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10.3390/toxins13100707
130,492,733
Crotamine, a toxin found in the venom of the South American rattlesnake Crotalus durissus terrificus, has been reported to have antinociceptive effects. We purified recombinant crotamine expressed in Escherichia coli and investigated its antinociceptive and anti-inflammatory effects using the hot-plate test, acetic-aci...
10.1038/s41570-022-00393-7
An in vivo study of the antinociceptive and anti-inflammatory activity of crotamine
10.3390/molecules26164896
126,988,209
The COVID-19 outbreak has rapidly spread on a global scale, affecting the economy and public health systems throughout the world. In recent years, peptide-based therapeutics have been widely studied and developed to treat infectious diseases, including viral infections. Herein, the antiviral effects of the lysine linke...
10.1038/s41570-022-00393-7
A report of snake venom peptides with antiviral activity towards SARS-CoV-2
10.1111/j.1460-9568.1989.tb00771.x
29,188,162
Abstract Wallerian degeneration of the distal stump of a severed peripheral nerve involves invasion by myelomonocytic cells, whose presence is necessary for destruction of myelin and for initiating mitosis in Schwann cells (Beuche and Friede, 1984). Degeneration of the distal ends of the axons themselves is assumed to ...
10.1038/s41583-020-0269-3
The discovery of the Wld S (formerly ‘Ola’) mouse, which initiated a molecular understanding of Wallerian degeneration
10.1038/srep43846
39,043,150
Abstract Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer’s, Huntington’s, Parkinson’s diseases. Here we developed a Meso Scale Disco...
10.1038/s41583-020-0269-3
This study shows a substantial variation of NMNAT2 expression level in humans and a correlation with dementia
10.1111/jns.12219
29,186,750
Abstract Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recen...
10.1038/s41583-020-0269-3
This study reports the alleviation of in vivo models of CIPN and metabolic disorder
10.1126/science.aal0092
104,171,641
Vitamin B 3 protects mice from glaucoma Glaucoma is the most common cause of age-related blindness in the United States. There is currently no cure, and once vision is lost, the condition is irreversible. Williams et al. now report that vitamin B 3 (also known as niacin) prevents eye degeneration in glaucoma-prone mice...
10.1038/s41583-020-0269-3
This study indicates the therapeutic potential of NMNAT and NAD in glaucoma
10.1186/1471-2350-10-86
64,267,891
Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal, degenerative neuromuscular disease characterized by a progressive loss of voluntary motor activity. About 95% of ALS patients are in "sporadic form"-meaning their disease is not associated with a family history of the disease. To date, the genetic fact...
10.1038/s41583-020-0269-3
In REFs 101 and 102 GWAS report a linkage between ALS and the SARM1 locuse
10.1073/pnas.1216204109
19,176,761
Axons actively self-destruct following genetic, mechanical, metabolic, and toxic insults, but the mechanism of axonal degeneration is poorly understood. The JNK pathway promotes axonal degeneration shortly after axonal injury, hours before irreversible axon fragmentation ensues. Inhibition of JNK activity during this p...
10.1038/s41583-020-0269-3
This study reports that SCG10 modifies the rate of Wallerian degeneration
10.1073/pnas.2118574119
126,765,375
Significance Sex differences in traits can occur when those traits are modified by genetic factors inherited on sex chromosomes. We investigated how sex differences emerge in a species with more than one set of sex chromosomes, measuring a variety of morphological, physiological, and behavioral traits. Rather than exhi...
10.1038/s41576-022-00524-2
A polygenic sex-determining mechanism may represent an initial stage of male morph evolution
10.1093/med/9780198739180.003.0002
88,627,590
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of immune dysregulation, autoreactive B and T cells, and the production of a broad, heterogeneous group of autoantibodies (autoAb). The pathogenesis of lupus can be divided into three stages: 1) genetic predisposition and environm...
10.1038/s41584-021-00726-8
This is a comprehensive and highly educative textbook on SLE.
10.1038/s41587-022-01361-8
132,926,845
Abstract Most methods for single-cell transcriptome sequencing amplify the termini of polyadenylated transcripts, capturing only a small fraction of the total cellular transcriptome. This precludes the detection of many long non-coding, short non-coding and non-polyadenylated protein-coding transcripts and hinders alte...
10.1038/s41587-022-01562-1
This paper reports a high-throughput method for sequencing the total transcriptome in single cells.
10.1126/science.1238842
104,300,001
Intestinal Villus Formation The intestinal villi are essential elaborations of the lining of the gut that increase the epithelial surface area for nutrient absorption. Shyer et al. (p. 212 , published online 29 August; see the Perspective by Simons ) show that in both the developing human and chick gut, the villi are f...
10.1038/s41580-020-00318-6
Shows that the different steps of avian gut villification result from a mechanical instability due to the expansion of the growing endoderm and the constraints imposed by surrounding muscle layers
10.1073/pnas.1722154115
55,322,433
We model the dynamics of formation of intercellular secretory lumens. Using conservation laws, we quantitatively study the balance between paracellular leaks and the build-up of osmotic pressure in the lumen. Our model predicts a critical pumping threshold to expand stable lumens. Consistently with experimental observa...
