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10.1126/science.1063736 | 82,868,626 | The functional architecture of the object vision pathway in the human brain was investigated using functional magnetic resonance imaging to measure patterns of response in ventral temporal cortex while subjects viewed faces, cats, five categories of man-made objects, and nonsense pictures. A distinct pattern of respons... | 10.1038/s41583-020-00393-w | This paper challenged the notion that face patches are specialized to process faces. It showed that different visual categories elicit widely distributed and overlapping responses across cortex and activity in face areas reliably distinguishes between different non-face categories |
10.1523/jneurosci.2659-14.2015 | 20,697,467 | The cerebral cortex of humans and macaques has specialized regions for processing faces and other visual stimulus categories. It is unknown whether a similar functional organization exists in New World monkeys, such as the common marmoset ( Callithrix jacchus ), a species of growing interest as a primate model in neuro... | 10.1038/s41583-020-00393-w | This paper demonstrated that marmosets also have at least six face-selective patches |
10.1126/science.1194140 | 62,195,908 | Reading, Writing, and Face Recognition Reading, not to mention writing and texting, is a relatively recent invention, and hence it is believed that a preliterate brain must adapt on the fly, so to speak, in learning how to process written words, rather than being able to rely upon evolutionarily ancient modifications o... | 10.1038/s41583-020-00393-w | This paper demonstrated an important role for experience in driving the formation of category-selective regions in ventral temporal cortex. Illiterate adults develop selective activation for words in the left fusiform gyrus after they learn to read and this induces a competition with faces in this region |
10.5194/essd-11-1603-2019 | 62,474,416 | Abstract. The Tibetan Plateau (TP), known as Asia's water tower, is quite sensitive to climate change, which is reflected by changes in hydrologic state variables such as lake water storage. Given the extremely limited ground observations on the TP due to the harsh environment and complex terrain, we exploited multiple... | 10.1038/s41558-022-01451-0 | This paper provides a methodology to estimate with high temporal resolution lake storage changes, which account for a large portion of TWS changes in the endorheic Tibetan Plateau. |
10.1038/s41467-018-05145-0 | 104,144,145 | Abstract Implementing Paris Climate Accord is inhibited by the high energy consumption of the state-of-the-art CO 2 capture technologies due to the notoriously slow kinetics in CO 2 desorption step of CO 2 capture. To address the challenge, here we report that nanostructured TiO(OH) 2 as a catalyst is capable of drasti... | 10.1038/s41467-019-13638-9 | This paper introduces a robust nanostructured TiO(OH) 2 catalyst for CO 2 capture at low temperature |
10.1038/ncomms15174 | 83,401,665 | Abstract The direct production of liquid fuels from CO 2 hydrogenation has attracted enormous interest for its significant roles in mitigating CO 2 emissions and reducing dependence on petrochemicals. Here we report a highly efficient, stable and multifunctional Na–Fe 3 O 4 /HZSM-5 catalyst, which can directly convert ... | 10.1038/s41467-019-13638-9 | This paper reports a multifunctional catalyst with three types of active sites for CO 2 hydrogenation to gasoline fuel |
10.1126/science.aal3573 | 123,199,486 | Synergy between copper and zinc oxide on a catalyst surface facilitates methanol synthesis via CO 2 hydrogenation. | 10.1038/s41467-019-13638-9 | This paper studies model catalysts and identifies a synergy of Cu and ZnO at the interface to form methanol through formate intermediates |
10.1126/science.aaf1835 | 62,300,859 | Small olefins from syngas The conversion of coal or natural gas to liquid fuels or chemicals often proceeds through the production of CO and H 2 . This mixture, known as syngas, is then converted to hydrocarbons with Fischer-Tropsch catalysts. For the light olefins (ethylene to butylenes) needed for chemical and polyme... | 10.1038/s41467-019-13638-9 | This paper presents an OX-ZEO catalyst with high selectivity towards light olefins that breaks through the limitation of the ASF model |
10.1126/science.aau5631 | 20,430,285 | Catalyst design in asymmetric reaction development has traditionally been driven by empiricism, wherein experimentalists attempt to qualitatively recognize structural patterns to improve selectivity. Machine learning algorithms and chemoinformatics can potentially accelerate this process by recognizing otherwise inscru... | 10.1038/s41467-019-13638-9 | This paper reports a computationally guided workflow for chiral catalyst selection that is significant for asymmetric reaction development |
10.1073/pnas.1710311114 | 125,272,139 | Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer’s disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the inn... | 10.1038/s41577-018-0051-1 | This work shows that dampening neurodegenerative microglial activation via TREM2 deletion reduces neurodegeneration at an advanced disease stage in a tauopathy mouse model, supporting a role of microglia in modulating neurodegeneration |
10.1084/jem.20171265 | 83,372,264 | One of the hallmarks of Alzheimer’s disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addit... | 10.1038/s41577-018-0051-1 | This work demonstrates that APOE is required for microglial association with plaques to perform a plaque-trimming function similar to that of TREM2, supporting an APOE–TREM2 axis in mediating microglial function |
10.1126/science.aaf7907 | 83,559,604 | INTRODUCTION The developmental path by which a fertilized egg gives rise to the cells of a multicellular organism is termed the cell lineage. In 1983, John Sulston and colleagues documented the invariant cell lineage of the roundworm Caenorhabditis elegans as determined by visual observation. However, tracing cell line... | 10.1038/s41576-021-00444-7 | This study uses CRISPR–Cas9 to introduce mutations at specific loci on the genome, which remain as ‘scars’ that register the cell lineage |
10.1126/science.aav9776 | 20,744,251 | Paralysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spin... | 10.1038/s41576-021-00444-7 | This paper is one of the first to use time-series spatial transcriptomics to study a dynamic biological process |
