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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10.2337/diacare.22.3.495 | 124,077,497 | OBJECTIVE: The predictive value of microalbuminuria (MA) in children with type 1 diabetes has not been defined. We describe the natural history of MA in a large cohort of children recruited at diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1985 and 1996, 514 children (279 male) who developed type 1 ... | 10.1038/nrneph.2018.9 | This research shows that kidney disease in diabetes begins much earlier than once thought and initiation does not require comorbidities such as hypertension or dyslipidaemia. |
10.1152/ajprenal.1981.240.5.f357 | 83,452,987 | A linear relationship has been observed between the rate of active ion transport and the oxygen consumption or lactate production rate in a variety of epithelia. Stoichiometries of ions transported per oxygen consumed or ATP utilized calculated from these relationships reflect actual properties of the active transport ... | 10.1038/nrneph.2018.9 | This research demonstrates the integral relationship that exists between renal solute transport and oxygen-dependent ATP production in the kidneys. |
10.1152/ajprenal.1979.237.2.f105 | 95,550,646 | A micromethod for the determination of Na-K-ATPase in discrete segments of nephrons from rabbit, rat, and mouse kidneys is described. To facilitate tubule microdissection, the kidneys were perfused with collagenase after it had been verified that collagenase had no effect on ATPase activity. Individual tubule segments ... | 10.1038/nrneph.2018.9 | This paper shows the expression of mitochondrial coupled Na + /K + ATPase in the nephron and how this is coupled to solute transport needs on the basis of the location. |
10.2337/diacare.24.2.382 | 103,934,122 | Studies conducted over the last 60 years in animals and in vitro have provided considerable evidence that the mammalian kidney can make glucose and release it under various conditions. Until quite recently, however, it was generally believed that the human kidney was not an important source of glucose except during aci... | 10.1038/nrneph.2018.9 | This article provides an excellent overview of renal gluconeogenesis and how it contributes to systemic glucose homeostasis. |
10.1152/ajpregu.00809.2010 | 19,067,845 | Diabetic nephropathy is a leading cause of end-stage renal disease. A better understanding of the molecular mechanism involved in the early changes of the diabetic kidney may permit the development of new strategies to prevent diabetic nephropathy. This review focuses on the proximal tubule in the early diabetic kidney... | 10.1038/nrneph.2018.9 | This paper provides an overview of the tubular hypothesis of DKD. |
10.1111/1440-1681.12034 | 80,961,381 | Summary The high renal oxygen (O 2 ) demand is associated primarily with tubular O 2 consumption ( Qo 2 ) necessary for solute reabsorption. Increasing O 2 delivery relative to demand via increased blood flow results in augmented tubular electrolyte load following elevated glomerular filtration, which, in turn, increas... | 10.1038/nrneph.2018.9 | This work highlights how oxygen is used by the diabetic kidney and how this may lead to hypoxia. |
10.2337/db09-0259 | 82,438,433 | OBJECTIVE To elucidate the molecular basis for mitochondrial dysfunction, which has been implicated in the pathogenesis of diabetes complications. RESEARCH DESIGN AND METHODS Mitochondrial matrix and membrane fractions were generated from liver, brain, heart, and kidney of wild-type and type 1 diabetic Akita mice. Comp... | 10.1038/nrneph.2018.9 | This conceptually interesting study describes mitochondrial changes in organs prone to diabetic complications. |
10.2337/db05-1438 | 124,111,563 | The in vitro behavior of skin fibroblasts from patients with or without diabetic nephropathy is associated with diabetic nephropathy risk. Here we compared skin fibroblast gene expression profiles from two groups of type 1 diabetic patients: 20 with very fast (“fast-track”) versus 20 with very slow (“slow-track”) rates... | 10.1038/nrneph.2018.9 | This article presents an early description of mitochondrial abnormalities in skin fibroblasts taken from individuals with DKD. |
10.1152/ajpendo.00233.2005 | 675,855 | Studies of cardiac fuel metabolism in mice have been almost exclusively conducted ex vivo. The major aim of this study was to assess in vivo plasma FFA and glucose utilization by the hearts of healthy control ( db/+) and diabetic ( db/db) mice, based on cardiac uptake of (R)-2-[9,10- 3 H]bromopalmitate ([ 3 H]R-BrP) an... | 10.1038/nrneph.2018.9 | This is a dynamic steady-state study of metabolic substrate flux in the diabetic heart. |
10.2337/db15-1356 | 125,211,396 | Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release. In type 2 diabetes (T2D), along with decrements in plasma glucose and insulin levels and increments in glucagon release, sodium–glucose cotransporter 2 (SGLT2) inhibitors induce stimulation of endogenous glucose ... | 10.1038/nrneph.2018.9 | This research shows the effects on fatty acid metabolism that occur following therapy to decrease proximal tubule Na + and glucose reabsorption. |
10.1111/dme.12763 | 40,967,448 | Abstract Aim To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms ( SNP s) that may contribute to mitochondrial dysfunction. Methods The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823 individuals with... | 10.1038/nrneph.2018.9 | This study shows that genes that alter mitochondrial function are altered in individuals with DKD. |
10.1046/j.1528-1157.43.s.5.16.x | 109,139,213 | Summary: Purpose: The linkage between autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and neuronal nicotinic acetylcholine receptor has been strongly reinforced by the report of five distinct mutations in the two genes coding for the major brain α4β2 nicotinic acetylcholine (ACh) receptors. As a first step ... | 10.1038/nrn1388 | The authors compare the distinct functional properties of four nAChR mutations associated with ADNFLE, and discuss their findings in the context of the latest knowledge of pyramidal cell function. |
10.1182/blood-2008-05-159301 | 20,197,588 | Abstract Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, GI tract, and broncheoalveolar lavage of HIV-infected and uninfected hum... | 10.1038/nrmicro2848 | This study demonstrates that T H 17 cells are preferentially lost in the gastrointestinal tract but not in the blood of HIV-infected individuals, but they are maintained in SIV-infected sooty mangabees. |
