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10.1093/genetics/144.4.1559
41,542,071
A molecular mapping experiment shows that a major gene effect on a quantitative trait, the level of alcohol dehydrogenase expression in Drosophila melanogaster, is due to multiple polymorphisms within the Adh gene. These polymorphisms are located in an intron, the coding sequence, and the 3′ untranslated region. Becaus...
10.1038/35047544
A summary of several experiments combining in vitro mutagenesis with P element transformation to determine the causal relationship between naturally occurring DNA sequence variation and quantitative variation in enzyme activity and protein stability. Evidence for multiple, interacting polymorphic sites within a single ...
10.1093/genetics/142.1.285
125,298,667
The problem of detecting minor quantitative trait loci (QTL) responsible for genetic variation not explained by major QTL is of importance in the complete dissection of quantitative characters. Two extensions of the permutation-based method for estimating empirical threshold values are presented. These methods, the con...
10.1038/35047544
References 80 and 81 elaborate the use of permutation testing to set the appropriate threshold above which to declare significant QTL, given multiple tests and correlated markers.
10.1073/pnas.230304397
16,745,750
High-resolution mapping of quantitative trait loci (QTL) in animals has proved to be difficult because the large effect sizes detected in crosses between inbred strains are often caused by numerous linked QTLs, each of small effect. In a study of fearfulness in mice, we have shown it is possible to fine map small-effec...
10.1038/35076585
References 36 and 37 introduced QTL mapping in outbred animals to mouse genetics.
10.1126/science.289.5476.85
41,663,901
Domestication of many plants has correlated with dramatic increases in fruit size. In tomato, one quantitative trait locus (QTL), fw2.2 , was responsible for a large step in this process. When transformed into large-fruited cultivars, a cosmid derived from the fw2.2 region of a small-fruited wild species reduced fruit ...
10.1038/35076585
The first QTL to be cloned by positional information and complementation.
10.4049/jimmunol.166.9.5331
29,004,015
Abstract CD28 provides an important costimulatory signal in T cell activation that regulates multiple cellular processes including proliferation and survival. Several signal transduction pathways are activated by CD28; however, the precise biochemical mechanism by which CD28 regulates T cell function remains controvers...
10.1038/35105024
Experiments performed using CD28-deficient T cells reconstituted by retroviral transduction with mutants of CD28 indicate that phosphorylation of Y170 might promote upregulation of Bcl-x L , whereas the C-terminal P-rich region might control IL–2 production and proliferation.
10.1084/jem.192.2.303
81,090,187
This report shows that cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) plays a key role in T cell–mediated dominant immunologic self-tolerance. In vivo blockade of CTLA-4 for a limited period in normal mice leads to spontaneous development of chronic organ-specific autoimmune diseases, which are immunopathological...
10.1038/35105024
Crosslinking of CTLA-4 is shown to be required for the suppression by CD25 + /CD4 + T cells of the proliferation of CD25 − /CD4 + T cells in vitro
10.1084/jem.192.2.295
61,519,251
It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25+CD45R...
10.1038/35105024
Blockade of CTLA-4 in vivo prevents the suppressor activity of CD25 + /CD4 + T cells, the transfer of which normally inhibits induction of inflammatory bowel disease in Rag-deficient mice injected with CD25 − /CD4 + T cells, indicating that CTLA-4 is required for the regulatory activity of CD25 + /CD4 + T cells.
10.4049/jimmunol.163.3.1128
139,042,661
Abstract Mice deficient for the expression of CTLA-4 develop a lethal lymphoproliferative syndrome and multiorgan inflammation leading to death at about 4 wk of age. Here we show that RAG2-deficient mice reconstituted with CTLA-4-deficient bone marrow do not develop a lymphoproliferative syndrome despite lymphocyte inf...
10.1038/35105024
CTLA-4-expressing cells prevent disease mediated by CTLA-4-deficient cells after adoptive transfer of bone marrow cells into lymphocyte-deficient recipients.
10.1242/dev.118.3.691
62,561,177
The proposed pathways of chick cranial neural crest migration and their relationship to the rhombomeres of the hindbrain have been somewhat controversial, with differing results emerging from grafting and DiI-labelling analyses. To resolve this discrepancy, we have examined cranial neural crest migratory pathways using...
10.1038/35039056
Important fate mapping data, which revealed that odd-numbered rhombomeres generate neural crest and that crest cells from these segments migrate in unusual routes generating contributions to several arches.
10.1242/dev.122.10.3229
83,558,828
To investigate the influence of hindbrain segmentation on craniofacial patterning we have studied the long term fate of neural crest (NC) subpopulations of individual rhombomeres (r), using quail-chick chimeras. Mapping of all skeletal and muscle connective tissues developing from these small regions revealed several n...
10.1038/35039056
Key fate-mapping data in avian embryos that shows the detailed register between neural crest and its contributions to branchial arch derivatives.
10.1242/dev.121.9.2707
41,476,638
In this study we have analysed the expression of Hoxb-4, Hoxb-1, Hoxa-3, Hoxb-3, Hoxa-4 and Hoxd-4 in the neural tube of chick and quail embryos after rhombomere (r) heterotopic transplantations within the rhombencephalic area. Grafting experiments were carried out at the 5-somite stage, i.e. before rhombomere boundari...
10.1038/35039056
Important evidence that hindbrain rhombomeres show plasticity in Hox gene expression when grafted to new locations. Suggested that genetic programs of anterior–posterior patterning were not autonomous as previously thought.
10.1242/dev.122.3.895
82,857,085
We have investigated the pattern and regulation of Hoxa3 expression in the hindbrain and associated neural crest cells in the chick embryo, using whole mount in situ hybridization in conjunction with DiI labeling of neural crest cells and microsurgical manipulations. Hoxa3 is expressed in the neural plate and later in ...
10.1038/35039056
Chick rotations experiments that revealed differential autonomy and plasticity of cranial neural crest depending on the rhombomere of origin. Showed that the dynamics of crest patterning are not uniform but vary with environmental influence.
10.1242/dev.127.13.2843
62,348,533
Previous analyses of single neural crest cell trajectories have suggested important roles for interactions between neural crest cells and the environment, and amongst neural crest cells. To test the relative contribution of intrinsic versus extrinsic information in guiding cells to their appropriate sites, we ablated s...