10.1038/s41580-020-00318-6
Quantitatively analyses the contributions of osmotic pressure, cortical tension, cell–cell contact geometry and paracellular leak in the expansion of intercellular lumens
10.1126/science.aaw7709
62,033,347
During mouse pre-implantation development, the formation of the blastocoel, a fluid-filled lumen, breaks the radial symmetry of the blastocyst. The factors that control the formation and positioning of this basolateral lumen remain obscure. We found that accumulation of pressurized fluid fractures cell-cell contacts in...
10.1038/s41580-020-00318-6
Illustrates how the formation of blastocoel and the first symmetry breaking event in the mouse embryo depend on a self-organized process of hydraulic fracturing of cell–cell contacts followed by contractility-directed coarsening of microlumens
10.1038/srep37217
17,303,675
Abstract Cellular biomechanics play a pivotal role in the pathophysiology of several diseases. Unfortunately, current methods to measure biomechanical properties are invasive and mostly limited to the surface of a cell. As a result, the mechanical behaviour of subcellular structures and organelles remains poorly charac...
10.1038/s41592-019-0543-3
In this work, high-contrast Brillouin microscopy revealed a liquid-to solid phase transition in intracellular stress granules in response to recruitment of a mutant ALS-linked protein
10.1126/scisignal.aaf6326
60,873,188
Fluorescence-Brillouin imaging reveals that plants regulate the mechanical properties of the extracellular matrix in response to light.
10.1038/s41592-019-0543-3
This paper provides a proof of principle for the organism-wide applicability of Brillouin microscopy by showing how cellular hydrostatic pressure and cytoplasm viscoelasticity modulate the mechanical signatures of plant extracellular matrices
10.1126/scitranslmed.aay9355
37,945,876
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only medical intervention that has led to an HIV cure. Whereas the HIV reservoir sharply decreases after allo-HSCT, the dynamics of the T cell reconstitution has not been comprehensively described. We analyzed the activation and differentiation of CD...
10.1038/s41591-023-02215-9
This study provides an in-depth longitudinal characterization of the T cell compartment in a cohort of 16 HIV-1 patients after allogeneic HSCT.
10.1073/pnas.0604970103
81,790,241
RNA-mediated pathogenesis is a recently developed disease model that proposes that certain types of mutant genes produce toxic transcripts that inhibit the activities of specific proteins. This pathogenesis model was proposed first for the neuromuscular disease myotonic dystrophy (DM), which is associated with the expa...
10.1038/s41580-021-00382-6
Kanadia et al. (2003) and Kanadia et al. (2006) establish in mice that sequestration of MBNL protein by CUG repeat RNA is sufficient to explain most of the muscle phenotypes observed in DM1
10.1038/s41467-018-04370-x
19,289,709
Abstract Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical c...
10.1038/s41580-021-00382-6
RBFOX proteins compete with MBNL proteins for binding sites on CCUG repeat RNAs, offering a novel mechanism by which RBP sequestration and toxicity can be attenuated through competition between proteins
10.1073/pnas.1013343108
20,347,382
Trinucleotide expansions cause disease by both protein- and RNA-mediated mechanisms. Unexpectedly, we discovered that CAG expansion constructs express homopolymeric polyglutamine, polyalanine, and polyserine proteins in the absence of an ATG start codon. This repeat-associated non-ATG translation (RAN translation) occu...
10.1038/s41580-021-00382-6
Repeat RNAs can be translated in the absence of an AUG start codon in many repeat expansion disorders
10.1126/scitranslmed.3008882
41,516,057
Sexual stages of the human malaria parasite Plasmodium falciparum use the hematopoietic system of the bone marrow as a developmental niche.
10.1038/s41579-019-0306-2
This study provides quantitative evidence for P. falciparum gametocyte enrichment in the human bone marrow
10.1128/mbio.00625-18
83,332,476
ABSTRACT Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. vivax asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that accumulation/sequestration in tissues is not an important phase in their development. Here, we present a s...
10.1038/s41579-019-0306-2
This study provides quantitative evidence for P. vivax gametocyte enrichment and an asexual reservoir in the bone marrow of non-human primates
10.1126/sciadv.aat3775
104,120,038
In vivo visualization of Plasmodium parasites reveals sublocalization, deformability, and mobility of gametocytes in the bone marrow.
10.1038/s41579-019-0306-2
This study shows a P. berghei asexual and gametocyte reservoir in the bone marrow and spleen of infected mice and provides the first description of parasite transmigration events across the endothelial barrier
10.1038/srep35025
44,135,762
Abstract The development of new drugs to disrupt malaria transmission requires the establishment of an in vivo model to address the biology of Plasmodium falciparum sexual stages (gametocytes). Herein we show that chemically immune-modulated NSG mice grafted with human erythrocytes support complete sexual development o...
10.1038/s41579-019-0306-2
This study demonstrates P. faciparum gametocyte enrichment in the bone marrow and spleen of humanized mice
10.1038/s41467-018-04108-9
107,184,553
Abstract Blood stage human malaria parasites may exploit erythropoietic tissue niches and colonise erythroid progenitors; however, the precise influence of the erythropoietic environment on fundamental parasite biology remains unknown. Here we use quantitative approaches to enumerate Plasmodium infected erythropoietic ...
10.1038/s41579-019-0306-2
This study provides evidence that an asexual P. berghei parasite reservoir in the spleen of infected mice can lead to recrudescence
10.1126/scitranslmed.aav3963
61,282,176
The recent decline in global malaria burden has stimulated efforts toward Plasmodium falciparum elimination. Understanding the biology of malaria transmission stages may provide opportunities to reduce or prevent onward transmission to mosquitoes. Immature P. falciparum transmission stages, termed stages I to IV gameto...