10.1534/genetics.104.035352 | 20,688,200 | Abstract The persistence phenotype is an epigenetic trait exhibited by a subpopulation of bacteria, characterized by slow growth coupled with an ability to survive antibiotic treatment. The phenotype is acquired via a spontaneous, reversible switch between normal and persister cells. These observations suggest that clo... | 10.1038/s41467-021-24733-1 | Model showing that stochastic transitioning into dormancy is beneficial in fluctuating environments. |
10.1098/rstb.2019.0243 | 61,006,921 | Much of Earth's biodiversity has the capacity to engage in dormancy, a reversible state of reduced metabolic activity. By increasing resilience to unfavourable conditions, dormancy leads to the accumulation of ‘seed banks’. These reservoirs of genetic and phenotypic diversity should diminish the strength of environment... | 10.1038/s41467-021-24733-1 | Combined field and modeling approach demonstrating that dormancy can alter biogeographic patterns. |
10.1073/pnas.1111266108 | 57,542,176 | Seed and egg dormancy is a prevalent life-history trait in plants and invertebrates whose storage effect buffers against environmental variability, modulates species extinction in fragmented habitats, and increases genetic variation. Experimental evidence for reliable differences in dormancy over evolutionary scales (e... | 10.1038/s41467-021-24733-1 | Infers seed bank quantities based on a coalescent theoretical model. |
10.1073/pnas.94.17.9171 | 83,316,287 | Theoretical models suggest that overlapping generations, in combination with a temporally fluctuating environment, may allow the persistence of competitors that otherwise would not coexist. Despite extensive theoretical development, this “storage effect” hypothesis has received little empirical attention. Herein I pres... | 10.1038/s41467-021-24733-1 | Dormancy in lake zooplankton contributes to maintenance of diversity via the storage effect. |
10.1017/cbo9780511546242 | 64,156,942 | All cellular life-forms can exist in replicating and non-replicating states. Organisms replicate only when the conditions are beneficial, and when not replicating they concentrate on survival of these environmental stresses. Many bacteria, harmful to humans, survive the period of infection in a low growth state. This 2... | 10.1038/s41467-021-24733-1 | Book describing how dormancy is involved in many human diseases. |
10.1239/aap/1308662484 | 20,688,964 | Organisms adapt to fluctuating environments by regulating their dynamics, and by adjusting their phenotypes to environmental changes. We model population growth using multitype branching processes in random environments, where the offspring distribution of some organism having trait t ∈ in environment e ∈ ε is given by... | 10.1038/s41467-021-24733-1 | Mathematical model for assessing optimality of transitioning in random environments. |
10.1242/dev.120.9.2397 | 62,348,425 | A combination of micromanipulative cell grafting and fluorescent cell labelling techniques were used to examine the developmental fate of the cranial paraxial mesoderm of the 8.5-day early-somite-stage mouse embryo. Mesodermal cells isolated from seven regions of the cranial mesoderm, identified on the basis of their t... | 10.1038/s41556-023-01113-z | This paper reports the distribution of somitomeres in head mesoderm in the mouse embryo. |
10.1126/science.aba7721 | 62,298,724 | The gene expression program underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of gene expression and chromatin accessibility in fetal tissues. For gene expression, we applied three-level combinatorial indexing to >110 samples representing 15 organs, ultimate... | 10.1038/s41556-023-01113-z | This paper reports single-cell transcriptomics of multiple human organs from 10 weeks to 26 weeks. |
10.1055/s-0037-1621710 | 59,338,640 | Abstract Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of primary liver cancer that affects adolescents and young adults without underlying liver disease. Surgery remains the mainstay of therapy; however, most patients are either not surgical candidates or suffer from recurrence. There is no approved syst... | 10.1038/s41575-022-00580-3 | This article is a review that emphasizes the molecular aspects of FLC |
10.1038/modpathol.2017.103 | 62,392,654 | Abstract Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic ge... | 10.1038/s41575-022-00580-3 | This article discusses a break-apart FISH assay for DNAJB1–PRKACA gene fusion and reports a correlation between the presence of the fusion and classic diagnostic criteria for FLC |
10.1126/science.1249484 | 104,366,356 | Oncogenic Suspect Exposed It can be difficult logistically to study the genomics of rare variants of common cancers. Nevertheless, Honeyman et al. (p. 1010 ) studied fibrolamellar hepatocellular carcinoma (FL-HCC), a rare and poorly understood liver tumor that affects adolescents and young adults and for which there is... | 10.1038/s41575-022-00580-3 | This article reports the discovery of the fusion oncogene of FLC and the chimeric protein it encodes |
10.1038/ncomms9070 | 81,973,497 | Abstract The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-... | 10.1038/s41575-022-00580-3 | This article describes the first PDX model of FLC and evidence for the cancer’s potential relationship to biliary tree stem cells |
10.1073/pnas.1716483114 | 40,802,337 | A segmental deletion resulting in DNAJB1–PRKACA gene fusion is now recognized as the signature genetic event of fibrolamellar hepatocellular carcinoma (FL-HCC), a rare but lethal liver cancer that primarily affects adolescents and young adults. Here we implement CRISPR-Cas9 genome editing and transposon-mediated somati... | 10.1038/s41575-022-00580-3 | Together with Engelholm et al. (2017), this study shows that the DNAJ–PKAc chimeric protein is oncogenic and can induce liver tumours in mice |
10.1126/scitranslmed.aat8549 | 83,541,620 | Cancer arises from the accumulation of genetic alterations, which can lead to the production of mutant proteins not expressed by normal cells. These mutant proteins can be processed and presented on the cell surface by major histocompatibility complex molecules as neoepitopes, allowing CD8 + T cells to mount responses ... | 10.1038/s41575-022-00580-3 | A study that sets the precedent for targeted immune therapy against a junctional epitope in an oncogenic fusion protein |
