peptides affected a host-directed therapy in an expanded murine model of severe malaria. | 10.1038/s41573-019-0058-8 | The first study to demonstrate effective adjuvant therapeutic potential of a IDR peptide with existing drugs in a parasitic infection model |
10.7554/elife.44341 | 123,019,631 | Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little vali... | 10.1038/s41573-019-0058-8 | Using a systematic knockout approach, this study demonstrates that CHDP have synergistic, additive and highly specific microbicidal effects in vivo |
10.1128/iai.00546-17 | 41,302,735 | ABSTRACT The development of antibiotic resistance by Pseudomonas aeruginosa is a major concern in the treatment of bacterial pneumonia. In the search for novel anti-infective therapies, the chicken-derived peptide cathelicidin-2 (CATH-2) has emerged as a potential candidate, with strong broad-spectrum antimicrobial act... | 10.1038/s41573-019-0058-8 | This study demonstrates that chicken cathelicidin CATH-2 kills P. aeruginosa in an immunogenically silent manner and controls lung inflammation in vivo, making a case for the development of CHDP-based anti-infectives with both antimicrobial and immunomodulatory functions |
10.1515/bc.2009.037 | 47,768,709 | Abstract Cathelicidins are effector molecules of the innate host defense system that establish an antimicrobial barrier at epithelial interfaces. The human cathelicidin LL-37, in addition to its antimicrobial activity, also exhibits immunomodulatory effects, such as inhibition of pro-inflammatory responses to bacterial... | 10.1038/s41573-019-0058-8 | The first study to interrogate the sequence–function relationship in the immunomodulatory functions of CHDP. |
10.1111/wrr.12211 | 124,756,397 | Abstract Venous leg ulcers ( VLUs ) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose–response efficacy of the human synthetic peptide LL ‐37 in the treatment of hard‐to‐heal VLUs . This first‐in‐man trial included 34 participants with VLUs and comprised a... | 10.1038/s41573-019-0058-8 | The first randomized clinical trial of a CHDP shown to be effective in hard-to-heal venous leg ulcers |
10.1038/srep26622 | 109,441,289 | Abstract Increasing antibiotic resistance and ever stricter control on antibiotic use are a driving force to develop alternatives to antibiotics. One such strategy is the use of multifunctional Host Defense Peptides. Here we examined the protective effect of prophylactic treatment with the D analog of chicken cathelici... | 10.1038/s41573-019-0058-8 | The first study to demonstrate that prophylactic cathelicidin treatment of chick embryos in ovo partially protects chickens from E. coli infection 10 days later, thus establishing the use in veterinary medicine |
10.4049/jimmunol.148.7.2207 | 139,063,456 | Abstract During normal tissue remodeling, macrophages remove unwanted cells, including those that have undergone programmed cell death, or apoptosis. This widespread process extends to the deletion of thymocytes (negative selection), in which cells expressing inappropriate Ag receptors undergo apoptosis, and are phagoc... | 10.1038/s41573-022-00470-y | This classic study identifies PS as a signal exposed on apoptotic cells and its recognition by macrophages as an ‘eat-me’ signal |
10.1189/jlb.0307192 | 100,971,580 | Abstract One of the most important functions of macrophages is the phagocytosis of apoptotic cells (ACs). ACs deliver large amounts membrane-derived cholesterol to phagocytes, which, if not handled properly, can be cytotoxic. In atherosclerosis, where the ACs are cholesterol-loaded, this situation is exaggerated, becau... | 10.1038/s41573-022-00470-y | This important study highlights the metabolic adaptability of macrophages, enabling them to handle the cholesterol burden derived from apoptotic cargo |
10.1073/pnas.1305569110 | 104,208,188 | Mobilization of the T-cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to harness antigen-presenting cells optimally to achieve an effective antitumor T-cell response. In this study, we show that anti-CD47 antibody–mediated phagocytosis of cancer by macrophages ... | 10.1038/s41573-022-00470-y | Together with Jaiswal et al. (2009), this paper presents early findings highlighting the role of CD47 in driving a poor cancer prognosis |
10.1126/science.282.5396.2072 | 62,239,816 | The trophoblast cell lineage is essential for the survival of the mammalian embryo in utero. This lineage is specified before implantation into the uterus and is restricted to form the fetal portion of the placenta. A culture of mouse blastocysts or early postimplantation trophoblasts in the presence of fibroblast grow... | 10.1038/s41576-019-0169-4 | This study describes the ground-breaking derivation of mouse trophoblast stem cells, thereby providing a fundamental research tool that has substantially advanced our understanding of the mechanistic principles underlying trophoblast development |
10.1126/science.aaj2239 | 103,762,457 | Positives and negatives of methylated CpG When the DNA bases cytosine and guanine are next to each other, a methyl group is generally added to the pyrimidine, generating a mCpG dinucleotide. This modification alters DNA structure but can also affect function by inhibiting transcription factor (TF) binding. Yin et al. s... | 10.1038/s41576-019-0169-4 | This paper systematically analyses the DNA-binding preferences of human transcription factors that depend on the methylation state of CpGs contained within their cognate motifs, thus directly linking the transcription factor network with the epigenome to explain cell fate specification and cellular commitment decisions |
10.1073/pnas.96.24.13638 | 81,688,544 | Combinatorial libraries of synthetic and natural products are an important source of molecular information for the interrogation of biological targets. Methods for the intracellular production of libraries of small, stable molecules would be a valuable addition to existing library technologies by combining the discover... | 10.1038/s41570-019-0159-2 | This paper reports the use of SICLOPPS inteins for cyclic-peptide generation |