10.1038/s41579-019-0306-2
This study identifies shared antigens on the asexual and gametocyte iRBC surface
10.1126/science.aaw2619
41,610,473
Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. We profiled the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire Plasmodiu...
10.1038/s41579-019-0306-2
This study provides a single-cell atlas of the P. falciparum life cycle
10.1098/rsos.171780
125,115,478
The evolutionary relationships among the apicomplexan blood pathogens known as the malaria parasites (order Haemosporida), some of which infect nearly 200 million humans each year, has remained a vexing phylogenetic problem due to limitations in taxon sampling, character sampling and the extreme nucleotide base composi...
10.1038/s41579-019-0306-2
This study presents a comprehensive phylogenetic analysis of Haemosporidia, proposing the polyphyletic status of the genus Plasmodium
10.1073/pnas.1501781112
123,212,167
Marine ecosystems are sensitive to stochastic environmental variability, with higher-amplitude, lower-frequency––i.e., “redder”––variability posing a greater threat of triggering large ecosystem changes. Here we show that fluctuations in the Pacific Decadal Oscillation (PDO) index have slowed down markedly over the obs...
10.1038/s41558-018-0160-7
Shows that the variability of the Pacific Decadal Oscillation has become redder in the period 1900–present and examines how this might affect (nonlinear) marine ecosystems.
10.1111/j.1600-0587.2000.tb00273.x
104,029,429
Positively autocorrelated red environmental noise is characterized by a strong dependence of expected sample variance on sample length. This dependence has to be taken into account when assessing extinction risk under red and white uncorrelated environmental noise. To facilitate a comparison between red and white noise...
10.1038/s41558-018-0160-7
Shows that because the sample variance of environmental noise is dependent on sample length, there cannot be general results on extinction risk in coloured environments.
10.1098/rstb.1994.0001
123,405,920
Temporal changes in population abundance display a great diversity of patterns. This diversity is acknowledged by reviewers of marine and terrestrial data, but their explanations tend to fall into two categories: internal factors related to population or com m unity structure; and external aspects determined by the env...
10.1038/s41558-018-0160-7
Shows that the diversity of patterns observed in populations is dependent on the relative timescales of forcing and response, indicating that the variability of environmental forces influences population dynamics.
10.3390/antiox9121254
101,634,319
The beginnings of redox biology are recalled with special emphasis on formation, metabolism and function of reactive oxygen and nitrogen species in mammalian systems. The review covers the early history of heme peroxidases and the metabolism of hydrogen peroxide, the discovery of selenium as integral part of glutathion...
10.1038/s41573-021-00233-1
This article provides a history of oxidative stress from a current perspective
10.1210/er.2001-0039
41,662,862
Abstract In both type 1 and type 2 diabetes, the late diabetic complications in nerve, vascular endothelium, and kidney arise from chronic elevations of glucose and possibly other metabolites including free fatty acids (FFA). Recent evidence suggests that common stress-activated signaling pathways such as nuclear facto...
10.1038/s41573-021-00233-1
This article examines the links between oxidative stress and type 2 diabetes mellitus
10.1152/ajpheart.1988.255.6.h1269
59,256,976
In this lecture, evidence is presented to support the following hypothesis regarding the roles of xanthine oxidase-derived oxidants and granulocytes in ischemia-reperfusion-induced microvascular injury. During the ischemic period, ATP is catabolized to yield hypoxanthine. The hypoxic stress also triggers the conversion...
10.1038/s41573-021-00233-1
This article documents the sources of oxidative stress in IRI
10.1073/pnas.90.19.9171
39,414,793
Glutathione monoesters in which the carboxyl group of the glycine residue is esterified were previously found, in contrast to glutathione itself, to be effectively transported into various types of cells and to be converted intracellularly into glutathione. Glutathione monoesters are thus useful for prevention of oxida...
10.1038/s41573-021-00233-1
This article demonstrates that glutathione diethyl ester is highly effective as a delivery agent for GSH in human cells to decrease oxidative stress
10.3390/molecules24193593
41,470,654
There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either t...
10.1038/s41573-021-00233-1
This article evaluates the current knowledge regarding bioavailability and efficacy of glucoraphanin and sulforaphane in terms of dose and route of administration
10.1155/2019/9372182
125,242,898
The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) triggers the first line of homeostatic responses against a plethora of environmental or endogenous deviations in redox metabolism, proteostasis, inflammation, etc. Therefore, pharmacological activation of NRF2 is a promising therapeutic approac...
10.1038/s41573-021-00233-1
This article reviewed electrophilic and non-electrophilic NRF2 activators in clinical trials for various chronic diseases including cancer
10.12688/f1000research.12111.1
80,869,882
Dimethyl fumarate (DMF) is an electrophilic compound previously called BG-12 and marketed under the name Tecfidera ® . It was approved in 2013 by the US Food and Drug Administration and the European Medicines Agency for the treatment of relapsing multiple sclerosis. One mechanism of action of DMF is stimulation of the ...
10.1038/s41573-021-00233-1
This article evaluates NRF2 activators designed to avoid the systemic side effects caused by electrophilic activators
10.1002/mc.22745
123,704,193
Targeting the transcription factor NRF2 has been recognized as a feasible strategy for cancer prevention and treatment, but many of the mechanistic details underlying its role in cancer development and progression are lacking. Therefore, careful mechanistic studies of the NRF2 pathway in cancer initiation and progressi...
