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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10.1126/science.aao3265 | 104,439,755 | mTOR complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple environmental cues. Nutrients signal via the Rag guanosine triphosphatases (GTPases) to promote the localization of mTORC1 to the lysosomal surface, its site of activation. We identified SAMTOR, a previously uncharacterized protein, wh... | 10.1038/s41568-019-0187-8 | This study defines a novel biochemical SAM-sensing mechanism through direct interaction with mTORC1 |
10.1160/th17-02-0079 | 67,543,905 | Summary The biochemical characterisation of the proteolytic pathways that constitute blood coagulation was one of the most relevant achievements in biomedical research during the second half of the 20th century. Understanding these pathways was of crucial importance for improving global health through application in ha... | 10.1038/s41573-020-0061-0 | The paper describes the coagulation protease cascade and its role in thrombosis, thrombo-inflammation and atherosclerosis |
10.1182/blood-2002-12-3882 | 20,401,508 | Abstract At sites of vascular injury, platelets come into contact with subendothelial collagen, which triggers their activation and the formation of a hemostatic plug. Besides glycoprotein Ib (GPIb) and αIIbβ3 integrin, which indirectly interact with collagen via von Willebrand factor (VWF), several collagen receptors ... | 10.1038/s41573-020-0061-0 | The paper describes the role of platelet GPVI in haemostasis and arterial thrombosis |
10.1182/blood-2013-12-540872 | 125,071,680 | Key Points Antisense oligonucleotides reduce levels of target hepatic mRNA and protein and decrease clotting activity in rabbits. Selective depletion of factors XI and XII in rabbits attenuates catheter thrombosis, whereas factor VII depletion does not. | 10.1038/s41573-020-0061-0 | The paper shows that knockdown of either FXII or FXI but not FVII prolonged the time to catheter occlusion in a rabbit model |
10.1126/scitranslmed.3006804 | 62,194,959 | Blocking the enzyme that initiates the intrinsic coagulation pathway protects against thrombosis in bypass systems and does not cause excess bleeding in vivo. | 10.1038/s41573-020-0061-0 | The paper shows that a FXII antibody inhibited thrombosis in an extracorporeal circuit as effectively as heparin without increasing bleeding in a rabbit model |
10.12688/f1000research.11174.1 | 67,555,233 | The direct oral anticoagulants (DOACs) have now supplanted vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. The DOACs are as effective for the prevention of recurrence ... | 10.1038/s41573-020-0061-0 | The paper describes the benefits of direct oral anticoagulants over vitamin K antagonists for the treatment of venous thromboembolism |
10.1182/blood-2018-04-848333 | 41,740,415 | Publisher's Note: There is a Blood Commentary on this article in this issue. | 10.1038/s41573-020-0061-0 | The trial showed that the use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with increased rates of thrombosis compared with warfarin |
10.1182/blood-2018-02-769026 | 104,013,863 | Abstract Protein C is a plasma serine protease zymogen whose active form, activated protein C (APC), exerts potent anticoagulant activity. In addition to its antithrombotic role as a plasma protease, pharmacologic APC is a pleiotropic protease that activates diverse homeostatic cell signaling pathways via multiple rece... | 10.1038/s41573-020-0061-0 | The paper describes the beneficial effects of an activated protein C variant in stroke |
10.1091/mbc.e10-11-0871 | 18,926,317 | Negatively regulating signaling by targeting key effectors for ubiquitination/destruction is essential for development and oncogenesis. The tumor suppressor adenomatous polyposis coli (APC), an essential negative regulator of Wnt signaling, provides a paradigm. APC mutations occur in most colon cancers. Acting in the ... | 10.1038/s41568-020-00307-z | This study discovers that the APC 20R2 region and CID are essential for a late step in destruction complex-mediated β-catenin turnover |
10.1126/science.1175145 | 62,051,295 | In and Out For over 40 years, Ca 2+ /H + antiport has been reported across plasma cell membranes and mitochondrial inner membranes, but the molecules responsible for the exchange have not been known. Jiang et al. (p. 144 ; see the Perspective by Demaurex and Poburko ) conducted a genome-wide RNA interference screen in ... | 10.1038/s41580-018-0052-8 | This study indicates that the IMM protein LETM1 functions as the HCXs |
10.1126/science.280.5370.1763 | 41,469,373 | The spatial relation between mitochondria and endoplasmic reticulum (ER) in living HeLa cells was analyzed at high resolution in three dimensions with two differently colored, specifically targeted green fluorescent proteins. Numerous close contacts were observed between these organelles, and mitochondria in situ forme... | 10.1038/s41580-018-0052-8 | This study demonstrates the crucial role of ER–mitochondria contacts in rapid mitochondrial Ca 2+ accumulation |
10.1126/science.aan6009 | 45,533,739 | Making the right contacts Contacts between the endoplasmic reticulum (ER) and mitochondria mediate key physiological processes such as Ca 2+ exchange and lipid biogenesis. wiIn yeast, ER and mitochondria are tethered by a complex of four proteins called ERMES. However, no functional orthologs of these ERMES complex pro... | 10.1038/s41580-018-0052-8 | This study identifies PDZD8 as the mammalian orthologue of Mmm1, the yeast ER component of the ERMES complex, a protein complex that tethers the ER to mitochondria |
10.1042/bj1800533 | 41,575,941 | 1. The effects of Ca2+ (mainly by using EGTA buffers), pH, ATP and ADP on the activity of the 2-oxoglutarate dehydrogenase complex from pig heart were explored. 2. Ca2+ (about 30 micrometer) resulted in a decrease in the apparent Km for 2-oxoglutarate from 2.1 to 0.16 mM (at pH 7) without altering the maximal velocity.... | 10.1038/s41580-018-0052-8 | This study demonstrates that increases in intramitochondrial free Ca 2+ result in activation of mitochondrial dehydrogenases and stimulation of ATP synthesis |
