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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10.1083/jcb.201809032 | 18,955,783 | A hallmark of autophagy is the de novo formation of double-membrane vesicles called autophagosomes, which sequester various cellular constituents for degradation in lysosomes or vacuoles. The membrane dynamics underlying the biogenesis of autophagosomes, including the origin of the autophagosomal membrane, are still el... | 10.1038/s41580-020-0241-0 | This work and Ge et al. (2017), Suzuki et al. (2013) and Graef et al. (2013) report the involvement of COPII vesicles in autophagosome biogenesis |
10.1083/jcb.201811173 | 83,508,987 | In the conserved autophagy pathway, autophagosomes (APs) engulf cellular components and deliver them to the lysosome for degradation. Before fusing with the lysosome, APs have to close via an unknown mechanism. We have previously shown that the endocytic Rab5-GTPase regulates AP closure. Therefore, we asked whether ESC... | 10.1038/s41580-020-0241-0 | This work and Takahashi et al. (2018), Zhen et al. (2019) and Takahashi et al. (2019) propose that the ESCRT machinery is involved in isolation membrane pore closure |
10.1126/science.1235294 | 82,861,437 | Identical and Still Different Even in monozygotic twins reared together, there are always observable differences reflecting the influence of individual responses. Freund et al. (p. 756 ; see the Perspective by Bergmann and Frisén ) developed an inbred mouse model for studying the environmental influences on genetically... | 10.1038/s41583-019-0120-x | This study reveals that longitudinal behavioural trajectories of locomotor activity correlate with interindividual differences in adult neurogenesis |
10.1073/pnas.97.23.12880 | 104,306,925 | An enriched environment is known to promote structural changes in the brain and to enhance learning and memory performance in rodents [Hebb, D. O. (1947) Am. Psychol. 2, 306–307]. To better understand the molecular mechanisms underlying these experience-dependent cognitive changes, we have used high-density oligonucleo... | 10.1038/s41583-019-0120-x | This paper presents one of the first studies attempting to relate changes in gene expression to the effects of environmental enrichment on the brain |
10.1126/science.877587 | 21,938,372 | The differential brain development induced by sensory enrichment or deprivation is most apparent in rats with low brain weights. These differences are hypothesized to represent the retarded development of environment-dependent neurons in the isolated animals. | 10.1038/s41583-019-0120-x | Complementary to reference 43, this article further refines the mechanistic ideas about environmental enrichment as prevalent during the high days of the field in the mid-1970s |
10.1111/j.1539-6053.2009.01034.x | 103,746,971 | In this monograph, we ask whether various kinds of intellectual, physical, and social activities produce cognitive enrichment effects—that is, whether they improve cognitive performance at different points of the adult life span, with a particular emphasis on old age. We begin with a theoretical framework that emphasiz... | 10.1038/s41583-019-0120-x | This extremely comprehensive and insightful review captures the state of ‘enrichment’ concepts under the human condition |
10.1146/annurev.earth.30.091201.141331 | 81,796,113 | ▪ Abstract The recent recognition of a potentially vast, unexplored hot microbial biosphere associated with active volcanism along the global mid-ocean ridge network has fundamentally shifted concepts of how planets and life coevolve. Many processes intrinsic to the dynamics of the spreading center volcanic system prov... | 10.1038/s41579-019-0160-2 | This is a comprehensive and thorough review of the fundamentals of geology, geochemistry and biology of mid-ocean ridge spreading centres |
10.1111/1462-2920.14011 | 103,813,752 | Summary At deep‐sea hydrothermal vents, microbial communities thrive across geochemical gradients above, at, and below the seafloor. In this study, we determined the gene content and transcription patterns of microbial communities and specific populations to understand the taxonomy and metabolism both spatially and tem... | 10.1038/s41579-019-0160-2 | This study is a good example of how a combination of molecular and geochemical approaches can provide insights into how metabolic functions are distributed across different microbial groups and how the distribution of microorganisms and metabolisms is linked to hydrothermal chemistry |
10.1038/ismej.2015.4 | 123,071,897 | Abstract Submarine hydrothermal vents perturb the deep-ocean microbiome by injecting reduced chemical species into the water column that act as an energy source for chemosynthetic organisms. These systems thus provide excellent natural laboratories for studying the response of microbial communities to shifts in marine ... | 10.1038/s41579-019-0160-2 | This study shows how coupled hydrodynamic and thermodynamic models, in tandem with microbiological and physical oceanographic observations, can be used to understand the source, transport and growth of microorganisms in hydrothermal plumes |
10.1073/pnas.1202690109 | 20,753,635 | Deep-sea hydrothermal vents are populated by dense communities of animals that form symbiotic associations with chemolithoautotrophic bacteria. To date, our understanding of which factors govern the distribution of host/symbiont associations (or holobionts) in nature is limited, although host physiology often is invoke... | 10.1038/s41579-019-0160-2 | This paper shows how microbial symbionts are linked to habitat partitioning of animals across different geochemical niches at deep-sea hydrothermal vents |
10.1038/ismej.2017.37 | 107,138,097 | Abstract At deep-sea hydrothermal vents, primary production is carried out by chemolithoautotrophic microorganisms, with the oxidation of reduced sulfur compounds being a major driver for microbial carbon fixation. Dense and highly diverse assemblies of sulfur-oxidizing bacteria (SOB) are observed, yet the principles o... | 10.1038/s41579-019-0160-2 | This paper shows how the niches of sulfur-oxidizing bacteria are partitioned according to the chemical environment across small spatial and temporal scales |