10.1038/s41573-021-00233-1
This article demonstrates that sulforaphane prevented the initiation of vinyl carbamate-induced lung cancer in mouse models but promoted the progression of pre-existing tumours
10.1126/scitranslmed.3007653
41,515,757
The antioxidants acetylcysteine and vitamin E accelerate tumor progression and reduce survival in mouse models of lung cancer by disrupting the ROS-p53 axis.
10.1038/s41573-021-00233-1
This article demonstrates that N -acetylcysteine and vitamin E markedly increased tumour progression and reduced survival in mouse models of lung cancer
10.1155/2014/757901
122,959,045
Oxidative stress contributes to both aging and tumorigenesis. The transcription factor Bach1, a regulator of oxidative stress response, augments oxidative stress by repressing the expression of heme oxygenase-1 (HO-1) gene ( Hmox1 ) and suppresses oxidative stress-induced cellular senescence by restricting the p53 tran...
10.1038/s41573-021-00233-1
This article demonstrates the effects of Bach1 knockout on the transcriptome, p53 −/− induced tumorigenesis and oxidative damage in a mouse model
10.1126/sciimmunol.aap8855
125,270,725
Biallelic TLR7 expression in immune cells may contribute to increased autoimmune disease risk in women.
10.1038/s41584-020-00544-4
This article documents the fact that TLR7 escapes complete inactivation on the silenced X chromosome in women, leading to a gender difference in its expression that might contribute to the higher incidence of SLE in women than in men
10.1126/scitranslmed.aan2306
41,670,992
Commensal bacterial orthologs of the human autoantigen Ro60 may trigger cross-reactive T and B cells that initiate and sustain chronic autoimmunity in lupus.
10.1038/s41584-020-00544-4
This work highlights the potential role of immune crossrecognition of self- and commensal bacterial-expressed Ro60 in triggering SLE
10.1084/jem.20161117
102,596,463
Toll-like receptors (TLRs) play an important role in immune responses to pathogens by transducing signals in innate immune cells in response to microbial products. TLRs are also expressed on B cells, and TLR signaling in B cells contributes to antibody-mediated immunity and autoimmunity. The SYK tyrosine kinase is esse...
10.1038/s41584-020-00544-4
This article implies a role for the BCR and its key signalling adaptor SYK in TLR signalling in B cells
10.1084/jem.20170580
82,800,594
Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a...
10.1038/s41584-020-00544-4
This article demonstrates that the formation of spontaneous germinal centres playing a key role in humoral immunity is controlled by the production of IL-6 by B cells, linking their antibody-dependent and antibody-independent functions
10.1029/2012gl051000
125,223,161
Arctic amplification (AA) – the observed enhanced warming in high northern latitudes relative to the northern hemisphere – is evident in lower‐tropospheric temperatures and in 1000‐to‐500 hPa thicknesses. Daily fields of 500 hPa heights from the National Centers for Environmental Prediction Reanalysis are analyzed over...
10.1038/s41558-019-0662-y
Influential early observational study arguing that Arctic amplification is contributing to more extreme weather in all seasons
10.1029/2008gl035607
4,835,745
Arctic climate system change has accelerated tremendously since the beginning of this century, and a strikingly extreme sea‐ice loss occurred in summer 2007. However, the greenhouse‐gas‐emissions forcing has only increased gradually and the driving role in Arctic climate change of the positively‐polarized Arctic/North ...
10.1038/s41558-019-0662-y
Identified radical spatial changes in the large-scale atmospheric circulation showing a contracted/weakened Icelandic low and a northwestward extended/strengthened Siberian high; linked the amplified Arctic warming/accelerated decrease in sea ice in the Barents–Kara seas to Eurasian cooling
10.1175/jcli-d-16-0197.1
100,542,587
Abstract The loss of Arctic sea ice is already having profound environmental, societal, and ecological impacts locally. A highly uncertain area of scientific research, however, is whether such Arctic change has a tangible effect on weather and climate at lower latitudes. There is emerging evidence that the geographical...
10.1038/s41558-019-0662-y
Observational and modelling showing the atmospheric to regional and pan-Arctic response to Arctic warming/sea ice loss
10.1002/grl.50880
107,184,083
Previous studies have suggested that Arctic amplification has caused planetary‐scale waves to elongate meridionally and slow down, resulting in more frequent blocking patterns and extreme weather. Here trends in the meridional extent of atmospheric waves over North America and the North Atlantic are investigated in thr...
10.1038/s41558-019-0662-y
Early paper that was sceptical of reported Arctic–mid-latitude linkages and found no evidence that Arctic amplification was contributing to increased blocking or extreme weather
10.1029/2008gl037079
45,290,128
Influence of low Arctic sea‐ice minima in early autumn on the wintertime climate over Eurasia is investigated. Observational evidence shows that significant cold anomalies over the Far East in early winter and zonally elongated cold anomalies from Europe to Far East in late winter are associated with the decrease of th...
10.1038/s41558-019-0662-y
Early paper showing through model experiments that sea ice loss in the Barents–Kara Seas can force in cold Siberian temperatures by exciting a Rossby wave train
10.1175/jcli3490.1
81,291,957
Abstract There are significant discrepancies between observational datasets of Arctic sea ice concentrations covering the last three decades, which result in differences of over 20% in Arctic summer sea ice extent/area and 5%–10% in winter. Previous modeling studies have shown that idealized sea ice anomalies have the ...