10.1038/35039056
An important study revealing the dynamic movements of cranial neural crest cells in ovo . It further confirmed the extensive cell interactions and connections between dispersed and migratory neural crest cells, and showed the importance of environmental signalling in neural crest migration.
10.1242/dev.125.17.3445
62,560,955
In addition to pigment cells, and neural and endocrine derivatives, the neural crest is characterized by its ability to yield mesenchymal cells. In amniotes, this property is restricted to the cephalic region from the mid-diencephalon to the end of rhombomere 8 (level of somites 4/5). The cephalic neural crest is divid...
10.1038/35039056
Critical paper revealing autonomy of the genetic programme of Hoxa2 . Clearly linked correct patterns of Hoxa2 expression with the morphogenesis of jaw structures. It raised a number of issues with respect to the ground state of cranial neural crest.
10.1242/dev.126.7.1483
104,228,780
Hoxa2 is expressed in cranial neural crest cells that migrate into the second branchial arch and is essential for proper patterning of neural-crest-derived structures in this region. We have used transgenic analysis to begin to address the regulatory mechanisms which underlie neural-crest-specific expression of Hoxa2. ...
10.1038/35039056
Key molecular evidence that the neural crest and hindbrain patterns of Hoxa2 gene expression are independently regulated. Argues against a pre-patterning model.
10.1126/science.8303277
83,045,050
The success of Mycobacterium species as pathogens depends on their ability to maintain an infection inside the phagocytic vacuole of the macrophage. Although the bacteria are reported to modulate maturation of their intracellular vacuoles, the nature of such modifications is unknown. In this study, vacuoles formed arou...
10.1038/35085034
This paper marked the transition from descriptive to experimental, biochemical analysis of the Mycobacterium -containing vacuole and provided an initial explanation as to why these vacuoles failed to acidify.
10.1084/jem.184.4.1349
61,378,903
Previous studies have demonstrated that the Mycobacterium tuberculosis phagosome in human monocyte-derived macrophages acquires markers of early and late endosomes, but direct evidence of interaction of the M. tuberculosis phagosome with the endosomal compartment has been lacking. Using the cryosection immunogold techn...
10.1038/35085034
This paper, together with reference 13 , showed that the Mycobacterium -containing vacuole was arrested within the transferrin recycling pathway of the host macrophage.
10.1084/jem.191.2.287
41,410,557
Complement receptor (CR)-mediated phagocytosis of Mycobacterium tuberculosis by macrophages results in intracellular survival, suggesting that M. tuberculosis interferes with macrophage microbicidal mechanisms. As increases in cytosolic Ca2+ concentration ([Ca2+]c) promote phagocyte antimicrobial responses, we hypothes...
10.1038/35085034
An extremely interesting experimental study linking calmodulin and calcium to the transition of the Mycobacterium -containing vacuole from an early endosomal to a lysosomal environment.
10.1073/pnas.110126897
20,782,678
γ-Secretase is a membrane-associated protease that cleaves within the transmembrane region of amyloid precursor protein to generate the C termini of the two Aβ peptide isoforms, Aβ40 and Aβ42. Here we report the detergent solubilization and partial characterization of γ-secretase. The activity of solubilized γ-secretas...
10.1038/35043065
Identification of nicastrin, a component of the presenilin complex that modulates γ-secretase activity
10.1113/jphysiol.1973.sp010366
82,694,058
1. Group Ia e.p.s.p.s were recorded from lumbosacral motoneurones in anaesthetized cats after almost complete section of the appropriate dorsal roots. The cable parameters of these same motoneurones were obtained from the voltage response to a brief intracellular current pulse, as described in Iansek & Redman (1973...
10.1038/35044552
Provides one of the first and most convincing demonstrations that the location dependence of synaptic amplitude can be reduced by increasing distal synaptic conductance. They have also used sophisticated analysis techniques to reach the same conclusions on the Schaffer collaterals (reference 11
10.1152/jn.1993.70.3.1249
102,031,342
1. The quantal nature of inhibitory synaptic noise recorded intracellularly from the lateral dendrite of the goldfish Mauthner cell was studied, using new detection and measurement procedures that eliminate operator intervention. In addition, we employed an analytical algorithm, not previously applied to this problem, ...
10.1038/35044552
Shows that the amplitude distal synaptic currents on goldfish Mauthner neurons are increased by the release of more than one single quantum of transmitter. The authors discuss evidence for an increased number of synaptic boutons with multiple release sites as the underlying mechanism for the normalization of the amplit...
10.1126/science.281.5384.1851
104,326,572
Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)–linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1...
10.1038/35097565
By using mouse genetics to increase or eliminate wild-type SOD1 (and its superoxide dismutase activity) in the presence of a familial, ALS-linked SOD1 mutant that itself had little enzymatic activity, these authors showed that toxicity was independent of SOD1 activity. In addition, they found aggregates containing SOD1...
10.1126/science.8209258
20,800,332
Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93—a change that has little effect on enzyme activity—caused motor neuron di...
10.1038/35097565
Represents the first report of a mouse model of familial ALS arising from expression of a transgene encoding a familial-ALS-linked SOD1 mutant. Disease arose in this model despite a very significant elevation of overall SOD1 activity, providing the first evidence that the disease cannot be caused by a diminution of SOD...
10.1126/science.288.5464.335
38,370,814
Mutations in the copper/zinc superoxide dismutase (SOD1) gene produce an animal model of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a subst...
10.1038/35097565
By implantation of a pump to slowly release a broad-spectrum caspase inhibitor, this report showed that chronic caspase inhibition can significantly extend the lifespan of mice that develop disease from expression of a familial-ALS-linked SOD1 mutant. This not only confirmed that a cascade of caspase activation was a f...
10.1002/ana.410380114
124,877,025
Abstract The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is unknown, but defects in synaptosomal high‐affinity glutamate transport have been observed. In experimental models, chronic loss of glutamate transport can produce a loss of motor neurons and, therefore, could contribute to the disease. With th...
10.1038/35097565
Represents the first in a series of reports linking a diminution in glutamate transport (itself arising from loss of the glutamate transporter EAAT2, originally named GLT-1) to sporadic ALS.
10.1177/096368970000900205
84,402,434
Neural transplantation is developing into a therapeutic alternative in Parkinson's disease. A major limiting factor is that only 3–20% of grafted dopamine neurons survive the procedure. Recent advances regarding how and when the neurons die indicate that events preceding actual tissue implantation and during the first ...