10.1126/science.203.4385.1073 | 104,255,069 | The submarine hydrothermal activity on and near the Galápagos Rift has been explored with the aid of the deep submersible Alvin . Analyses of water samples from hydrothermal vents reveal that hydrothermal activity provides significant or dominant sources and sinks for several components of seawater; studies of conducti... | 10.1038/s41579-019-0160-2 | This paper describes the discovery of deep-sea hydrothermal-vent ecosystems and lays out the hypothesis that chemosynthesis is the main source of primary production |
10.1126/science.1217622 | 41,542,986 | Unnatural Bases The genetic basis of all life on the planet is comprised of deoxyribonucleic acid (DNA) with four nitrogenous nucleotide bases, abbreviated to A, G, C, and T. But there are variations on this theme, and Pinheiro et al. (p. 341 ; see the Perspective by Joyce ) describe the directed evolution of unnatural... | 10.1038/s41589-018-0056-x | This paper presents the development of xenobiological systems that replace canonical nucleosides with different types of synthetic analogs. |
10.1038/s41467-020-15831-7 | 59,985,782 | Abstract Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoi... | 10.1038/s41577-021-00538-7 | This is a hallmark paper showing that gut barrier leakiness is linked to rheumatoid arthritis development with the perspective of migration of the inflammatory cells from gut to joints and the prevention and treatment of arthritis in mice by healing epithelial barriers |
10.1073/pnas.1814558116 | 41,596,238 | Low-grade intestinal inflammation and alterations of gut barrier integrity are found in patients affected by extraintestinal autoimmune diseases such as type 1 diabetes (T1D), but a direct causal link between enteropathy and triggering of autoimmunity is yet to be established. Here, we found that onset of autoimmunity ... | 10.1038/s41577-021-00538-7 | This is an interesting study showing that loss of gut barrier integrity can lead to the activation of pancreatic islet-specific T cells within the intestinal mucosa and to autoimmune diabetes in mice |
10.1073/pnas.0500178102 | 17,660,060 | Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whethe... | 10.1038/s41577-021-00538-7 | This paper shows that zonulin-induced intestinal TJ barrier disruption is involved in the pathogenesis of type 1 diabetes development in a diabetes-prone rat model |
10.1177/1352458519863133 | 124,296,325 | Background: Recent evidence suggests a role for the gut–brain axis in the pathophysiology of multiple sclerosis (MS). Materials and methods: We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls ... | 10.1038/s41577-021-00538-7 | This paper clinical links multiple sclerosis with biomarkers of intestinal barrier integrity |
10.1183/13993003.00198-2019 | 83,168,874 | Introduction Evidence is accumulating that Staphylococcus aureus plays an important role as disease modifier in upper and lower airway diseases. Sensitisation to S. aureus enterotoxins (SEs) was associated with an increased risk of severe asthma in previous cross-sectional studies, but evidence from longitudinal studie... | 10.1038/s41577-021-00538-7 | This article demonstrates that a high prevalence of IgE antibodies to S. aureus is related to asthma severity and risk of asthma exacerbations |
10.1186/s12974-020-01977-0 | 101,409,652 | Abstract Objective Air pollution has been recently identified as a risk factor for multiple sclerosis. Aim of this study was to investigate the immunological mechanism underlying the clinical association between air pollution, namely exposure to particulate matter 10 (PM10), and inflammatory activity of multiple sclero... | 10.1038/s41577-021-00538-7 | A hallmark article showing that exposure of the respiratory system to particulate matter 10 pollution increases the inflammatory activity in multiple sclerosis brain lesions and proposes inflammatory T H 17 cells and their migration to brain as a mechanism |
10.3390/ijms21051711 | 82,988,210 | Amyloid plaques in Alzheimer’s disease (AD) are associated with inflammation. Recent studies demonstrated the involvement of the gut in cerebral amyloid-beta (Aβ) pathogenesis; however, the mechanisms are still not well understood. We hypothesize that the gut bears the Aβ burden prior to brain, highlighting gut–brain a... | 10.1038/s41577-021-00538-7 | This paper demonstrates in a mouse model of Alzheimer disease that gut barrier disruption is the initial event before the development of cerebral amyloid-β aggregation |
10.1159/000358801 | 104,370,311 | <b><i>Background:</i></b> Hereditary cerebellar ataxias (HCA) and hereditary spastic paraplegias (HSP) are two groups of neurodegenerative disorders that usually present with progressive gait impairment, often leading to permanent disability. Advances in genetic research in the last decades have... | 10.1038/s41572-019-0074-3 | This systemic review provides an overview of the available prevalence studies of SCAs |
10.1126/scitranslmed.aaf9074 | 123,458,250 | Corticosterone is as effective as cortisol for ACTH suppression but lacks metabolic adverse effects. | 10.1038/s41574-022-00745-9 | This study shows the specificity of ABCC1 for the transport of corticosterone over cortisol in humans and rodents adipose |
10.1126/science.aav7102 | 20,745,788 | ABCB1, also known as P-glycoprotein, actively extrudes xenobiotic compounds across the plasma membrane of diverse cells, which contributes to cellular drug resistance and interferes with therapeutic drug delivery. We determined the 3.5-angstrom cryo–electron microscopy structure of substrate-bound human ABCB1 reconstit... | 10.1038/s41574-022-00745-9 | This paper provides novel insights into the structure and mechanism of human ABCB1 |
10.1126/sciadv.abe4497 | 79,582,870 | Chronic activation and dysregulation of the neuroendocrine stress response have severe physiological and psychological consequences, including the development of metabolic and stress-related psychiatric disorders. We provide the first unbiased, cell type–specific, molecular characterization of all three components of t... | 10.1038/s41574-022-00745-9 | The authors use a variety of approaches to show the role of ABCB1 in humans and rodents in modulating steroid secretion and the HPA axis. Single-cell RNA profiling details expression of Abcb1a and Abcb1b across the axis |