10.1038/s41558-019-0662-y
Modelling paper that showed no relationship between sea ice variability and the North Atlantic Oscillation, an early precursor for many more modelling studies
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/s41594-021-00601-w
The P granule was the first biomolecular condensate demonstrated to have liquid-like properties, such as droplet fusion, wetting and dripping
10.1126/science.aar7432
104,294,738
RNA and membraneless organelles Membraneless compartments can form in cells through liquidliquid phase separation (see the Perspective by Polymenidou). But what prevents these cellular condensates from randomly fusing together? Using the RNA-binding protein (RBP) Whi3, Langdon et al. demonstrated that the secondary str...
10.1038/s41594-021-00601-w
Manipulating RNA sequence and secondary structure alters the identity of the biomolecules incorporated into phase-separated droplets
10.1126/science.aaz4427
125,306,652
The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplas...
10.1038/s41594-021-00601-w
The physiochemical composition of small molecules determines their partitioning into biological condensates, which may be harnessed for improved therapeutic design
10.1126/science.1097211
83,016,486
The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 to 2003. Although there was remarkable correspondence between antigenic and genetic evolution, significant differences were observed: Antigenic evolution was more punctuated than genetic evolution...
10.1038/s41572-018-0002-y
This study describes the concept of antigenic cartography and uses antigenic cartography for the visualization and quantification of antigenic drift of human H3N2 influenza A viruses over 35 years
10.1126/science.1136212
103,749,846
The 1918 influenza pandemic was a catastrophic series of virus outbreaks that spread across the globe. Here, we show that only a modest change in the 1918 influenza hemagglutinin receptor binding site alters the transmissibility of this pandemic virus. Two amino acid mutations that cause a switch in receptor binding pr...
10.1038/s41572-018-0002-y
This study provides the first evidence that the receptor specificity of the HA of influenza A virus plays a major role in the respiratory transmission of these viruses
10.1038/ncomms7833
103,645,793
Abstract The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery to prolonged hospitalization. Using a multicolour assay for monitoring adaptive and innate immunity, here we dissect the kinetic emergence of di...
10.1038/s41572-018-0002-y
This manuscript provides evidence that early cross-reactive CD8 + T cell immunity plays an important part in recovery from severe avian influenza A H7N9 virus-induced disease
10.1093/ofid/ofx180.001
39,008,689
Abstract Background Cap-dependent endonuclease (CEN) resides in the PA subunit of influenza virus polymerase and mediates the “cap-snatching” process during viral mRNA biosynthesis. S-033188 is a potent, selective, small molecule inhibitor of CEN. Here we report clinical and virologic outcomes from a global Phase 3 stu...
10.1038/s41572-018-0002-y
This paper reports clinical trial results of baloxavir marboxil, a new influenza drug approved in Japan in 2018
10.1126/science.1232458
41,740,034
DNA Sensing Is a (c)GAS DNA is normally localized to the nucleus, and so its cytoplasmic localization sends off alarm bells to the immune system because it indicates that a virus may have entered. But how does the immune system actually detect the DNA (see the Perspective by O'Neill )? Sun et al. (p. 786 , published on...
10.1038/s41577-022-00751-y
This paper for the first time identifies cGAS as a cytosolic DNA sensor.
10.1126/science.aaa5612
4,632,311
Transcriptional control of cell senescence Senescent cells that have stopped proliferating secrete molecules that influence the cells around them. Prevention of this senescence-activated secretory phenotype seems to slow organismal aging. Kang et al. explored the regulatory process behind cell senescence and found that...
10.1038/s41577-022-00751-y
This paper describes the activation of NF-κB by DNA damage independently of cGAS.
10.1073/pnas.1705499114
62,292,459
Cellular senescence is a natural barrier to tumorigenesis and it contributes to the antitumor effects of several therapies, including radiation and chemotherapeutic drugs. Senescence also plays an important role in aging, fibrosis, and tissue repair. The DNA damage response is a key event leading to senescence, which i...
10.1038/s41577-022-00751-y
This study demonstrates the essential role of cGAS in cellular senescence.
10.1161/circulationaha.105.593046
103,676,303
Background— Although lymphocyte recruitment and activation are associated with cerebral ischemia-reperfusion (I/R) injury, the contributions of specific lymphocyte subpopulations and lymphocyte-derived interferon-γ (IFN-γ) to stroke remain unknown. The objectives of this study were to define the contribution of specifi...
10.1038/s41582-019-0221-1
This seminal paper demonstrates that T cells make an essential contribution to ischaemia–reperfusion injury after transient cerebral ischaemia in mice
10.1182/blood-2009-10-249078
103,683,699
Abstract T cells contribute to the pathophysiology of ischemic stroke by yet unknown mechanisms. Mice with transgenic T-cell receptors (TCRs) and mutations in costimulatory molecules were used to define the minimal immunologic requirements for T cell–mediated ischemic brain damage. Stroke was induced in recombination a...