10.1101/470476 | 29,129,533 | Abstract Post-translational modifications of alpha-synuclein (aSyn), particularly phosphorylation at Serine 129 (Ser129-p) and truncation of its C-terminus (CTT), have been implicated in Parkinson’s disease (PD) pathology. To gain more insight in the relevance of Ser129-p and CTT aSyn under physiological and pathologic... | 10.1038/s41583-020-00416-6 | This article examines the distribution of α-syn species and neurofilaments in nigral LBs and demonstrates concentric structural organization of LBs with truncated α-syn species dominating the core region, which is surrounded by layers of phosphorylated α-syn species and neurofilaments |
10.1073/pnas.1913904117 | 20,640,821 | Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, the processes that govern α-syn fibrillization and LB formation r... | 10.1038/s41583-020-00416-6 | This study describes a neuronal seeding-based model that reproduces several key events leading to the formation of LBs, including seeding, fibrillization and formation of inclusions that recapitulate many of the key biochemical, morphological and organizational features of bona fide LBs |
10.1073/pnas.95.11.6469 | 125,277,293 | Lewy bodies and Lewy neurites are the defining neuropathological characteristics of Parkinson’s disease and dementia with Lewy bodies. They are made of abnormal filamentous assemblies of unknown composition. We show here that Lewy bodies and Lewy neurites from Parkinson’s disease and dementia with Lewy bodies are stain... | 10.1038/s41583-020-00416-6 | This study shows that α-syn filaments can be isolated from LBs and suggests that α-syn forms the major filamentous component of LBs seen in previous EM studies of LBs |
10.1073/pnas.1906124116 | 103,276,426 | Many neurodegenerative diseases are characterized by the accumulation of abnormal protein aggregates in the brain. In Parkinson’s disease (PD), α-synuclein (α-syn) forms such aggregates called Lewy bodies (LBs). Recently, it has been reported that aggregates of α-syn with a cross-β structure are capable of propagating ... | 10.1038/s41583-020-00416-6 | Using microbeam X-ray diffraction, this study confirms that α-syn-positive LBs in the brains of patients contain fibrils that possess the cross-β structure characteristics for amyloid fibrils |
10.1111/j.1750-3639.2007.00048.x | 82,540,212 | Lewy body (LB) inclusions are one of the pathological hallmarks of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). One way to better understand the process leading to LB formation and associated pathogenesis responsible for neurodegeneration in PD and DLB is to examine the content of LB inclusions. Here, ... | 10.1038/s41583-020-00416-6 | This is one of the first studies that sought to define the proteome of LBs by performing a proteomics investigation on 2,500 cortical LBs isolated by laser capture microdissection |
10.1073/pnas.1512876113 | 38,201,780 | Lewy bodies (LBs) are intraneuronal inclusions consisting primarily of fibrillized human α-synuclein (hα-Syn) protein, which represent the major pathological hallmark of Parkinson's disease (PD). Although doubling hα-Syn expression provokes LB pathology in humans, hα-Syn overexpression does not trigger the formation of... | 10.1038/s41583-020-00416-6 | This study demonstrates that the lack of human α-syn fibrillization in rodent neuronal models could be due to interactions between human α-syn and the endogenously expressed mouse α-syn homologue, and shows that transient expression of human WT α-syn in Snca -knockout neurons leads to the formation of spheroid fibrilla... |
10.1073/pnas.152339799 | 20,392,526 | Parkinson's disease (PD) is characterized by the progressive loss of substantia nigra dopaminergic neurons and the presence of cytoplasmic inclusions named Lewy bodies. Two missense mutations of the α-synuclein (α-syn; A30P and A53T) have been described in several families with an autosomal dominant form of PD. α-Syn a... | 10.1038/s41583-020-00416-6 | This study reports a lentiviral α-syn overexpression-based model of PD that exhibits selective loss of nigral dopaminergic neurons and the appearance of human α-syn non-fibrillar positive inclusions and neuritic pathology. Similar inclusions are formed by rat α-syn in the absence of neuronal loss |
10.1073/pnas.0409713102 | 38,410,021 | In animals, sporadic injections of the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively damage dopaminergic neurons but do not fully reproduce the features of human Parkinson's disease. We have now developed a mouse Parkinson's disease model that is based on continuous MPTP administra... | 10.1038/s41583-020-00416-6 | This study demonstrates that continuous low-dose administration of MPTP produces progressive behavioural changes, causes α-syn-dependent inhibition of the ubiquitin–proteasome system and results in the formation of inclusions immunoreactive for ubiquitin and α-syn |
10.1002/mds.22481 | 4,838,038 | Abstract The recent knowledge that 10 years after transplantation surviving human fetal neurons adopt the histopathology of Parkinson's disease suggests that Lewy body formation takes a decade to achieve. To determine whether similar histopathology occurs in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐primate m... | 10.1038/s41583-020-00416-6 | In this study, the authors demonstrate that MPTP administration in monkeys induces the accumulation of α-syn, but is not sufficient to trigger the formation of classical LBs |
10.1111/j.1750-3639.2008.00140.x | 100,310,892 | Abstract Lewy bodies (LBs) and Lewy neurites (LNs) are the hallmarks of Parkinson's disease (PD). Although LBs and LNs, frequently coexistent, share some histological properties, their appearances are quite different under conventional two‐dimensional observation. In order to clarify how these apparently different stru... | 10.1038/s41583-020-00416-6 | In this study, the authors use three-dimensional confocal image reconstruction of serial tissue sections that were triply immunolabelled with antibodies to α-syn, ubiquitin and neurofilaments to reveal the internal three-layered structure of LBs and LNs, and provide evidence in support of the hypothesis that LNs and LB... |