10.1111/j.1476-4431.2006.00196.x | 103,166,378 | Abstract Objective: To evaluate the hypothalamic–pituitary–adrenal (HPA) axis in MDR1‐1Δ (dogs with the MDR1 mutation associated with ivermectin sensitivity) and MDR1 wildtype dogs. Design: Prospective study. Setting: Institutional vivarium. Animals: Seven healthy Collie dogs. Measurements: MDR1 genotyping was used for... | 10.1038/s41574-022-00745-9 | The importance of ABCB1 in modulating the HPA axis in a cortisol-dominant species is highlighted by these affected canines |
10.1073/pnas.1114210108 | 16,798,125 | Although the importance of the cellular microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the microenvironment on cancer cells at the molecular level. Here, we show that an experimental strateg... | 10.1038/s41572-018-0055-y | This study demonstrates that the brain microenvironment (‘soil’) can reprogramme metastatic tumour cells (‘seed’) to gain neuronal cell characteristics |
10.1182/blood-2016-09-736892 | 62,104,066 | Key Points Apilimod has broad anticancer activity in vitro and in vivo across all subtypes of B-NHL. Apilimod induces B-NHL cytotoxicity through a unique mechanism of action that involves the disruption of lysosomal function. | 10.1038/s41573-022-00582-5 | This article described the application of the PIKfyve specific inhibitor apilimod as a potential therapeutic in B-NHL through disruption of lysosome homeostasis |
10.1073/pnas.1718471115 | 104,352,450 | Plasma membrane (PM) phosphoinositides play essential roles in cell physiology, serving as both markers of membrane identity and signaling molecules central to the cell’s interaction with its environment. The first step in PM phosphoinositide synthesis is the conversion of phosphatidylinositol (PI) to PI4P, the precurs... | 10.1038/s41573-022-00582-5 | This study reveals molecular insight into the architechture and assembly of the PI4KA–TTC7–FAM126 complex that generates PI4P at the plasma membrane |
10.1073/pnas.0902693106 | 61,485,476 | Hepatitis C virus (HCV) reorganizes cellular membranes to establish sites of replication. The required host pathways and the mechanism of cellular membrane reorganization are poorly characterized. Therefore, we interrogated a customized small interfering RNA (siRNA) library that targets 140 host membrane-trafficking ge... | 10.1038/s41573-022-00582-5 | This is one of the first studies to identify the role of PI4KA and its product PI4P as essential in the viral replication of HCV |
10.1126/science.1253397 | 81,966,864 | How to recruit membrane trafficking machinery PI4KIIIβ is a lipid kinase that underlies Golgi function and is enlisted in biological responses that require rapid delivery of membrane vesicles, such as during the extensive membrane remodeling that occurs at the end of cell division. Burke et al. determined the structure... | 10.1038/s41573-022-00582-5 | This study reveals molecular insight into the structure and inhibition of PI4KB, and how it can be regulated by protein-binding partners |
10.1126/scitranslmed.aad9735 | 61,484,039 | MMV390048, a member of a new class of inhibitors of the Plasmodium phosphatidylinositol 4-kinase, shows potential for both treatment and prophylaxis. | 10.1038/s41573-022-00582-5 | This article describes the pre-clinical efficacy of the first plasmodium PI4K inhibitor to enter clinical trials as a potential therapeutic towards malaria |
10.1038/s41594-022-00730-w | 136,032,596 | Abstract Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poo... | 10.1038/s41573-022-00582-5 | This study describes the first molecular insight into how the class II PI3Ks are regulated by inhibitory interactions with their regulatory domains, and into their inhibition by small-molecule inhibitors |
10.1126/science.abk0410 | 132,024,633 | ESCRTing lenses away from senescence ESCRT proteins control membrane fusion in various key cellular processes, but the mechanisms involved are still incompletely understood. Gulluni et al . report that ESCRT recruitment at the cytokinetic bridge is mediated by the binding of an ESCRT-II subunit to the signaling lipid p... | 10.1038/s41573-022-00582-5 | This work identifies the crucial role of PIK3C2A in cytokinetic abscission in the lens of the eye, identifying the pathogenic mechanism of cataract development in patients with loss-of-function mutations in PIK3C2A |
10.1126/scitranslmed.aar8430 | 103,799,503 | Arterial thrombosis causes heart attacks and most strokes and is the most common cause of death in the world. Platelets are the cells that form arterial thrombi, and antiplatelet drugs are the mainstay of heart attack and stroke prevention. Yet, current drugs have limited efficacy, preventing fewer than 25% of lethal c... | 10.1038/s41573-022-00582-5 | This study reveals the potential of class II PI3K inhibitors as potent anti-thrombotic agents, with limited effect on activation-dependent platelet function |
10.1038/s41589-022-01118-z | 141,733,616 | Abstract Phosphatidylinositol 3-kinase type 2α (PI3KC2α) and related class II PI3K isoforms are of increasing biomedical interest because of their crucial roles in endocytic membrane dynamics, cell division and signaling, angiogenesis, and platelet morphology and function. Herein we report the development and character... | 10.1038/s41573-022-00582-5 | This study reports the identification and structural characterization of the first truly selective class II PI3K inhibitors, opening up the possibilities of class II PI3K inhibitors as therapeutics |
10.1126/science.aac7365 | 19,976,737 | Opening up Vps34 protein complexes During intracellular membrane trafficking, large protein complexes regulate and adapt the activity of signal transducer enzymes such as the class III phosphatidylinositol 3-kinase Vps34. These large enzyme complexes are present in all eukaryotic cells, having widespread importance in ... | 10.1038/s41573-022-00582-5 | This study reveals the first molecular insight into the assembly of complex II of the class III PI3K complex, providing unique insight into its architechture and regulation |
10.1038/s41467-021-21695-2 | 23,482,643 | Abstract The lipid phosphatidylinositol-3-phosphate (PI3P) is a regulator of two fundamental but distinct cellular processes, endocytosis and autophagy, so its generation needs to be under precise temporal and spatial control. PI3P is generated by two complexes that both contain the lipid kinase VPS34: complex II on en... | 10.1038/s41573-022-00582-5 | This article reports on the molecular basis for how class III PI3Ks are activated on membranes by Rab GTPases, and reveals crucial differences between complex I and complex II that may be exploited for complex-specific targeting |