10.1038/s41582-019-0221-1
This article presents a comprehensive analysis of T cell subpopulations, co-stimulatory factors and their effects on ischaemia–reperfusion injury in the tMCAO mouse model
10.1161/circulationaha.107.691279
38,287,883
Background— Ischemic stroke is a frequent and serious disease with limited treatment options. Platelets can adhere to hypoxic cerebral endothelial cells by binding of their glycoprotein (GP) Ib receptor to von Willebrand factor. Exposure of subendothelial matrix proteins further facilitates firm attachment of platelets...
10.1038/s41582-019-0221-1
This study demonstrates that platelet tethering and activation by GPIb and GPVI signalling, but not GPIIb/IIIa-mediated platelet aggregation, are involved in ischaemic lesion formation in experimental stroke
10.1126/scitranslmed.aaa9853
20,712,296
A multicenter preclinical, randomized, controlled trial (pRCT) of a potential stroke treatment in mice demonstrates the feasibility of performing clinical trial–like investigations in animal models.
10.1038/s41582-019-0221-1
This article presents results from the first preclinical randomized controlled multicentre trial to assess the contribution of α4-integrin-mediated T cell responses in different experimental models of brain ischaemia
10.1161/circulationaha.115.016371
123,169,717
Background— Inflammatory and immune responses triggered by brain ischemia worsen clinical outcomes of stroke and contribute to hemorrhagic transformation, massive edema, and reperfusion injury associated with intravenous alteplase. We assessed whether a combination of the immune-modulator fingolimod and alteplase is sa...
10.1038/s41582-019-0221-1
This paper presents results from a pilot clinical trial in which the immune modulator fingolimod was combined with alteplase to treat acute ischaemic stroke
10.1084/jem.20021098
20,587,081
Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an...
10.1038/s41582-019-0221-1
This article provides the first description of stroke-induced immunodepression in mice and the underlying activation of the sympathetic nervous system
10.1155/2013/363859
99,491,393
Behcet’s disease (BD) is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. Recently, we found that Th17 cells, a new helper T (Th) cell subset, were increase...
10.1038/s41572-021-00301-1
This paper discusses the important part that T cells play in the pathogenesis of Behçet syndrome
10.1002/jmri.24643
40,123,223
Purpose To develop navigator‐gated free‐breathing 3D spiral late gadolinium enhancement (LGE) imaging of the left ventricle at 3T and compare it with conventional breath‐hold 2D Cartesian imaging. Materials and Methods Equivalent slices from 3D spiral and multislice 2D Cartesian acquisitions were compared in 15 subject...
10.1038/s41572-021-00301-1
This paper reviews the importance and utility of a non-invasive imaging method such as MRI in the management of vascular involvement in Behçet syndrome
10.1002/ana.24714
61,559,676
Objective Although commonly used in clinical practice, there remains much uncertainty about whether perfusion computed tomography (CTP) should be used to select stroke patients for acute reperfusion therapy. In this study, we tested the hypothesis that a small acute perfusion lesion predicts good clinical outcome regar...
10.1038/s41582-020-0390-y
A controversial article in which the benefit of thrombolysis for patients with a perfusion lesion <15 ml is questioned
10.1111/j.1466-8238.2007.00358.x
62,581,935
ABSTRACT The area under the receiver operating characteristic (ROC) curve, known as the AUC, is currently considered to be the standard method to assess the accuracy of predictive distribution models. It avoids the supposed subjectivity in the threshold selection process, when continuous probability derived scores are ...
10.1038/s41582-020-0390-y
An important analytical piece that shows how to interpret statistical results
10.1038/s41467-020-17291-5
107,138,444
Abstract Blood vascular endothelial cells (BECs) control the immune response by regulating blood flow and immune cell recruitment in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain unclear. Here we profile transcriptomes of BEC from peripheral lymph nodes and map phen...
10.1038/s41577-022-00694-4
This scRNA-seq study identifies non-high-vein ECs in murine lymph nodes which are important for myeloid cell migration into inflamed lymph nodes
10.1038/s41467-018-06318-7
62,216,524
Abstract The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We prov...
10.1038/s41577-022-00694-4
This study provides a description of LSECs from different hepatic zones with distinct transcriptomes and putative immunomodulatory functions based on scRNA-seq data
10.1126/scitranslmed.3009524
20,376,178
Ultrasmall inorganic hybrid optical-PET imaging particles were found to be safe and physiologically stable in patients with melanoma.
10.1038/s41578-018-0038-3
This paper reports human trials of renal-clearable inorganic nanoparticles, testing 124 I-labelled silica nanoparticles (C-dots)
10.1002/anie.201707819
17,257,524
Abstract With more and more engineered nanoparticles (NPs) being designed renal clearable for clinical translation, fundamental understanding of their transport in the different compartments of kidneys becomes increasingly important. Here, we report noninvasive X‐ray imaging of renal clearable gold NPs (AuNPs) in norma...
10.1038/s41578-018-0038-3
This paper reports gold nanoparticles for X-ray imaging of kidney function
10.1002/anie.201507868
19,829,315
Abstract Noninvasive imaging of kidney clearance kinetics (KCK) of renal clearable probes is key to studying unilateral kidney function diseases, but such imaging is highly challenging to achieve with in vivo fluorescence. While this long‐standing challenge is often attributed to the limited light penetration depth, we...
10.1038/s41578-018-0038-3
This paper reports that non-invasive fluorescence imaging of kidneys can be achieved at high contrast by using renal-clearable NIR-emitting gold nanoparticles as contrast agents
10.1073/pnas.1103573108
62,193,688
Nanoparticles are being investigated for numerous medical applications and are showing potential as an emerging class of carriers for drug delivery. Investigations on how the physicochemical properties (e.g., size, surface charge, shape, and density of targeting ligands) of nanoparticles enable their ability to overcom...