10.1073/pnas.0908005106 | 41,620,662 | Cytoplasmic inclusions containing α-synuclein (α-Syn) fibrils, referred to as Lewy bodies (LBs), are the signature neuropathological hallmarks of Parkinson's disease (PD). Although α-Syn fibrils can be generated from recombinant α-Syn protein in vitro, the production of fibrillar α-Syn inclusions similar to authentic L... | 10.1038/s41583-020-00416-6 | This study demonstrates that exogenous addition of PFFs to cultured cells leads to seeding and formation of inclusions that recapitulate several key features of LBs, including being fibrillar, insoluble, hyperphosphorylated and ubiquitinated |
10.1101/500058 | 81,929,976 | Although converging evidence point to alpha-synuclein (a-syn) aggregation and Lewy body (LB) formation as central events in Parkinson's disease (PD), the molecular mechanisms that regulate these processes and their role in disease pathogenesis remain poorly understood. Herein, we applied an integrative biochemical, str... | 10.1038/s41583-020-00416-6 | This study establishes the critical role of postfibrillization C-terminal truncation in the processing of α-syn fibrils, α-syn seeding, fibrillization, and LB formation and maturation |
10.1002/anie.201813996 | 83,270,259 | Abstract Metal–organic frameworks (MOFs) enable the design of host–guest systems with specific properties. In this work, we show how the confinement of anthracene in a well‐chosen MOF host leads to reversible yellow‐to‐purple photoswitching of the fluorescence emission. This behavior has not been observed before for an... | 10.1038/s41565-020-0652-2 | Confinement of four anthracene molecules within a single cavity leads to selective photodimerization of only two anthracene molecules because of steric restraints |
10.1126/science.aaa7169 | 20,368,535 | Biodegradable and renewable polymers, such as polylactic acid, are benign alternatives for petrochemical-based plastics. Current production of polylactic acid via its key building block lactide, the cyclic dimer of lactic acid, is inefficient in terms of energy, time, and feedstock use. We present a direct zeolite-base... | 10.1038/s41565-020-0652-2 | Shape-selectivity under confinement allows stereoselective conversion of l -lactic acid to ( l , l )-lactide in near-quantitative yields surpassing the industrial state-of-the-art |
10.1038/s41467-019-11885-4 | 104,201,061 | Abstract On-command changes in the emission color of functional materials is a sought-after property in many contexts. Of particular interest are systems using light as the external trigger to induce the color changes. Here we report on a tri-component cocktail consisting of a fluorescent donor molecule and two photoch... | 10.1038/s41565-020-0652-2 | Confinement of blue fluorescent donor molecules with red and green photochromic acceptor molecules within micelles allows energy transfer between the confined species, resulting in controlled emission throughout the entire RGB colour system |
10.1126/science.1246738 | 38,423,279 | We report a strategy for realizing tunable electrical conductivity in metal-organic frameworks (MOFs) in which the nanopores are infiltrated with redox-active, conjugated guest molecules. This approach is demonstrated using thin-film devices of the MOF Cu 3 (BTC) 2 (also known as HKUST-1; BTC, benzene-1,3,5-tricarboxyl... | 10.1038/s41565-020-0652-2 | Unique example in which charge transfer between a confined species and the metal–organic framework of its environment results in conductivity throughout the material |
10.1126/science.aan6619 | 20,811,966 | Programmed recognition of microbiota Increasingly, we recognize that the gut is a specialized organ for maintaining microbial symbioses alongside nutritional functions. The gut produces large quantities of immunoglobulin A (IgA), which adheres to the surface of gut microbes. Bunker et al. discovered that antibodies pro... | 10.1038/s41590-022-01346-4 | This study profiled the antigen specificities of a large collection of mouse IgA-producing PCs, and showed that many of them are innate-like and microbiota reactive. |
10.1101/2020.04.07.028837 | 33,600,931 | Abstract Our understanding of the host component of sepsis has made significant progress. However, detailed study of the microorganisms causing sepsis, either as single pathogens or microbial assemblages, has received far less attention. Metagenomic data offer opportunities to characterise the microbial communities fou... | 10.1038/s41564-023-01364-4 | Study investigating microbial signatures in sepsis that inspired the current study. |
10.1146/annurev-physchem-103019-033434 | 37,903,343 | Gram-negative bacteria are protected by a multicompartmental molecular architecture known as the cell envelope that contains two membranes and a thin cell wall. As the cell envelope controls influx and efflux of molecular species, in recent years both experimental and computational studies of such architectures have se... | 10.1038/s41579-021-00638-0 | This review discusses recent progress in and challenges for computational simulations of the inner and outer membranes and the periplasm, with an emphasis on molecular interactions and the spatial organization of membrane structures |
10.1038/s41467-020-15489-1 | 38,789,778 | Abstract The mechanical properties of the cell envelope in Gram-negative bacteria are controlled by the peptidoglycan, the outer membrane, and the proteins interacting with both layers. In Escherichia coli , the lipoprotein Lpp provides the only covalent crosslink between the outer membrane and the peptidoglycan. Here,... | 10.1038/s41579-021-00638-0 | With use of AFM, the lipoprotein Lpp was found to affect the dimensions and the mechanical stiffness of E. coli cells |
10.1073/pnas.1420588112 | 20,597,049 | In general, phages cause lysis of the bacterial host to effect release of the progeny virions. Until recently, it was thought that degradation of the peptidoglycan (PG) was necessary and sufficient for osmotic bursting of the cell. Recently, we have shown that in Gram-negative hosts, phage lysis also requires the disru... | 10.1038/s41579-021-00638-0 | Fusion of the cytoplasmic membrane and the outer membrane, which serves as the last step in phage-induced cell lysis, is found to be mediated by the phage-encoded protein spanin |