10.1073/pnas.1508249112 | 60,048,776 | With aging, significant changes in circadian rhythms occur, including a shift in phase toward a “morning” chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here, we used a previously described time-of-death analysis... | 10.1038/s41583-018-0088-y | This is the largest-scale study of circadian rhythms of gene expression in human post-mortem brain tissue, revealing age-related decline in the expression of core circadian genes and the emergence of other rhythmic pathways in older subjects |
10.1192/bjp.bp.111.096321 | 20,700,485 | Background Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions. Aims A systematic exploration of circadian time patterns in individuals with schizophrenia with recurrent slee... | 10.1038/s41583-018-0088-y | This study reports notable circadian misalignment (phase delays and advances) of sleep–wake cycles and melatonin rhythms in patients with schizophrenia despite other factors, including mood, cognitive status and pharmacological treatments |
10.1126/science.aam9080 | 20,587,912 | Human-derived neurons provide the answers Pathways involved in energy metabolism and removal of cellular debris by lysosomes play an important role in protecting our brain from degeneration in Parkinson's disease. Burbulla et al. identified a toxic cascade of mitochondrial and lysosomal dysfunction in human neurons der... | 10.1038/s41583-018-0088-y | This study demonstrates that mitochondrial stress promotes the accumulation of oxidized dopamine, consequently increasing -synuclein aggregates in neurons derived from patients with PD, an effect selective to human neurons |
10.1126/science.1241224 | 62,665,890 | Taking Out the Trash The purpose of sleep remains mysterious. Using state-of-the-art in vivo two-photon imaging to directly compare two arousal states in the same mouse, Xie et al. (p. 373 ; see the Perspective by Herculano-Houzel ) found that metabolic waste products of neural activity were cleared out of the sleeping... | 10.1038/s41583-018-0088-y | A landmark study in mice demonstrating that wakefulness suppresses the outflow of cerebral spinal fluid from the brain, whereas sleep leads to an increase in convective fluxes of fluid, effectively promoting the clearance of neurotoxic metabolics, including Aβ |
10.1073/pnas.0609625104 | 62,076,228 | Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of ... | 10.1038/s41583-018-0088-y | This study demonstrates mice harbouring a mutation in Clock display a behavioural repertoire similar to human mania and provides evidence for CLOCK specifically in the ventral tegmental area to be important for these behaviours via modulation of dopamine cell firing. |
10.1073/pnas.1800314115 | 103,664,302 | Circadian clocks play a key role in regulating a vast array of biological processes, with significant implications for human health. Accurate assessment of physiological time using transcriptional biomarkers found in human blood can significantly improve diagnosis of circadian disorders and optimize the delivery time o... | 10.1038/s41583-018-0088-y | This study demonstrates the use of a set of computational algorithms called TimeSignature to predict the endogenous phase of an individual based on the particular gene signatures from the blood acquired at a single timepoint |
10.1002/anie.202009546 | 123,483,317 | Abstract By use of a macrocyclic phosphinite pincer ligand and bulky substrate substituents, we demonstrate how the mechanical bond can be leveraged to promote the oxidative addition of an interlocked 1,3‐diyne to a rhodium(I) center. The resulting rhodium(III) bis(alkynyl) product can be trapped out by reaction with c... | 10.1038/s41570-021-00348-4 | An exciting demonstration of the ability of the mechanical bond to generate unique reactivity, a principle that could provide breakthroughs in mechanically interlocked molecule catalysis |
10.1002/anie.201908330 | 27,056,296 | Abstract We report on a switchable rotaxane molecular shuttle that features a pseudo‐ meso 2,5‐disubstituted pyrrolidine catalytic unit on the axle whose local symmetry is broken according to the position of a threaded benzylic amide macrocycle. The macrocycle can be selectively switched (with light in one direction; w... | 10.1038/s41570-021-00348-4 | A molecular shuttle in which the different mechanical states of the switch create pseudo-enantiomeric environments around a catalytic functional group |
10.1002/anie.201704647 | 125,037,806 | Abstract Interlocked molecules, such as catenanes, rotaxanes, and molecular knots, have become interesting candidates for the development of sophisticated chemical catalysts. Herein, we report the first application of a catenane‐based catalyst in asymmetric organocatalysis, revealing that the catenated catalyst shows d... | 10.1038/s41570-021-00348-4 | The first example of enantioselective catalysis using a catenane, including a clear demonstration of the potential for the flexible environment of the mechanical bond to enhance selectivity by increasing the effective molarity of cooperating catalytic functional groups |
10.1084/jem.20122588 | 37,581,263 | The small intestine epithelium (SI-Ep) harbors millions of unconventional (γδ and CD4− CD8− NK1.1− TCRαβ) and conventional (CD8αβ and CD4) T cells, designated intraepithelial lymphocytes (IELs). Here, we identified the circulating pool of SI-Ep–tropic T cells and studied their capacity to colonize the SI-Ep under stead... | 10.1038/s41577-018-0013-7 | This study demonstrates that unconventional TCRγδ + IELs exit the thymus as naive cells and acquire effector properties in gut-associated lymphoid tissues. |
10.1126/sciimmunol.aaf7471 | 28,251,664 | A single T cell receptor can give rise to two distinct T cell types at distinct anatomical locations. | 10.1038/s41577-018-0013-7 | References 22 and 23 demonstrate plasticity between lamina propria FOXP3 + T reg cells and IELs in response to microbial stimulation. |
10.1073/pnas.1603388113 | 41,556,443 | We recently developed a high-resolution genome-wide assay for mapping DNA excision repair named eXcision Repair-sequencing (XR-seq) and have now used XR-seq to determine which regions of the genome are subject to repair very soon after UV exposure and which regions are repaired later. Over a time course, we measured re... | 10.1038/s41576-021-00376-2 | This study creates a single-nucleotide resolution map of NER activity in UV-irradiated cells |