10.1126/scitranslmed.3000632 | 61,603,449 | Patients with AIDS have fewer immune cells to defend against microbial invasion through the gut, a critical loss that may be caused by a tryptophan metabolite produced by other immune cells. | 10.1038/nrmicro2848 | In this study, induction of IDO1 is associated with a relative loss of T H 17 cells and gain of T Reg cells and may thereby perpetuate increased microbial translocation. |
10.1182/blood-2009-03-210179 | 80,022,815 | Abstract HIV infection is associated with an increased risk of thrombosis; and as antiretroviral therapy has increased the lifespan of HIV-infected patients, their risk for cardiovascular events is expected to increase. A large clinical study found recently that all-cause mortality for HIV+ patients was related to plas... | 10.1038/nrmicro2848 | The findings of this study suggest that microbial translocation may drive the procoagulant state observed in HIV-infected individuals. |
10.1046/j.1471-4159.2000.0751878.x | 19,235,539 | Abstract: The membrane‐permeant oxidizing agent 2,2′‐dithiodipyridine (DTDP) can induce Zn 2+ release from metalloproteins in cell‐free systems. Here, we report that brief exposure to DTDP triggers apoptotic cell death in cultured neurons, detected by the presence of both DNA laddering and asymmetric chromatin formatio... | 10.1038/nrn1671 | Introduces the notion of thiol-liberated free zinc as a generic apoptosis death signal. |
10.1073/pnas.93.25.14934 | 82,598,817 | The murine ZnT3 gene was cloned by virtue of its homology to the ZnT2 gene, which encodes a membrane protein that facilitates sequestration of zinc in endosomal vesicles. ZnT-3 protein is predicted to have six transmembrane domains and shares 52% amino acid identity with ZnT-2, with the homology extending throughout th... | 10.1038/nrn1671 | The first evidence to indicate that the ZnT3 protein is necessary for zinc accumulation in neuronal vesicles. |
10.1126/science.272.5264.1013 | 82,848,584 | Zinc is present in presynaptic nerve terminals throughout the mammalian central nervous system and likely serves as an endogenous signaling substance. However, excessive exposure to extracellular zinc can damage central neurons. After transient forebrain ischemia in rats, chelatable zinc accumulated specifically in deg... | 10.1038/nrn1671 | The first demonstation that chelation of metals can rescue neurons from ischaemic injury and death. |
10.1523/jneurosci.0297-04.2004 | 103,216,173 | Cerebral amyloid angiopathy (CAA) is common in Alzheimer's disease (AD) and may contribute to dementia and cerebral hemorrhage. Parenchymal β-amyloid deposition is dependent on the activity of zinc transporter 3 (ZnT3), a neocortical synaptic vesicle membrane protein that causes enrichment of exchangeable Zn 2+ in the ... | 10.1038/nrn1671 | The precipitation of amyloid-β in the post-mortem brain tissue of patients with Alzheimer's disease is reversible with zinc chelation. |
10.1126/science.256.5055.385 | 83,406,012 | Water rapidly crosses the plasma membrane of red blood cells (RBCs) and renal tubules through specialized channels. Although selective for water, the molecular structure of these channels is unknown. The CHIP28 protein is an abundant integral membrane protein in mammalian RBCs and renal proximal tubules and belongs to ... | 10.1038/nrn1252 | Identification of the first member of the aquaporin family (Chip28, later renamed Aqp1). |
10.1523/jneurosci.17-01-00171.1997 | 29,105,225 | Membrane water transport is critically involved in brain volume homeostasis and in the pathogenesis of brain edema. The cDNA encoding aquaporin-4 (AQP4) water channel protein was recently isolated from rat brain. We used immunocytochemistry and high-resolution immunogold electron microscopy to identify the cells and me... | 10.1038/nrn1252 | High resolution immunogold analysis revealed a concentration of Aqp4 in subpial and perivascular endfeet, and in ependymal cells, that is, at the interfaces between brain and extracerebral liquids (blood and CSF). |
10.1073/pnas.0437946100 | 79,782,597 | The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astrocytes. These membranes form the interface between the neuropil and extracerebral liquid spaces. AQP4 is anchored at these membranes by its carboxyl terminus to α-syntrophin, an adapter protein associated with dystrophin. T... | 10.1038/nrn1252 | This study showed that selective removal of perivascular Aqp4 by α-Syn deletion reduced the extent of post-ischaemic oedema and that the binding between Aqp4 and α-Syn is sensitive to ischaemia. |
10.1073/pnas.192457099 | 65,263,119 | Cerebral water accumulation was studied during induction of brain edema in dystrophin-null transgenic mice ( mdx- β geo ) and control mice. Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null brains revealed a dramatic reduction of AQP4 (aquaporin-4) in astroglial end-feet surrounding capillar... | 10.1038/nrn1252 | Mdx mice that lacked Aqp4 at the interfaces between brain and blood/CSF showed a delayed development of hyponatremic oedema, compared with wild-type mice. |
10.1126/science.1169405 | 103,702,379 | Decisive Monkeys Decision-making is a central theme in current research in cognitive neuroscience. Behavioral protocols have provided an entry into explorations of the neural processes that underlie decision-making. Empirical studies have provided support for a diffusion model in which information accumulates over time... | 10.1038/nrn3289 | Demonstration of LIP neurons that fire in accordance with a temporal integrator model in such a way that their firing reflects sensory uncertainty and predicts behaviour. |
10.1126/science.1105370 | 20,821,180 | It is important for animals to estimate the value of rewards as accurately as possible. Because the number of potential reward values is very large, it is necessary that the brain's limited resources be allocated so as to discriminate better among more likely reward outcomes at the expense of less likely outcomes. We f... | 10.1038/nrn3289 | Shows adaption of dopaminergic midbrain neurons. Among other issues, it is demonstrated that prediction error signals are scaled by outcome uncertainty. |
10.1126/science.1077349 | 103,154,774 | Uncertainty is critical in the measure of information and in assessing the accuracy of predictions. It is determined by probability P , being maximal at P = 0.5 and decreasing at higher and lower probabilities. Using distinct stimuli to indicate the probability of reward, we found that the phasic activation of dopamine... | 10.1038/nrn3289 | Report of slowly ramping activity in dopaminergic midbrain neurons correlating with outcome uncertainty. |