10.1126/science.aah6066 | 125,199,539 | Now you feel it, now you don't What determines the detection of a sensory stimulus? To address this question, Takahashi et al. combined in vivo two-photon imaging, electrophysiology, optogenetics, and behavioral analysis in a study of mice. Calcium signals in apical dendrites of pyramidal neurons in the somatosensory c... | 10.1038/s41583-020-0301-7 | This work is one of the very few experimental studies that causally link dendritic activity in a primary sensory area with a high-level cognitive function, namely sensory perception |
10.1126/science.1189664 | 61,390,444 | Discriminating Dendrites Can dendrites read out spatiotemporal input sequences? Combining two-photon glutamate uncaging and two-photon calcium imaging, electrophysiology, and computational modeling, Branco et al. (p. 1671 , published online 12 August; see the Perspective by Destexhe ) discovered that single dendrites w... | 10.1038/s41583-020-0301-7 | This study, by combining experiments with biophysical modelling, reveals that dendrites can detect the activation order of their incoming inputs, confirming Rall’s (1964) early theoretical prediction, owing to the non-linear activation of NMDARs and the impedance gradient along the somato-dendritic axis |
10.1126/science.aan3846 | 62,339,567 | A different form of synaptic plasticity How do synaptic or other neuronal changes support learning? This subject has been dominated by Hebb's postulate of synaptic change. Although there is strong experimental support for Hebbian plasticity in a number of preparations, alternative ideas have also been developed over th... | 10.1038/s41583-020-0301-7 | This study, through the combination of in vivo, in vitro and modelling approaches, shows a dendritic mechanism for one-shot learning: a single strong Ca 2+ plateau potential in neuronal dendrites paired with spatial inputs can be sufficient to produce place cells |
10.1126/science.aax6239 | 62,476,080 | The active electrical properties of dendrites shape neuronal input and output and are fundamental to brain function. However, our knowledge of active dendrites has been almost entirely acquired from studies of rodents. In this work, we investigated the dendrites of layer 2 and 3 (L2/3) pyramidal neurons of the human ce... | 10.1038/s41583-020-0301-7 | This study, through a combination of electrophysiology and biophysical modelling, discovers a new type of dendritic action potential that enables human neurons — or, in fact, their dendrites — to solve the XOR problem |
10.7554/elife.89674.2 | 144,039,067 | One of the most fundamental laws of physics is the principle of least action. Motivated by its predictive power, we introduce a neuronal least-action principle for cortical processing of sensory streams to produce appropriate behavioural outputs in real time. The principle postulates that the voltage dynamics of cortic... | 10.1038/s41583-020-0301-7 | This work presents circuit-level implementation of a biologically plausible backpropagation algorithm, where the prediction error is produced by a mismatch of feedback excitation and local inhibition in the apical dendrites of model neurons |
10.1101/566588 | 122,828,348 | Abstract Pyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron’s stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron’s dend... | 10.1038/s41583-020-0301-7 | The laser ablation technique introduced in this study allows the causal manipulation of dendritic contributions to function; experiments showed no effect of apical-tree ablation in orientation-tuning properties, whereas modelling predicted that a diverse structure of inputs to the basal dendrites best explains experime... |
10.1038/s41467-020-14381-2 | 41,134,858 | Abstract Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. ... | 10.1038/s41568-022-00446-5 | This proteogenomic study of core needle biopsy samples establishes proof of concept for genomic and proteomic profiling starting from small sample quantities |
10.1038/ncomms10842 | 38,325,982 | Abstract Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption t... | 10.1038/s41580-018-0049-3 | This is the first detailed study on the role of kinetics in GPCR biased agonism that highlights the importance of considering kinetic context in the design and interpretation of biased agonism |
10.1073/pnas.1110499108 | 38,429,912 | A third of marketed drugs act by binding to a G-protein-coupled receptor (GPCR) and either triggering or preventing receptor activation. Although recent crystal structures have provided snapshots of both active and inactive functional states of GPCRs, these structures do not reveal the mechanism by which GPCRs transiti... | 10.1038/s41580-018-0049-3 | This study provides long-timescale, atomic-level simulations that reveal the dynamics associated with activation of a GPCR as it transitions between multiple conformational states |
10.1126/science.aaa5264 | 20,525,035 | How a receptor transmits a signal G protein–coupled receptors (GPCRs) transmit diverse external signals into the cell. When activated by an outside stimulus, they bind to a G protein inside the cell and accelerate exchange of a bound guanosine diphosphate (GDP) nucleotide for guanosine triphosphate, which initiates int... | 10.1038/s41580-018-0049-3 | This study used atomic-level simulations to elucidate the nucleotide release mechanism, which is critical for G protein activation |
10.1126/science.1215802 | 41,514,186 | Choosing a Path The β 2 -adrenergic receptor (β 2 AR) is a G protein–coupled receptor that recognizes diverse ligands to trigger signaling in the cell. Besides binding G proteins, activated β 2 AR can be phosphorylated and bind arrestin, which redirects signaling to other pathways. Some β 2 AR ligands are “biased” in t... | 10.1038/s41580-018-0049-3 | This study uses NMR techniques to observe conformational differences induced in a GPCR by biased ligands |
10.1073/pnas.1205756110 | 40,876,560 | G protein-coupled receptors (GPCRs) participate in ubiquitous transmembrane signal transduction processes by activating heterotrimeric G proteins. In the current “canonical” model of GPCR signaling, arrestins terminate receptor signaling by impairing receptor–G-protein coupling and promoting receptor internalization. H... | 10.1038/s41580-018-0049-3 | This study is one of the first to report a GPCR that promotes persistent G protein signalling from intracellular endosomal compartments, which is mediated by β-arrestins |