10.1038/s41467-020-15912-7 | 104,175,411 | Abstract Cells possess an armamentarium of DNA repair pathways to counter DNA damage and prevent mutation. Here we use C. elegans whole genome sequencing to systematically quantify the contributions of these factors to mutational signatures. We analyse 2,717 genomes from wild-type and 53 DNA repair defective background... | 10.1038/s41576-021-00376-2 | This article is a comprehensive study of the mutational footprints of DNA mutagens and repair deficiencies in Caenorhabditis elegans |
10.1126/science.aao4426 | 62,160,543 | Brain mutations, young and old Most neurons that make up the human brain are postmitotic, living and functioning for a very long time without renewal (see the Perspective by Lee). Bae et al. examined the genomes of single neurons from the prenatal developing human brain. Both the type of mutation and the rates of accum... | 10.1038/s41576-021-00376-2 | This study describes mutational processes that operate in non-dividing neurons |
10.1038/ncomms11383 | 84,535,090 | Abstract Somatic mutations in human cancers show unevenness in genomic distribution that correlate with aspects of genome structure and function. These mutations are, however, generated by multiple mutational processes operating through the cellular lineage between the fertilized egg and the cancer cell, each composed ... | 10.1038/s41576-021-00376-2 | This study investigates differences in mutation rate distributions between mutational processes |
10.1101/gr.219915.116 | 19,981,296 | Mismatch repair (MMR) is one of the main systems maintaining fidelity of replication. Differences in correction of errors produced during replication of the leading and the lagging DNA strands were reported in yeast and in human cancers, but the causes of these differences remain unclear. Here, we analyze data on human... | 10.1038/s41576-021-00376-2 | This paper provides statistical evidence that MMR is more active on the lagging strand in human cells |
10.1101/850453 | 19,980,861 | Abstract Mutational signature analysis is an essential part of the cancer genome analysis toolkit. Conventionally, mutational signature analysis extracts patterns of different mutation types across many cancer genomes. Here we present TensorSignatures, an algorithm to learn mutational signatures jointly across all vari... | 10.1038/s41576-021-00376-2 | This article presents a fascinating tool that uses differences in the spatial distribution of mutational processes to extract mutational signatures from cancer genomes |
10.1101/2020.01.10.893024 | 102,265,170 | Mechanistic processes underlying human germline mutations remain largely unknown. Variation in mutation rate and spectra along the genome is informative about the biological mechanisms. We statistically decompose this variation into separate processes using a blind source separation technique. The analysis of a large-s... | 10.1038/s41576-021-00376-2 | This study is the first to use variation in mutational spectra across the genome to extract mutational processes in the human germ line |
10.1126/science.aau1043 | 38,373,370 | Genetic diversity arises from recombination and de novo mutation (DNM). Using a combination of microarray genotype and whole-genome sequence data on parent-child pairs, we identified 4,531,535 crossover recombinations and 200,435 DNMs. The resulting genetic map has a resolution of 682 base pairs. Crossovers exhibit a m... | 10.1038/s41576-021-00376-2 | This study provides direct genome-wide data on the relation between crossovers, complex crossovers and the mutation rate |
10.1210/endrev/bnaa011 | 125,154,349 | Abstract Abstract Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic, and viral infections. The severe acute respiratory syndrome (SARS)-CoV-2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informin... | 10.1038/s41574-020-00435-4 | This review covers the pathophysiology and treatment of type 2 diabetes mellitus in the context of coronavirus infection |
10.1038/ncomms11756 | 19,671,298 | Abstract Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell po... | 10.1038/s41574-021-00568-0 | This study uses cell surface makers to separate four populations of human β-cells that show both transcriptional and functional differences, which was further validated in ref. 20 |
10.1369/jhc.5c6684.2005 | 104,407,383 | The recent success of pancreatic islet transplantation has generated considerable enthusiasm. To better understand the quality and characteristics of human islets used for transplantation, we performed detailed analysis of islet architecture and composition using confocal laser scanning microscopy. Human islets from si... | 10.1038/s41574-021-00568-0 | An in-depth description of the differences in cytoarchitecture between mouse and human islets, both in situ and isolated from the pancreas. |
10.1101/2020.12.22.424082 | 83,455,849 | Abstract Insulin-secreting β-cells are functionally heterogeneous. Subpopulations of β-cells can control islet function and the regulation of hormone release, such as driving the second (oscillatory) phase of free-calcium ([Ca 2+ ]) following glucose elevation. Whether there exists a subpopulation that drives the first... | 10.1038/s41574-021-00568-0 | This article identifies a β-cell subpopulation that drives the initial first phase response to nutrient stimulation but which represents a transient state of the cell. |
10.4049/jimmunol.1900838 | 121,836,398 | Abstract At steady state, the CNS parenchyma has few to no lymphocytes and less potent Ag-presentation capability compared with other organs. However, the meninges surrounding the CNS host diverse populations of immune cells that influence how CNS-related immune responses develop. Interstitial and cerebrospinal fluid p... | 10.1038/s41577-022-00684-6 | The role of meningeal lymphatics in communication between the brain and the peripheral immune system is discussed within the context of CNS-related immune responses |
10.1126/scitranslmed.aai7795 | 62,060,809 | Crohn’s disease (CD)–associated variants in the LRRK2 gene for risk (N2081D) and for protection (N551K) mediate shared effects in CD and Parkinson’s disease. | 10.1038/s41577-022-00684-6 | Exosome sequencing studies revealed shared LRRK2 alleles in PD and Crohn’s disease providing insight into potential underlying disease mechanisms |