10.1152/physrev.00009.2013 | 62,058,875 | Our understanding of the functions of motor system evolved remarkably in the last 20 years. This is the consequence not only of an increase in the amount of data on this system but especially of a paradigm shift in our conceptualization of it. Motor system is not considered anymore just a “producer” of movements, as it... | 10.1038/nrn.2016.135 | This rich, exhaustive review describes the functional organization of the cortical motor system and the goal-directed mirror mechanism in monkeys and humans. |
10.1523/jneurosci.4803-10.2011 | 123,223,256 | In both monkeys and humans, the observation of actions performed by others activates cortical motor areas. An unresolved question concerns the pathways through which motor areas receive visual information describing motor acts. Using functional magnetic resonance imaging (fMRI), we mapped the macaque brain regions acti... | 10.1038/nrn.2016.135 | This detailed connectional study combines fMRI and neural tracer techniques, and defines the functional paths by which visual information concerning others' actions reaches the premotor cortex. |
10.1073/pnas.1200143109 | 82,849,038 | In the last few years, the insula has been the focus of many brain-imaging studies, mostly devoted to clarify its role in emotions and social communication. Physiological data, however, on which one may ground these correlative findings are almost totally lacking. Here, we investigated the functional properties of the ... | 10.1038/nrn.2016.135 | This detailed study of the physiological organization of the monkey insula shows the profound functional heterogeneity of different sectors of the insula. |
10.1073/pnas.1512133112 | 83,319,206 | Vitality form is a term that describes the style with which motor actions are performed (e.g., rude, gentle, etc.). They represent one characterizing element of conscious and unconscious bodily communication. Despite their importance in interpersonal behavior, vitality forms have been, until now, virtually neglected in... | 10.1038/nrn.2016.135 | This fMRI study was the first to provide evidence for the presence ofthe mirror mechanism for vitality forms in the dorsocentral insula. |
10.1128/jvi.76.15.7651-7660.2002 | 61,378,636 | ABSTRACT Gene therapy vectors based on adeno-associated viruses (AAVs) show promise for the treatment of retinal degenerative diseases. In prior work, subretinal injections of AAV2, AAV5, and AAV2 pseudotyped with AAV5 capsids (AAV2/5) showed variable retinal pigmented epithelium (RPE) and photoreceptor cell transducti... | 10.1038/nrn1104 | Demonstrated the specific tropism of AAV serotypes for neural and epithelial layers in the eye. |
10.1073/pnas.120474397 | 60,421,164 | Although adenoviral vectors provide prolonged gene expression in the brain by comparison to peripheral organs, expression is eliminated by a severe inflammatory infiltration (i.e., activated macrophages/microglia and T-lymphocytes) after peripheral infection with adenovirus. Here, we demonstrate that high-capacity aden... | 10.1038/nrn1104 | This study showed that 'gutless' adenovirus vectors produced less inflammation in the brain, even in the presence of previous peripheral inoculation. |
10.1159/000055451 | 66,159,795 | Three different herpes simplex virus (HSV) mutants, designated hrR3, MGH-1 and R3616, were used to infect Y79 retinoblastoma cells grown in suspension. Two parameters were assayed: (a) vector-mediated gene expression, measured by histochemical staining of a transferred <i>LacZ</i> transgene, and (b) virus-m... | 10.1038/nrn1104 | The first example of HSV recombinant virus vectors being used to deliver genes to neurons in the brain. |
10.1073/pnas.89.2.693 | 27,910,133 | Recombinant retroviruses encoding the histochemically detectable enzyme beta-galactosidase have been used to investigate lineage in the vertebrate nervous system. Identification of the descendants of individual progenitors is straightforward when progeny cells are arranged in a reproducible, clustered pattern, but diff... | 10.1038/nrn1104 | References 30 and 31 demonstrated the utility of retroviruses in lineage analysis in the developing nervous system. |
10.1128/jvi.71.9.6641-6649.1997 | 125,312,539 | The identification of monogenic and complex genes responsible for neurological disorders requires new approaches for delivering therapeutic protein genes to significant numbers of cells in the central nervous system. A lentivirus-based vector capable of infecting dividing and quiescent cells was investigated in vivo by... | 10.1038/nrn1104 | The first demonstration of the utility of lentivirus vectors for gene delivery to the brain. |
10.1073/pnas.082011999 | 16,753,662 | Gene transfer vectors based on lentiviruses can transduce terminally differentiated cells in the brain; however, their ability to reverse established behavioral deficits in animal models of neurodegeneration has not previously been tested. When recombinant feline immunodeficiency virus (FIV)-based vectors expressing β-... | 10.1038/nrn1104 | Functional recovery of a behavioural phenotype after gene therapy in an animal model of progressive CNS disease caused by a lysosomal enzyme deficiency. |
10.1101/2023.05.10.540250 | 155,980,363 | Abstract Mammalian orthoreovirus (MRV) is a clinically benign oncolytic virus which has been investigated for use in multiple cancer types, including breast cancer (BC). In human clinical trials, MRV has been shown to be safe, and multiple BC patients have shown partial responses to intratumoral and intravenous virus d... | 10.1038/nrn1104 | An early demonstration of the ability to target adenovirus vectors to specific cells by modification of the capsid. |
10.1128/jvi.76.18.9378-9388.2002 | 81,321,809 | ABSTRACT Vectors derived from lentiviruses provide a promising gene delivery system. We examined the in vivo gene transfer efficiency and tissue or cell tropism of a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the glycoproteins from Ross River Virus (RRV). RRV glycoproteins were efficie... | 10.1038/nrn1104 | References 51 and 52 show the importance of components of the envelope of lentivirus vectors with regard to the types of cells that can be transduced and the ability of the vector to be transported within neurons. |