10.1126/science.1093857 | 125,149,857 | We have applied âwhole-genome shotgun sequencingâ to microbial populations collected en masse on tangential flow and impact filters from seawater samples collected from the Sargasso Sea near Bermuda. A total of 1.045 billion base pairs of nonredundant sequence was generated, annotated, and analyzed to elucidate the... | 10.1038/s41579-020-0364-5 | This study applies high-throughput DNA sequencing to produce a large data set of microbial community genome fragments from surface seawaters of the Sargasso Sea and identifies more than 1.2 million previously unknown genes, illustrating the diversity of ocean microbial life |
10.1126/science.1261498 | 104,311,166 | Viruses influence ecosystems by modulating microbial population size, diversity, metabolic outputs, and gene flow. Here, we use quantitative double-stranded DNA (dsDNA) viral-fraction metagenomes (viromes) and whole viral community morphological data sets from 43 Tara Oceans expedition samples to assess viral community... | 10.1038/s41579-020-0364-5 | This article describes the first of the Tara Oceans efforts to investigate the diversity and structure of double-stranded DNA viral communities in the oceans, supporting a model of passive global transport by ocean currents and selection by local environmental conditions |
10.1126/science.1261359 | 41,685,499 | Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and meso... | 10.1038/s41579-020-0364-5 | This study catalogues 40 million ocean microbial genes and shows temperature to be a main driver of open-ocean microbial community composition in the epipelagic zone at a global scale |
10.1126/science.1261605 | 41,543,108 | Marine plankton support global biological and geochemical processes. Surveys of their biodiversity have hitherto been geographically restricted and have not accounted for the full range of plankton size. We assessed eukaryotic diversity from 334 size-fractionated photic-zone plankton communities collected across tropic... | 10.1038/s41579-020-0364-5 | This study surveys the eukaryotic diversity of ocean plankton from the smallest protists to millimetre-sized animals by 18S ribosomal RNA gene amplicon sequencing, revealing 150,000 taxonomic groups dominated by protistan parasites and symbiotic hosts |
10.1126/science.1262073 | 62,587,594 | Species interaction networks are shaped by abiotic and biotic factors. Here, as part of the Tara Oceans project, we studied the photic zone interactome using environmental factors and organismal abundance profiles and found that environmental factors are incomplete predictors of community structure. We found associatio... | 10.1038/s41579-020-0364-5 | This study evaluates the effect of abiotic and biotic factors on organismal interactions among bacteria, archaea, eukaryotes and viruses, emphasizing the role of grazing, pathogenicity and parasitism as predictors of plankton community structure |
10.1126/science.aac4785 | 62,314,738 | Let me comfort you Consolation behavior promotes stress reduction of one by another. We know that consolation occurs in humans and apes. Burkett et al. observed that within a pair of monogamous prairie voles, an unstressed partner increased its grooming of a stressed partner. Furthermore, the unstressed partner matched... | 10.1038/s41583-018-0072-6 | This study demonstrates that consoling behaviour in prairie voles displays multiple qualities that are characteristic of empathy and is regulated by OT receptors in the anterior cingulate cortex |
10.1038/tp.2015.73 | 83,170,825 | Abstract Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity... | 10.1038/s41583-018-0072-6 | This paper shows that daily neonatal social isolations disrupt adult pair bond formation and that those animals with many OXTRs in the NAc are resilient to the effects of this model of neglect |
10.1126/science.aac5791 | 81,545,421 | From faithfulness to spatial memory Natural selection shapes traits to be as adaptive as possible for a given environment. Okhovat et al. show that such varying selection also shapes variation in social behavior and the brain (see the Perspective by Robinson). Variation in male fidelity among monogamous prairie voles r... | 10.1038/s41583-018-0072-6 | This study demonstrates that sequence variation in the vasopressin receptor gene influences expression in a brain region involved in spatial memory and influences sexual fidelity in a naturalistic setting |
10.1126/science.aaf7003 | 20,654,673 | The medial temporal lobe, including the hippocampus, has been implicated in social memory. However, it remains unknown which parts of these brain regions and their circuits hold social memory. Here, we show that ventral hippocampal CA1 (vCA1) neurons of a mouse and their projections to nucleus accumbens (NAc) shell pla... | 10.1038/s41583-018-0072-6 | This study demonstrates the existence of a social engram, or a collection of neurons whose firing represents the identity of another individual, in the ventral hippocampus that projects to the NAc |
10.2337/dci17-0045 | 82,993,642 | The placenta plays a key role in sustaining fetal growth and development. Due to its position between mother and fetus, it is exposed to changes in the intrauterine environment in both circulations. The relative influence of changes in those circulations depends on the period of gestation. Early in pregnancy, maternal ... | 10.1038/s41572-019-0098-8 | This article provides a comprehensive overview of placental structure and function in diabetic pregnancy |
10.1073/pnas.1605245113 | 38,313,972 | Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using 18 F-fluorodopa and 11 C-raclopride positron emission tomography. Here we report the postmortem analysis of... | 10.1038/s41586-018-0087-1 | A key study showing good graft survival and transplantation in a patient with Parkinson’s disease 24 years after transplantation. |
10.1126/science.346.6206.237 | 104,227,100 | Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 ... | 10.1038/s41586-018-0087-1 | This work shows the in vivo conversion of astrocytes into neurons solely by removing Notch signalling and that this conversion occurs in an interesting region-specific manner only in the striatum, showing that these astrocytes are more prone to neurogenesis than others. |