10.1073/pnas.96.24.13807 | 107,240,685 | In recent years, mitochondria have emerged as important targets of agonist-dependent increases in cytosolic Ca 2+ concentration. Here, we analyzed the significance of Ca 2+ signals for the modulation of organelle function by directly measuring mitochondrial and cytosolic ATP levels ([ATP] m and [ATP] c , respectively) ... | 10.1038/s41580-018-0052-8 | Reinforces findings presented in reference 136, showing that mitochondrial Ca 2+ rises stably elevate mitochondrial [ATP] |
10.1126/sciadv.abc2695 | 121,448,748 | This study reports the occurrence of intense atmospheric rivers (ARs) during the two large Weddell Polynya events in November 1973 and September 2017 and investigates their role in the opening events via their enhancement of sea ice melt. Few days before the polynya openings, persistent ARs maintained a sustained posit... | 10.1038/s41558-023-01601-y | This paper reports the polynya events induced by ARs in Antarctica. |
10.1126/scitranslmed.3003586 | 123,168,974 | Preexisting immunity to BCG improves treatment response to intravesical BCG therapy for bladder cancer in mouse models and humans. | 10.1038/s41585-018-0055-4 | Reference 48 demonstrates that mice with pre-existing cellular immunity to BCG have a more rapid immune response to BCG therapy and are better protected against tumour challenge following intravesical BCG instillation; patients with BCG immune memory also demonstrate superior protection following BCG therapy |
10.1002/cncr.22588 | 103,907,653 | Abstract BACKGROUND PD‐L1 (programmed death ligand 1, B7‐H1) is a cell surface glycoprotein that can impair T‐cell function. PD‐L1 is aberrantly expressed by multiple human malignancies and has been shown to carry a highly unfavorable prognosis in patients with kidney cancer. The role of PD‐L1 was evaluated as a mechan... | 10.1038/s41585-018-0055-4 | Several years before the advent of checkpoint blockade inhibition in bladder cancer, reference 149 reports a link between PD-L1 expression, response to BCG, and bladder cancer stage progression |
10.1126/science.1074129 | 82,902,653 | Celiac Sprue, a widely prevalent autoimmune disease of the small intestine, is induced in genetically susceptible individuals by exposure to dietary gluten. A 33-mer peptide was identified that has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in Celiac Sprue pati... | 10.1038/s41572-018-0054-z | This excellent study demonstrates the proteolytic resistance of gliadin and is the first to suggest a new treatment modality based on proteolytic breakdown of gluten peptides |
10.1111/j.1365-2958.2012.08206.x | 26,837,619 | Summary Pathogenic mycobacteria require type VII secretion ( T7S ) systems to transport virulence factors across their complex cell envelope. These bacteria have up to five of these systems, termed ESX ‐1 to ESX ‐5. Here, we show that ESX ‐5 of M ycobacterium tuberculosis mediates the secretion of EsxN , PPE and PE_PGR... | 10.1038/s41579-021-00560-5 | This study provides the first biochemical evidence that EccB–EccE form a secretion complex in the mycobacterial cell wall |
10.1073/pnas.1409345111 | 45,284,030 | Significance Mycobacterium tuberculosis ( Mtb ) infects nearly a third of the global population, and understanding how Mtb establishes infection and evades host responses is key to development of improved therapies. Two mysterious protein families, called Pro-Glu motif–containing (PE) and Pro-Pro-Glu motif–containing (... | 10.1038/s41579-021-00560-5 | This study presents the first structure of a PE–PPE substrate heterodimer bound to the chaperone EspG and shows that PE–PPE substrates interact specifically with their cognate chaperones |
10.1038/srep42704 | 121,785,318 | Abstract Type VII secretion (T7S) systems are specialized machineries used by mycobacterial pathogens to transport important virulence factors across their highly hydrophobic cell envelope. There are up to five mycobacterial T7S systems, named ESX-1 to ESX-5, at least three of which specifically secrete a different sub... | 10.1038/s41579-021-00560-5 | Together with the study of Ekiert and Cox (2014), this study establishes that EspG determines the system specificity of PE–PPE substrates |
10.1126/science.aav5912 | 107,190,653 | Mycobacterium tuberculosis has an unusual outer membrane that lacks canonical porin proteins for the transport of small solutes to the periplasm. We discovered that 3,3- bis -di(methylsulfonyl)propionamide (3bMP1) inhibits the growth of M. tuberculosis , and resistance to this compound is conferred by mutation within a... | 10.1038/s41579-021-00560-5 | Wang et al. provide the first detailed study of porins formed by PE–PPE proteins in the mycobacterial cell envelope |
10.1073/pnas.1119453109 | 4,789,440 | Mycobacterial pathogens use specialized type VII secretion (T7S) systems to transport crucial virulence factors across their unusual cell envelope into infected host cells. These virulence factors lack classical secretion signals and the mechanism of substrate recognition is not well understood. Here we demonstrate tha... | 10.1038/s41579-021-00560-5 | This study identifies the amino acid sequence YXXXD/E as a general type VII secretion signal |
10.1126/science.1131167 | 41,703,965 | Mycobacterium tuberculosis uses the ESX-1/Snm system [early secreted antigen 6 kilodaltons (ESAT-6) system 1/secretion in mycobacteria] to deliver virulence factors into host macrophages during infection. Despite its essential role in virulence, the mechanism of ESX-1 secretion is unclear. We found that the unstructure... | 10.1038/s41579-021-00560-5 | This study shows that the C terminus of WXG100 contains a signal peptide crucial for the interactions of these proteins with the C-terminal segment of the EssC coupling protein |