10.1126/science.3201248 | 102,947,406 | Fibroblasts were genetically modified to secrete nerve growth factor (NGF) by infection with a retroviral vector and then implanted into the brains of rats that had surgical lesions of the fimbria-fornix. The grafted cells survived and produced sufficient NGF to prevent the degeneration of cholinergic neurons that woul... | 10.1038/nrn1104 | The first example of grafting of genetically modified cells into the brain to achieve delivery of a growth factor. |
10.1073/pnas.97.23.12846 | 107,146,666 | One of the impediments to the treatment of brain tumors (e.g., gliomas) has been the degree to which they expand, infiltrate surrounding tissue, and migrate widely into normal brain, usually rendering them “elusive” to effective resection, irradiation, chemotherapy, or gene therapy. We demonstrate that neural stem cell... | 10.1038/nrn1104 | Showed that neural precursor cells can migrate to tumours within the brain. |
10.1073/pnas.95.4.1858 | 82,130,864 | Nerve growth factor (NGF) is able to restore spatial learning and reverse forebrain cholinergic neuron atrophy when administered intracerebrally to behaviorally impaired aged rats. In the present study, behaviorally unimpaired, middle-aged rats (14–16 months old) received transplants of ex vivo transduced, clonal NGF-s... | 10.1038/nrn1104 | This study showed the effects of NGF on protection from age-related neurodegeneration. |
10.1073/pnas.221450098 | 79,469,692 | The treatment of brain diseases with gene therapy requires the gene to be expressed throughout the central nervous system, and this is possible by using gene targeting technology that delivers the gene across the blood–brain barrier after i.v. administration of a nonviral formulation of the gene. The plasmid DNA is tar... | 10.1038/nrn1104 | The use of luciferase in imaging of gene transfer in live mice. |
10.1073/pnas.87.6.2211 | 81,543,083 | Cellular sequences flanking integrated copies of the adeno-associated virus (AAV) genome were isolated from a latently infected clonal human cell line and used to probe genomic blots derived from an additional 21 independently derived clones of human cells latently infected with AAV. In genomic blots of uninfected huma... | 10.1038/nrn1104 | Showed that AAV integrates into a specific chromosomal site in the human genome. |
10.1126/science.275.5301.838 | 59,289,352 | Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival of dopaminergic (DA) neurons. A replication-defective adenoviral (Ad) vector encoding human GDNF injected near the rat substantia nigra was found to protect DA neurons from the progressive degeneration induced by the neurotoxin 6-hydroxydop... | 10.1038/nrn1104 | This study showed that GDNF gene therapy protects against dopaminergic neuron loss in an animal model of Parkinson's disease. It was followed up in primates with lentiviruses in Reference 146. |
10.1073/pnas.96.6.3211 | 122,095,243 | To test the utility of gene therapeutic approaches for the treatment of pain, a recombinant herpes simplex virus, type 1, has been engineered to contain the cDNA for an opioid peptide precursor, human preproenkephalin, under control of the human cytomegalovirus promoter. This virus and a similar recombinant containing ... | 10.1038/nrn1104 | HSV recombinant vectors can down-moderate pain responses by delivery of enkephalin to sensory neurons. |
10.1126/science.1138140 | 20,870,775 | Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or ... | 10.1038/nrmicro3279 | This study provides the first experimental evidence that the CRISPR–Cas system is an adaptive immune system. |
10.1046/j.1365-2958.2002.02839.x | 103,779,316 | Summary Using in silico analysis we studied a novel family of repetitive DNA sequences that is present among both domains of the prokaryotes (Archaea and Bacteria), but absent from eukaryotes or viruses. This family is characterized by direct repeats, varying in size from 21 to 37 bp, interspaced by similarly sized non... | 10.1038/nrmicro3279 | This paper reports the discovery of the link between repetitive arrays (that is, CRISPR sequences) and CRISPR-associated ( cas ) genes. |
10.1126/science.1225829 | 20,844,166 | Ditching Invading DNA Bacteria and archaea protect themselves from invasive foreign nucleic acids through an RNA-mediated adaptive immune system called CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated (Cas). Jinek et al. (p. 816 , published online 28 June; see the Perspective by Brou... | 10.1038/nrmicro3279 | This study characterizes the mechanism of action of Cas9 and reveals a requirement for both the crRNA and tracrRNA (or an sgRNA fusion) for target cleavage. In addition, it presents the first experimental evidence for Cas9-directed genome editing. |
10.1126/science.1247997 | 20,589,274 | Introduction Bacteria and archaea defend themselves against invasive DNA using adaptive immune systems comprising CRISPR (clustered regularly interspaced short palindromic repeats) loci and CRISPR-associated (Cas) genes. In association with Cas proteins, small CRISPR RNAs (crRNAs) guide the detection and cleavage of co... | 10.1038/nrmicro3279 | This paper reports the crystal structures of Cas9 endonucleases and cryo-EM structures that demonstrate major conformational changes in Cas9 following binding of the sgRNA. |
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/nrmicro3279 | This study reports the discovery of the Cascade complex that, together with Cas3, is responsible for CRISPR-based DNA interference in type I systems. |
10.1242/dev.126.19.4257 | 123,021,352 | Previous work has shown that the posteriorising agent retinoic acid can accelerate anterior neuronal differentiation in Xenopus laevis embryos (Papalopulu, N. and Kintner, C. (1996) Development 122, 3409–3418). To elucidate the role of retinoic acid in the primary neurogenesis cascade, we investigated whether retinoic ... | 10.1038/nrn963 | This paper considers the involvement of RA in primary neurogenesis, and how prepattern genes, proneural genes and neural differentiation genes are linked together by a cascade that starts with RA. |
10.1242/dev.124.2.373 | 20,780,555 | The vertebrate central nervous system (CNS) is induced by signals emanating from the dorsal mesoderm, or organizer, that divert the ectoderm away from an epidermal and towards a neural fate. Additional signals from the organizer pattern the neural ectoderm along the anteroposterior axis. We devised highly specific meth... | 10.1038/nrn963 | An analysis of the effects of dominant-negative and constitutively active RARs on the AP patterning of gene expression in the Xenopus CNS. |