10.1126/sciadv.aax7881 | 103,823,540 | One of the major challenges limiting the efficacy of anti–PD-1/PD-L1 therapy in nonresponding patients is the failure of T cells to penetrate the tumor microenvironment. We showed that genetic or pharmacological inhibition of Vps34 kinase activity using SB02024 or SAR405 (Vps34i) decreased the tumor growth and improved... | 10.1038/s41573-022-00582-5 | This article describes the potential of class III PI3K inhibitors as anti-cancer therapeutics based on mouse models of melanoma and colorectal cancer tumours, specifically in combination with immunotherapy approaches |
10.1186/s13059-019-1828-7 | 62,584,245 | Abstract Recent research into structural variants (SVs) has established their importance to medicine and molecular biology, elucidating their role in various diseases, regulation of gene expression, ethnic diversity, and large-scale chromosome evolution—giving rise to the differences within populations and among specie... | 10.1038/s41576-021-00367-3 | The review articles by Ho et al. and Mahmoud et al. provide an overview of structural variation calling and why long reads are important |
10.1101/848366 | 59,772,920 | Long-read sequencing (LRS) promises to improve characterization of structural variants (SVs), a major source of genetic diversity. We generated LRS data on 3,622 Icelanders using Oxford Nanopore Technologies, and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions), spann... | 10.1038/s41576-021-00367-3 | A large population-scale sequencing study involving 3,622 individuals, using the ONT PromethION platform to identify diversity and correlate it with disease phenotypes in an Icelandic population |
10.1038/s41587-020-0503-6 | 41,754,295 | Abstract De novo assembly of a human genome using nanopore long-read sequences has been reported, but it used more than 150,000 CPU hours and weeks of wall-clock time. To enable rapid human genome assembly, we present Shasta, a de novo long-read assembler, and polishing algorithms named MarginPolish and HELEN. Using a ... | 10.1038/s41576-021-00367-3 | This study reports a method to rapidly assemble and polish genomes, showcasing the throughput on ONT data by establishing 11 human genomes in 9 days |
10.1038/s41467-020-17195-4 | 20,791,144 | Abstract Structural variation (SV) constitutes an important type of genetic mutations providing the raw material for evolution. Here, we uncover the genome-wide spectrum of intra- and interspecific SV segregating in natural populations of seven songbird species in the genus Corvus . Combining short-read ( N = 127) and ... | 10.1038/s41576-021-00367-3 | A large-scale sequencing study in crows highlights segregation of structural variation in natural populations |
10.1101/gr.264879.120 | 59,779,202 | An increasingly important scenario in population genetics is when a large cohort has been genotyped using a low-resolution approach (e.g., microarrays, exome capture, short-read WGS), from which a few individuals are resequenced using a more comprehensive approach, especially long-read sequencing. The subset of individ... | 10.1038/s41576-021-00367-3 | This article describes a method for optimized sample selection given an existing variation catalogue |
10.1038/s41586-020-2547-7 | 62,650,826 | Abstract After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist 1,2 . Here we present a human genome assembly that surpasses the ... | 10.1038/s41576-021-00367-3 | This study reports the first assembly of a human chromosome resolved from end to end by leveraging long reads |
10.1186/s13059-019-1856-3 | 80,408,262 | Abstract Technological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per individual achieves 30× human genome coverage and enables accurate assessment of tandem repeats inclu... | 10.1038/s41576-021-00367-3 | Nanopore sequencing of patients with Alzheimer disease to investigate an associated variable number of tandem repeats expansion |
10.1126/science.1172046 | 104,414,944 | P Granule Conundrum In many organisms, the presumptive germ cells can be distinguished from somatic cells by the presence of distinctive cytoplasmic granules. In Caenorhabditis elegans , these P granules are more or less uniformly distributed in the oocyte and one-cell stage of the fertilized egg. By the end of the fir... | 10.1038/s41589-022-01046-y | This pioneering study noted that the behavior of a cellular body was not that of a standard membrane-bound organelle but rather more like liquid droplets that arise by phase separation |
10.5194/tc-14-3935-2020 | 19,733,610 | Abstract. Observations and models agree that the Greenland Ice Sheet (GrIS) surface mass balance (SMB) has decreased since the end of the 1990s due to an increase in meltwater runoff and that this trend will accelerate in the future. However, large uncertainties remain, partly due to different approaches for modelling ... | 10.1038/s41558-022-01382-w | This paper presents the results of an intercomparison of the major models of surface mass balance of the Greenland ice sheet |
10.1073/pnas.69.6.1537 | 104,292,836 | Drosophila melanogaster , which had been reared under standard conditions (25° and a 24-hr light/dark cycle involving 12 hr of light) were exposed, on the first day of adult life, to four environments (all at 25°) as follows: ( i ) a 24-hr day consisting of 12 hr light and 12 hr dark; ( ii ) a 21-hr day (10.5 hr light,... | 10.1038/s41580-019-0179-2 | This study presents a theoretical framework for the adaptive advantage of having a circadian clock. |
10.1073/pnas.68.9.2112 | 41,569,169 | Three mutants have been isolated in which the normal 24-hour rhythm is drastically changed. One mutant is arrhythmic; another has a period of 19 hr; a third has a period of 28 hr. Both the eclosion rhythm of a population and the locomotor activity of individual flies are affected. All these mutations appear to involve ... | 10.1038/s41580-019-0179-2 | This landmark paper describes the discovery of the first D. melanogaster clock mutants. |