10.1038/35104055
Only about 3–20% of grafted dopaminergic cells survive beyond the first week after transplantation. The authors examine the mechanisms that might trigger cell death, and how the survival of dopaminergic neurons could be improved.
10.1073/pnas.86.18.7248
79,648,800
Retinae were transplanted from embryonic rats to a location over the midbrain of unilaterally anucleated newborn rats. At maturity, the rats were trained to "lever-press" for a food reward. By using a Pavlovian conditioned suppression paradigm, it was found that light delivered to the transplant could be recognized by ...
10.1038/35104055
This paper describes a seminal experiment, showing that the graft can process primary information, and not only have a modulatory or trophic effect. More importantly, it also showed that specific training of the grafted animals improves their performance.
10.1111/j.1460-9568.1992.tb00858.x
29,264,658
Abstract Peformance in a prelearned choice reaction time task was studied 6 months after surgery in rats with ibotenate‐induced lesions of the striatum either with or without striatal grafts, and in sham‐operated controls. The long postoperative interval allowed full transplant maturation and the establishment of appro...
10.1038/35104055
The origin of the expression 'learning to use the graft'. The authors proposed that for functional recovery to occur, explicit retraining might be required to re-establish previously learned behaviours.
10.1073/pnas.96.18.10524
86,157,203
Striatal lesions disrupt both motor and cognitive performance in rats, many aspects of which can be restored by striatal transplants. Because the normal striatum is involved in the formation and maintenance of motor habits, it has been hypothesized that grafted animals may require explicit retraining to relearn previou...
10.1038/35104055
A demonstration of the specificity of the 'learning to use the graft' effect in rats with striatal lesions and grafts. Recovery is dependent on relearning specific stimulus–response associations within the grafted hemisphere.
10.1083/jcb.135.6.1457
123,172,732
Ran is a nuclear Ras-like GTPase that is required for the bidirectional transport of proteins and ribnucleoproteins across the nuclear pore complex (NPC). A key regulator of the Ran GTP/GDP cycle is the 70-kD Ran-GTPase-activating protein RanGAP1. Here, we report the identification and localization of a novel form of R...
10.1038/35056591
RanGAP1 is identified as the first substrate for SUMO and the role of sumoylation in regulating the localization of RanGAP1 is shown.
10.1083/jcb.147.5.981
82,331,640
SUMO is a ubiquitin-related protein that functions as a posttranslational modification on other proteins. SUMO conjugation is essential for viability in Saccharomyces cerevisiae and is required for entry into mitosis. We have found that SUMO is attached to the septins Cdc3, Cdc11, and Shs1/Sep7 specifically during mito...
10.1038/35056591
This comprehensive study identifies septins as the major substrates for SUMO in yeast and suggests a role of septin sumoylation in cytokinesis.
10.1091/mbc.6.7.793
28,271,163
The MIF2 gene of Saccharomyces cerevisiae has been implicated in mitosis. Here we provide genetic evidence that MIF2 encodes a centromere protein. Specifically, we found that mutations in MIF2 stabilize dicentric minichromosomes and confer high instability (i.e., a synthetic acentric phenotype) to chromosomes that bear...
10.1038/35056591
This work initially identifies the yeast SMT3 gene among other genes as a suppressor of MIF2 mutations, suggesting a role of SUMO for the maintenance of genomic integrity.
10.1093/genetics/119.4.933
45,288,850
Abstract The murine dilute suppressor gene, dsu, was identified because of its ability to suppress the dilute coat color of mice homozygous for the retrovirally induced allele (dv) of the dilute locus (d). dsu is unlinked to the d locus and has recently been shown to be semidominantly inherited. The dilute phenotype of...
10.1038/35056009
References 29 and 30 discuss the characterization of one of the few known suppressor mutations in mice.
10.1126/science.8202715
123,105,888
In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM1 and peripherin/ RDS , in which only double heterozygotes develop retinitis...
10.1038/35056009
This is a classic example of digenic inheritance — when alleles of two genes are needed for the trait to appear.
10.1083/jcb.143.7.2009
81,901,563
Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance of a blastocoel cavity. Throughout development, they increase in size and number and are especially abundant in epidermis and heart muscle. Desmosomes mediate cell–cell adhesion through desmos...
10.1038/35043032
This paper, describing the phenotype in desmoplakin-null mice, is notable owing to the extremely early stage at which the embryos show defects, and shows that desmoplakin is required both for the assembly of desmosomes and integrity of the early embryonic endoderm.
10.1083/jcb.116.5.1197
18,755,330
Specific interactions between desmoplakins I and II (DP I and II) and other desmosomal or cytoskeletal molecules have been difficult to determine in part because of the complexity and insolubility of the desmosome and its constituents. We have used a molecular genetic approach to investigate the role that DP I and II m...
10.1038/35043032
This was the first paper to show that the carboxyl terminus of a plakin family member, desmoplakin, associates with intermediate filaments. Subsequently, this domain of bullous pemphigoid antigen and plectin were also shown to interact with intermediate filaments.
10.1083/jcb.127.4.1049
102,486,939
In epidermal cells, keratin intermediate filaments connect with desmosomes to form extensive cadherin-mediated cytoskeletal architectures. Desmoplakin (DPI), a desmosomal component lacking a transmembrane domain, has been implicated in this interaction, although most studies have been conducted with cells that contain ...
10.1038/35043032
This paper showed that the desmoplakin carboxyl terminus interacts directly with intermediate filament polypeptides, specifically type II epidermal keratins.
10.1083/jcb.134.4.985
122,362,479
The desmosomal plaque protein desmoplakin (DP), located at the juncture between the intermediate filament (IF) network and the cytoplasmic tails of the transmembrane desmosomal cadherins, has been proposed to link IF to the desmosomal plaque. Consistent with this hypothesis, previous studies of individual DP domains in...
10.1038/35043032
This paper used a dominant-negative approach to show for the first time that desmoplakin is required for anchoring intermediate filaments to the desmosomal plaque and that it may be involved in segregating adherens junctions and desmosomes.
10.1083/jcb.105.1.57
38,595,215
Extracts of metabolically labeled cultured epithelial cells have been analyzed by immunoprecipitation followed by SDS-PAGE, using antisera to the major high molecular mass proteins and glycoproteins (greater than 100 kD) from desmosomes of bovine muzzle epidermis. For nonstratifying cells (Madin-Darby canine kidney [MD...