10.1242/dev.116.2.357 | 83,558,647 | Exogenous retinoic acid (RA) has teratogenic effects on vertebrate embryos and alters Hox-C gene expression in vivo and in vitro. We wish to examine whether RA has a role in the normal regulation of Hox-C genes, and whether altered Hox-C gene expression in response to RA leads to abnormal morphology. The expression of ... | 10.1038/nrn963 | A thorough analysis of the effect of RA on the induction of ectopic Hox gene expression in mouse embryos, relating it to the concentration, time and position of the gene in the Hox cluster. |
10.1242/dev.128.12.2199 | 41,610,965 | Several recent studies have shown that retinoic acid signalling is required for correct patterning of the hindbrain. However, the data from these studies are disparate and the precise role of retinoic acid signalling in patterning the anteroposterior axis of the neural tube remains uncertain. To help clarify this issue... | 10.1038/nrn963 | This paper shows that the hindbrain responds in a graded way to loss of RA by gradually losing rhombomeres, rather than in an all-or-nothing manner. |
10.1242/dev.128.11.2031 | 20,780,715 | Mutants mice carrying targeted inactivations of both retinoic acid receptor (RAR) α and RARγ (Aα/Aγ mutants) were analyzed at different embryonic stages, in order to establish the timing of appearance of defects that we previously observed during the fetal period. We show that embryonic day (E)9.5 Aα/Aγ embryos display... | 10.1038/nrn963 | Different combinations of RAR knockouts result in different types of hindbrain defect in mouse embryos. |
10.1242/dev.125.21.4133 | 104,430,376 | The aim of these experiments was to determine the endogenous distribution of retinoic acid (RA) across a wide range of embryonic stages in the chick embryo. By high pressure liquid chromatography, it was revealed that didehydroRA is the most prevalent retinoic acid in the chick embryo and that the tissues of the stage ... | 10.1038/nrn963 | A detailed analysis of endogenous retinoids in the chick embryo, showing the anteroposterior boundary of RA at very early stages, as well as data on later stages. |
10.1073/pnas.91.15.7194 | 102,368,473 | The embryonic spinal cord is known to be rich in retinoic acid, and several indirect lines of evidence point to a dorsoventral concentration difference of this compound. Previous measurements of dorsoventral retinoic acid levels, however, showed only minor differences. By a combination of microdissection and bioassay t... | 10.1038/nrn963 | This paper reveals the presence of a RA-synthesizing enzyme (RALDH1) in a specific set of neurons in the adult brain, and shows that these neurons are involved in Parkinson's disease. Could loss of RALDH1 be an aetiological factor in Parkinson's disease? |
10.1073/pnas.0705985105 | 82,904,090 | The capacity to use tools is a fundamental evolutionary achievement. Its essence stands in the capacity to transfer a proximal goal (grasp a tool) to a distal goal (e.g., grasp food). Where and how does this goal transfer occur? Here, we show that, in monkeys trained to use tools, cortical motor neurons, active during ... | 10.1038/nrn2805 | This single-neuron recording study provides crucial evidence that the ventral premotor cortex (area F5) encodes the goal of motor acts. |
10.1093/oso/9780199217984.001.0001 | 149,161,503 | Abstract Emotions and actions are powerfully contagious; when we see someone laugh, cry, show disgust, or experience pain, in some sense, we share that emotion. When we see someone in distress, we share that distress. When we see a great actor, musician or sportsperson perform at the peak of their abilities, it can fee... | 10.1038/nrn2805 | An exhaustive review and discussion of the cognitive functions of the motor system. |
10.1126/science.1166818 | 20,370,860 | Actions performed by others may have different relevance for the observer, and thus lead to different behavioral responses, depending on the regions of space in which they are executed. We found that in rhesus monkeys, the premotor cortex neurons activated by both the execution and the observation of motor acts (mirror... | 10.1038/nrn2805 | This single-neuron recording study shows that mirror-based goal encoding can be modulated by the position in space in which the observed action takes place and by the possibility of interacting with the object that is acted upon. |
10.1523/jneurosci.2040-09.2009 | 103,216,747 | Though other species of primates also use tools, humans appear unique in their capacity to understand the causal relationship between tools and the result of their use. In a comparative fMRI study, we scanned a large cohort of human volunteers and untrained monkeys, as well as two monkeys trained to use tools, while th... | 10.1038/nrn2805 | An elegant fMRI study showing that the observation of tool actions activates the parieto-frontal mirror circuit plus a specific parietal region involved in both tool use and the understanding of tool use. |
10.1073/pnas.0706273104 | 104,137,671 | Experiments in monkeys demonstrated that many parietal and premotor neurons coding a specific motor act (e.g., grasping) show a markedly different activation when this act is part of actions that have different goals (e.g., grasping for eating vs. grasping for placing). Many of these “action-constrained” neurons have m... | 10.1038/nrn2805 | A fundamental study that shows the presence of motor chains in humans and how their impairment may account for the deficit in intention understanding in children with autism. |
10.1162/jocn.2009.21185 | 122,008,945 | Parietal cortex contributes to body representations by integrating visual and somatosensory inputs. Because mirror neurons in ventral premotor and parietal cortices represent visual images of others' actions on the intrinsic motor representation of the self, this matching system may play important roles in recognizing ... | 10.1038/nrn2805 | An elegant study showing the involvement of mirroring in the recognition of the peripersonal space of others. |
10.1073/pnas.0401860101 | 60,480,869 | γ-Aminobutyric acid type A receptors (GABA A Rs) are the major sites of fast synaptic inhibition in the brain. An essential determinant for the efficacy of synaptic inhibition is the regulation of GABA A R cell surface stability. Here, we have examined the regulation of GABA A R endocytic sorting, a critical regulator ... | 10.1038/nrn2370 | This study demonstrated that GABA A Rs are internalized and either rapidly recycled to the cell-surface membrane or targeted for lysosomal degradation. It also demonstrated that this sorting decision can be regulated by a direct interaction of GABA A Rs with HAP1. |