10.1038/npjparkd.2015.2 | 102,998,077 | Abstract Background: The common noncoding single-nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson’s disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechan... | 10.1038/s41577-022-00684-6 | Immunophenotyping studies of human peripheral blood mononuclear cells support functional consequences of gene-by-environment interplay between specific pesticide exposure and an HLA-DRA polymorphism associated with risk for late-onset PD |
10.1093/brain/awy077 | 41,741,647 | Abstract Missense mutations in the leucine rich repeat kinase 2 (LRRK2) gene result in late-onset Parkinson’s disease. The incomplete penetrance of LRRK2 mutations in humans and LRRK2 murine models of Parkinson’s disease suggests that the disease may result from a complex interplay of genetic predispositions and persis... | 10.1038/s41577-022-00684-6 | Studies of immune challenge in bone-marrow chimeric mice with wild-type LRRK2 in the brain and mutant LRRK2 in the periphery support the primacy of the peripheral immune system genotype in the neurodegeneration outcome |
10.1126/scitranslmed.aas9292 | 41,576,682 | Variants in the leucine-rich repeat kinase-2 ( LRRK2 ) gene are associated with Parkinson’s disease, leprosy, and Crohn’s disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested ... | 10.1038/s41577-022-00684-6 | LRRK2 alleles modulate the outcome of Salmonella and reovirus-induced encephalitic microbial infections in mice |
10.1073/pnas.1207889109 | 80,422,080 | Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the acid β-glucocerebrosidase gene. To model GD, we generated human induced pluripotent stem cells (hiPSC), by reprogramming skin fibroblasts from patients with type 1 (N370S/N370S), type 2 (L444P/Rec NciI ), and type 3 (L444P/L444P) GD. Plu... | 10.1038/s41577-022-00684-6 | Inflammatory phenotypes and glucocerebrosidase deficits in human islet-derived precursor cells from patients with Gaucher’s disease |
10.1002/mds.28411 | 38,442,140 | Abstract Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α‐synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non‐motor symptoms, and extent of central and peripheral i... | 10.1038/s41577-022-00684-6 | Environmental factors (pesticides and infections) increase the risk for idiopathic PD via the immune system. This review highlights the major PD-relevant genes expressed in immune cells and key environmental factors that activate immune cells and that, alone or in combination with other factors, may contribute to idiop... |
10.1038/s41531-016-0002-0 | 125,072,329 | Abstract The state of the intestinal environment can have profound effects on the activity of the central nervous system through the physiological contributions of the microbiota, regulation of intestinal barrier function, and altered activity of peripheral neurons. The common language employed for much of the gut-brai... | 10.1038/s41577-022-00684-6 | Evidence that intestinal dysfunction is present in PD and that it may reflect the earliest manifestations of disease pathology, and the link to dysregulated immune activity is reviewed along with potential mechanisms associated to neuropathology |
10.1126/science.1159689 | 104,329,341 | Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats (CRISPRs). Here we show how virus-derived sequences contained in CRISPRs are used by CRISPR-associated (Cas) proteins from the host to mediate an antiviral response ... | 10.1038/s41579-021-00663-z | This article provides the first insights into the molecular mechanism of antiviral defence by CRISPR–Cas, including the use of designed CRISPRs for dedicated DNA interference |
10.1126/sciadv.aaz4849 | 38,400,968 | CRISPR-Cas9 systems are enriched in human pathogenic bacteria and have been linked to cytotoxicity by an unknown mechanism. Here, we show that upon infection of human cells, Campylobacter jejuni secretes its Cas9 (CjeCas9) nuclease into their cytoplasm. Next, a native nuclear localization signal enables CjeCas9 nuclear... | 10.1038/s41579-021-00663-z | This study demonstrates that guide-free Cas9 from C. jejuni causes guide-independent, non-specific host-cell DNA damage |
10.1073/pnas.1709035114 | 83,118,563 | A survey of bacterial and archaeal genomes shows that many Tn7-like transposons contain minimal type I-F CRISPR-Cas systems that consist of fused cas8f and cas5f , cas7f , and cas6f genes and a short CRISPR array. Several small groups of Tn7-like transposons encompass similarly truncated type I-B CRISPR-Cas. This minim... | 10.1038/s41579-021-00663-z | This article provides the first description of derived CRISPR–Cas systems encoded in Tn 7 -like transposons and predicts their function in RNA-guided transposition |
10.1126/science.aax9181 | 104,187,801 | CRISPR-Cas nucleases are powerful tools for manipulating nucleic acids; however, targeted insertion of DNA remains a challenge, as it requires host cell repair machinery. Here we characterize a CRISPR-associated transposase from cyanobacteria Scytonema hofmanni (ShCAST) that consists of Tn7-like transposase subunits an... | 10.1038/s41579-021-00663-z | Complementary to Klompe et al. (2019), this work reveals that inactivated CRISPR–Cas subtype V-U5 effector proteins encoded in Tn 7 -like transposons form a complex with the transposase subunit and enable crRNA-guided transposition |
10.1534/genetics.106.056473 | 29,105,135 | Abstract Rice (Oryza sativa) was cultivated by Asian Neolithic farmers >11,000 years ago, and different cultures have selected for divergent starch qualities in the rice grain during and after the domestication process. An intron 1 splice donor site mutation of the Waxy gene is responsible for the absence of amy... | 10.1038/s41576-018-0024-z | This study provides an early demonstration of the genomic footprint of selection associated with a culturally significant trait |
10.1073/pnas.1515919112 | 19,843,542 | Intensive rice breeding over the past 50 y has dramatically increased productivity especially in the indica subspecies, but our knowledge of the genomic changes associated with such improvement has been limited. In this study, we analyzed low-coverage sequencing data of 1,479 rice accessions from 73 countries, includin... | 10.1038/s41576-018-0024-z | This study identifies two major groups of indica rice, based on breeding signatures, that resulted from independent breeding activities in different regions of Asia |