10.1038/35043032
References 64 and 65 were the first of a series of important papers from these two groups that analysed the biosynthesis and processing of desmosomal components.
10.1083/jcb.136.4.919
100,813,366
Squamous epithelial cells have both adherens junctions and desmosomes. The ability of these cells to organize the desmosomal proteins into a functional structure depends upon their ability first to organize an adherens junction. Since the adherens junction and the desmosome are separate structures with different molecu...
10.1038/35043032
This paper provides some of the first evidence that desmosome assembly is dependent on adherens junctions because of the common junction component, plakoglobin, and its required association with E-cadherin.
10.1083/jcb.138.1.193
82,874,425
Human fibrosarcoma cells, HT-1080, feature extensive adherens junctions, lack mature desmosomes, and express a single known desmosomal protein, Desmoglein 2 (Dsg2). Transfection of these cells with bovine Desmocollin 1a (Dsc1a) caused dramatic changes in the subcellular distribution of endogenous Dsg2. Both cadherins c...
10.1038/35043032
The first paper to provide direct evidence for an interaction between desmoglein and desmocollin extracellular domains, consistent with the idea that heterophilic cadherin interactions may be involved in desmosomal adhesion.
10.1242/dev.127.11.2283
20,779,936
MacroH2As are core histone proteins with a hybrid structure consisting of a domain that closely resembles a full-length histone H2A followed by a large nonhistone domain. We recently showed that one of the macroH2A subtypes, macroH2A1.2, is concentrated in the inactive X chromosome in adult female mammals. Here we exam...
10.1038/35047580
This paper describes the unexpectedly early association of macroH2A with the X chromosome during imprinted X inactivation, which contrasts with its much later association during random X inactivation.
10.1126/science.290.5496.1578
123,508,892
To study whether cloning resets the epigenetic differences between the two X chromosomes of a somatic female nucleus, we monitored X inactivation in cloned mouse embryos. Both X chromosomes were active during cleavage of cloned embryos, followed by random X inactivation in the embryo proper. In the trophectoderm (TE), ...
10.1038/35047580
The first use of somatic nuclear transfer to explore facets of the biology of X inactivation.
10.1242/dev.113.supplement_1.55
62,102,606
Since Robert Hooke observed the froth-like texture of sectioned plant tissue, there have been numerous attempts to describe the geometrical properties of cells and to account for the patterns they form. Some aspects of biological patterning can be mimicked by compressed spheres and by liquid foams, implying that compre...
10.1038/35048050
An interesting review summarizing a series of studies published by Clive Lloyd and his colleages during the period 1988–1991, leading to a new model for how cell shape and mechanical forces influence the choice of division plane.
10.1242/jcs.97.3.527
38,195,817
Time-lapse video microscopy of dividing Tradescantia stamen hair cells that are undergoing cytokinesis has revealed that the maturation of the new cell wall is aided by factors at the site where the preprophase band of microtubules forms before mitosis. The wall changes from being fluid and wrinkled before it is insert...
10.1038/35048050
A classic study showing that when new cell walls are forced to attach somewhere other than the former PPB site, they fail to mature normally. This leads to the proposal that the PPB directs the deposition of cell wall maturation factors at the division site during prophase, which are transferred to the new wall if it a...
10.1242/jcs.103.4.977
41,626,757
We have visualised F-actin and microtubules in living Tradescantia virginiana stamen hair cells by confocal laser scanning microscopy after microinjecting rhodamine-phalloidin or carboxyfluorescein-labelled brain tubulin. We monitored these components of the cytoskeleton as the cells prepared for division at preprophas...
10.1038/35048050
The first description of an actin-depleted zone in the cell cortex of dividing plant cells that marks the former PPB site throughout mitosis and cytokinesis.
10.1083/jcb.152.1.231
84,500,706
Spatial control of cytokinesis in plant cells depends on guidance of the cytokinetic apparatus, the phragmoplast, to a cortical “division site” established before mitosis. Previously, we showed that the Tangled1 (Tan1) gene of maize is required for this process during maize leaf development (Cleary, A.L., and L.G. Smit...
10.1038/35048050
Molecular analysis of the Tangled1 gene and protein suggesting that TAN1 protein participates in the orientation of cytoskeletal structures in dividing cells through an association with microtubules
10.1242/dev.126.20.4623
104,328,462
In plant cells, cytokinesis depends on a cytoskeletal structure called a phragmoplast, which directs the formation of a new cell wall between daughter nuclei after mitosis. The orientation of cell division depends on guidance of the phragmoplast during cytokinesis to a cortical site marked throughout prophase by anothe...
10.1038/35048050
Analysis of two mutants that disrupt the spatial regulation of asymmetric divisions in the maize leaf epidermis by interfering with phragmoplast guidance.
10.1126/science.286.5442.1141
79,455,195
The Caenorhabditis elegans heterochronic genes control the relative timing and sequence of many events during postembryonic development, including the terminal differentiation of the lateral hypodermis, which occurs during the final (fourth) molt. Inactivation of the heterochronic gene lin-42 causes hypodermal terminal...
10.1038/35088566
Demonstration that lin-42 encodes a PAS-domain protein most similar to that of Drosophila Per, thereby providing a molecular link between the circadian and developmental timing pathways. Also, lin-42 mRNA levels are shown to oscillate relative to the molting cycles of post-embryonic development.
10.1073/pnas.74.12.5463
125,332,567
A new method for determining nucleotide sequences in DNA is described. It is similar to the “plus and minus” method [Sanger, F. & Coulson, A. R. (1975) J. Mol. Biol. 94, 441-448] but makes use of the 2′,3′-dideoxy and arabinonucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific cha...
10.1038/35084503
Reports the Nobel prize-winning method developed by Fred Sanger and colleagues for sequencing DNA — called dideoxy chain termination sequencing. Roughly 25 years later, this continues to be the state-of-the-art technique for large-scale DNA sequencing.
10.1101/gr.8.3.195
62,624,571
Sequencing of large clones or small genomes is generally done by the shotgun approach (Anderson et al. 1982). This has two phases: (1) a shotgun phase in which a number of reads are generated from random subclones and assembled into contigs, followed by (2) a directed, or finishing phase in which the assembly is inspec...