10.1126/science.aao0318 | 62,270,022 | Daily transcription cycling in the baboon Much of our knowledge about the important effects of circadian rhythms in physiology comes from studies of mice, which are nocturnal. Mure et al. report transcriptional profiles from many tissues and brain regions in baboons over a 24-hour period (see the Perspective by Millius... | 10.1038/s41580-019-0179-2 | This article presents the first atlas of circadian gene expression from a diurnal primate. |
10.1126/science.1057499 | 41,569,170 | Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian rhythm variant; affected individuals are “morning larks” with a 4-hour advance of the sleep, temperature, and melatonin rhythms. Here we report localization of the FASPS gene near the telomere of chromosome 2q. A strong candidate gene (h ... | 10.1038/s41580-019-0179-2 | This paper describes the discovery of a PER2 mutation in human familial advanced sleep phase disorder. |
10.1101/gad.249417.114 | 123,950,671 | The mammalian circadian clock is based on a transcription–translation feedback loop (TTFL) in which CLOCK and BMAL1 proteins act as transcriptional activators of Cryptochrome and Period genes, which encode proteins that repress CLOCK–BMAL1 with a periodicity of ∼24 h. In this model, the mechanistic roles of CRY and PER... | 10.1038/s41580-019-0179-2 | This paper shows that mammalian CRY proteins can inhibit the transcriptional activity of CLOCK–BMAL1 either through direct blocking of DNA binding or through displacement of CLOCK–BMAL1 from promoters. |
10.1126/science.2305266 | 100,648,768 | The pacemaker role of the suprachiasmatic nucleus in a mammalian circadian system was tested by neural transplantation by using a mutant strain of hamster that shows a short circadian period. Small neural grafts from the suprachiasmatic region restored circadian rhythms to arrhythmic animals whose own nucleus had been ... | 10.1038/s41580-019-0179-2 | This paper shows that reciprocal SCN transplantation between normal and short-period mutant hamsters switches their circadian period. |
10.1126/science.aat4104 | 40,857,159 | Circadian (~24-hour) rhythms depend on intracellular transcription-translation negative feedback loops (TTFLs). How these self-sustained cellular clocks achieve multicellular integration and thereby direct daily rhythms of behavior in animals is largely obscure. The suprachiasmatic nucleus (SCN) is the fulcrum of this ... | 10.1038/s41580-019-0179-2 | This paper shows that restoring clock function in SCN astrocytes is sufficient to restore locomotor rhythms in clock-less mice. |
10.1073/pnas.0308709101 | 20,600,976 | Mammalian circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), and current dogma holds that the SCN is required for the expression of circadian rhythms in peripheral tissues. Using a PERIOD2::LUCIFERASE fusion protein as a real-time reporter of circadian dynamics in mice, we report that, contrary to pr... | 10.1038/s41580-019-0179-2 | This study presents ex vivo measurements of peripheral clock rhythms using a PER2–luciferase knock-in reporter. |
10.1126/science.1256682 | 41,035,824 | Midnight snacks are bad for the heart Circadian clocks help animals coordinate their active and rest periods with the daily cycles of light and darkness. As anyone who has suffered jet lag or worked night shifts knows, losing this coordination can have deleterious effects. Gill et al. compared fruit flies that were all... | 10.1038/s41580-019-0179-2 | This paper shows that diurnal feeding improves cardiac health in D. melanogaster. |
10.1126/science.291.5503.490 | 41,570,069 | Circadian rhythms of behavior are driven by oscillators in the brain that are coupled to the environmental light cycle. Circadian rhythms of gene expression occur widely in peripheral organs. It is unclear how these multiple rhythms are coupled together to form a coherent system. To study such coupling, we investigated... | 10.1038/s41580-019-0179-2 | Together with Damiola et al. (2000), this paper shows that the circadian clock in the liver is entrained by the timing of food intake. |
10.1073/pnas.0603044103 | 122,475,296 | Chlamydia trachomatis entry into host cells results from a parasite-directed remodeling of the actin cytoskeleton. A type III secreted effector, TARP (translocated actin recruiting phosphoprotein), has been implicated in the recruitment of actin to the site of internalization. To elucidate the role of TARP in actin rec... | 10.1038/s41579-023-00860-y | This study shows interaction of TarP with actin and provides insight into the regulation of actin dynamics by TarP. |
10.1073/pnas.1212831109 | 84,512,930 | Chlamydia trachomatis is among the most clinically significant human pathogens, yet their obligate intracellular nature places severe restrictions upon research. Chlamydiae undergo a biphasic developmental cycle characterized by an infectious cell type known as an elementary body (EB) and an intracellular replicative f... | 10.1038/s41579-023-00860-y | This study reveals G6P and ATP as different energy sources for elementary bodies and reticulate bodies, respectively, in axenic medium. |
10.1038/s41467-017-02432-0 | 62,167,389 | Abstract Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection. It produces an unusual intracellular infection in which a vegetative form, called the reticulate body (RB), replicates and then converts into an elementary body (EB), which is the infectious form. Here we use quantitati... | 10.1038/s41579-023-00860-y | This study provides evidence that reticulate body size regulates the timing of the reticulate body to elementary body conversion. |
10.1128/iai.52.3.664-670.1986 | 38,788,121 | Chlamydia psittaci and Chlamydia trachomatis elementary bodies (EB) incubated in the presence of complement or specific antibody or both caused chemotaxis of human polymorphonuclear leukocytes (PMN) in vitro. Reticulate bodies and culture supernatants had no effect on these cells. The ability of chlamydiae to enter and... | 10.1038/s41579-023-00860-y | This is the first study showing that Chlamydia spp. can survive and remain infectious after neutrophil phagocytosis. |
10.1126/science.aat0271 | 62,630,459 | Engineering multilayered cellular structures The ability to program the manufacture of biological structures may yield new biomaterials or synthetic tissues and organs. Toda et al. engineered mammalian “sender” and “receiver” cells with synthetic cell surface ligands and receptors that controlled gene regulatory circui... | 10.1038/s41578-021-00279-y | This study reports the generation of self-organizing structures employing a purely synthetic biology approach |