10.1002/prot.20897 | 4,741,808 | Abstract In this article we introduce a new method for the identification and the accurate characterization of protein surface cavities. The method is encoded in the program SCREEN (Surface Cavity REcognition and EvaluatioN). As a first test of the utility of our approach we used SCREEN to locate and analyze the surfac... | 10.1038/s41573-019-0024-5 | This article describes a classifier to identify drug-binding cavities on the basis of physicochemical, structural and geometric attributes of proteins |
10.1039/c8sc00148k | 103,641,633 | The to date largest comparative study of nine state-of-the-art drug target prediction methods finds that deep learning outperforms all other competitors. The results are based on a benchmark of 1300 assays and half a million compounds. | 10.1038/s41573-019-0024-5 | This research paper describes the methodology being used by the winners of almost all categories of the Tox21 Challenge |
10.1038/s41467-018-05044-4 | 18,621,749 | Abstract Sustained clinical remission (CR) without drug treatment has not been achieved in patients with rheumatoid arthritis (RA). This implies a substantial difference between CR and the healthy state, but it has yet to be quantified. We report a longitudinal monitoring of the drug response at multi-omics levels in t... | 10.1038/s41573-019-0024-5 | This work identifies molecular signatures that are resistant to drug treatments and illustrates a multi-omics approach to understanding drug response |
10.1038/srep46450 | 62,592,702 | Abstract With the increasing ability to routinely and rapidly digitize whole slide images with slide scanners, there has been interest in developing computerized image analysis algorithms for automated detection of disease extent from digital pathology images. The manual identification of presence and extent of breast ... | 10.1038/s41573-019-0024-5 | This is one of the first papers to apply DL to identify regions of breast cancer on digital pathology images and shows that the algorithmic approach outperforms breast cancer pathologists. It is one of the first studies to have a large data set of cases (>600) with independent training and validation sets. |
10.1038/srep32706 | 102,050,489 | Abstract Early stage estrogen receptor positive (ER+) breast cancer (BCa) treatment is based on the presumed aggressiveness and likelihood of cancer recurrence. Oncotype DX (ODX) and other gene expression tests have allowed for distinguishing the more aggressive ER+ BCa requiring adjuvant chemotherapy from the less agg... | 10.1038/s41573-019-0024-5 | This article applies DL to identify the presence and location of tubules in breast pathology images and subsequently demonstrates that the number of detected tubules correlates with the risk assessments of breast cancer via a genomic test. It is one of the first papers to show how DL can be used to establish genotype–p... |
10.1158/1078-0432.ccr-18-2013 | 123,940,665 | Abstract Purpose: The presence of a high degree of tumor-infiltrating lymphocytes (TIL) has been proven to be associated with outcome in patients with non–small cell lung cancer (NSCLC). However, recent evidence indicates that tissue architecture is also prognostic of disease-specific survival and recurrence. We show a... | 10.1038/s41573-019-0024-5 | In this paper, the spatial arrangement, and not just the density, of tumour-infiltrating lymphocytes in early-stage lung cancer pathology images is shown to be prognostic of recurrence. A comprehensive comparison is provided, showing that computer-extracted features of spatial arrangement of tumour-infiltrating lymphoc... |
10.1126/science.aay6779 | 82,900,664 | Achieving time-domain control of quantum states with atomic-scale spatial resolution in nanostructures is a long-term goal in quantum nanoscience and spintronics. Here, we demonstrate coherent spin rotations of individual atoms on a surface at the nanosecond time scale, using an all-electric scheme in a scanning tunnel... | 10.1038/s41565-021-00994-1 | Experimental work on the coherent manipulation of individual spins on a surface in scanning probe microscopy |
10.1126/science.1249802 | 104,394,831 | Electrical control of nuclear spin qubits Quantum bits of information (qubits) that are based on spins of atomic nuclei are an attractive option for quantum information processing. It can sometimes be tricky to manipulate these qubits using magnetic fields directly. Thiele et al. developed a technique for electrically ... | 10.1038/s41565-021-00994-1 | Quantum-coherent control of an individual molecular spin in an electronic device |
10.1126/science.aar4054 | 125,126,202 | Coupling light to single spins To help develop quantum circuits, much effort has been directed toward achieving the strong-coupling regime by using gate-defined semiconductor quantum dots. Potentially, the magnetic dipole, or spin, of a single electron for use as a qubit has advantages over charge-photon coupling owing... | 10.1038/s41565-021-00994-1 | Refs. 117,118 demonstrate hybrid quantum nanoelectronic devices in which an electron spin coherently couples to a microwave photon via the electron’s charge |
10.1101/2022.03.06.483177 | 128,015,758 | Abstract Two analytic traditions characterize fMRI language research. One relies on averaging activations voxel-wise across individuals. This approach has limitations: because of inter-individual variability in the locations of language areas, a location in a common brain space cannot be meaningfully linked to function... | 10.1038/s41593-022-01115-4 | Describes the fMRI approach adopted here and quantifies inter-individual variability. |
10.1002/anie.201303822 | 104,002,461 | Abstract Self‐replication is a fundamental concept. The idea of an entity that can repeatedly create more of itself has captured the imagination of many thinkers from von Neumann to Vonnegut. Beyond the sciences and science fiction, autocatalysis has found currency in economics and language theory, and has raised ethic... | 10.1038/s41565-021-00975-4 | This review provides guidelines on the mechanisms of autocatalysis, particularly focusing on template mechanisms, asymmetric autocatalysis and prebiotically relevant processes |