10.1073/pnas.0506653102 | 79,474,128 | The efficacy of synaptic inhibition depends on the number of γ-aminobutyric acid type A receptors (GABA A Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA A R endocytosis and, hence, surface receptor number. Here, we identify a previously unchara... | 10.1038/nrn2370 | This paper identified a novel AP2 binding motif in β 3 GABA A R subunits. Furthermore, phosphorylation of this motif was demonstrated to decrease AP2 binding, showing that phospho-dependent modulation of AP2 binding to GABA A Rs can regulate endocytosis and receptor cell-surface levels. |
10.1073/pnas.0700163104 | 80,642,467 | A form of autosomal dominant juvenile myoclonic epilepsy is caused by a nonconservative missense mutation, A322D, in the GABA A receptor α1 subunit M3 transmembrane helix. We reported previously that the A322D mutation reduced total and surface α1(A322D) subunit protein and that residual α1(A322D) subunit resided in th... | 10.1038/nrn2370 | This paper presented a biochemical mechanism for how a mutation in the GABA A R α 1 subunit might result in a form of human epilepsy. The mutation was demonstrated to lead to subunit misfolding followed by ER-associated degradation, which resulted in reduced GABA A R cell-surface expression. |
10.1073/pnas.1302816110 | 121,969,650 | The trans -translation pathway for protein tagging and ribosome release plays a critical role for viability and virulence in a wide range of pathogens but is not found in animals. To explore the use of trans -translation as a target for antibiotic development, a high-throughput screen and secondary screening assays wer... | 10.1038/nrmicro3438 | This paper describes the identification of trans -translation inhibitors and demonstrates that they have antibacterial activity. |
10.1126/science.1228985 | 61,054,677 | Translation elongation factor P (EF-P) is critical for virulence in bacteria. EF-P is present in all bacteria and orthologous to archaeal and eukaryotic initiation factor 5A, yet the biological function has so far remained enigmatic. Here, we demonstrate that EF-P is an elongation factor that enhances translation of po... | 10.1038/nrmicro3438 | References 29 and 30 demonstrate that ribosomes stall at polyproline sequences in the absence of EF-P. |
10.1046/j.1365-2958.2003.03512.x | 82,621,802 | Summary RelE of Escherichia coli is a global inhibitor of translation that is activated by nutritional stress. Activation of RelE depends on Lon‐mediated degradation of RelB, the antagonist that neutralizes RelE. In vitro , RelE cleaves synthetic mRNAs positioned at the ribosomal A‐site. We show here that in vivo overe... | 10.1038/nrmicro3438 | References 40 and 41show that toxin-mediated mRNA cleavage targets ribosomes to rescue pathways. |
10.1126/science.1217039 | 99,370,723 | Ribosome Rescue Ribosomes stall when they reach the end of defective messenger RNAs (mRNAs). In bacteria, the most-studied ribosomal rescue pathway involves a ribonucleoprotein complex comprising tmRNA (which acts as both transfer RNA and mRNA) and the protein SmpB. In an alternative pathway, some Gram-negative bacteri... | 10.1038/nrmicro3438 | This study shows how the tmRNA–SmpB complex recognizes the absence of an mRNA sequence beyond the decoding centre in a non-stop ribosome. |
10.1073/pnas.1310642110 | 18,854,625 | Significance During protein synthesis, ribosomes catalyze peptide-bond formation between amino acids with differing efficiency. We show that two or more consecutive prolines induce ribosome stalling, and that stalling strength is influenced by the amino acid preceding and following the prolines. In bacteria, the elonga... | 10.1038/nrmicro3438 | In this study, mass spectrometry was used to identify changes in the proteome caused by EF-P, and the stalling propensities of sequences flanking PP motifs were determined. |
10.1073/pnas.0910794107 | 83,442,514 | The biologic underpinnings of posttraumatic stress disorder (PTSD) have not been fully elucidated. Previous work suggests that alterations in the immune system are characteristic of the disorder. Identifying the biologic mechanisms by which such alterations occur could provide fundamental insights into the etiology and... | 10.1038/nrn3339 | This study provided evidence of a biological model of PTSD aetiology in which an externally experienced traumatic event induces downstream alterations in immune function by reducing methylation levels of immune-related genes. |
10.1046/j.1365-2826.1999.00288.x | 29,233,171 | Hippocampal glucocorticoid receptors (GR and MR) play an important role in glucocorticoid negative feedback. Abnormalities in negative feedback are found in depression and in post‐traumatic stress disorder (PTSD), suggesting that GR and MR might be involved in the pathophysiology of these disorders. Enhanced negative f... | 10.1038/nrn3339 | This study demonstrated the construct validity of the SPS animal model of PTSD. |
10.1128/jcm.24.6.1034-1037.1986 | 103,513,506 | A new group of Chlamydia psittaci strains has been identified. They are called TWAR after the laboratory designation of the first two isolates. Twelve strains were isolated from pharyngeal swabs of different persons with acute respiratory disease in Seattle, Wash., during 1983 to 1986. One strain was obtained from the ... | 10.1038/nrmicro796 | Reported the characterization of novel Chlamydia isolates from patients with respiratory infection. This seminal paper formed the basis for the classification of a new species. |
10.1084/jem.148.1.335 | 82,437,340 | Of four groups of chickens, two (groups I and II) were infected with MDV and two were not (groups III and IV). Groups I and III were fed diets low in lipid, and groups II and IV were fed cholesterol-supplemented diets. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and ma... | 10.1038/nrmicro796 | The first report that demonstrates experimentally that an infectious agent can contribute to atherogenesis. |
10.1161/01.atv.13.10.1501 | 81,045,851 | Recent evidence has shown the presence of Chlamydia pneumoniae antigens and nucleic acid in coronary artery atheromas from autopsy patients in South Africa. In this study, the immunocytochemical technique was used to demonstrate C pneumoniae antigens in atheromas of the aorta in autopsy patients from retrospective aort... | 10.1038/nrmicro796 | This report identified C. pneumoniae in foam cells derived from macrophages and smooth-muscle cells in the atherosclerotic lesion. |