10.1126/science.1188302 | 83,477,929 | Just Breathe Design of artificial systems that mimic in vivo organs could provide a better alternative for understanding mechanisms underlying physiological responses than current cell-based models or animal tests. Huh et al. (p. 1662 ) have created a tissue-tissue interface of human-cultured epithelial cells and endot... | 10.1038/s41578-021-00279-y | This groundbreaking work describes an organ-on-a-chip approach to emulate lung functions in vitro |
10.1073/pnas.1612906114 | 104,352,115 | Significance Monitoring human organ-on-a-chip systems presents a significant challenge, where the capability of in situ continual monitoring of organ behaviors and their responses to pharmaceutical compounds over extended periods of time is critical in understanding the dynamics of drug effects and therefore accurate p... | 10.1038/s41578-021-00279-y | This work reports a multi-organ microfluidics platform with automated and continuous monitoring of cultured organoids |
10.1111/jmi.12834 | 124,126,318 | Summary Although high‐resolution single‐particle cryo‐electron microscopy (cryo‐EM) is now producing a rapid stream of breakthroughs in structural biology, it nevertheless remains the case that the preparation of suitable frozen‐hydrated samples on electron microscopy grids is often quite challenging. Purified samples ... | 10.1038/s41592-021-01130-6 | This overview of sample preparation methods can serve as a guideline for new users or when experiencing difficulties with novel specimens |
10.1126/science.abb7927 | 59,744,989 | Most information loss in cryogenic electron microscopy (cryo-EM) stems from particle movement during imaging, which remains poorly understood. We show that this movement is caused by buckling and subsequent deformation of the suspended ice, with a threshold that depends directly on the shape of the frozen water layer s... | 10.1038/s41592-021-01130-6 | The authors introduce a new specimen support that minimizes beam-induced motion of the ice layer, reducing information loss |
10.1111/j.1365-2818.1982.tb04625.x | 4,745,242 | SUMMARY Thin layers of pure water or aqueous solutions are frozen in the vitreous state or with the water phase in the form of hexagonal or cubic crystals, either by using a spray‐freezing method or by spreading the liquid on alkylamine treated films. The specimens are observed in a conventional and in a scanning trans... | 10.1038/s41592-021-01130-6 | The authors demonstrate the structure of various samples and the influence of the electron beam on them |
10.1126/scitranslmed.3003110 | 83,042,213 | Early cancer detection using current clinical blood-based biomarker assays may not be possible within the first 10 years of tumor growth. | 10.1038/s41568-021-00389-3 | In this study, the authors develop a mathematical model to determine how early a clinical blood biomarker can be used to detect cancer |
10.1126/scitranslmed.aaw0262 | 83,042,309 | Lung cancer is the leading cause of cancer-related death, and patients most commonly present with incurable advanced-stage disease. U.S. national guidelines recommend screening for high-risk patients with low-dose computed tomography, but this approach has limitations including high false-positive rates. Activity-based... | 10.1038/s41568-021-00389-3 | This study demonstrates the use of a 14-plex library of synthetic biomarkers for early detection of lung cancer in genetically engineered mouse models |
10.1073/pnas.1506925112 | 122,342,707 | Advances in nanomedicine are providing sophisticated functions to precisely control the behavior of nanoscale drugs and diagnostics. Strategies that coopt protease activity as molecular triggers are increasingly important in nanoparticle design, yet the pharmacokinetics of these systems are challenging to understand wi... | 10.1038/s41568-021-00389-3 | This study develops a physiologically based pharmacokinetic model to predict the performance of protease-activated synthetic biomarkers for early cancer detection in humans |
10.1002/anie.201906261 | 17,132,175 | Abstract The development of efficient protocols for cancer diagnosis remains highly challenging. An emerging approach relies on the detection in exhaled breath of volatile organic compounds (VOC) produced by tumours. In this context, described here is a novel strategy in which a VOC‐based probe is converted selectively... | 10.1038/s41568-021-00389-3 | The authors of this study report the use of a deuterated metabolite that is released as a VOC in exhaled breath for cancer diagnosis in mice |
10.1126/scitranslmed.aaa3519 | 38,412,163 | Probiotics programmed to generate specific metabolites traffic from the gut to tumors and enable cancer detection through the urine. | 10.1038/s41568-021-00389-3 | The authors of this study engineer the probiotic E. coli Nissle to colonize and report on the presence of liver tumours in mice by producing a colorimetric readout in urine |
10.1038/s41598-017-12811-8 | 83,116,281 | Abstract Numerous studies have employed repeated social defeat stress (RSDS) to study the neurobiological mechanisms of depression in rodents. An important limitation of RSDS studies to date is that they have been conducted exclusively in male mice due to the difficulty of initiating attack behavior directed toward fem... | 10.1038/s41583-019-0221-6 | To our knowledge, this article and that of reference 80 are the only two studies to have designed chronic social defeat stress protocols for use in female mice |
10.1126/science.aan4491 | 82,431,493 | An early window of stress susceptibility defines a mouse’s response to stress in adulthood. | 10.1038/s41583-019-0221-6 | In this mouse study, maternal separation within a specific time window (postnatal days 10–17 or 10–20) increased the susceptibility of offspring to social defeat stress in adulthood |
10.1002/bies.201800012 | 62,062,872 | An intriguing question in the field of stress is what makes an individual more likely to be susceptible or resilient to stress‐induced depression. Predisposition to stress susceptibility is believed to be influenced by genetic factors and early adversity. However, beyond genetics and life experiences, recent evidence h... | 10.1038/s41583-019-0221-6 | The authors of this study showed that the dominant mouse in a group of four co-housed mice was more susceptible to chronic social defeat stress than subordinate mice |