10.1002/anie.200504313 | 123,028,794 | Abstract The widespread use of controlled molecular‐level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machine... | 10.1038/s41565-021-00975-4 | A major review that dispelled the ‘motion = machine’ view of artificial molecular machines, explained the difference between switches and motors, and introduced ratchet mechanisms from physics as design elements for synthetic molecular systems |
10.1038/s41467-019-11402-7 | 19,678,111 | Abstract Molecular machines carry out their function by equilibrium mechanical motions in environments that are far from thermodynamic equilibrium. The mechanically equilibrated character of the trajectories of the macromolecule has allowed development of a powerful theoretical description, reminiscent of Onsager’s tra... | 10.1038/s41565-021-00975-4 | This seminal perspective elaborates the fundamental role of kinetic asymmetry in driving non-equilibrium systems through information ratchet mechanisms |
10.1002/anie.202014678 | 61,595,455 | Abstract Biochemical systems accomplish many critical functions with by operating out‐of‐equilibrium using the energy of chemical fuels. The formation of a transient covalent bond is a simple but very effective tool in designing analogous reaction networks. This Minireview focuses on the fuel chemistries that have been... | 10.1038/s41565-021-00975-4 | This minireview summarizes the various transient covalent bonds exploited in dissipative assembly in the context of the corresponding reaction cycles and makes the connection to molecular machines |
10.1073/pnas.1920413117 | 104,112,436 | Interleukin (IL)-2 and IL-21 dichotomously shape CD8 + T cell differentiation. IL-2 drives terminal differentiation, generating cells that are poorly effective against tumors, whereas IL-21 promotes stem cell memory T cells (T SCM ) and antitumor responses. Here we investigated the role of metabolic programming in the ... | 10.1038/s41577-021-00537-8 | This study uncovers the metabolic reprogramming endowing the prostemness effect of IL-21 on CD8 + T cells and shows its synergy with LDH inhibition in promoting CD8 + T cell antitumour immunity |
10.1126/sciimmunol.aan2543 | 82,893,887 | The semi-activation state of IELs is maintained by an altered cardiolipin makeup of their mitochondrial membranes. | 10.1038/s41577-021-00537-8 | This study shows how the lipid composition of the mitochondria of tissue-resident memory CD8 + T cells of the intestine, specifically the cardiolipins, sustains their controlled activation state and empowers their proliferation and effector responses |
10.1126/sciimmunol.aay9283 | 103,765,758 | Tissue-resident memory T (T RM ) cells exist throughout the body, where they are poised to mediate local immune responses. Although studies have defined a common mechanism of residency independent of location, there is likely to be a level of specialization that adapts T RM cells to their given tissue of lodgment. It h... | 10.1038/s41577-021-00537-8 | This study shows that tissue-resident memory CD8 + T cells metabolically adapt to tissues by varying FABP expression profiles, a mechanism required for lipid utilization and development of tissue-specific residency programmes |
10.1126/science.aav2588 | 104,407,712 | The metabolic characteristics of tumors present considerable hurdles to immune cell function and cancer immunotherapy. Using a glutamine antagonist, we metabolically dismantled the immunosuppressive microenvironment of tumors. We demonstrate that glutamine blockade in tumor-bearing mice suppresses oxidative and glycoly... | 10.1038/s41577-021-00537-8 | This study demonstrates the inherent metabolic plasticity of T cells by using glutamine blockade in vivo to inhibit tumour metabolism while allowing for enhanced CD8 + TIL function due to T cells’ ability to utilize other types of metabolism in the face of glutamine inhibition |
10.1073/pnas.2003656117 | 59,659,634 | Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the micro... | 10.1038/s41577-021-00537-8 | This study shows that antiviral CD8 + T cell responses promote anorexia and blooms of a fasting-associated gut commensal, which can suppress the CD8 + T cell response |
10.1002/cam4.3063 | 27,997,892 | Abstract Background Racial/ethnic differences in mortality have not been well studied for either non‐cardia gastric cancer (NCGC) or cardia gastric cancer (CGC). The aim of this study was to examine the US mortality rates for these cancer subtypes, as well as esophageal adenocarcinoma (EAC) as a comparator. Methods We ... | 10.1038/s41575-022-00591-0 | A study showing that racial disparities in GAC are linked to distal GAC. |
10.1634/theoncologist.2018-0273 | 38,084,802 | Abstract Background Microsatellite instability (MSI)-high (MSI-H) colorectal cancer is known to be associated with increased tumor-infiltrating lymphocytes (TILs), elevated host systemic immune response, and a favorable prognosis. In gastric cancer, however, MSI status has rarely been evaluated in the context of TILs a... | 10.1038/s41575-022-00591-0 | This article discusses the relationship between MSI-H status, immune microenvironment and GAC response to treatment. |
10.1042/bj20091177 | 64,210,795 | Shh (Sonic Hedgehog) is a morphogen involved in gastric fundic gland differentiation in the adult. Shh expression is reduced in Helicobacter pylori-associated intestinal metaplastic change of the gastric epithelium and mice that lack Shh show intestinal transformation of the gastric mucosa. Similarly, in the stomach of... | 10.1038/s41575-022-00591-0 | This study shows that SHH is repressed and CDX2 is expressed in intestinal-type GAC. |
10.3390/cancers11050648 | 102,325,994 | Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adapt... | 10.1038/s41575-022-00591-0 | This article describes the role of TLRs in polarizing the immune microenvironment prior to GAC. |
10.1073/pnas.0603119103 | 61,246,515 | Exposure to UV radiation induces skin cancer and suppresses the immune response. To induce immune suppression, the electromagnetic energy of UV radiation must be absorbed by an epidermal photoreceptor and converted into a biologically recognizable signal. Two photoreceptors have been recognized: DNA and trans -urocanic... | 10.1038/s41577-019-0185-9 | The first in vivo study to show that increased immunosuppression mediated by UVR exposure is associated with the metabolically stable analogue of platelet-activating factor (PAF) and dependent on the activation of the PAF receptor. This study also explores the possibility that oxidants are involved in the formation of ... |