10.1128/jcm.33.9.2411-2414.1995 | 123,532,925 | Chlamydia pneumoniae is a common respiratory pathogen. Recent studies have demonstrated the presence of C. pneumoniae in coronary and aortic atherosclerotic lesions. To study the role of C. pneumoniae in atherosclerosis, we investigated the susceptibilities of three different cells of the human vascular wall to infecti... | 10.1038/nrmicro796 | Shows that endothelial cells, macrophages, and smooth-muscle cells are susceptible to infection. |
10.1128/iai.64.11.4872-4875.1996 | 123,513,157 | Chlamydia pneumoniae was able to survive and to multiply in the human monocytic cell line Mono Mac 6. Growth of C. pneumoniae induced production of tumor necrosis factor alpha, interleukin 1beta, and interleukin 6, as well as up-regulation of the CD14 molecule in a time-dependent manner. Infection of monocytic cells an... | 10.1038/nrmicro796 | Describes another mechanism by which Chlamydia pneumoniae could contribute to inflammatory processes of atherosclerosis. |
10.1161/01.cir.98.4.300 | 124,296,746 | Background —Recent evidence has implicated Chlamydia pneumoniae in the aggravation of atherosclerosis. However, the mechanisms by which this agent affects atherogenesis remain poorly understood. Chlamydiae produce large amounts of heat shock protein 60 (HSP 60) during chronic, persistent infections, and C pneumoniae lo... | 10.1038/nrmicro796 | Showed the presence of a C. pneumoniae antigen associated with a delayed type-hypersensitivity response in the atherosclerotic lesion and that C. pneumoniae could induce an enzyme that leads to plaque destabilization. |
10.1161/01.res.0000059982.43865.75 | 82,143,562 | Recent studies have suggested that infection with Chlamydia pneumoniae (C pneumoniae) may contribute to the instability of atherosclerotic plaques and thrombosis and is associated with acute coronary events. Tissue factor (TF), a potent prothrombotic molecule, is expressed by macrophages and other cell types within ath... | 10.1038/nrmicro796 | Showed that induction of tissue factor, a pro-thrombotic molecule, was by activation of the transcription factor EGR-1, which is pro-atherogenic. |
10.1161/01.cir.97.7.633 | 18,400,205 | Background — Chlamydia pneumoniae infection has been associated with atherosclerosis by serological studies and detection of bacterial antigen within plaque. We sought to evaluate a possible causal role in an animal model. Methods and Results —Thirty New Zealand White rabbits were given three separate intranasal inocul... | 10.1038/nrmicro796 | This report shows that C. pneumoniae infection accelerated atherosclerosis in a rabbit model and that the acceleration could be prevented by treatment with an anti-chlamydial antibiotic. |
10.1128/aac.46.8.2321-2326.2002 | 121,976,687 | ABSTRACT Chlamydia pneumoniae may play a role in atherogenesis and vascular diseases, and antibiotics may prove useful in these conditions. Three groups of New Zealand White rabbits (24 per group) were infected via the nasopharynx with C. pneumoniae on three separate occasions (2 weeks apart). Group I was untreated and... | 10.1038/nrmicro796 | This report shows that early administration of antibiotics post-infection is crucial in preventing acceleration of atherosclerosis by C. pneumoniae |
10.1128/iai.70.9.5332-5334.2002 | 101,106,818 | ABSTRACT Chlamydia pneumoniae has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. This study showed that C. pneumoniae did not accelerate lesion development in mice if a high-fat/high-cholesterol diet was started after infection, indicating that C. pneumoniae is a co-risk factor w... | 10.1038/nrmicro796 | Demonstrated that C. pneumoniae and hyperlipidaemia are co-risk factors for atherosclerosis. |
10.1128/mr.58.4.686-699.1994 | 20,598,613 | Chlamydiae are medically important bacteria responsible for a wide range of human infections and diseases. Repeated episodes of infection promote chronic inflammation associated with detrimental immune system-mediated pathologic changes. However, the true nature of chlamydial pathogenesis may encompass repeated infecti... | 10.1038/nrmicro796 | An excellent review on the microbiology of chlamydiae, emphasizing the establishment of persistent infection. |
10.1085/jgp.200409029 | 17,613,168 | Receptor-mediated modulation of KCNQ channels regulates neuronal excitability. This study concerns the kinetics and mechanism of M1 muscarinic receptor–mediated regulation of the cloned neuronal M channel, KCNQ2/KCNQ3 (Kv7.2/Kv7.3). Receptors, channels, various mutated G-protein subunits, and an optical probe for phosp... | 10.1038/nrn1785 | Provides a comprehensive kinetic description of the sequence of events that occur between muscarinic receptor activation and M-channel closure by PtdIns(4,5)P 2 depletion, based on the University of Connecticut 'Virtual Cell' model (see also reference 51). |
10.1085/jgp.200208783 | 122,736,787 | To quantify the modulation of KCNQ2/3 current by [Ca2+]i and to test if calmodulin (CaM) mediates this action, simultaneous whole-cell recording and Ca2+ imaging was performed on CHO cells expressing KCNQ2/3 channels, either alone, or together with wild-type (wt) CaM, or dominant-negative (DN) CaM. We varied [Ca2+]i fr... | 10.1038/nrn1785 | The authors show that calmodulin binds to KCNQ2/3 channels through C-terminal tail binding sites (see also references 60 and 61). Using an ionomycin Ca 2+ -loading method, they confirm the results reported in reference 58 and further show the calmodulin-dependence of Ca 2+ -mediated inhibition. They also provide eviden... |
10.1038/ismej.2007.63 | 47,099,495 | Abstract Planctomycetes are widely distributed in marine environments, where they supposedly play a role in carbon recycling. To deepen our understanding about the ecology of this sparsely studied phylum six planctomycete fosmids from two marine upwelling systems were investigated and compared with all available planct... | 10.1038/nrmicro2578 | Important comparative genomic analysis of all the available planctomycete genome data, revealing the absence of C 1 transfer genes in anammox organisms. |
10.1073/pnas.0502088102 | 41,543,134 | In many oceanic regions, growth of phytoplankton is nitrogen-limited because fixation of N 2 cannot make up for the removal of fixed inorganic nitrogen (NH + 4 , NO - 2 , and NO - 3 ) by anaerobic microbial processes. Globally, 30-50% of the total nitrogen loss occurs in oxygen-minimum zones (OMZs) and is commonly attr... | 10.1038/nrmicro2578 | First evidence of the global relevance of anammox planctomycetes for the nitrogen cycle. |