10.1126/science.1217139 | 104,101,823 | Inhibiting the Inhibitors Excitatory neurons in the hippocampus and entorhinal cortex are under control of local γ-aminobutyric acid–releasing (GABAergic) interneurons that are the major source of inhibition in the adult brain. In contrast to the wealth of knowledge regarding connectivity in the hippocampus, much less ... | 10.1038/s41583-020-0344-9 | Taking recourse to AAVs that enabled the identification and characterization of defined GABAergic projections and employing optogenetically induced axonal stimulation, this study is the first to demonstrate inhibitory postsynaptic currents on functionally identified target cells that were all GABAergic interneurons |
10.1038/s41467-018-05136-1 | 107,139,981 | Abstract The basal forebrain cholinergic system is widely assumed to control cortical functions via non-synaptic transmission of a single neurotransmitter. Yet, we find that mouse hippocampal cholinergic terminals invariably establish GABAergic synapses, and their cholinergic vesicles dock at those synapses only. We de... | 10.1038/s41583-020-0344-9 | In this study, the authors infer that ACh and GABA are packaged into distinct vesicles at terminals of septo–hippocampal projections and demonstrate that the synaptic release of GABA alone accounts for the suppression of hippocampal SWR and epileptiform activity; ACh and GABA transmission is differentially regulated by... |
10.1002/hipo.22696 | 124,510,094 | ABSTRACT Long‐range glutamatergic and GABAergic projections participate in temporal coordination of neuronal activity in distributed cortical areas. In the hippocampus, GABAergic neurons project to the medial septum and retrohippocampal areas. Many GABAergic projection cells express somatostatin (SOM+) and, together wi... | 10.1038/s41583-020-0344-9 | This study describes the rhythmic activity and phase-coupling of several molecularly and morphologically defined hippocampal GABAergic projecting neurons in freely moving rats and adds to our understanding of the diversity of GABAergic hippocampal projecting neurons |
10.1126/science.aaa5694 | 38,281,630 | Fine-tuned information flow in the brain In addition to providing well-characterized excitatory inputs, the entorhinal cortex also sends long-range inhibitory projections to the hippocampus. Basu et al. described this input in detail and characterized its role for learning and memory. Multimodal sensory stimuli activat... | 10.1038/s41583-020-0344-9 | This study characterizes GABAergic projections from the LEC to the hippocampus that, via disinhibition, induce facilitation of glutamatergic inputs to the hippocampus, thereby supporting context and object recognition memory |
10.1038/s41467-018-07162-5 | 19,295,326 | Abstract GABAergic interneurons in the hippocampus provide for local and long-distance coordination of neurons in functionally connected areas. Vasoactive intestinal peptide-expressing (VIP+) interneurons occupy a distinct niche in circuitry as many of them specialize in innervating GABAergic cells, thus providing netw... | 10.1038/s41583-020-0344-9 | In this study, the authors identified defined VIP + hippocampal GABAergic projecting neurons that are distinct from VIP + neurons with local axons and that exhibit increased Ca 2+ dynamics during immobility |
10.1042/bj1880789 | 39,110,665 | The concentration-dependence on exogenous ATP of activation and inhibition of mast-cell histamine secretion, phosphatidylinositol labelling and leakage of metabolites shows that all these functions are regulated by the free acid ATP4-. Maximal histamine secretion and phosphatidylinositol labelling occur with ATP4- at a... | 10.1038/s41568-018-0037-0 | This study provides rigorous characterization of ATP-induced changes in plasma membrane permeability and postulates the expression of specific plasma membrane receptors for extracellular ATP. |
10.1126/science.1208347 | 103,786,089 | The release of adenosine triphosphate through autophagy can promote antitumor immune responses. | 10.1038/s41568-018-0037-0 | This study shows that autophagy drives ATP release into the TME and that an increased ATP level in the TME is needed for an efficient chemotherapeutic response. |
10.1146/annurev-immunol-032712-100008 | 104,343,268 | Depending on the initiating stimulus, cancer cell death can be immunogenic or nonimmunogenic. Immunogenic cell death (ICD) involves changes in the composition of the cell surface as well as the release of soluble mediators, occurring in a defined temporal sequence. Such signals operate on a series of receptors expresse... | 10.1038/s41568-018-0037-0 | This report provides a thorough and authoritative description of the process of ICD and its implications for cancer therapy. |
10.1126/scitranslmed.aaf8463 | 124,605,416 | Single-domain antibodies called nanobodies block P2X7, an inflammatory ion channel, reducing skin and kidney inflammation in mice. | 10.1038/s41568-018-0037-0 | This study reports the first application of anti-P2X7R nanobodies in an in vivo model of inflammation. |
10.1038/s41467-019-11311-9 | 38,374,051 | Abstract Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18–109), of whom 5512 died during ... | 10.1038/s41591-022-01992-z | A landmark study linking NMR metabolomics profiles to mortality risk. |
10.1038/s41467-020-18700-5 | 105,394,404 | Abstract The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 ( emm 12) Streptococcus pyogenes (group A Streptococcus , GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encodi... | 10.1038/s41579-023-00865-7 | This paper reports the thiol-activated bacterial superantigen, showcasing the relationship between prophage exotoxins and virulence phenotypes of scarlet fever-causing GAS. |
10.1038/s41467-022-34243-3 | 139,929,161 | Abstract Described antimicrobial resistance mechanisms enable bacteria to avoid the direct effects of antibiotics and can be monitored by in vitro susceptibility testing and genetic methods. Here we describe a mechanism of sulfamethoxazole resistance that requires a host metabolite for activity. Using a combination of ... | 10.1038/s41579-023-00865-7 | This study uses a combination of in vitro evolution and metabolic rescue experiments to demonstrate that a new antimicrobial resistance mechanism — undetectable using traditional laboratory testing methods — is responsible for high levels of resistance to sulfamethoxazole in GAS. |