10.1002/dev.21491 | 60,105,862 | Abstract We investigated the consequences of chronic social instability (CSI) during adulthood on social and maternal behavior in females and social behavior of their offspring in a rat model. CSI consisted of changing the social partners of adult females every 2–3 days for 28 days, 2 weeks prior to mating. Females exp... | 10.1038/s41583-019-0221-6 | This paper showed that adult female rats exposed to the social instability paradigm were pro-social towards female intruders; interestingly, their offspring had impaired growth and were socially anxious |
10.1210/en.2008-0633 | 80,121,339 | Chronic early-life stress (ES) exerts profound acute and long-lasting effects on the hypothalamic-pituitary-adrenal system, with relevance to cognitive function and affective disorders. Our ability to determine the molecular mechanisms underlying these effects should benefit greatly from appropriate mouse models becaus... | 10.1038/s41583-019-0221-6 | The first description of a chronic early life stress paradigm involving fragmented nursing, which has been utilized to assess intergenerational effects |
10.1038/tp.2016.109 | 62,037,369 | Abstract Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic–pituitar... | 10.1038/s41583-019-0221-6 | This study demonstrated the intergenerational effects of paternal corticosterone treatment: F1 males were hyper-anxious and F2 males had a depressive-like phenotype |
10.1126/science.aaw7570 | 82,917,516 | Outdated gender stereotypes are influencing experimental design in laboratory animals | 10.1038/s41583-019-0221-6 | A recent perspective piece on the importance of addressing sex bias in research, which also outlines when and when not to consider tracking the oestrus cycle of experimental female rodents |
10.1038/srep44182 | 62,221,546 | Abstract The microbiome is a regulator of host immunity, metabolism, neurodevelopment, and behavior. During early life, bacterial communities within maternal gut and vaginal compartments can have an impact on directing these processes. Maternal stress experience during pregnancy may impact offspring development by alte... | 10.1038/s41583-019-0221-6 | The study showed that early prenatal stress had long-lasting effects on the microbiome of the dam, which in turn led to a disruption of the neonatal microbiome |
10.1038/s41398-019-0450-5 | 83,464,595 | Abstract The recent successful genome-wide association studies (GWASs) for depression have yielded more than 80 replicated loci and brought back the excitement that had evaporated during the years of negative GWAS findings. The identified loci provide anchors to explore their relevance for depression, but this comes wi... | 10.1038/s41583-019-0221-6 | References 199, 200 and 201 are the most successful GWAS of depression to date |
10.1111/j.1365-2222.2008.03194.x | 124,833,471 | Summary Food allergy is an important health issue. With an increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches suitable for the characterization of the allergenic potential of proteins. There are methods available currently (such as homology ... | 10.1038/s41583-019-0221-6 | In addition to developmental system drift as a concept that undermines the strength of rodent–human translational genetic studies, this review also discusses other factors such as positive selection and pseudo-orthology |
10.1002/cpt.59 | 124,031,006 | The concept of adaptive licensing (AL) has met with considerable interest. Yet some remain skeptical about its feasibility. Others argue that the focus and name of AL should be broadened. Against this background of ongoing debate, we examine the environmental changes that will likely make adaptive pathways the preferre... | 10.1038/s41583-019-0221-6 | In this state-of-the-art paper, the authors discuss the concept of adaptive licensing in which the drug development timeline is fundamentally restructured to accelerate approval of compounds to the clinic for a targeted population. Postmarketing reviews of safety and efficacy are then regularly carried out, which lead ... |
10.4049/jimmunol.202.supp.178.6 | 139,002,759 | Abstract Genome-wide association studies have linked the gene encoding phospholipase D3 (PLD3) to Alzheimer’s disease and have linked PLD4 to rheumatoid arthritis and systemic sclerosis. PLD3 and PLD4 are endolysosomal proteins that we recently discovered are nucleases. PLD4-deficient mice have an inflammatory disease,... | 10.1038/s41577-021-00577-0 | This paper describes how two lysosomal nucleases are crucial for the removal of self-DNA capable of activating TLR9 |
10.1126/sciimmunol.aap8855 | 125,270,725 | Biallelic TLR7 expression in immune cells may contribute to increased autoimmune disease risk in women. | 10.1038/s41577-021-00577-0 | This paper shows biallelic expression of TLR7 in a proportion of immune cells from women, and men with Klinefelter’s syndrome (47,XXY karyotype), leading to enhanced responses to TLR7 agonists |
10.1002/ana.24620 | 61,559,672 | Background Quantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) is essential to understand the pathogenesis of the disease and to evaluate promyelinating therapies. Selectively binding myelin in the central nervous system white matter, Pittsburgh compound B ([ 11 C]PiB) can be... | 10.1038/s41589-022-01115-2 | The myelin-targeted in vivo human imaging here provided important proof of concept that remyelination correlated with functional recovery in MS |
10.1093/nar/gkz576 | 38,393,973 | Abstract Thousands of eukaryotic protein-coding genes generate circular RNAs that have covalently linked ends and are resistant to degradation by exonucleases. To prove their circularity as well as biochemically enrich these transcripts, it has become standard in the field to use the 3′-5′ exonuclease RNase R. Here, we... | 10.1038/s41592-022-01487-2 | A modified protocol for circRNA enrichment facilitates a better separation between circular and linear RNAs |
10.1038/s41467-021-24975-z | 132,898,924 | Abstract Circular RNA (circRNA) is a class of covalently joined non-coding RNAs with functional roles in a wide variety of cellular processes. Their composition shows extensive overlap with exons found in linear mRNAs making it difficult to delineate their composition using short-read RNA sequencing, particularly for l... | 10.1038/s41592-022-01487-2 | This study developed a long-read sequencing protocol that reveals the complexity and internal composition of large, multi-exon circRNAs |