10.1038/ncomms6087 | 41,554,929 | Abstract Even as the study of plant genomics rapidly develops through the use of high-throughput sequencing techniques, traditional plant phenotyping lags far behind. Here we develop a high-throughput rice phenotyping facility (HRPF) to monitor 13 traditional agronomic traits and 2 newly defined traits during the rice ... | 10.1038/s41576-018-0024-z | This work reports a high-throughput phenotyping facility and demonstrates that the data can be used for GWAS of agronomic traits |
10.1126/science.1223702 | 18,001,258 | Conquering Rice Sterility The hybrid sterility occurring among rice species has long been a puzzle and hampers progress in breeding crops with improved performance and yield characteristics. Yang et al. (p. 1336 ) have identified three linked genes encoding a killer, a partner, and a protector protein. The killer and p... | 10.1038/s41576-018-0024-z | This study characterizes the S5 locus for reproductive isolation between indica and japonica subspecies, which consists of three adjacent genes forming a killer–protector system. This gene is widely used in intersubspecific hybrid rice breeding |
10.1002/cncr.24465 | 103,714,050 | Abstract BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents aged <20 years; its etiology remains largely unknown. It is believed that embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS), the most common subtypes, arise through distinct biologic mechanisms. The aut... | 10.1038/s41572-018-0051-2 | This paper demonstrates increasing incidence of RMS in the United States |
10.1002/gepi.1370120504 | 100,376,695 | Abstract Rhabdomyosarcoma (RMS) is an uncommon malignant soft tissue sarcoma whose cause is largely unknown. Reported risk factors include genetic alterations (e.g., p53 mutations, a defective gene at 11p15.5, or specific chromosomal translocation of t(2:13)), and parents' use of drugs around the time of conception. We... | 10.1038/s41572-018-0051-2 | This paper reports the important addition of RMS to the cancer susceptibility imposed by heritable genetic defects, including NF1 mutation |
10.1101/gad.1244004 | 83,062,188 | Alveolar rhabdomyosarcoma is an aggressive childhood muscle cancer for which outcomes are poor when the disease is advanced. Although well-developed mouse models exist for embryonal and pleomorphic rhabdomyosarcomas, neither a spontaneous nor a transgenic mouse model of alveolar rhabdomyosarcoma has yet been reported. ... | 10.1038/s41572-018-0051-2 | This elegant study demonstrates the power of genetically engineered mouse models in the study of translocation-driven sarcomas |
10.1002/cncr.20544 | 124,034,018 | Abstract BACKGROUND Following their previous report on the activity of vinorelbine in the treatment of rhabdomyosarcoma, the authors report the results of a pilot study aimed at defining the optimal dose of vinorelbine when this agent is used in conjunction with continuous, orally administered low‐dose cyclophosphamide... | 10.1038/s41572-018-0051-2 | This early report demonstrates the potential value of low-dose ‘maintenance’ chemotherapy — an emerging concept that provides a new opportunity to improve survival for those with the highest-risk disease |
10.1042/bj20091609 | 38,581,731 | The HIF (hypoxia-inducible factor) hydroxylases [PHDs or EGLNs (prolyl hydroxylases), which in humans are PHD isoforms 1–3, and FIH (factor inhibiting HIF)] regulate HIF levels and activity. These enzymes are Fe(II)/2-oxoglutarate-dependent oxygenases, many of which are stimulated by ascorbate. We have investigated the... | 10.1038/s41568-020-00303-3 | This study shows that hydroxylation of HIF proteins by EGLN prolyl hydroxylases and FIH is stimulated by reducing agents in an enzyme and substrate-specific manner |
10.1073/pnas.0606877103 | 101,289,583 | Studies on hypoxia-sensitive pathways have revealed a series of Fe(II)-dependent dioxygenases that regulate hypoxia-inducible factor (HIF) by prolyl and asparaginyl hydroxylation. The recognition of these unprecedented signaling processes has led to a search for other substrates of the HIF hydroxylases. Here we show th... | 10.1038/s41568-020-00303-3 | This study identifies numerous ankyrin repeat proteins as non-HIF substrates of FIH and suggested that they indirectly influence the amount of FIH available to hydroxylate HIF |
10.1126/science.aau5870 | 62,058,527 | Oxygen is essential for the life of most multicellular organisms. Cells possess enzymes called molecular dioxygenases that depend on oxygen for activity. A subclass of molecular dioxygenases is the histone demethylase enzymes, which are characterized by the presence of a Jumanji-C (JmjC) domain. Hypoxia can alter chrom... | 10.1038/s41568-020-00303-3 | This study demonstrates that the H3K4 histone lysine demethylase KDM5A is an oxygen sensor |
10.1126/science.1231677 | 41,515,595 | Focusing on the Right Metabolite A variety of human cancers, including acute leukemias and brain tumors, have mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1, IDH2), which cause overproduction of a metabolite called 2-hydroxyglutarate (2HG). Losman et al. (p. 1621 , published online 7 February) sh... | 10.1038/s41568-020-00303-3 | This study shows that R -2HG acts as an oncometabolite at least in part by inhibiting TET2 and that its effects can be reversed in preclinical models. The latter finding has galvanized efforts to develop drugs that block 2-HG production by mutant IDH |
10.1038/embor.2011.43 | 125,144,015 | Mutations in isocitrate dehydrogenases (IDHs) have a gain‐of‐function effect leading to R (−)‐2‐hydroxyglutarate ( R‐ 2HG) accumulation. By using biochemical, structural and cellular assays, we show that either or both R ‐ and S ‐2HG inhibit 2‐oxoglutarate (2OG)‐dependent oxygenases with varying potencies. Half‐maximal... | 10.1038/s41568-020-00303-3 | This study shows that R -2HG is able to inhibit specific 2OGDDs |
10.1126/science.1229386 | 83,341,971 | Pressing Pause The pausing of RNA polymerase II (Pol II) near promoters is an important and distinct regulatory step in the process of transcribing DNA into RNA. Although protein factors and DNA elements involved in pausing have been identified, the post-initiation events that lead to pausing are poorly understood. Kwa... | 10.1038/s41576-019-0159-6 | This article describes PRO-seq, which maps active Pol II positions at single-nucleotide resolution genome-wide |