10.1111/andr.299 | 102,978,390 | Summary Recent years have led to a better understanding of the mechanisms underlying cisplatin response and resistance in germ cell tumours (GCT), and several promising targets have been identified. Two main mechanisms of the responsiveness to DNA damaging agents have been postulated. Firstly, GCT readily activate a DN... | 10.1038/s41585-019-0154-x | This is a summary of molecular mechanisms known to provide cisplatin resistance in GCTs |
10.1101/gad.276568.115 | 41,490,867 | The pattern of DNA methylation at cytosine bases in the genome is tightly linked to gene expression, and DNA methylation abnormalities are often observed in diseases. The ten eleven translocation (TET) enzymes oxidize 5-methylcytosines (5mCs) and promote locus-specific reversal of DNA methylation. TET genes, and especi... | 10.1038/s41585-019-0154-x | This is a paper on the function of TET enzymes in active DNA demethylation and their implications in cancer development |
10.1038/s41467-017-02242-4 | 28,170,071 | Abstract Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entin... | 10.1038/s41585-019-0154-x | This publication describes the development of the hybrid inhibitor corin and its efficacy in a multitarget pharmacology approach |
10.1111/jcmm.13059 | 103,144,264 | Abstract Type II testicular germ cell cancers (TGCT) are the most frequently diagnosed tumours in young men (20–40 years) and are classified as seminoma or non‐seminoma. TGCTs are commonly treated by orchiectomy and chemo‐ or radiotherapy. However, a subset of metastatic non‐seminomas (embryonal carcinomas) displays on... | 10.1038/s41585-019-0154-x | This paper describes the effects of BET inhibition in GCT models |
10.1073/pnas.180316397 | 102,362,420 | The p38 family of mitogen-activated protein kinases (MAPKs) mediates signaling in response to environmental stresses and inflammatory cytokines, but the requirements for the p38 MAPK pathway in normal mammalian development have not been elucidated. Here, we show that targeted disruption of the p38 α MAPK gene results i... | 10.1038/s41580-020-00322-w | Together with Adams et al. (2000), this paper provides in vivo evidence for a critical role of p38α in the regulation of a process unrelated to the acute stress response |
10.1126/science.1067289 | 58,564,184 | Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38α MAPK that does not involve the prototypic kinase cascade. Rather it depends on ... | 10.1038/s41580-020-00322-w | This paper presents evidence for a non-canonical mechanism of p38α activation based on TAB1-induced autophosphorylation |
10.1073/pnas.1721441115 | 42,575,570 | Mitogen-activated protein kinases, which include p38, are essential for cell differentiation and autophagy. The current model for p38 activation involves activation-loop phosphorylation with subsequent substrate binding leading to substrate phosphorylation. Despite extensive efforts, the molecular mechanism of activati... | 10.1038/s41580-020-00322-w | Together with Kuzmanic et al. (2017) and Tokunaga et al. (2014), this paper provides detailed insights into the mechanism of p38α kinase activation using NMR and molecular modelling |
10.3171/2020.10.peds20839 | 18,194,749 | OBJECTIVE Congenital intracranial cysts account for a significant portion of intracranial lesions in the pediatric population. The efficiency of surgical treatment in a pediatric cohort with intracranial arachnoid cysts (ACs) at different locations regarding clinical symptoms and mass effect was evaluated. METHODS A re... | 10.1038/s41591-023-02239-1 | This paper reports on outcomes of surgical intervention for ACs and highlights the differential responses of acute and chronic sequelae to surgery. |
10.1093/cercor/bhac257 | 142,538,553 | Abstract Arachnoid cysts (ACs) are the most common space-occupying lesions in the human brain and present significant challenges for clinical management. While most cases of ACs are sporadic, nearly 40 familial forms have been reported. Moreover, ACs are seen with increased frequency in multiple Mendelian syndromes, in... | 10.1038/s41591-023-02239-1 | This review article presents the current known genetic landscape of ACs. |
10.1111/head.12572 | 40,975,304 | This review aims to understand the prevalence of premonitory symptoms in migraine, postulate their mechanisms, and compare these with functional imaging studies. A thorough literature review was conducted using P ub M ed for prevalence studies of premonitory symptoms in migraine and functional imaging studies in the pr... | 10.1038/s41582-018-0098-4 | A seminal paper in which the premonitory phase of migraine was imaged with functional neuroimaging for the first time |
10.1152/physrev.00034.2015 | 41,750,873 | Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the “humors” ... | 10.1038/s41582-018-0098-4 | An important and comprehensive review that outlines the understood neurobiology of migraine on the basis of animal, human and functional imaging studies |
10.1126/science.aaf9050 | 41,652,160 | An activity lift for platinum Platinum is an excellent but expensive catalyst for the oxygen reduction reaction (ORR), which is critical for fuel cells. Alloying platinum with other metals can create shells of platinum on cores of less expensive metals, which increases its surface exposure, and compressive strain in th... | 10.1038/s41586-021-03482-7 | This study achieves high specific and mass activity using ultrafine jagged platinum nanowires for oxygen reduction, suggesting a promising approach to realizing high-current-density fuel cells |
10.1038/s41467-019-08622-2 | 83,356,361 | Abstract Proton exchange membranes with short-pathway through-plane orientated proton conductivity are highly desirable for use in proton exchange membrane fuel cells. Magnetic field is utilized to create oriented structure in proton exchange membranes. Previously, this has only been carried out by proton nonconductive... | 10.1038/s41586-021-03482-7 | This study develops composite membranes with through-plane-aligned proton channels, showing that thus oriented channels improve proton conductivity and durability, and that microporous channels strongly retain water |