10.1038/35084503
The most commonly used suite of computer programs for carrying out base calling, sequence assembly and viewing of sequence assemblies are Phred (references 16 and 17 ), Phrap and Consed (reference 18 ), respectively. Reference 20 describes an important extension of Consed (a program called Autofinish) that automates so...
10.1126/science.282.5396.2012
83,343,642
The 97-megabase genomic sequence of the nematode Caenorhabditis elegans reveals over 19,000 genes. More than 40 percent of the predicted protein products find significant matches in other organisms. There is a variety of repeated sequences, both local and dispersed. The distinctive distribution of some repeats and high...
10.1038/35084503
Reports the genome sequence of the first multicellular organism, the nematode worm Caenorhabditis elegans , by the sequencing groups at Washington University and the Sanger Centre.
10.1101/gr.7.11.1072
41,438,494
As part of the Human Genome Project, the Washington University Genome Sequencing Center has commenced systematic sequencing of human chromsome 7. To organize and supply the effort, we have undertaken the construction of sequence-ready physical maps for defined chromosomal intervals. Map construction is a serial process...
10.1038/35084503
Approach for constructing sequence-ready BAC contig maps by restriction enzyme digest-based fingerprint analysis. This general method, which essentially represents an extension of earlier mapping techniques (for example, see references 57–59 ), has been used to generate BAC contig maps of the human, mouse, Arabidopsis ...
10.1073/pnas.83.20.7821
41,083,148
A technique for digital characterization and comparison of DNA fragments, using restriction enzymes, is described. The technique is being applied to fragments from the nematode Caenorhabditis elegans ( i ) to facilitate cross-indexing of clones emanating from different laboratories and ( ii ) to construct a physical ma...
10.1038/35084503
References 57–59 represent classic descriptions of restriction enzyme digest-based fingerprint analysis, as used to construct physical maps of the Saccharomyces cerevisiae and Caenorhabditis elegans genomes. In both cases, the resulting maps paved the way towards the sequencing of these genomes, as well as provided key...
10.1126/science.7542802
123,244,815
The naturally transformable, Gram-negative bacterium Haemophilus influenzae Rd preferentially takes up DNA of its own species by recognizing a 9-base pair sequence, 5′-AAGTGCGGT, carried in multiple copies in its chromosome. With the availability of the complete genome sequence, 1465 copies of the 9-base pair uptake si...
10.1038/35084503
Publication reporting the genome sequence of the first prokaryotic organism, the bacterium Haemophilus influenzae . This effort was the first report of using a whole-genome shotgun-sequencing strategy to sequence the genome of a free-living organism.
10.1126/science.287.5461.2196
20,235,656
We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addit...
10.1038/35084503
References 86 and 87 report the initial genome sequence of Drosophila melanogaster generated by a hybrid strategy that involved both whole-genome shotgun sequencing and clone-by-clone shotgun sequencing. This project reflected a collaboration between the public Human Genome Project and Celera Genomics.
10.1083/jcb.141.1.163
45,527,187
Pericentrin and γ-tubulin are integral centrosome proteins that play a role in microtubule nucleation and organization. In this study, we examined the relationship between these proteins in the cytoplasm and at the centrosome. In extracts prepared from Xenopus eggs, the proteins were part of a large complex as demonstr...
10.1038/35089575
Identifies pericentrin as a protein that interacts with the γ-tubulin ring complex and co-localizes with γ-tubulin at the centrosome (also see reference 34
10.1083/jcb.151.3.709
82,114,172
Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. We cloned and sequenced a Chlamydomonas cDNA encoding the IFT88 subunit of the IFT particle and identified a Chlamydomonas insertional m...
10.1038/35089575
Demonstration that a centriole protein required for formation of cilia and flagella is involved in polycystic kidney disease.
10.1083/jcb.143.6.1575
59,500,648
Glutamylation is the major posttranslational modification of neuronal and axonemal tubulin and is restricted predominantly to centrioles in nonneuronal cells (Bobinnec, Y., M. Moudjou, J.P. Fouquet, E. Desbruyères, B. Eddé, and M. Bornens. 1998. Cell Motil. Cytoskel. 39:223–232). To investigate a possible relationship ...
10.1038/35089575
Shows that disruption of centrioles causes dispersion of PCM components, indicating a role for centrioles in centrosome organization.
10.1083/jcb.144.4.721
39,332,395
γ-tubulin exists in two related complexes in Drosophila embryo extracts (Moritz, M., Y. Zheng, B.M. Alberts, and K. Oegema. 1998. J. Cell Biol. 142:1– 12). Here, we report the purification and characterization of both complexes that we name γ-tubulin small complex (γTuSC; ∼280,000 D) and Drosophila γTuRC (∼2,200,000 D)...
10.1038/35089575
Identification of two γ-tubulin complexes of different sizes in Drosophila embryos.
10.1073/pnas.97.11.5919
100,815,869
Eukaryotic chromosome segregation depends on the mitotic spindle apparatus, a bipolar array of microtubules nucleated from centrosomes. Centrosomal microtubule nucleation requires attachment of γ-tubulin ring complexes to a salt-insoluble centrosomal core, but the factor(s) underlying this attachment remains unknown. I...
10.1038/35089575
Shows that an apparent isoform of human pericentrin, pericentrinB/kendrin has a calmodulin-binding domain that is homologous to the yeast protein Spc110, which binds γ-tubulin complexes at the spindle pole body (also see reference 6
10.1242/jcs.113.17.3013
104,437,692
The novel concept of a centrosomal anchoring complex, which is distinct from the gamma-tubulin nucleating complex, has previously been proposed following studies on cochlear epithelial cells. In this investigation we present evidence from two different cell systems which suggests that the centrosomal protein ninein is ...
10.1038/35089575
Identification of a protein ninein that localizes to unique microtubule minus-end anchoring sites in epithelial cells and to specializations on the maternal centriole involved in microtubule anchoring (also see reference 41
10.1083/jcb.147.3.481
100,820,707
Pericentrin is a conserved protein of the centrosome involved in microtubule organization. To better understand pericentrin function, we overexpressed the protein in somatic cells and assayed for changes in the composition and function of mitotic spindles and spindle poles. Spindles in pericentrin-overexpressing cells ...