10.1084/jem.158.1.84 | 100,767,954 | UV irradiation of mice causes a systemic immune alteration that can be detected either by suppression of the immunologic rejection of UV-induced tumors, or by suppression of contact hypersensitivity (CHS). Suppression of these two immunologic responses has similar photobiologic characteristics and in both cases is asso... | 10.1038/s41577-019-0185-9 | The first demonstration that UV-irradiated mice are unable to reject UVR-induced tumours, which are highly antigenic and are thus rejected by normal syngeneic recipients |
10.1111/j.1751-1097.1999.tb08286.x | 103,851,427 | Abstract Many studies have implicated cu‐urocanic acid (cu‐UCA) in UVB‐induced immunomodulation. The strongest evidence came from studies in mice whereby a cis‐ UCA antibody blocked UVB‐induced suppression of de‐layed‐type hypersensitivity responses. Furthermore, in several studies, the cis ‐UCA antibody at least parti... | 10.1038/s41577-019-0185-9 | This study shows that the anti-inflammatory cytokine IL-10 produced by mast cells limits the extent of lymphocyte infiltration during contact hypersensitivity |
10.1073/pnas.030528897 | 79,469,217 | Ultraviolet-B (UVB) (290–320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic ... | 10.1038/s41577-019-0185-9 | The first demonstration that the generation of cyclobutane pyrimidine dimers in human skin has immunosuppressive effects |
10.1073/pnas.0701764104 | 125,149,830 | UVB radiation-induced signaling in mammalian cells involves two major pathways: one that is initiated through the generation of DNA photoproducts in the nucleus and a second one that occurs independently of DNA damage and is characterized by cell surface receptor activation. The chromophore for the latter one has been ... | 10.1038/s41577-019-0185-9 | The first demonstration that UVBR activates the aryl hydrocarbon receptor in keratinocytes through the generation of trytophan photoproducts and thereby elicits a gene response including expression of COX2 |
10.1126/science.278.5343.1626 | 62,237,794 | Natural killer T (NKT) lymphocytes express an invariant T cell antigen receptor (TCR) encoded by the V α 14 and J α 281 gene segments. A glycosylceramide-containing α-anomeric sugar with a longer fatty acyl chain (C 26 ) and sphingosine base (C 18 ) was identified as a ligand for this TCR. Glycosylceramide-mediated pro... | 10.1038/s41570-020-00244-3 | This paper reports the identification of α-GalCer as the first CD1d-presented lipid antigen for invariant natural killer T cells |
10.1002/chem.201403923 | 40,902,050 | Abstract In many Gram‐negative bacteria, lipopolysaccharide (LPS) and its lipid A moiety are pivotal for bacterial survival. Depending on its structure, lipid A carries the toxic properties of the LPS and acts as a potent elicitor of the host innate immune system via the Toll‐like receptor 4/myeloid differentiation fac... | 10.1038/s41570-020-00244-3 | This review summarizes the structural features, physico-chemical properties and structure–activity relationships of lipopolysaccharides |
10.1126/science.1240248 | 125,226,065 | Move Over, TLR4 The innate immune system senses bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 (TLR4) (see the Perspective by Kagan ). However, Kayagaki et al. (p 1246 , published online 25 July) and Hagar et al. (p. 1250 ) report that the hexa-acyl lipid A component of LPS from Gramnegative bacteria i... | 10.1038/s41570-020-00244-3 | This study reports evidence of a TLR4-independent mechanism for innate immune recognition of LPS via caspase 11 activation by the non-canonical inflammasome |
10.1126/science.1138963 | 38,301,373 | The inflammatory toxicity of lipopolysaccharide (LPS), a component of bacterial cell walls, is driven by the adaptor proteins myeloid differentiation factor 88 (MyD88) and Toll-interleukin 1 receptor domain–containing adapter inducing interferon-β (TRIF), which together mediate signaling by the endotoxin receptor Toll-... | 10.1038/s41570-020-00244-3 | This work shows that the low pro-inflammatory effects and reduced toxicity of monophosphoryl lipid A compared with lipid A is associated with a bias towards TRIF signalling over the MyD88 pathway |
10.1146/annurev-immunol-030409-101159 | 28,242,538 | The capsular polysaccharides (CPSs) of most pathogenic bacteria are T cell–independent antigens whose conjugation to carrier proteins evokes a carbohydrate-specific response eliciting T cell help. However, certain bacterial CPSs, known as zwitterionic polysaccharides (ZPSs), activate the adaptive immune system through ... | 10.1038/s41570-020-00244-3 | This review highlights structural features, biological roles and immunological significance of zwitterionic polysaccharides as immunomodulators, describing their processing and presentation by the MHC-II pathway, leading to T cell activation and adaptive immune responses |
10.1084/jem.20062008 | 80,091,743 | Commensalism is critical to a healthy Th1/Th2 cell balance. Polysaccharide A (PSA), which is produced by the intestinal commensal Bacteroides fragilis, activates CD4+ T cells, resulting in a Th1 response correcting the Th2 cell skew of germ-free mice. We identify Toll-like receptors as crucial to the convergence of inn... | 10.1038/s41570-020-00244-3 | This paper reports the identification of TLR2 as a polysaccharide A (PSA) receptor that plays a key role in initiating innate immunity by mediating activation of antigen-presenting cells and NF-κB-dependent NO production, which, in turn, is critical for PSA processing and presentation, and T cell activation |
10.1111/imr.12889 | 41,133,040 | Abstract Therapeutic vaccination offers great promise as an intervention for a diversity of infectious and non‐infectious conditions. Given that most chronic health conditions are thought to have an immune component, vaccination can at least in principle be proposed as a therapeutic strategy. Understanding the nature o... | 10.1038/s41570-020-00244-3 | This review discusses currently available adjuvants and their important role in directing antibody and cellular immune responses in the context of therapeutic vaccines |
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