10.1126/science.aar6343 | 103,695,996 | Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assembli... | 10.1038/s41576-022-00568-4 | This study uses long-read sequencing to produce ape genome assemblies not guided by the human reference genome to systematically identify structural genomic variation across apes |
10.1073/pnas.0900544106 | 83,127,049 | In development, timing is of the utmost importance, and the timing of developmental processes often changes as organisms evolve. In human evolution, developmental retardation, or neoteny, has been proposed as a possible mechanism that contributed to the rise of many human-specific features, including an increase in bra... | 10.1038/s41576-022-00568-4 | This study uses microarrays to investigate developmental trajectories of human, chimpanzee and macaque postnatal gene expression, highlighting a human-specific delay in neuronal development in cortical frontal lobe |
10.1038/s41467-021-27899-w | 132,536,860 | Abstract The evolution of uniquely human traits likely entailed changes in developmental gene regulation. Human Accelerated Regions (HARs), which include transcriptional enhancers harboring a significant excess of human-specific sequence changes, are leading candidates for driving gene regulatory modifications in human... | 10.1038/s41576-022-00568-4 | This study precisely reconstructs human and chimpanzee alleles at the orthologous locus in mouse for a conserved enhancer that experienced accelerated nucleotide substitutions in the human lineage, confirming that human-specific sequence changes increase GBX2 expression in the developing limb and demonstrating that str... |
10.1126/science.abb2401 | 20,783,906 | The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene ARHGAP11B in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that ARHGAP11B causes expansio... | 10.1038/s41576-022-00568-4 | This study demonstrates that the human-specific gene, ARHGAP11B , can increase basal progenitor number and developing brain size when introduced into marmoset at a low copy number driven by the human promoter |
10.1002/zoo.1430030405 | 62,365,616 | Abstract Biologic material from exotic species is difficult to obtain for scientists. Yet much depends on the availability of such materials for a better understanding of evolutionary relationships and genetics of animals. Zoos have an obligation to participate in the safeguarding of some of these tissues by preserving... | 10.1038/s41576-022-00568-4 | This foundational study outlines practices for preserving cells, serum and organs to use for future experiments to understand genomic and cell biological relationships between animals |
10.1038/s41598-018-33478-9 | 19,689,115 | Abstract Comparative genomic studies in primates have the potential to reveal the genetic and mechanistic basis for human specific traits. These studies may also help us better understand inter-species phenotypic differences that are clinically relevant. Unfortunately, the obvious limitation on sample collection and ex... | 10.1038/s41576-022-00568-4 | This study demonstrates that iPSC-derived human and chimpanzee cardiomyocytes recapitulate gene expression divergence observed in primary heart samples, supporting the use of iPSC models for comparative evo-devo approaches where primary samples are not accessible |
10.1073/pnas.2007049118 | 61,610,774 | Genetic changes that altered the function of gene regulatory elements have been implicated in the evolution of human traits such as the expansion of the cerebral cortex. However, identifying the particular changes that modified regulatory activity during human evolution remain challenging. Here we used massively parall... | 10.1038/s41576-022-00568-4 | This study measures the impact of human-specific nucleotide substitutions in accelerated regions and human-gained enhancers on the gene regulatory potential of these loci by measuring reporter gene activity using a pooled reporter gene assay in neural stem cells |
10.1126/science.aat5031 | 125,121,640 | Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immune cells. We used single-cell RNA sequencing to resolve the spatiotemporal immune topology of the human kidney. We reveal anatomically defined expression patt... | 10.1038/s41576-022-00449-w | This paper illustrates the principle of immune zonation by demonstrating the specific position of phagocyte subsets across the kidney pseudo-depth |
10.1126/science.aba6500 | 41,699,592 | The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leverage... | 10.1038/s41576-022-00449-w | This study shows the relevance of fetal-like endothelial cell expansion in inflamed human skin and defined cell–cell interactions with immune subsets |
10.1038/s41467-019-12464-3 | 20,449,048 | Abstract Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isol... | 10.1038/s41576-022-00449-w | This paper exemplifies the power of analysing matched tissue and blood samples to determine the dynamics of an in vivo immune response to a viral infection |
10.1182/blood-2006-03-001164 | 125,264,914 | Abstract The detection of a monoclonal immunoglobulin in serum or urine usually raises concerns about the size of the underlying B-cell-derived clone and possible systemic effects caused by its expansion. However, a small clone can synthesize a very toxic protein, producing devastating systemic damage and protean clini... | 10.1038/s41572-018-0034-3 | This paper presents pioneering work that introduces the concept that small, indolent clones can produce systemic damage through the production of immunoglobulin or fragments thereof |
10.1073/pnas.92.10.4299 | 19,064,649 | Extracellular deposition of amyloid fibrils is responsible for the pathology in the systemic amyloidoses and probably also in Alzheimer disease [Haass, C. & Selkoe, D. J. (1993) Cell 75, 1039-1042] and type II diabetes mellitus [Lorenzo, A., Razzaboni, B., Weir, G. C. & Yankner, B. A. (1994) Nature (London) 368... | 10.1038/s41572-018-0034-3 | This study supports the role of SAP in preventing amyloid resorption, and the findings from this study led to anti-SAP therapies |