10.1038/35089575
Demonstration that pericentrin interacts directly with a component of cytoplasmic dynein, the light intermediate chain (LIC), suggesting a role for LIC in centrosome assembly.
10.1083/jcb.147.5.969
17,592,683
We identified Xenopus pericentriolar material-1 (PCM-1), which had been reported to constitute pericentriolar material, cloned its cDNA, and generated a specific pAb against this molecule. Immunolabeling revealed that PCM-1 was not a pericentriolar material protein, but a specific component of centriolar satellites, mo...
10.1038/35089575
Shows cytoplasmic dynein-dependent recruitment of pericentrin and PCM-1, to centrosomes, as well as time-lapse imaging of these movements.
10.1126/science.1057330
109,156,801
As an organelle coupling nuclear and cytoplasmic divisions, the centrosome is essential to mitotic fidelity, and its inheritance could be critical to understanding cell transformation. Investigating the behavior of the centrosome in living mitotic cells, we documented a transient and remarkable postanaphase repositioni...
10.1038/35089575
Suggests a novel requirement for centrioles in the completion of cytokinesis.
10.1126/science.1056866
102,590,323
Centrosomes were microsurgically removed from BSC-1 African green monkey kidney cells before the completion of S phase. Karyoplasts (acentrosomal cells) entered and completed mitosis. However, postmitotic karyoplasts arrested before S phase, whereas adjacent control cells divided repeatedly. Postmitotic karyoplasts ass...
10.1038/35089575
Shows that surgical removal of centrosomes does not affect spindle assembly but inhibits progression from G1 to S phase.
10.1083/jcb.153.1.237
101,173,535
When centrosomes are destroyed during prophase by laser microsurgery, vertebrate somatic cells form bipolar acentrosomal mitotic spindles (Khodjakov, A., R.W. Cole, B.R. Oakley, and C.L. Rieder. 2000. Curr. Biol. 10:59–67), but the fate of these cells is unknown. Here, we show that, although these cells lack the radial...
10.1038/35089575
Shows that laser ablation of centrosomes causes defects in cytokinesis and blocks cell cycle progression from G1 to S phase.
10.1073/pnas.96.6.2817
60,151,872
Centrosomes nucleate microtubules and duplicate once per cell cycle. This duplication and subsequent segregation in mitosis results in maintenance of the one centrosome/cell ratio. Centrosome duplication occurs during the G 1 /S transition in somatic cells and must be coupled to the events of the nuclear cell cycle; fa...
10.1038/35089575
References 92 and 93 report the identification of Cdk2–cyclinE/A as regulators of centrosome duplication in Xenopus embryos and extracts.
10.1126/science.290.5492.809
105,394,416
Until now, genome-wide transcriptional profiling has been limited to single-cell organisms. The nematode Caenorhabditis elegans is a well-characterized metazoan in which the expression of all genes can be monitored by oligonucleotide arrays. We used such arrays to quantitate the expression of C. elegans genes throughou...
10.1038/35088523
Affymetrix DNA chips were used to profile gene expression changes during development and ageing. The paper showed that genes conserved in yeast show less developmental regulation than non-conserved genes, possibly because they perform core cell biological functions and are ubiquitously expressed.
10.1073/pnas.98.1.218
59,125,931
We have constructed DNA microarrays containing 17,871 genes, representing about 94% of the 18,967 genes currently annotated in the Caenorhabditis elegans genome. These DNA microarrays can be used as a tool to define a nearly complete molecular profile of gene expression levels associated with different developmental st...
10.1038/35088523
In this study, gene expression changes during development and in the two sexes were analysed using DNA microarrays.
10.1126/science.287.5450.116
103,766,459
Protein interaction mapping using large-scale two-hybrid analysis has been proposed as a way to functionally annotate large numbers of uncharacterized proteins predicted by complete genome sequences. This approach was examined in Caenorhabditis elegans , starting with 27 proteins involved in vulval development. The res...
10.1038/35088523
A pilot study showing that a semi-automated yeast two-hybrid approach could be used to identify protein interactions for large numbers of C. elegans proteins in parallel. The study focused on 27 proteins known to be involved in vulval differentiation, including several pairs of proteins that are known to interact.
10.1126/science.288.5475.2357
103,698,794
Definition of cellular responses to cytokines often involves cross-communication through their respective receptors. Here, signaling by interferon-γ (IFN-γ) is shown to depend on the IFN-α/β receptor components. Although these IFNs transmit signals through distinct receptor complexes, the IFN-α/β receptor component, IF...
10.1038/35073080
First demonstration and elucidation of the signalling cross-talk mechanism between IFN-α/β and IFN-γ.
10.1146/annurev.immunol.19.1.623
41,536,954
Interferon regulatory factors (IRFs) constitute a family of transcription factors that commonly possess a novel helix-turn-helix DNA-binding motif. Following the initial identification of two structurally related members, IRF-1 and IRF-2, seven additional members have now been reported. In addition, virally encoded IRF...
10.1038/35073080
Recent review on the regulation of host defence by the IRF family of transcription factors.
10.1126/science.8009221
125,114,982
Mice lacking the known subunit of the type I interferon (IFN) receptor were completely unresponsive to type I IFNs, suggesting that this receptor chain is essential for type I IFN-mediated signal transduction. These mice showed no overt anomalies but were unable to cope with viral infections, despite otherwise normal i...
10.1038/35073080
Clear demonstration of the non-redundant antiviral functions between the IFN-α/β and IFN-γ signalling pathways. This paper also presents initial data on the IFNAR1-dependent IFN-γ response.
10.1046/j.1365-2443.1996.08008.x
27,975,083
Background: Interferons (IFNs) are a class of cytokines which confer cellular resistance against viral infections. Type I (IFN‐α and ‐β) and type II (IFN‐γ) IFNs utilize distinct receptors, the stimulation of which results in the induction of downstream target genes. These target genes usually contain within their prom...
10.1038/35073080
Describes generation of the p48 IRF-9 knockout mouse, and provides evidence for the role of IR-9 in both type I and type II interferon responses
10.1101/gad.13.1.125
124,514,632
The PRDI-BF1/Blimp-1 protein is a transcriptional repressor required for normal B-cell differentiation, and it has been implicated in the repression of β-interferon ( IFN-β ) and c- myc gene expression. Here, we show that PRDI-BF1 represses transcription of the IFN-β promoter and of an artificial promoter through an ac...