10.1038/s41467-020-20459-8 | 82,634,739 | Abstract Circular RNAs (circRNAs) have emerged as an important class of functional RNA molecules. Short-read RNA sequencing (RNA-seq) is a widely used strategy to identify circRNAs. However, an inherent limitation of short-read RNA-seq is that it does not experimentally determine the full-length sequences and exact exo... | 10.1038/s41592-022-01487-2 | This study developed a long-read sequencing protocol that reveals the complexity and internal composition of large, multi-exon circRNAs |
10.1101/gad.251926.114 | 103,689,048 | Recent deep sequencing studies have revealed thousands of circular noncoding RNAs generated from protein-coding genes. These RNAs are produced when the precursor messenger RNA (pre-mRNA) splicing machinery “backsplices” and covalently joins, for example, the two ends of a single exon. However, the mechanism by which th... | 10.1038/s41592-022-01487-2 | This study showed that base pairing between inverted repeat sequences in introns flanking the circularizing exons can drive circRNA formation |
10.1038/s41467-020-18355-2 | 20,649,177 | Abstract Circular RNAs (circRNAs) have recently gained substantial attention in the cancer research field where most, including the putative oncogene ciRS-7 (CDR1as), have been proposed to function as competitive endogenous RNAs (ceRNAs) by sponging specific microRNAs. Here, we report the first spatially resolved cellu... | 10.1038/s41592-022-01487-2 | This study found that a presumably oncogenic circRNA is only expressed in stromal cells, not in cancer cells, thereby highlighting the limitations of bulk RNA-seq analysis for circRNA profiling of tissue |
10.1038/s41746-021-00428-1 | 2,373,864 | Abstract Chronic Kidney Disease (CKD) represents a slowly progressive disorder that is typically silent until late stages, but early intervention can significantly delay its progression. We designed a portable and scalable electronic CKD phenotype to facilitate early disease recognition and empower large-scale observat... | 10.1038/s41591-022-01871-7 | Design and validation of a portable and scalable e-phenotype for CKD diagnosis and staging |
10.1242/dev.102798 | 41,579,413 | Heart failure due to cardiomyocyte loss after ischemic heart disease is the leading cause of death in the United States in large part because heart muscle regenerates poorly. The endogenous mechanisms preventing mammalian cardiomyocyte regeneration are poorly understood. Hippo signaling, an ancient organ size control p... | 10.1038/s41580-018-0086-y | This paper shows that Hippo signalling is an endogenous repressor of adult cardiomyocyte renewal and regeneration and that Hippo deficiency enhances cardiomyocyte regeneration after adult myocardial infarction |
10.1073/pnas.1313192110 | 62,614,910 | The adult mammalian heart has limited potential for regeneration. Thus, after injury, cardiomyocytes are permanently lost, and contractility is diminished. In contrast, the neonatal heart can regenerate owing to sustained cardiomyocyte proliferation. Identification of critical regulators of cardiomyocyte proliferation ... | 10.1038/s41580-018-0086-y | This paper demonstrates that forced expression of constitutively active YAP-1SA stimulates cardiac regeneration in the adult heart through the activation of embryonic and proliferative gene programmes in cardiomyocytes |
10.1073/pnas.1116136109 | 62,578,192 | Heart growth is tightly controlled so that the heart reaches a predetermined size. Fetal heart growth occurs through cardiomyocyte proliferation, whereas postnatal heart growth involves primarily physiological cardiomyocyte hypertrophy. The Hippo kinase cascade is an important regulator of organ growth. A major target ... | 10.1038/s41580-018-0086-y | In this study, fetal activation of YAP1 is shown to stimulate cardiomyocyte proliferation in postnatal hearts |
10.1073/pnas.1216462110 | 20,526,994 | The Hippo signaling pathway inhibits cell growth and regulates organ size through a kinase cascade that leads to the phosphorylation and nuclear exclusion of the growth-promoting transcriptional coactivator Yes-associated protein (YAP)/Yorkie. It mediates contact inhibition of cell growth downstream of cadherin adhesio... | 10.1038/s41580-018-0086-y | This study demonstrates that treatment with the reversible MST1/MST2 inhibitor XMU-MP-1 can promote mouse intestinal and liver regeneration by hyperactivating YAP |
10.1126/science.1199010 | 104,281,228 | Heart size is controlled through an antagonistic interaction between Hippo and Wnt signaling pathways. | 10.1038/s41580-018-0086-y | In this study, embryonic deletion of Hippo core kinases is shown to induce cardiomyocyte proliferation and heart overgrowth by interaction of the Hippo effector YAP with β-catenin on Sox2 and Snai2 genes |
10.1101/gad.1903310 | 62,311,718 | Yes-associated protein (YAP) is a potent transcription coactivator acting via binding to the TEAD transcription factor, and plays a critical role in organ size regulation. YAP is phosphorylated and inhibited by the Lats kinase, a key component of the Hippo tumor suppressor pathway. Elevated YAP protein levels and gene ... | 10.1038/s41580-018-0086-y | This study shows that YAP is inactivated during ES cell differentiation and elevated during iPS cell reprogramming |
10.1126/science.1200708 | 104,406,757 | The heart in a newborn mouse can rebuild itself after injury, but this regenerative capacity is lost within a few days. | 10.1038/s41580-018-0086-y | This paper demonstrates that hearts of 1-day-old neonatal mice can regenerate after partial surgical resection, but this capacity is lost by 7 days of age |
10.1093/icb/icaa049 | 103,408,943 | Synopsis Epigenetics represents a widely accepted set of mechanisms by which organisms respond to the environment by regulating phenotypic plasticity and life history transitions. Understanding the effects of environmental control on phenotypes and fitness, via epigenetic mechanisms, is essential for understanding the ... | 10.1038/s41572-021-00334-6 | This review identifies areas of future research in epigenetic responses to environmental temperature change |
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