10.1161/01.res.0000126569.75419.74 | 20,575,222 | Primary amyloidosis is a systemic disorder characterized by the clonal production and tissue deposition of immunoglobulin light chain (LC) proteins. Congestive heart failure remains the greatest cause of death in primary amyloidosis, due to the development of a rapidly progressive amyloid cardiomyopathy. Amyloid cardio... | 10.1038/s41572-018-0034-3 | This is a pioneering paper on the cardiotoxicity of amyloidogenic light chains |
10.1182/blood-2014-04-570010 | 80,828,265 | Key Points A staging system based on proteinuria and glomerular filtration rate discriminates patients at different risk of progression to dialysis. Changes in proteinuria and glomerular filtration rate allow early assessment of renal response to therapy. | 10.1038/s41572-018-0034-3 | This study presents a validated staging system for renal outcomes and criteria for renal response |
10.1200/jco.2013.50.0892 | 80,200,900 | Purpose Patients with immunoglobulin light chain amyloidosis (AL amyloidosis) generally present with advanced organ dysfunction and have a high risk of early death. We sought to characterize monoclonal immunoglobulin (M-Ig) light chains before clinical presentation of AL amyloidosis. Patients and Methods We obtained pr... | 10.1038/s41572-018-0034-3 | Among the 20 patients with AL amyloidosis in this study, a monoclonal protein is shown to be present by free light chain assay and/or immunofixation in 100%, 80% and 42% of patients at <4 years, 4–11 years and >11 years before diagnosis, respectively |
10.1161/01.cir.0000068314.02595.b2 | 102,910,415 | Background— Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure and after myocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). We investigated th... | 10.1038/s41572-018-0034-3 | This study introduces NT-proBNP as a sensitive marker for the diagnosis and follow-up after therapy of amyloid cardiac dysfunction |
10.1200/jco.2011.37.7614 | 41,709,926 | Purpose To identify the criteria for hematologic and cardiac response to treatment in immunoglobulin light chain (AL) amyloidosis based on survival analysis of a large patient population. Patients and Methods We gathered for analysis 816 patients with AL amyloidosis from seven referral centers in the European Union and... | 10.1038/s41572-018-0034-3 | This paper provides new consensus criteria for haematological and cardiac response, which are now universally used |
10.1182/blood.v88.7.2801.bloodjournal8872801 | 61,482,421 | The morbidity and lethality of AL amyloidosis is caused by the deposition of lg light chains as fibrillar amyloid protein in vital organs, disrupting their function, and not by the generally low burden of clonal plasma cells that produce the paraproteins. Survival of patients with AL amyloidosis is no more than 1 to 2 ... | 10.1038/s41572-018-0034-3 | This report introduces autologous stem cell transplantation as an effective treatment for AL amyloidosis |
10.1182/blood-2017-01-763599 | 103,002,814 | Key Points Daratumumab is highly active in AL amyloidosis. | 10.1038/s41572-018-0034-3 | This paper shows that daratumumab is rapidly effective in relapsed and/or refractory patients |
10.1182/blood-2016-08-730978 | 80,460,441 | Key Points Amyloidogenic PCs show unique PI susceptibility and altered organelle homeostasis, consistent with defective autophagy. Amyloidogenic LC production is an intrinsic cellular stressor that sensitizes to PI toxicity. | 10.1038/s41572-018-0034-3 | This paper shows that amyloidogenic light chain production is an intrinsic cellular stressor that sensitizes to proteasome inhibitor toxicity |
10.1126/science.aar7366 | 38,411,829 | 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/s41583-019-0222-5 | This study elegantly shows the important role that RNA plays in regulating the phase separation dynamics of membraneless organelles |
10.1126/science.aan6398 | 41,670,978 | Subcellular membraneless assemblies are a reinvigorated area of study in biology, with spirited scientific discussions on the forces between the low-complexity protein domains within these assemblies. To illuminate these forces, we determined the atomic structures of five segments from protein low-complexity domains as... | 10.1038/s41583-019-0222-5 | This study shows how different types of amino acid interactions, such as π–π and π–cation binding, control the formation of membraneless organelles and insoluble amyloids |
10.1073/pnas.1310249110 | 40,853,447 | Deposition of insoluble protein aggregates is a hallmark of neurodegenerative diseases. The universal presence of β-amyloid and tau in Alzheimer’s disease (AD) has facilitated advancement of the amyloid cascade and tau hypotheses that have dominated AD pathogenesis research and therapeutic development. However, the und... | 10.1038/s41583-019-0222-5 | This paper shows that many RBPs accumulate as protein aggregates in AD, often in cells lacking histologically evident tau aggregates |
10.1002/anie.201806795 | 96,500,049 | Abstract An electrochemical approach is developed that allows for the control of both proton and electron transfer rates in the O 2 reduction reaction (ORR). A dinuclear Cu ORR catalyst was prepared that can be covalently attached to thiol‐based self‐assembled monolayers (SAMs) on Au electrodes using azide–alkyne click... | 10.1038/s41570-022-00433-2 | This pioneering work establishes the simultaneous control of both electron and proton transfer rates in oxygen reduction to achieve precise regulation of electrocatalytic activity and product selectivity without altering the core molecular structure of an HBM construct |
10.1126/science.1135844 | 83,471,370 | We studied the selectivity of a functional model of cytochrome c oxidase's active site that mimics the coordination environment and relative locations of Fe a3 , Cu B , and Tyr 244 . To control electron flux, we covalently attached this model and analogs lacking copper and phenol onto self-assembled monolayer–coated go... | 10.1038/s41570-022-00433-2 | This exemplary work establishes how electron flux can be used to control the oxygen reduction behaviour of an Fe porphyrin that has been attached onto self-assembled monolayers with various electron transfer rates |