10.1038/s41578-018-0038-3
This paper reports the systematic investigation of the interactions of non-renal-clearable nanoparticles with the kidneys and shows the uptake of these nanoparticles by the mesangium
10.1002/ange.201511148
61,559,588
Abstract As a “silent killer”, kidney disease is often hardly detected at an early stage but can cause lethal kidney failure later on. Thus, a preclinical imaging technique that can readily differentiate between the stages of kidney dysfunction is highly desired for improving our fundamental understanding of kidney dis...
10.1038/s41578-018-0038-3
This paper reports the use of luminescent renal-clearable gold nanoparticles for the detection and staging of kidney dysfunction by non-invasive in vivo fluorescence imaging
10.1084/jem.20161759
82,954,195
MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a hom...
10.1038/s41573-019-0043-2
This is the first report of a homozygous missense mutation in IFIH1 in humans, resulting in increased susceptibility to viral infection
10.1038/ncomms15618
83,351,016
Abstract Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12–18 Gy in different cancer cells, and attenuates their i...
10.1038/s41573-019-0043-2
This article demonstrates that the cytosolic exonuclease TREX1 is upregulated by radiation doses greater than 12–14 Gy in most cancer cells, resulting in limited availability of dsDNA for cGAS activation and hence reduced secretion of type I interferon
10.1038/s41467-017-00573-w
62,591,487
Abstract Mammalian cells use cytosolic nucleic acid receptors to detect pathogens and other stress signals. In innate immune cells the presence of cytosolic DNA is sensed by the cGAS–STING signalling pathway, which initiates a gene expression programme linked to cellular activation and cytokine production. Whether the ...
10.1038/s41573-019-0043-2
This article and reference 162 demonstrate that robust STING agonism mediates cytostatic and cytotoxic effects in T cells, hence being detrimental to (rather than beneficial for) anticancer immune responses
10.1523/jneurosci.2712-16.2017
82,434,494
The relative contributions of glycolysis and oxidative phosphorylation to neuronal presynaptic energy demands are unclear. In rat hippocampal neurons, ATP production by either glycolysis or oxidative phosphorylation alone sustained basal evoked synaptic transmission for up to 20 min. However, combined inhibition of bot...
10.1038/s41583-021-00535-8
This study shows that basal evoked synaptic transmission can be sustained by activity-boosted glycolysis, but that intensive synaptic activity requires oxidative phosphorylation
10.1073/pnas.91.22.10625
83,038,395
Glutamate, released at a majority of excitatory synapses in the central nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly via Na(+)-dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in add...
10.1038/s41583-021-00535-8
This pioneering study led to the proposal of the astrocyte–neuron lactate shuttle hypothesis
10.1113/jp275107
45,353,287
Key points Synapses have high energy demands which increase during intense activity. We show that presynaptic terminals can utilise extracellular glucose or lactate to generate energy to maintain synaptic transmission. Reducing energy substrates induces a metabolic stress: presynaptic ATP depletion impaired synaptic tr...
10.1038/s41583-021-00535-8
This study shows that presynaptic ATP depletion at the calyx of Held accelerates synaptic depression during HFS owing to the failed replenishment of the readily releasable vesicle pool
10.1083/jcb.201302040
2,694,896
Axonal mitochondria are recruited to synaptic terminals in response to neuronal activity, but the mechanisms underlying activity-dependent regulation of mitochondrial transport are largely unknown. In this paper, using genetic mouse model combined with live imaging, we demonstrate that syntaphilin (SNPH) mediates the a...
10.1038/s41583-021-00535-8
This study shows that SNPH stably anchors axonal mitochondria by coordinating with MIRO1–Ca 2+ signalling
10.1073/pnas.0808953105
125,107,058
Calcium oscillations suppress mitochondrial movements along the microtubules to support on-demand distribution of mitochondria. To activate this mechanism, Ca 2+ targets a yet unidentified cytoplasmic factor that does not seem to be a microtubular motor or a kinase/phosphatase. Here, we have studied the dependence of m...
10.1038/s41583-021-00535-8
This study shows that MIRO1 arrests mitochondrial transport by sensing Ca 2+
10.1083/jcb.131.5.1315
41,748,883
A large body of evidence indicates that microtubules (MTs) conduct organelle transport in axons, but recent studies on extruded squid axoplasm have suggested that actin microfilaments (MFs) may also play a role in this process. To investigate the separate contributions to transport of each class of cytoskeletal element...
10.1038/s41583-021-00535-8
This study reveals that F-actin and microtubules mediate axonal mitochondrial transport with different velocities and properties
10.1002/dneu.22149
82,671,550
ABSTRACT During development, axons are guided to their target areas and provide local branching. Spatiotemporal regulation of axon branching is crucial for the establishment of functional connections between appropriate pre‐ and postsynaptic neurons. Common understanding has been that neuronal activity contributes to t...
10.1038/s41583-021-00535-8
This study shows that AMPK activation enhances mitochondrial transport and facilitates mitochondrial distribution at presynaptic terminals
10.1523/jneurosci.0028-05.2005
20,467,702
Mutations in the Pak3 gene lead to nonsyndromic mental retardation characterized by selective deficits in cognition. However, the underlying mechanisms are yet to be elucidated. We report here that the knock-out mice deficient in the expression of p21-activated kinase 3 (PAK3) exhibit significant abnormalities in synap...