10.1126/science.1181421 | 83,351,116 | To Stall or Not to Stall Recent studies in mammals and Drosophila have shown that RNA polymerase II frequently stalls shortly after initiating messenger RNA synthesis and that this stalling is important for proper expression of genes. Although several protein factors that affect polymerase stalling are known, the role ... | 10.1038/s41576-019-0159-6 | This study describes Start-seq, which was used to identify initiating and promoter-proximal pausing positions across the D. melanogaster genome |
10.1126/science.aad9841 | 125,182,978 | TT-Seq maps a transient transcriptome RNA expression is related to protein abundance and cellular function. However, the amounts of RNA generated at any one time-point have been difficult to determine. Schwalb et al. developed a method, transient transcriptome sequencing (TT-Seq), to collect and sequence all RNA segmen... | 10.1038/s41576-019-0159-6 | This article describes TT-seq, which uses short metabolic labeling times to capture newly transcribed RNAs in human cells |
10.1126/science.1162228 | 41,536,477 | RNA polymerases are highly regulated molecular machines. We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and map... | 10.1038/s41576-019-0159-6 | This article describes GRO-seq and demonstrates widespread promoter-proximal pausing and bidirectional transcription across the human genome |
10.1101/gr.225755.117 | 20,406,904 | Transcription factors (TFs) exert their regulatory influence through the binding of enhancers, resulting in coordination of gene expression programs. Active enhancers are often characterized by the presence of short, unstable transcripts termed enhancer RNAs (eRNAs). While their function remains unclear, we demonstrate... | 10.1038/s41576-019-0159-6 | This study uses computational tools to identify enhancers from RO-seq data and demonstrates that these data can identify active transcription factor motifs |
10.1126/science.274.5295.2025 | 4,903,913 | The origin of cholera has been elusive, even though scientific evidence clearly shows it is a waterborne disease. However, standard bacteriological procedures for isolation of the cholera vibrio from environmental samples, including water, between epidemics generally were unsuccessful. Vibrio cholerae , a marine vibrio... | 10.1038/s41572-018-0005-8 | This article provides a comprehensive overview on the effect of climate on cholera epidemics. |
10.1128/cmr.00025-06 | 83,099,852 | SUMMARY Vibrio parahaemolyticus is recognized as a cause of food-borne gastroenteritis, particularly in the Far East, where raw seafood consumption is high. An unusual increase in admissions of V. parahaemolyticus cases was observed at the Infectious Diseases Hospital in Calcutta, a city in the northeastern part of Ind... | 10.1038/s41572-018-0005-8 | This paper presents a succinct and historical overview of the pandemic spread of V. parahaemolyticus |
10.1111/j.1348-0421.2005.tb03731.x | 82,485,104 | Abstract Vibrio vulnificus is an estuarine bacterium which is the causative agent of both food‐borne disease and wound infection. Although V. vulnificus is commonly found in molluscan shellfish at high numbers, the incidence of disease is relatively low, leading to the hypothesis that not all strains of V. vulnificus a... | 10.1038/s41572-018-0005-8 | This article describes a PCR method to rapidly differentiate the two genotypes of V. vulnificus and their correlation to isolation source |
10.1126/science.272.5270.1910 | 62,359,437 | Vibrio cholerae , the causative agent of cholera, requires two coordinately regulated factors for full virulence: cholera toxin (CT), a potent enterotoxin, and toxin-coregulated pili (TCP), surface organelles required for intestinal colonization. The structural genes for CT are shown here to be encoded by a filamentous... | 10.1038/s41572-018-0005-8 | This paper presents the first description of the structural genes for CT encoded by a filamentous bacteriophage. |
10.1126/science.1120096 | 125,338,766 | The mosaic-structured Vibrio cholerae genome points to the importance of horizontal gene transfer (HGT) in the evolution of this human pathogen. We showed that V. cholerae can acquire new genetic material by natural transformation during growth on chitin, a biopolymer that is abundant in aquatic habitats (e.g., from cr... | 10.1038/s41572-018-0005-8 | This study shows the crucial role of chitin in the acquisition of new genetic material via natural transformation; the role of chitin is crucial to understand the role of zooplankton in the evolution and life cycle of Vibrio spp. |
10.1038/ismej.2011.89 | 60,029,658 | Abstract The long-term effects of ocean warming on prokaryotic communities are unknown because of lack of historical data. We overcame this gap by applying a retrospective molecular analysis to the bacterial community on formalin-fixed samples from the historical Continuous Plankton Recorder archive, which is one of th... | 10.1038/s41572-018-0005-8 | This study shows the role of rapid climate warming on changing the abundance of Vibrio spp. in the marine environment using novel retrospective molecular methods |
10.1128/aem.60.7.2597-2601.1994 | 81,268,928 | In 1991 and 1992, toxigenic Vibrio cholerae O1, serotype Inaba, biotype El Tor, was recovered from nonpotable (ballast, bilge, and sewage) water from five cargo ships docked in ports of the U.S. Gulf of Mexico. Four of these ships had taken on ballast water in cholera-infected countries; the fifth took on ballast in a ... | 10.1038/s41572-018-0005-8 | This study is the first to describe the role of cargo ships in the dispersal of pathogenic Vibrio spp. via discharges of ballast water |
10.1038/s41467-021-22291-0 | 103,699,399 | Abstract Electrifying chemical manufacturing using renewable energy is an attractive approach to reduce the dependence on fossil energy sources in chemical industries. Primary amines are important organic building blocks; however, the synthesis is often hindered by the poor selectivity because of the formation of secon... | 10.1038/s41570-022-00379-5 | This work demonstrates the key factors behind electrochemical acetonitrile hydrogenation |
10.1002/mus.25973 | 124,961,339 | ABSTRACT Myasthenia gravis (MG) is an archetypal autoimmune disease. The pathology is characterized by autoantibodies to the acetylcholine receptor (AChR) in most patients or to muscle‐specific tyrosine kinase (MuSK) in others and to a growing number of other postsynaptic proteins in smaller subsets. A decrease in the ... | 10.1038/s41582-018-0110-z | An up-to-date review on B cells in MG, including excellent B cell molecular immunology |