10.1073/pnas.1431443100 | 104,175,229 | Pirellula sp. strain 1 (“ Rhodopirellula baltica ”) is a marine representative of the globally distributed and environmentally important bacterial order Planctomycetales . Here we report the complete genome sequence of a member of this independent phylum. With 7.145 megabases, Pirellula sp. strain 1 has the largest cir... | 10.1038/nrmicro2578 | Only published detailed account of the significant annotated features of a complete planctomycete genome. |
10.1186/1471-2180-9-5 | 123,344,470 | Abstract Background The phylum Verrucomicrobia is a divergent phylum within domain Bacteria including members of the microbial communities of soil and fresh and marine waters; recently extremely acidophilic members from hot springs have been found to oxidize methane. At least one genus, Prosthecobacter , includes speci... | 10.1038/nrmicro2578 | Demonstration that the planctomycete shared cell plan is also found in another bacterial phylum, the Verrucomicrobia. |
10.1099/00221287-143-3-739 | 15,322,858 | A distinct type of cellular organization was found in two species of the planctomycete genus Pirellula, Pirellula marina and Pirellula staleyi . Both species possess two distinct regions within the cell which are separated by a single membrane. The major region of the cell, the pirellulosome, contains the fibrillar con... | 10.1038/nrmicro2578 | First recognition of a major intracellular membrane-bound compartment that is now known to be present in all planctomycetes. |
10.1111/j.1365-2958.2010.07242.x | 4,801,113 | Summary Anaerobic ammonium‐oxidizing (anammox) bacteria are divided into three compartments by bilayer membranes (from out‐ to inside): paryphoplasm, riboplasm and anammoxosome. It is proposed that the anammox reaction is performed by proteins located in the anammoxosome and on its membrane giving rise to a proton‐moti... | 10.1038/nrmicro2578 | Evidence that ATP synthase is found in membranes of the anammox planctomycete anammoxosome, consistent with a model for anammox biochemistry involving PMF generation. |
10.1073/pnas.1001085107 | 39,171,398 | Endocytosis is a process by which extracellular material such as macromolecules can be incorporated into cells via a membrane-trafficking system. Although universal among eukaryotes, endocytosis has not been identified in Bacteria or Archaea. However, intracellular membranes are known to compartmentalize cells of bacte... | 10.1038/nrmicro2578 | First description of macromolecule uptake in bacteria that is similar to receptor-mediated eukaryotic endocytosis. |
10.1083/jcb.201010129 | 45,482,838 | Although the nonrandom nature of interphase chromosome arrangement is widely accepted, how nuclear organization relates to genomic function remains unclear. Nuclear subcompartments may play a role by offering rich microenvironments that regulate chromatin state and ensure optimal transcriptional efficiency. Technologic... | 10.1038/nsmb.2474 | This comprehensive overview of basic principles of genome organization includes a discussion of the concept of self-organized genome architecture |
10.1101/gad.559610 | 39,605,377 | To understand whether the spatial organization of the genome reflects the cell's differentiated state, we examined whether genes assume specific subnuclear positions during Caenorhabditis elegans development. Monitoring the radial position of developmentally controlled promoters in embryos and larval tissues, we found ... | 10.1038/nsmb.2474 | This study reveals a developmental stage–specific and cell differentiation–specific regulation of gene positioning in the 3D space of the nucleus in C. elegans , opening the way to genetic dissection of developmental determinants of nuclear organization and function |
10.1111/j.1460-9568.1993.tb00507.x | 107,091,224 | Abstract The axonal and dendritic domains of neurons with extensive, locally arborizing axons were delineated in the dentate gyrus of the rat hippocampus. In horizontally cut slice preparations neurons were briefly recorded and subsequently filled with biocytin when one or several of the following physiological propert... | 10.1038/nrn.2016.87 | References 14 and 15 proposed an organization of the dentate gyrus interneurons according to the location of the cell body and terminal field of the axon. |
10.1126/science.2879352 | 81,582,882 | The occurrence of seizure activity in human temporal lobe epilepsy or status epilepticus is often associated with a characteristic pattern of cell loss in the hippocampus. An experimental model that replicates this pattern of damage in normal animals by electrical stimulation of the afferent pathway to the hippocampus ... | 10.1038/nrn.2016.87 | This paper showed that mossy cells were vulnerable to seizures but that many GABAergic neurons were not, which was surprising because a loss of GABAergic neurons was considered to be a cause of epilepsy. |
10.1002/cne.901820508 | 40,249,495 | Abstract The morphology of neurons in the “hilar region” of the hippocampus (fields CA 3c and CA 4 of Lorente de Nó, '34) was analyzed with several variants of the Golgi technique. Hippocampi were dissected from the brains of 28‐day‐old rats, fixed and impregnated by immersion, and sectioned perpendicular to the long a... | 10.1038/nrn.2016.87 | This paper provided the first detailed description of hilar cells and mossy cells. |
10.1002/hipo.450040108 | 40,860,893 | Abstract The mossy cells represent a prominent cell type of the hilar region. Whereas the morphology of these neurons, their synaptic connections, and physiological characteristics have been described in some detail, information about their neurotransmitter is still lacking. Using immunocytochemistry in combination wit... | 10.1038/nrn.2016.87 | This paper provided the first evidence that mossy cells were glutamatergic. |
10.1152/jn.1995.74.1.179 | 80,344,793 | 1. The hypothesis that dentate hilar "mossy" cells are excitatory was tested by simultaneous intracellular recording in rat hippocampal slices. Mossy cells were recorded simultaneously with their potential targets, granule cells and interneurons. The gamma-amino-butyric acid-A (GABAA) receptor antagonist bicuculline wa... | 10.1038/nrn.2016.87 | This paper showed that mossy cells directly excite granule cells and dentate gyrus interneurons. |
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