10.1038/s41583-021-00535-8
This study finds that Pak3 -knockout mice exhibit significant abnormalities in synaptic plasticity
10.1158/1055-9965.epi-15-0145
28,886,517
Abstract Background: Hodgkin lymphoma in young adults is inexplicably linked to economic development. Methods: We conducted a nested case–control study of the 656 servicemen with Hodgkin lymphoma diagnosed between ages 17 to 32 while on active duty in the U.S. military during 1950–68. Controls, chosen randomly from the...
10.1038/s41572-020-0189-6
This study shows that Hodgkin lymphoma incidence is influenced by sibship size, socio-economic status and level of education.
10.1200/jco.2010.32.8401
103,817,737
Hodgkin's lymphoma (HL) represents the most common subtype of malignant lymphoma in young people in the Western world. Most patients can be cured with modern treatment strategies, although approximately 20% will die after relapse or progressive disease. The histologic hallmark of the disease is the presence of the char...
10.1038/s41572-020-0189-6
This study provides molecular biological evidence for the primary influence of the tumour microenvironment in the pathophysiology of Hodgkin lymphoma
10.1182/blood.v106.11.965.965
55,178,295
Abstract Background: POKEMON (for POK, Erythroid, Myeloid ONtogenic factor) has recently been shown to be a novel proto-oncogene, playing a key role in cellular transformation and repression of ARF. Pokemon overexpression leads to overt oncogenic transformation both in vitro and in vivo in transgenic mice. Because thes...
10.1038/s41572-020-0189-6
This study established the necessity for immunophenotypic profiling to determine the diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma and to distinguish it from lymphocyte-rich classic Hodgkin lymphoma
10.1002/cncr.30824
24,635,918
On the basis of the putative origin from germinal center B cells, the gene expression profile, the expression of the B‐cell phenotype, and the propensity to progress toward large B‐cell lymphoma, nodular lymphocyte‐predominant Hodgkin lymphoma should be classified as a special type of B‐cell lymphoma with a follicular ...
10.1038/s41572-020-0189-6
Hodgkin lymphoma is a heterogeneous disease that includes classic forms and other forms closer to germinal centre-derived non-Hodgkin lymphoma
10.1002/path.4558
17,739,978
Abstract Classical Hodgkin's lymphoma ( cHL ), a distinct disease entity with characteristic clinical and pathological features, accounts for approximately 10% of all malignant lymphomas. cHL can be considered a prototype model for how the tumour microenvironment influences cancer pathogenesis. Cellular components of t...
10.1038/s41572-020-0189-6
This study of the tumour microenvironment is the basis for selecting cellular or humoral targets for innovative therapies in individuals affected by cHL and refractory to conventional therapies
10.2218/ijdc.v10i1.354
88,920,816
Research Data Management (RDM) provides a framework that supports researchers and their data throughout the course of their research and is increasingly regarded as one of the essential areas of responsible conduct of research. New tools and infrastructures make possible the generation of large volumes of digital resea...
10.1038/s41596-021-00645-8
A case study illustrating how ELNs can be integrated directly with a university data repository, allowing users to deposit data through the ELN for compliance with an RDM policy.
10.1126/science.1251086
41,497,281
A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into the many components of our immune system, the BLUEPRINT consortium examined the regulation of DNA and RNA transcription to dissect the molecular traits that govern blood cell differentiation. By inducin...
10.1038/s41577-020-0285-6
This article shows that modification of the epigenetic landscape is behind the effects of trained immunity in human monocytes
10.1126/science.1250684
20,656,203
A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into the many components of our immune system, the BLUEPRINT consortium examined the regulation of DNA and RNA transcription to dissect the molecular traits that govern blood cell differentiation. By inducin...
10.1038/s41577-020-0285-6
This study reports that metabolic rewiring of cells is crucial for the induction of trained immunity
10.1126/science.1225829
20,844,166
Ditching Invading DNA Bacteria and archaea protect themselves from invasive foreign nucleic acids through an RNA-mediated adaptive immune system called CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated (Cas). Jinek et al. (p. 816 , published online 28 June; see the Perspective by Brou...
10.1038/s41582-020-0373-z
This study demonstrates site-specific DNA cleavage by a complex of Cas9 and guide RNAs
10.1126/science.1232033
125,274,783
Genome Editing Clustered regularly interspaced short palindromic repeats (CRISPR) function as part of an adaptive immune system in a range of prokaryotes: Invading phage and plasmid DNA is targeted for cleavage by complementary CRISPR RNAs (crRNAs) bound to a CRISPR-associated endonuclease (see the Perspective by van d...
10.1038/s41582-020-0373-z
Together with Cong et al. (2013), this study demonstrates the use of CRISPR–Cas9-based genome engineering in human cells
10.1126/science.1246981
20,829,308
The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 system for genome editing has greatly expanded the toolbox for mammalian genetics, enabling the rapid generation of isogenic cell lines and mice with modified alleles. Here, we describe a pooled, loss-of-function genetic screening app...
10.1038/s41582-020-0373-z
Together with Koike-Yusa al. (2014) and Shalem et al. (2014), this paper describes the use of Cas9-based platforms for genome-wide knockout screens in mammalian cells