10.1038/35073080
Identification and characterization of NF-κB-repressing factor (NRF), which inhibits the transcriptional activity of NF-κB and is engaged in IFN-β gene silencing in the absence of viral infection.
10.1101/gad.870201
81,496,347
We report that the bacterial transposon Tn7 selects targets by recognizing features associated with DNA replication using the transposon-encoded DNA-binding protein TnsE. We show that Tn7 transposition directed by TnsE occurs in one orientation with respect to chromosomal DNA replication, indicating that a structure or...
10.1038/35099006
Together with reference 28 , this study showed that TnsE-mediated transposition recognizes structures associated with DNA replication.
10.1126/science.289.5478.444
61,893,818
The guanosine triphosphatase Rab1 regulates the transport of newly synthesized proteins from the endoplasmic reticulum to the Golgi apparatus through interaction with effector molecules, but the molecular mechanisms by which this occurs are unknown. Here, the tethering factor p115 was shown to be a Rab1 effector that b...
10.1038/35052055
Shows that the previously identified tethering factor, p115, is a Rab1 effector and direct ly interacts with the SNARE machinery. The functional importance of an interaction between a Rab effector and the cis -SNARE complex during vesicle budding highlights the multiple roles of Rab effectors.
10.1083/jcb.148.6.1231
19,078,765
The homotypic fusion of yeast vacuoles requires Sec18p (NSF)-driven priming to allow vacuole docking, but the mechanism that links priming and docking is unknown. We find that a large multisubunit protein called the Vam2/6p complex is bound to cis-paired SNAP receptors (SNAREs) on isolated vacuoles. This association of...
10.1038/35052055
These experiments have shown that the HOPS complex is an effector of Ypt7p in vacuole tethering. Furthermore, this work, together with References 57 and 86 provided the first demonstrations of the dynamics of the interactions between Rab effector and SNARE machineries.
10.1126/science.279.5350.580
79,485,905
Rab guanosine triphosphatases regulate vesicular transport and membrane traffic within eukaryotic cells. Here, a kinesin-like protein that interacts with guanosine triphosphate (GTP)–bound forms of Rab6 was identified. This protein, termed Rabkinesin-6, was localized to the Golgi apparatus and shown to play a role in t...
10.1038/35052055
A yeast two-hybrid search for effectors identified a kinesin as a Rab6-interacting protein. In line with the concept that Rab proteins can have different functions, this result suggests that a Rab protein might be functionally connected with the microtubule-dependent motility of vesicles and organelles.
10.1126/science.8385367
61,633,875
The VPS 34 gene product (Vps34p) is required for protein sorting to the lysosome-like vacuole of the yeast Saccharomyces cerevisiae . Vps34p shares significant sequence similarity with the catalytic subunit of bovine phosphatidylinositol (PI) 3-kinase [the 110-kilodalton (p110) subunit of PI 3-kinase], which is known t...
10.1038/35052055
First demonstration of a functional connection between PI(3)K and membrane transport.
10.1091/mbc.11.8.2657
60,984,096
EEA1 is an early endosomal Rab5 effector protein that has been implicated in the docking of incoming endocytic vesicles before fusion with early endosomes. Because of the presence of complex endosomal pathways in polarized and nonpolarized cells, we have examined the distribution of EEA1 in diverse cell types. Ultrastr...
10.1038/35052055
References 57 68 – 70 support the idea that Rab proteins and their effectors are compartmentalized in early endosomes and show a non-random distribution.
10.1038/jcbfm.1993.67
17,699,424
Transforming growth factor-β 1 (TGF-β 1 ) has been shown to be an injury-related peptide growth factor within the mammalian central nervous system. We tested whether TGF-β 1 has the capacity to protect rat neocortical neurons against excitotoxic damage in vitro and mouse neocortex against ischemic injury in vivo. After...
10.1038/35094583
An early study showing neuroprotective effects of TGFβ in vivo against cerebral ischaemia, and in vitro against glutamate toxicity on primary neuronal cultures.
10.1097/00004647-199702000-00013
123,858,312
Tumor necrosis factor alpha (TNF- α) is expressed in the ischemic brain; however, its precise role is not fully understood. We studied the effect of the dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp) on focal cerebral ischemia in mice using a permanent middle cerebral arterial occ...
10.1038/35094583
An early study indicating that endogenous TNFα mediates ischaemic brain damage in vivo . TNF-binding protein — a naturally occurring inhibitor of TNF — reduced damage caused by focal cerebral ischaemia in mice.
10.1073/pnas.96.15.8721
42,567,357
The present study evaluated behavioral and histopathological outcome after controlled cortical impact (CCI) brain injury in mice deficient in tumor necrosis factor [TNF(−/−)] and their wild-type (wt) littermates. Mice were subjected to CCI brain injury [TNF(−/−), n = 10; wt, n = 10] or served as uninjured controls [TNF...
10.1038/35094583
This study might provide an explanation for seemingly conflicting reports indicating that endogenous TNFα is either neurotoxic (based largely on acute interventions) or neuroprotective (based largely on stadies on genetically modified animals). It reports that functional outcomes in TNFα-null mice were improved early a...
10.1097/00004647-199611000-00007
125,294,047
A series of experiments was performed to determine the role of interleukin (IL)-1 in the induction of tolerance to global ischemia in Mongolian gerbils. In Group I, a 2-min “preconditioning” ischemia protected CA1 hippocampal neurons in gerbils subjected to 3.5 min ischemia 3 days later. CA1 neuronal density was: sham,...
10.1038/35094583
The first demonstration that endogenous IL-1 can mediate ischaemic tolerance. Pre-treatment of gerbils three days before global ischaemia reduced brain injury. IL-1 was induced by a brief period of 'preconditionary' ischaemia.
10.1084/jem.185.3.579
103,324,459
Microglial cells express a peculiar plasma membrane receptor for extracellular ATP, named P2Z/P2X7 purinergic receptor, that triggers massive transmembrane ion fluxes and a reversible permeabilization of the plasma membrane to hydrophylic molecules of up to 900 dalton molecule weight and eventual cell death (Di Virgili...
10.1038/35094583
An early study showing that IL-1β is released from microglia by activation of purinergic, P2X7 receptors. Bacterial LPS is required for activation of microglial IL-1β expression, whereas ATP induced cleavage and release.