10.1073/pnas.1120645109 | 38,812,904 | Platelets are important mediators of blood coagulation that lack nuclei, but contain mitochondria. Although the presence of mitochondria in platelets has long been recognized, platelet mitochondrial function remains largely unaddressed. On the basis of a small amount of literature that suggests platelet mitochondria ar... | 10.1038/s41570-022-00433-2 | Electrochemical results from this HBM work contribute to the understanding of how heterocycles deter mitochondrial platelet stimulation and subsequently inhibit blood clotting |
10.1038/ncomms12981 | 40,992,540 | Abstract In biological systems, intercellular communication is mediated by membrane proteins and ion channels that regulate traffic of ions and small molecules across cell membranes. A bioelectronic device with ion channels that control ionic flow across a supported lipid bilayer (SLB) should therefore be ideal for int... | 10.1038/s41570-022-00433-2 | This work illustrates the integration of complex transmembrane ion channels into HBMs for the construction of functional bioprotonic devices |
10.1126/science.185.4147.263 | 109,171,435 | Lassa fever is a severe febrile illness of man, first recognized in West Africa in 1969. During an epidemic in Sierra Leone, Lassa virus was isolated for the first time from wild rodents of Mastomys natalensis . A high prevalence of infected Mastomys was found in houses occupied by patients with Lassa fever. The data p... | 10.1038/s41579-022-00789-8 | This work is the first demonstration that Lassa virus is rodent-borne. |
10.1126/science.aam7260 | 18,060,472 | The crystal structure of an antibody–viral glycoprotein complex illuminates viral entry mechanisms and provides a blueprint for vaccine design. | 10.1038/s41579-022-00789-8 | This work reveals the structure of the native trimeric structure of the Lassa virus glycoprotein. |
10.1073/pnas.211053698 | 62,257,322 | Mammalian cells can respond to damage or stress by entering a state of arrested growth and altered function termed cellular senescence. Several lines of evidence suggest that the senescence response suppresses tumorigenesis. Cellular senescence is also thought to contribute to aging, but the mechanism is not well under... | 10.1038/s41570-019-0108-0 | This paper was the first to report that senescent cells secrete soluble factors with biological activity on non-senescent neighbour cells. In this particular case, the authors found that the secretome of senescent cells stimulates the tumorigenic properties of cancer cells |
10.1073/pnas.92.20.9363 | 62,247,869 | Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppressive mechanism and an underlying cause of aging. There is ample evidence that escape from senescence, or imm... | 10.1038/s41570-019-0108-0 | This paper was the first to report a useful marker of senescence, namely, senescence-associated β-galactosidase (SA-β-Gal). Many current methods to detect senescence are based on their elevated SA-β-Gal |
10.1002/anie.201309399 | 103,777,403 | Abstract Aryl sulfonyl chlorides (e.g. Ts‐Cl) are beloved of organic chemists as the most commonly used S VI electrophiles, and the parent sulfuryl chloride, O 2 S VI Cl 2 , has also been relied on to create sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the ... | 10.1038/s41570-021-00352-8 | This is the report that sparked the current interest in S(VI)-F-containing electrophiles |
10.1002/anie.202012229 | 19,967,444 | Abstract Sulfonyl fluorides have widespread applications in many fields. In particular, their unique biological activity has drawn considerable research interest in the context of chemical biology and drug discovery in the past years. Therefore, new and efficient methods for the synthesis of sulfonyl fluorides are high... | 10.1038/s41570-021-00352-8 | An example of generating and using the fluorosulfonyl radical in a synthetically useful transformation |
10.1002/anie.202009699 | 100,654,623 | Abstract A convenient protocol to selectively access various arylsulfur(VI) fluorides from commercially available aryl halides in a divergent fashion is presented. Firstly, a novel sulfenylation reaction with the electrophilic N ‐(chlorothio)phthalimide (Cl‐S‐Phth) and arylzinc reagents afforded the corresponding Ar‐S‐... | 10.1038/s41570-021-00352-8 | This shows oxidative chlorination followed by fluorination, using a convenient more sustainable chlorinating reagent |
10.1002/ejoc.202000022 | 19,003,702 | A simple and practical synthesis of sulfonyl fluorides from sulfonamides is reported. The method capitalizes on the formation of the sulfonyl chloride by virtue of the reaction of Pyry‐BF 4 and MgCl 2 , and subsequent in situ conversion to the more robust and stable sulfonyl fluoride by the presence of KF. The mild con... | 10.1038/s41570-021-00352-8 | This report shows how widely available primary sulfonamides can be used as substrates to access sulfonyl fluorides |
10.1002/cbic.201600427 | 101,769,347 | Abstract Sulfonyl fluoride (SF)‐based activity probes have become important tools in chemical biology. Herein, exploiting the relative chemical stability of SF to carry out a number of unprecedented SF‐sparing functional group manipulations, we report the chemoselective synthesis of a toolbox of highly functionalized a... | 10.1038/s41570-021-00352-8 | An example of how sulfonyl fluorides can tolerate the multiple reactions needed to prepare a collection of complex chemical probe reagents |
10.1002/anie.201506253 | 83,235,812 | Abstract Polymer brushes present a unique architecture for tailoring surface functionalities due to their distinctive physicochemical properties. However, the polymerization chemistries used to grow brushes place limitations on the monomers that can be grown directly from the surface. Several forms of click chemistry h... | 10.1038/s41570-021-00352-8 | This is an impressive example of using SuFEx reactivity to modify polymer surfaces, again exploiting the combination of silyl-activated nucleophiles and sulfonyl fluoride electrophiles |