10.1212/wnl.0000000000004365 | 101,585,814 | Objective: To investigate the efficacy, tolerability, and safety of subcutaneous immunoglobulin (SCIg) in patients with mild to moderate myasthenia gravis (MG) exacerbation. Methods: We performed a prospective, open-label, phase 3 trial in patients with MG aged 18 years or older and mild to moderate worsening (transiti... | 10.1038/s41582-018-0110-z | A useful study that describes the experience of treating MG with subcutaneous IgG |
10.1002/ana.25119 | 20,724,082 | Monoclonal antibodies that target CD20 expressing B cells represent an important new treatment option for patients with multiple sclerosis (MS). B‐cell‐depleting therapy is highly effective against relapsing forms of the disease and is also the first treatment approach proven to protect against disability worsening in ... | 10.1038/s41582-018-0110-z | An excellent review of B cell therapies in multiple sclerosis and implications in other autoimmune neurological diseases |
10.1534/genetics.107.083782 | 36,978,075 | Abstract We extended the use of Drosophila beyond being a model for signaling pathways required for pattern recognition immune signaling and show that the fly can be used to identify genes required for pathogenesis and host–pathogen interactions. We performed a forward genetic screen to identify Drosophila mutations al... | 10.1038/s41589-018-0018-3 | This study identified D. melanogaster mutants that were more susceptible to L. monocytogenes infection, though their ability to control bacterial burden was unchanged compared to wild type. |
10.1126/science.aad5497 | 62,626,779 | Regulatory use of endogenous retroviruses Mammalian genomes contain many endogenous retroviruses (ERVs), which have a range of evolutionary ages. The propagation and maintenance of these genetic elements have been attributed to their ability to contribute to gene regulation. Chuong et al. demonstrate that some ERV fami... | 10.1038/s41576-020-00305-9 | This study provides an example of the co-option of ancient genomic elements (endogenous retroviruses) to create new regulatory elements in mammalian immune systems |
10.1159/000500317 | 54,429,980 | Evolutionary thinking can inform the choice and assessment of model species in neuroscience, particularly when such models are intended to generate knowledge that will translate to humans. Avoiding errors that arise from oversimplified notions of phylogeny or genotype-phenotype mapping is one contribution; evolutionary... | 10.1038/s41576-020-00305-9 | This review provides guidelines for considering evolutionary context in the selection of model organisms for translational research |
10.1073/pnas.0914634107 | 83,506,526 | Darwinian evolution of humans from our common ancestors with nonhuman primates involved many gene–environment interactions at the population level, and the resulting human-specific genetic changes must contribute to the “Human Condition.” Recent data indicate that the biology of sialic acids (which directly involves le... | 10.1038/s41576-020-00305-9 | This article demonstrates that genes involved in sialic acid biology are a ‘hot spot’ of genetic and physiological changes during recent evolution with implications for human-specific disease |
10.1101/gr.202440.115 | 110,016,112 | The role of rare alleles in complex phenotypes has been hotly debated, but most rare variant association tests (RVATs) do not account for the evolutionary forces that affect genetic architecture. Here, we use simulation and numerical algorithms to show that explosive population growth, as experienced by human populatio... | 10.1038/s41576-020-00305-9 | This study demonstrates how the recent demographic and selective history of human populations poses challenges for the identification and interpretation of genetic variants that cause disease |
10.1126/science.aad2149 | 104,326,298 | The legacy of human-Neandertal interbreeding Non-African humans are estimated to have inherited on average 1.5 to 4% of their genomes from Neandertals. However, how this genetic legacy affects human traits is unknown. Simonti et al. combined genotyping data with electronic health records. Individual Neandertal alleles ... | 10.1038/s41576-020-00305-9 | This paper uses a large biobank cohort to demonstrate that admixture between Neanderthals and the ancestors of modern Eurasians influences disease risk |
10.1534/genetics.115.180471 | 124,672,863 | Abstract Although the human germline mutation rate is higher than that in any other well-studied species, the rate is not exceptional once the effective genome size and effective population size are taken into consideration. Human somatic mutation rates are substantially elevated above those in the germline, but this i... | 10.1038/s41576-020-00305-9 | This article explores the implications of the recent removal of many selective pressures from the natural environment on the human genome, risk for disease and precision medicine |
10.1158/0008-5472.can-17-1550 | 103,754,596 | Abstract Prostate cancer incidence and mortality rates in African and African American men are greatly elevated compared with other ethnicities. This disparity is likely explained by a combination of social, environmental, and genetic factors. A large number of susceptibility loci have been reported by genome-wide asso... | 10.1038/s41576-020-00305-9 | This analysis shows that haplotypes with protective effects against prostate cancer may have risen to higher frequency in non-African populations because of selection on the nearby variants associated with skin pigmentation |
10.1038/s41467-020-17258-6 | 100,275,977 | Abstract Currently, there is no comprehensive framework to evaluate the evolutionary forces acting on genomic regions associated with human complex traits and contextualize the relationship between evolution and molecular function. Here, we develop an approach to test for signatures of diverse evolutionary forces on tr... | 10.1038/s41576-020-00305-9 | This article demonstrates that a mosaic of diverse selective pressures has shaped the genetic loci that influence risk for preterm birth, a common complex disease |
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