10.1073/pnas.96.17.9879
18,506,436
Heightened expression of both a proinflammatory cytokine, tumor necrosis factor α (TNF-α), and a survival peptide, insulin-like growth factor I (IGF-I), occurs in diverse diseases of the central nervous system, including Alzheimer’s disease, multiple sclerosis, the AIDS-dementia complex, and cerebral ischemia. Conventi...
10.1038/35094583
This study provided a potential explanation for indirect effects of the proinflammatory cytokine TNFα on neuronal survival through modification of the signalling pathway of a protective growth factor, IGF. This mechanism might apply to other neurotoxic cytokines.
10.1073/pnas.93.11.5635
122,098,554
We compare here the mechanisms of apoptotic death of PC12 cells induced by down-regulation of Cu2+,Zn2+ superoxide dismutase (SOD1) and withdrawal of trophic support (serum/nerve growth factor). Our previous results indicated that the initiating causes of death are different in each paradigm. However, bcl-2 rescues cel...
10.1038/35094583
An early study reporting the contribution of ICE (caspase 1) to apoptosis in a neuronal cell line (PC12 cells) and indicating that ICE acts through modification of superoxide dismutase 1.
10.1126/science.272.5263.864
60,479,032
The extent of racemization of aspartic acid, alanine, and leucine provides criteria for assessing whether ancient tissue samples contain endogenous DNA. In samples in which the D/L ratio of aspartic acid exceeds 0.08, ancient DNA sequences could not be retrieved. Paleontological finds from which DNA sequences purported...
10.1038/35072071
Presents amino-acid analysis as a tool to substantiate claims that DNA can (or cannot) survive in ancient organic remains.
10.1101/gad.12.12.1825
39,470,583
Neuregulins (NDF, heregulin, GGF ARIA, or SMDF) are EGF-like growth and differentiation factors that signal through tyrosine kinase receptors of the ErbB family. Here, we report a novel phenotype in mice with targeted mutations in the erbB2, erbB3, or neuregulin-1 genes. These three mutations cause a severe hypoplasia ...
10.1038/35052073
By targeting ErbB2, ErbB3 and NRG1, the authors revealed that the ternary complex has an essential role in the developing sympathetic nervous system. Apparently, signalling by this complex drives migration of sympathetic cells from the neural crest.
10.1126/science.3798106
104,442,629
The HER-2/ neu oncogene is a member of the erb B-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigat...
10.1038/35052073
First demonstration of the prognostic value of ErbB2 amplification in breast cancer. Gene amplification was correlated with several disease parameters, and was a significant predictor of patient survival and time to relapse.
10.1101/gad.12.23.3663
28,256,861
Ligand-induced down-regulation of two growth factor receptors, EGF receptor (ErbB-1) and ErbB-3, correlates with differential ability to recruit c-Cbl, whose invertebrate orthologs are negative regulators of ErbB. We report that ligand-induced degradation of internalized ErbB-1, but not ErbB-3, is mediated by transient...
10.1038/35052073
First report of the endocytic-sorting function of c-Cbl, a ubiquitin ligase that is a major substrate of ErbB1. Unlike sorting by c-Cbl to the late endosome, the oncogenic viral form, v-Cbl, shunts internalized receptors to the recycling pathway.
10.1002/cne.902860306
18,958,308
Abstract An investigation of the architectonic organization and intrinsic connections of the prefrontal cortex was conducted in rhesus monkeys. Cytoarchitectonic analysis indicates that in the prefrontal cortex there are two trends of gradual change in laminar characteristics that can be traced from limbic periallocort...
10.1038/35077500
An evolutionary perspective on cyto- and myelo-architecture and cortico–cortical connectivity of the monkey prefrontal cortex, including the cingulate cortex.
10.1523/jneurosci.11-03-00667.1991
29,095,238
We determined the origin of corticospinal neurons in the frontal lobe. These neurons were labeled by retrograde transport of tracers after injections into either the dorsolateral funiculus at the second cervical segment or the gray matter of the spinal cord throughout the cervical enlargement. Using retrograde transpor...
10.1038/35077500
A landmark study on the organization of corticospinal projections in the monkey lateral and medial frontal cortex.
10.1002/cne.902790208
62,543,888
Abstract The organization of the cortical monoamine systems, dopamine (DA), and noradrenaline (NA), which have been studied extensively in the rat and more recently in the monkey, had not yet been investigated directly in the human brain. We report here the first systematic account of the regional and laminar distribut...
10.1038/35077500
The first systematic account of the regional and laminar distribution of catecholamine-mediated innervation of the human cerebral cortex.
10.1002/cne.903110403
20,382,229
Abstract The mesial agranular frontal cortex that lies rostral to area 4 (F1) is formed by two distinct cytoarchitectonic areas: F3, located caudally, and F6, located rostrally. In the present experiments we investigated the organization of F3 and F6 by observing the motor responses evoked by their intracortical electr...
10.1038/35077500
The first microstimulation study of cingulate motor areas in the macaque monkey.
10.1152/jn.1991.65.2.188
122,651,498
1. Single-unit activity in the cingulate cortex of the monkey was recorded during the performance of sensorially (visual, auditory, or tactile) triggered or self-paced forelimb key press movements. 2. Microelectrodes were inserted into the broad rostrocaudal expanse of the cingulate cortex, including the upper and lowe...
10.1038/35077500
The first demonstration of functional specialization of the rostral and caudal cingulate motor areas in the monkey.
10.1126/science.288.5472.1835
62,145,367
Theories of the regulation of cognition suggest a system with two necessary components: one to implement control and another to monitor performance and signal when adjustments in control are needed. Event-related functional magnetic resonance imaging and a task-switching version of the Stroop task were used to examine ...
10.1038/35077500
An fMRI study of task preparation and execution, which provides the first functional evidence for differential engagement of the lateral prefrontal cortex and the anterior cingulate cortex during the performance of the Stroop task.
10.1002/cne.903590310
123,147,872
Abstract The surface morphology land cytoarchitecture of human cingulate cortex was evaluated in the brains of 27 neurologically intact individuals. Variations in surface features included a single cingulate sulcus (CS) with or without segmentation or double parallel sulci with or without segmentation. The single CS wa...
10.1038/35077500
Systematic study of the cingulate cytoarchitecture and its relationship to the sulcal pattern in the human brain.