10.1002/jlcr.3667 | 81,042,841 | Fluorine‐18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling bi... | 10.1038/s41570-021-00352-8 | This shows how ESF, an important reagent for the introduction of sulfonyl fluorides, can be adapted to 18 F-labelling |
10.1002/anie.201611048 | 29,206,465 | Abstract Sulfur(VI) fluoride exchange (SuFEx) is a new family of click chemistry based transformations that enable the synthesis of covalently linked modules via S VI hubs. Here we report thionyl tetrafluoride (SOF 4 ) as the first multidimensional SuFEx connector. SOF 4 sits between the commercially mass‐produced gase... | 10.1038/s41570-021-00352-8 | An impressive demonstration of how simple nucleophiles can be combined using multi-reactive electrophilic S-F hubs to construct a range of S( vi )-functional groups |
10.1042/bcj20160510 | 125,332,724 | The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the ... | 10.1038/s41575-019-0173-3 | This article provides current understanding of the development and composition of the human gut microbiota, and its effects on gut integrity and host health |
10.3920/bm2016.0222 | 59,542,832 | The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess... | 10.1038/s41575-019-0173-3 | An ISAPP working group article that looks at how microbiome programming in early life influences the gut microbiota communication with distant sites, such as airways, heart and brain, and influences metabolism |
10.1111/j.1461-0248.2010.01482.x | 20,441,246 | Ecology Letters (2010) 13: 819–828 Abstract Nitrogen (N) effects on ecosystem carbon (C) budgets are critical to understand as C sequestration is considered as a mechanism to offset anthropogenic CO 2 emissions. Interactions between aboveground C and N cycling are more clearly characterized than belowground processes. ... | 10.1038/s41561-022-01083-1 | A review article that presents the responses of belowground carbon cycling under nitrogen addition in terrestrial ecosystems. |
10.1126/science.aan2874 | 125,096,209 | In a 26-year soil warming experiment in a mid-latitude hardwood forest, we documented changes in soil carbon cycling to investigate the potential consequences for the climate system. We found that soil warming results in a four-phase pattern of soil organic matter decay and carbon dioxide fluxes to the atmosphere, with... | 10.1038/s41561-022-01083-1 | This paper reports the long-term pattern of soil respiration in response to warming in a temperate forest. |
10.1111/ele.14065 | 132,681,959 | Abstract Increased nitrogen (N) inputs are widely recognised to reduce soil respiration (Rs), but how N deposition affects the temporal dynamics of Rs remains unclear. Using a decade‐long fertilisation experiment in a boreal larch forest ( Larix gmelini ) in northeast China, we found that the effects of N additions on ... | 10.1038/s41561-022-01083-1 | This paper reports the effects of nitrogen addition on soil respiration in a boreal forest. |
10.1002/ana.23529 | 101,846,846 | Abstract Objective: Inflammation is increasingly viewed as a new therapeutic target in subacute stages of brain infarction. However, apart from causing secondary damage, inflammation could equally promote beneficial lesion remodeling and repair. Distinct subpopulations of monocytes/macrophages (MOs/MPs) may critically ... | 10.1038/s41583-023-00690-0 | This study shows that infiltration of macrophages prevents the exacerbation of stroke pathology. |
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/s41583-023-00690-0 | According to this study, the antigen-specific reactions through T cell receptors are not implicated in ischaemic neuronal injury. |
10.1038/ncomms11499 | 104,211,812 | Abstract Microglia are the main immune cells of the brain and contribute to common brain diseases. However, it is unclear how microglia influence neuronal activity and survival in the injured brain in vivo . Here we develop a precisely controlled model of brain injury induced by cerebral ischaemia combined with fast in... | 10.1038/s41583-023-00690-0 | This article demonstrates the reparative roles of microglia after ischaemic stroke. |
10.1038/jcbfm.2009.233 | 105,339,126 | In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a large ischemic lesion is formed where macrophage-like cells massively accumulate, many of which express a macrophage marker, Iba1, and an oligodendrocyte progenitor cell marker, NG2 chondroitin sulfate proteoglycan (NG2); therefore, the cell... | 10.1038/s41583-023-00690-0 | This study describes the characteristics of the reparative microglia in ischaemic stroke. |
10.1084/jem.20040180 | 41,506,608 | In the nonobese diabetic (NOD) mouse model of type 1 diabetes, the immune system recognizes many autoantigens expressed in pancreatic islet β cells. To silence autoimmunity, we used dendritic cells (DCs) from NOD mice to expand CD25+ CD4+ suppressor T cells from BDC2.5 mice, which are specific for a single islet autoan... | 10.1038/s41577-019-0232-6 | Together with Tang et al. (2004), this paper shows that antigen-specific T reg cells are more potent than polyclonal T reg cells at controlling autoimmune diabetes in vivo. |
10.1126/scitranslmed.aad4134 | 103,721,459 | Autologous regulatory T cells can be expanded and are well tolerated in patients with recent-onset type 1 diabetes. | 10.1038/s41577-019-0232-6 | This paper presents results of a phase I clinical trial in which recent-onset T1D patients were given expanded polyclonal T reg cells and reports the absence of adverse events in patients and the long-term survival of the infused T reg cells in vivo, supporting the good safety profile of this approach. |
10.4049/jimmunol.155.3.1151 | 139,038,805 | Abstract Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inocu... | 10.1038/s41577-019-0232-6 | This article is the first demonstration that a small subset of CD4 + T cells expressing CD25 was essential for the maintenance self-tolerance. |
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